Blocking key mutated hotspot residues in the RBD of the omicron variant (B.1.1.529) with medicinal compounds to disrupt the RBD-hACE2 complex using molecular screening and simulation approaches

A new variant of SARS-CoV-2 known as the omicron variant (B.1.1.529) reported in South Africa with 30 mutations in the whole spike protein, among which 15 mutations are in the receptor-binding domain, is continuously spreading exponentially around the world. The omicron variant is reported to be highly contagious with antibody-escaping activity. The emergence of antibody-escaping variants is alarming, and thus the quick discovery of small molecule inhibitors is needed. Hence, the current study uses computational drug screening and molecular dynamics simulation approaches (replicated) to identify novel drugs that can inhibit the binding of the receptor-binding domain (RBD) with hACE2. Screening of the North African, East African and North-East African medicinal compound databases by employing a multi-step screening approach revealed four compounds, namely (−)-pipoxide (C1), 2-(p-hydroxybenzyl) benzofuran-6-ol (C2), 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol (C3), and Rhein (C4), with excellent anti-viral properties against the RBD of the omicron variant. Investigation of the dynamics demonstrates stable behavior, good residue flexibility profiles, and structural compactness. Validation of the top hits using computational bioactivity analysis, binding free energy calculations and dissociation constant (K_D) analysis also indicated the anti-viral properties of these compounds. In conclusion, this study will help in the design and discovery of novel drug therapeutics, which may be used against the emerging omicron variant of SARS-CoV-2.

A new variant of SARS-CoV-2 known as the omicron variant (B.1.1.529) reported in South Africa with 30 mutations in the whole spike protein, among which 15 mutations are in the receptor-binding domain, is continuously spreading exponentially around the world.     

Antibody responses and SARS-CoV-2 infection after BNT162b2 mRNA booster vaccination among healthcare workers in Japan

IntroductionVaccine effectiveness against SARS-CoV-2 infections decreases due to waning immunity, and booster vaccination was therefore introduced. We estimated the anti-spike antibody (AS-ab) recovery by booster vaccination and analyzed the risk factors for SARS-CoV-2 infections.MethodsThe subjects were health care workers (HCWs) in a Chiba University Hospital vaccination cohort. They had received two doses of vaccine (BNT162b2) and a booster vaccine (BNT162b2). We retrospectively analyzed AS-ab titers and watched out for SARS-CoV-2 infection for 90 days following booster vaccination.ResultsAS-ab titer eight months after two-dose vaccinations had decreased to as low as 587 U/mL (median, IQR (interquartile range) 360–896). AS-ab titer had then increased to 22471 U/mL (15761–32622) three weeks after booster vaccination. There were no significant differences among age groups.A total of 1708 HCWs were analyzed for SARS-CoV-2 infection, and 48 of them proved positive. SARS-CoV-2 infections in the booster-vaccinated and non-booster groups were 1.8% and 4.0%, respectively, and were not significant. However, when restricted to those 20–29 years old, SARS-CoV-2 infections in the booster-vaccinated and non-booster groups were 2.9% and 13.6%, respectively (p = 0.04). After multivariate logistic regression, COVID-19 wards (adjusted odds ratio (aOR):2.9, 95% confidence interval (CI) 1.5–5.6) and those aged 20–49 years (aOR:9.7, 95%CI 1.3–71.2) were risk factors for SARS-CoV-2 infection.ConclusionsBooster vaccination induced the recovery of AS-ab titers. Risk factors for SARS-CoV-2 infection were HCWs of COVID-19 wards and those aged 20–49 years. Increased vaccination coverage, together with implementing infection control, remains the primary means of preventing HCWs from SARS-CoV-2 infection.     

Determinants of mental health service use in the national mental health survey of the elderly in Singapore

Background

Despite high prevalence of mental health problems, only a minority of elderly people seek treatment. Although need-for-care factors are primary determinants of mental health service use, personal predisposing or enabling factors including health beliefs are important but are not well studied.

Method

In the National Mental Health Survey of Elderly in Singapore, 2003, 1092 older adults aged 60 and above were interviewed for diagnosis of mental disorders (using Geriatric Mental State) and treatment, and their health beliefs about the curability of mental illness, embarrassment and stigma, easiness discussing mental problems, effectiveness and safety of treatment and trust in professionals.

Results

The prevalence of mental disorders was 13%, but only a third of mentally ill respondents had sought treatment. Increased likelihood of seeking treatment was significantly associated with the presence of a mental disorder (OR = 5.27), disability from mental illness (OR = 79.9), and poor or fair self-rated mental health (OR = 2.63), female gender (OR = 2.25), and formal education (OR = 2.40). The likelihood of treatment seeking was lower in those reporting financial limitations for medical care (OR = 0.38), but also higher household income (OR = 0.31). Negative beliefs showed no meaningful associations, but the positive belief that 'to a great extent mental illness can be cured' was associated with increased mental health service use (OR = 6.89). The availability of family caregiver showed a negative association (OR = 0.20).

Conclusion

The determinants of mental health service use in the elderly included primary need factors, and female gender and socioeconomic factors. There was little evidence of influences by negative health beliefs, but a positive health belief that 'mental illness can be cured' is a strongly positive determinant The influence of family members and care-givers on senior's use of mental health service should be further explored.

     

Features of antibody responses after SARS-COV-2 infection in healthcare workers in the first wave of COVID-19 pandemic in Mexico City

ObjectiveTo investigate the antibody response to SARS-CoV-2 and identify associated factors in frontline and second-line healthcare workers (HCWs) at a large hospital in Mexico City during the first wave of COVID-19 pandemic.MethodsThis was a cross-sectional study of HCWs returning to work following mandatory isolation after recovering from COVID-19. Immunoglobulin (Ig) M and IgG antibodies elicited by SARS-CoV-2 were semiquantitatively measured using densitometric analysis of band intensities in lateral flow assay (LFA) devices. The mean pixel intensity (dots-per-inch [dpi]) of each band on the LFA was considered a measure of antibody titre.ResultsOf the 111 HCWs involved in the study, antibody responses were detected in 73/111 (66%) participants. Severe COVID symptoms was associated with old age. No differences in IgM intensity were observed between men and women, but IgG intensity was significantly higher in men than in women. Second-line HCWs produced a higher IgG intensity than firstline HCWs. The IgG intensity was high in severe cases.ConclusionsFor HCWs who may acquire SARS-CoV-2 infection, it is necessary to establish a routine program for detection of the virus to avoid risk of infection and spread of COVID-19.     

Nosocomial transmission of SARS-CoV-2 from infected children to uninfected caregivers: A retrospective cohort study in a Japanese tertiary children's hospital

BackgroundThe transmission rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear when caregivers accompany pediatric COVID-19 patients in the same isolation room in a hospital setting.AimWe investigated SARS-CoV-2 transmission from infected children to caregivers at our hospital.MethodsThis retrospective cohort study included 34 discordant pairs of patients admitted between September 2020 and April 2022.FindingsThe median ages of the children and caregivers were 3.7 years (interquartile range [IQR]: 1.6–8.1) and 33.1 years (IQR: 28.3–43.4), respectively. Of the 34 caregivers, 31 were mothers, two were fathers, and one was a relative. Sixteen caregivers received at least two doses of the mRNA vaccine. The mean duration of the hospital stays was 7.7 ± 4.1 days (range: 3–19). Two unvaccinated caregivers developed COVID-19 after admission; the onset was within 48 h after admission. It is likely that they had been infected in their household prior to admission, since the incubation period for COVID-19 is usually >2 days.ConclusionsNosocomial SARS-CoV-2 transmission from infected children to caregivers was not confirmed in this study. The combination of negative-pressure rooms, vaccinations, and infection-control bundles appears to be effective at preventing SARS-CoV-2 transmission. It is acceptable to allow caregivers to accompany pediatric COVID-19 patients in a hospital ward if they can comply with basic infection control measures.     

Effectiveness of personal protective equipment in preventing severe acute respiratory syndrome coronavirus 2 infection among healthcare workers

IntroductionInformation on the effectiveness of personal protective equipment (PPE) for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers (HCWs), especially among HCWs with frequent contact with patients with SARS-CoV-2, is limited.MethodsWe conducted a prospective cohort study on 49 HCWs who worked in close contact with patients with SARS-CoV-2 infection. HCWs had blood samples taken every 2 weeks to test for SARS-CoV-2 antibodies using two different types of assay.ResultsForty-nine participants (31 nurses, 15 doctors, 3 other workers) were enrolled. In total, 112 blood samples are obtained from participants. The median work days in 2 weeks was 9 (interquartile range (IQR): 5–10) days. In a single work day, 30 of the 49 participants (61.5%) had contact with patients with suspected or conformed SARS-CoV-2 at least 8 times, and approximately 60% of participants had more than 10 min of contact with a single patient. The median self-reported compliance to PPE was 90% (IQR: 80–100%). Seven participants tested positive for SARS-CoV-2 antibody using enzyme-linked immunosorbent assay (ELISA); however, none were seropositive for SARS-CoV-2 neutralizing antibody, so the positive ELISA results were assumed to be false-positive.ConclusionsThe study provides evidence that appropriate PPE is sufficient to prevent infection amongHCWs. It is necessary to establish a system that provides a stable supply of PPE for HCWs to perform their duties.     

Association of ALOX5, LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China

BACKGROUND:

Genetic variations of the 5-lipoxygenase activating protein and leukotriene A4 hydrolase genes that confer an increased risk of ischemic stroke have implicated the family of leukotrienes as potential mediators of ischemic stroke. This study aimed to explore the association of ALOX5, LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China.

METHODS:

This case-control study consisted of 690 patients with ischemic stroke and 690 controls. Polymorphisms of ALOX5 rs2029253 A/G, LTA4H rs6538697 T/C, and LTC4S rs730012 A/C were genotyped by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. The multivariate logistic regression model was used to exclude the effects of conventional risk factors on ischemic stroke.

RESULTS:

Carriers of C allele in rs730012 were more susceptible to ischemic stroke (OR: 1.37; 95%CI: 1.08–1.73; P=0.009). The rs2029253 GG genotype showed a risk-reducing effect on ischemic stroke (OR: 0.72; 95%CI: 0.55–0.93; P=0.013) while the rs6538697 CC genotype had an increased risk of ischemic stroke (OR: 1.77; 95%CI: 1.09–2.89; P=0.022). The rs730012 variant was not associated with ischemic stroke risk after adjusting confounding factors (P>0.05).

CONCLUSION:

The present study suggested that gene polymorphisms in the leukotrienes pathway may exert influences, with independent genetic effects, on ischemic stroke susceptibility in a cohort of Chinese in east China.KEY WORDS: Leukotrienes, Gene polymorphisms, Risk factors, Ischemic stroke     

Searching for escape-resistant anti–SARS-CoV-2 neutralizing antibodies

A major goal of SARS-CoV-2 vaccination is the induction of neutralizing antibodies (nAbs) capable of blocking infection by preventing interaction of the SARS-CoV-2 Spike protein with ACE2 on target cells. Cocktails of monoclonal nAbs can reduce the risk of severe disease if administered early in infection. However, multiple variants of concern (VOCs) have arisen during the pandemic that may escape from nAbs. In this issue of the JCI, Jia Zou, Li Li, and colleagues used yeast display libraries to identify mAbs that bind to Spike proteins with a vast array of single amino acid substitutions. The authors identified mutation-resistant monoclonal nAbs for potential use as therapeutics. Multimerization further improved the potency of selected nAbs. These findings suggest a way forward in development of better nAb cocktails. However, the emergence of the highly mutated omicron (B.1.1.529) variant heightens the importance of finding effective anti–SARS-CoV-2 nAb therapeutics despite rapid viral evolution.     

SARS-CoV-2 seroprevalence in healthcare workers in a high-volume ophthalmology centre in Guatemala

PurposeTo determine the seroprevalence of SARS-CoV-2 antibodies in eye healthcare workers (EHCW) in the largest ophthalmology centre in Guatemala and factors associated with antibody positivity.MethodsWe conducted a cross sectional sero-survey in all the staff at the largest ophthalmology centre in Guatemala. Serum samples were collected and tested for total antibodies against SARS-CoV-2 employing Roche Elecsys Anti-SARS-CoV-2 Immunoassay. Results were reported as reactive or non-reactive. According to patient exposure the staff were divided into low risk (technicians, domestic and administrative staff) and high risk (nurses, ophthalmologists, anaesthesiologists, and optometrists). Among those with positive antibodies, they were given a survey that included demographic characteristics, COVID-19 exposure, and related symptomatology. Logistic regression was used to determine the factors associated with antibody positivity.ResultsOn November 25th a total of 94 healthcare workers were sero-surveyed, mean age was 34.15 years (±8.41), most (57.44%) were females. Seroprevalence was 18%, the majority (77%) were in the low-risk group; while 64% at high-risk, tested negative. Those at low exposure, were five times more likely to have antibodies than those at high exposure (OR:5.69; 95% CI 1.69–19.13). Age and gender were not associated to seropositivity.ConclusionsWe found a similar seroprevalence of SARS-CoV-2 antibodies in EHCW to what has been reported in other healthcare groups. Seropositivity was higher among HCW with fewer patient exposure, hence the probability of community transmission.

Key messages

• Even though eye healthcare workers are believed to be at higher risk of infection, the prevalence of antibodies against SARS-CoV-2 in this group is comparable to what has been reported previously in other healthcare groups.

     

Transmission of SARS-CoV-2 during air travel: a descriptive and modelling study

ObjectivesTo explore the potential of SARS-CoV-2 spread during air travel and the risk of in-flight transmission.MethodsWe enrolled all passengers and crew suspected of being infected with SARS-CoV-2, who bounded for Beijing on international flights. We specified the characteristics of all confirmed cases of COVID-19 infection and utilised Wells-Riley equation to estimate the infectivity of COVID-19 during air travel.ResultsWe screened 4492 passengers and crew with suspected COVID-19 infection, verified 161 confirmed cases (mean age 28.6 years), and traced two confirmed cases who may have been infected in the aircraft. The estimated infectivity was 375 quanta/h (range 274–476), while the effective infectivity was only 4 quanta/h (range 2–5). The risk of per-person infection during a 13 h air travel in economy class was 0.56‰ (95% CI 0.41‰–0.72‰).ConclusionWe found that the universal use of face masks on the flight, together with the plane''s ventilation system, significantly decreased the infectivity of COVID-19.

KEY MESSAGES

• The COVID-19 pandemic is changing the lifestyle in the world, especially air travel which has the potential to spread SARS-CoV-2.
• The universal use of face masks on the flight, together with the plane''s ventilation system, significantly decreased the infectivity of COVID-19 on an aircraft.
• Our findings suggest that the risk of infection in aircraft was negligible.

     

Utilization of a mobile medical van for delivering pediatric care in the bateys of the Dominican Republic

Background

Bateys are impoverished areas of housing for migrant Haitian sugar cane workers in the Dominican Republic (DR). In these regions, preventative health care is almost non-existent, public service accessibility is limited, and geographic isolation prevents utilization of care even by those families with resources. Consequently, the development of a viable mobile system is vital to the delivery of acute and preventative health care in this region.

Aims

This study evaluated an existing mobile medical system. The primary goal was to describe the population served, diseases treated, and resources utilized. A secondary goal was to determine qualitatively an optimal infrastructure for sustainable health care delivery within the bateys.

Methods

Information on basic demographic data, diagnosis, chronicity of disease, and medications dispensed was collected on all pediatric patients seen in conjunction with an existing mobile medical system over a 3-month period in the DR. Health statistics for the region were collected and interviews were conducted with health care workers (HCWs) and community members on existing and optimal health care infrastructure.

Results

Five hundred eighty-four pediatric patients were evaluated and treated. Median age was 5 years (range 2 weeks to 20 years), and 53.7% of patients seen were 5 years of age or younger. The mean number of complaints per patient was 2.8 (range 0 to 6). Thirty-six percent (373) of all diagnoses were for acute complaints, and 64% (657) were chronic medical problems. The most common pediatric illnesses diagnosed clinically were gastrointestinal parasitic infection (56.6%), skin/fungal infection (46.2%), upper respiratory tract infections (URIs) (22.8%), previously undiagnosed asthma and allergies (8.2%), and symptomatic anemia (7.2%). Thirty HCWs and community members were interviewed, and all cited the need for similar resources: a community clinic and hospital referral site, health promoters within each community, and the initiation of pediatric training for community HCWs.

Conclusion

A mobile medical system is a sustainable, efficient mechanism for delivering acute and preventive care in the Haitian bateys of the Dominican Republic. The majority of patients served were 8 years of age or younger with multiple presenting symptoms. A pediatric protocol for identifying the most appropriate drugs and supplies for mobile units in the DR can be created based upon diseases evaluated. Qualitative data from HCWs and community members identified the need for an integrative health care delivery infrastructure and community health promoters versed in pediatric care who can aid in education of batey members and monitor chronic and acute illnesses. We are planning follow-up visits to implement these programs.     

Inactivation of SARS-CoV-2 infectivity in platelet concentrates or plasma following treatment with ultraviolet C light or with methylene blue combined with visible light

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unlikely to be a major transfusion-transmitted pathogen; however, convalescent plasma is a treatment option used in some regions. The risk of transfusion-transmitted infections can be minimized by implementing Pathogen Inactivation (PI), such as THERAFLEX MB-plasma and THERAFLEX UV-Platelets systems. Here we examined the capability of these PI systems to inactivate SARS-CoV-2.

Study Design and Methods

SARS-CoV-2 spiked plasma units were treated using the THERAFLEX MB-Plasma system in the presence of methylene blue (~0.8 μmol/L; visible light doses: 20, 40, 60, and 120 [standard] J/cm²). SARS-CoV-2 spiked platelet concentrates (PCs) were treated using the THERAFLEX UV-platelets system (UVC doses: 0.05, 0.10, 0.15, and 0.20 [standard] J/cm²). Samples were taken prior to the first and after each illumination dose, and viral infectivity was assessed using an immunoplaque assay.

Results

Treatment of spiked plasma with the THERAFLEX MB-Plasma system resulted in an average ≥5.03 log₁₀ reduction in SARS-CoV-2 infectivity at one third (40 J/cm²) of the standard visible light dose. For the platelet concentrates (PCs), treatment with the THERAFLEX UV-Platelets system resulted in an average ≥5.18 log₁₀ reduction in SARS-CoV-2 infectivity at the standard UVC dose (0.2 J/cm²).

Conclusions

SARS-CoV-2 infectivity was reduced in plasma and platelets following treatment with the THERAFLEX MB-Plasma and THERAFLEX UV-Platelets systems, to the limit of detection, respectively. These PI technologies could therefore be an effective option to reduce the risk of transfusion-transmitted emerging pathogens.     

A large cohort study of the effects of Lewis,ABO, 13 other blood groups,and secretor status on COVID-19 susceptibility,severity, and long COVID-19

Background

Previous studies have reported Blood type O to confer a lower risk of SARS-CoV-2 infection, while secretor status and other blood groups have been suspected to have a similar effect as well.

Study design and methods

To determine whether any other blood groups influence testing positive for SARS-CoV-2, COVID-19 severity, or prolonged COVID-19, we used a large cohort of 650,156 Danish blood donors with varying available data for secretor status and blood groups ABO, Rh, Colton, Duffy, Diego, Dombrock, Kell, Kidd, Knops, Lewis, Lutheran, MNS, P1PK, Vel, and Yt. Of these, 36,068 tested positive for SARS-CoV-2 whereas 614,088 tested negative between 2020-02-17 and 2021-08-04. Associations between infection and blood groups were assessed using logistic regression models with sex and age as covariates.

Results

The Lewis blood group antigen Le^a displayed strongly reduced SARS-CoV-2 susceptibility OR 0.85 CI[0.79–0.93] p < .001. Compared to blood type O, the blood types B, A, and AB were found more susceptible toward infection with ORs 1.1 CI[1.06–1.14] p < .001, 1.17 CI[1.14–1.2] p < .001, and 1.2 CI[1.14–1.26] p < .001, respectively. No susceptibility associations were found for the other 13 blood groups investigated. There was no association between any blood groups and COVID-19 hospitalization or long COVID-19. No secretor status associations were found.

Discussion

This study uncovers a new association to reduced SARS-CoV-2 susceptibility for Lewis type Le^a and confirms the previous link to blood group O. The new association to Le^a could be explained by a link between mucosal microbiome and SARS-CoV-2.     

Risk factors and prognostic predictors of unexpected intensive care unit admission within 3 days after ED discharge

Objective

Our objective was to investigate the risk factors and prognostic predictors of unexpected intensive care unit (ICU) admission within 3 days after emergency department (ED) discharge.

Methods

From January 1, 2001, through December 31, 2005, patients admitted to the ICU unexpectedly within 3 days after being discharged from the ED were enrolled. Medical records of these patients were retrospectively reviewed. We categorized each patient's characteristics into dichotomous groups and used the χ² test to identify risk factors for unexpected ICU admission within 3 days after ED discharge. A multiple logistic regression was applied to examine possible independent predictors of poor prognoses.

Results

During the study period, 365 321 patients visited our ED; 241(0.07%) were unexpectedly admitted to the ICU within 3 days after being discharged from the ED. Mean patient age was 74.2 ± 16.4 years. The rate of ICU admissions caused by medical error was 0.019% ± 0.004% of all visits and 29.0% ± 5.7% of all unexpected ICU admissions. The overall mortality rate was 19.9% (48/241). Risk factors for unexpected ICU admission within 3 days after discharge from the ED were age of 65 years or older (odds ratio [OR], 5.4; 95% confidence interval [CI], 4.0-7.4), ambulance transport (OR, 5.1; 95% CI, 3.9-6.5), no accompanying family (OR, 3.5; 95% CI, 2.7-4.5), nonambulatory status (OR, 4.2; 95% CI, 2.9-5.0), not living at home (OR, 2.5; 95% CI, 1.9-3.3), Medicaid insurance (OR, 3.6; 95% CI, 2.8-4.7), and emergency stay of more than 24 hours (OR, 4.4; 95% CI, 3.4-5.7). The independent predictors of mortality were age of 65 years or older (OR, 2.4; 95% CI, 1.7-3.6), multiple comorbidities (OR, 4.0; 95% CI, 1.8-8.5), medical error leading to ICU admission (OR, 3.9; 95% CI, 1.8-8.3), and Acute Physiology and Chronic Health Evaluation II score of 20 or higher (OR, 2.9; 95% CI, 1.1-7.8).

Conclusions

In our study, the risk factors and prognostic predictors of unexpected ICU admission within 3 days after ED discharge were identified. Based on these risk and prognostic prediction factors, further strategies for decreasing the incidence of serious adverse events of ED-discharged patients can be implemented.     

Changes in knowledge, beliefs, and perceptions throughout a multifaceted behavioral program aimed at preventing ventilator-associated pneumonia

Purpose

Prevention of ventilator-associated pneumonia (VAP) requires a complex approach that should include factors affecting healthcare workers’ (HCWs) behavior. This study attempted to assess change of individual factors throughout a multifaceted program focusing on VAP prevention.

Methods

The prevention program involved all HCWs in a 20-bed medical intensive care unit (ICU) and included a multidisciplinary task force, an educational session, direct observations and performance feedback, technical improvements, and reminders. Knowledge, beliefs, and perceptions (cognitive factors) were assessed with a test and a self-reporting questionnaire based on social-cognitive theories. They were completed before and 1 and 12 months after the educational session.

Results

Of the 100 HCWs initially evaluated, 84 were present 1 year later. Overall, individual factors (knowledge and cognitive factors) changed positively and significantly, immediately after the educational session. Five cognitive factors were significantly associated with knowledge: perceived susceptibility, seriousness, knowledge, benefits, and self-efficacy (P < 0.05). The other factors, i.e., perceived barriers, subjective and behavioral norm, intention to perform action, and motivation, were not. The positive cognitive change was significantly reinforced at 1 year. Three distinct cognitive profiles derived from answers to the baseline questionnaire were individualized. The positive impact of our behavioral approach was highest for the HCW group with the lowest baseline cognitive profiles.

Conclusions

Behavior changed gradually throughout the program and was especially pronounced for HCWs with the lowest baseline cognitive profiles.     

Risk factors for recurrent emergency department visits for hyperglycemia in patients with diabetes mellitus

Background

Patients with poorly controlled diabetes mellitus may present repeatedly to the emergency department (ED) for management and treatment of hyperglycemic episodes, including diabetic ketoacidosis and hyperosmolar hyperglycemic state. The objective of this study was to identify risk factors that predict unplanned recurrent ED visits for hyperglycemia in patients with diabetes within 30 days of initial presentation.

Methods

We conducted a 1-year health records review of patients ≥18 years presenting to one of four tertiary care EDs with a discharge diagnosis of hyperglycemia, diabetic ketoacidosis, or hyperosmolar hyperglycemic state. Trained research personnel collected data on patient characteristics and determined if patients had an unplanned recurrent ED visit for hyperglycemia within 30 days of their initial presentation. Multivariate logistic regression models using generalized estimating equations to account for patients with multiple visits determined predictor variables independently associated with recurrent ED visits for hyperglycemia within 30 days.

Results

There were 833 ED visits for hyperglycemia in the 1-year period. 54.6% were male and mean (SD) age was 48.8 (19.5). Of all visitors, 156 (18.7%) had a recurrent ED visit for hyperglycemia within 30 days. Factors independently associated with recurrent hyperglycemia visits included a previous hyperglycemia visit in the past month (odds ratio [OR] 3.5, 95% confidence interval [CI] 2.1–5.8), age <25 years (OR 2.6, 95% CI 1.5–4.7), glucose >20 mmol/L (OR 2.2, 95% CI 1.3–3.7), having a family physician (OR 2.2, 95% CI 1.0–4.6), and being on insulin (OR 1.9, 95% CI 1.1–3.1). Having a systolic blood pressure between 90–150 mmHg (OR 0.53, 95% CI 0.30–0.93) and heart rate >110 bpm (OR 0.41, 95% CI 0.23–0.72) were protective factors independently associated with not having a recurrent hyperglycemia visit.

Conclusions

This unique ED-based study reports five risk factors and two protective factors associated with recurrent ED visits for hyperglycemia within 30 days in patients with diabetes. These risk factors should be considered by clinicians when making management, prognostic, and disposition decisions for diabetic patients who present with hyperglycemia.

     

Risk Factors for Falls in Community Stroke Survivors: A Systematic Review and Meta-Analysis

Objective

To identify the risk factors for falls in community stroke survivors.

The end of life of patients with COVID-19 in intensive care unit and the stress level on their family members: A cross-sectional study

Background

During the Coronavirus disease 2019 (COVID-19) pandemic, hospital visits were suspended and video calls were offered to connect patients with their family members, especially toward the end of life (EoL).

Aim

The primary aim was to describe EoL care for COVID-19 patients dying in an intensive care unit (ICU). The secondary aim was to explore whether making video calls and allowing visits was associated with lower death-related stress in family members.

Design

Single centre cross-sectional study. The setting was the ICU of a COVID-19 center in northern Italy, during the first year of the pandemic. Data on patients who died in the ICU were collected; death-related stress on their family members was measured using the Impact of Event Scale-Revised (IES-R). The statistical association was tested by means of logistic regression.

Results

The study sample included 70 patients and 56 family members. All patients died with mechanical ventilation, hydration, nutrition, analgesia and sedation ongoing. Resuscitation procedures were performed in 5/70 patients (7.1%). Only 6/56 (10.7%) of the family members interviewed had visited their loved ones in the ICU and 28/56 (50%) had made a video call. EoL video calls were judged useful by 53/56 family members (94.6%) but all (56/56, 100%) wished they could have visited the patient. High-stress levels were found in 38/56 family members (67.9%), regardless of whether they were allowed ICU access or made a video call. Compared with other degrees of kinship, patients' offspring were less likely to show a positive IES-R score (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.05 to 0.89).

Conclusions

During the first year of the COVID-19 pandemic, patients died without their family members at the bedside while on life-sustaining treatment. Stress levels were high in most family members, especially in patients' spouses. Video calls or ICU visits were judged favourably by family members but insufficient to alleviate death-related stress.

Relevance for Clinical Practice

During a pandemic, ICU access by patients' family members should be considered, particularly as the time of death approaches. Although generally appreciated by family members, EoL video calls should be arranged together with other measures to alleviate death-related stress, especially for the patient's spouse.     

BCG vaccination history associates with decreased SARS-CoV-2 seroprevalence across a diverse cohort of health care workers

BACKGROUNDSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 1 million deaths worldwide; thus, there is an urgent need to develop preventive and therapeutic strategies. The antituberculosis vaccine bacillus Calmette-Guérin (BCG) demonstrates nonspecific, protective innate immune–boosting effects. Here, we determined whether a history of BCG vaccination was associated with decreased SARS-CoV-2 infection and seroconversion in a longitudinal, retrospective observational study of a diverse cohort of health care workers (HCWs).METHODSWe assessed SARS-CoV-2 seroprevalence and collected medical questionnaires, which included information on BCG vaccination status and preexisting demographic and clinical characteristics, from an observational cohort of HCWs in a multisite Los Angeles health care organization. We used multivariate analysis to determine whether a history of BCG vaccination was associated with decreased rates of SARS-CoV-2 infection and seroconversion.RESULTSOf the 6201 HCWs, 29.6% reported a history of BCG vaccination, whereas 68.9% had not received BCG vaccination. Seroprevalence of anti–SARS-CoV-2 IgG as well as the incidence of self-reported clinical symptoms associated with coronavirus disease 2019 (COVID-19) were markedly decreased among HCWs with a history of BCG vaccination compared with those without BCG vaccination. After adjusting for age and sex, we found that a history of BCG vaccination, but not meningococcal, pneumococcal, or influenza vaccination, was associated with decreased SARS-CoV-2 IgG seroconversion.CONCLUSIONSA history of BCG vaccination was associated with a decrease in the seroprevalence of anti–SARS-CoV-2 IgG and a lower number of participants who self-reported experiencing COVID-19–related clinical symptoms in this cohort of HCWs. Therefore, large randomized, prospective clinical trials of BCG vaccination are urgently needed to confirm whether BCG vaccination can confer a protective effect against SARS-CoV-2 infection.     

A multicentre analysis of catheter-related infection based on a hierarchical model

Purpose

To decrease intensive care unit (ICU)-acquired catheter-related infections (CRI), it is essential that healthcare workers receive training and that quality improvement programmes are in place. The aim of our study was to evaluate risk factors for catheter colonisation and infection, focussing specifically on local care bundles.

Methods

Data were collected prospectively in 51 ICUs [7,188 patients, 8,626 central venous catheters (CVCs)] during two 6-month periods in 2007 and 2008, using a standardized questionnaire on catheter insertion, care and removal. Colonisation and CRI incidence were 6.1 and 2.2/1,000 CVC-days, respectively. A hierarchical mixed logistic model was used to identify risk factors for CRI and colonisation.

Results

Written CVC protocols were available in 46 (90?%) ICUs and were strictly followed in 38 ICUs. Factors significantly associated with CRI fell into three overall categories: (1) patient-related factors—immunosuppression [odds ratio (OR) 1.42, p?=?0.02], medical diagnosis at admission (OR 1.64, p?=?0.03) and trauma patient (OR 2.54, p?p?p?p??4); (3) centre-related factors—quantitative tip culture method (OR 2.55, p?=?0.005) and alcohol-based povidone-iodine [OR 0.68, 95?% confidence interval (CI) 0.49–0.96] or alcohol-based chlorhexidine preparations (OR 0.69, 95?% CI 0.34–1.39) as compared to an aqueous povidone-iodine preparation (p?Conclusions We identified several risk factors for CRI that are amenable to improvement (preference for the subclavian route and use of an antiseptic solution containing alcohol). However, several patient-related factors were also found, and the use of quantitative catheter culture methods increased culture sensitivity, thereby increasing the CRI rate. Case-mix issues and the culture method should be taken into account when assessing the risk of CRI across centres.