ABSTRACT
Background Past research has suggested a cross-sectional association between COVID-19-related discrimination and PTSD symptom severity. However, no cohort study has examined the longitudinal association that allows causal interpretation. Also, even if such an association genuinely exists, the mechanism remains unclear.Methods We conducted a two-year follow-up study, obtaining data from healthcare workers in a hospital setting. We first evaluated how COVID-19-related discrimination in 2021 was associated with subsequent PTSD symptom severity in 2023. Thereafter, we conducted causal mediation analysis to examine how this association was mediated by psychological distress in 2022, accounting for exposure-mediator interaction. Missing data were handled using random forest imputation.Results A total of 660 hospital staff were included. The fully adjusted model showed greater PTSD symptom severity in individuals who experienced any COVID-19-related discrimination compared with those without such experiences (β, 0.44; 95% CI, 0.04–0.90). Regarding each type of discrimination, perceived discrimination was associated with greater PTSD symptom severity (β, 0.52; 95% CI, 0.08–0.96), whereas verbal discrimination did not reach statistical significance. Psychological distress consistently mediated 28.1–38.8% of the observed associations.Conclusions COVID-19-related discrimination is associated with subsequent PTSD symptom severity in healthcare workers. Psychological distress may serve as an important mediator, underscoring the potential need for interventions targeting this factor.
Subject(s)
COVID-19 , Stress Disorders, Post-TraumaticABSTRACT
Condition:
Healthy VolunteersIntervention:
Drug: TAK-279;Drug: TAK-279 Placebo;Drug: Moxifloxacin;Drug: Moxifloxacin PlaceboPrimary outcome:
Placebo-corrected Change From Baseline in QTc Interval (??QTc) for TAK-279Criteria:
Inclusion Criteria:
1. Understand the study procedures in the informed consent form (ICF) and be willing and
able to comply with the protocol.
2. Healthy, adult, male or female, 18-55 years of age, inclusive, at the screening visit.
3. Female participants of childbearing potential must follow protocol specified
contraception guidance as described in protocol.
4. Continuous non-smoker who has not used nicotine- and tobacco-containing products for
at least 3 months prior to the first baseline cardiodynamic measurement (Day -1) based
on participant self-reporting.
5. BMI greater than or equal to (>=) 18.0 and less than or equal to (<=) 32.0 kilograms
per meter square (kg/m^2) at the screening visit.
6. Medically healthy with no clinically significant medical history, physical
examination, laboratory profiles, vital signs, and electrocardiograms (ECGs), as
deemed by the Investigator or designee, including the following:
- Supine blood pressure is >=90/40 millimeter of mercury (mmHg) and <=140/90 mmHg
at the screening visit.
- Supine pulse rate is >=40 beats per minute (bpm) and <=99 bpm at the screening
visit.
- QTc using Fridericia's formula (QTcF) interval is <=450 milliseconds (msec)
(males) and <=460 msec (female) at the screening visit.
- QRS interval <=110 msec at the screening visit (if >110 msec, result will be
confirmed by a manual over read).
- PR interval <=220 msec at the screening visit.
- eGFR >=80 milliliter per minute per 1.73 meter square (mL/min/1.73m^2) at the
screening visit.
- Liver function tests including alanine aminotransferase (ALT), aspartate
aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin <=upper
limit of normal (ULN) at the screening visit and at check-in.
- No clinically significant hypokalemia, hypomagnesemia, or other electrolyte
abnormalities at the screening visit.
Exclusion Criteria:
1. Is mentally or legally incapacitated or has significant emotional problems at the time
of the screening visit or expected during the conduct of the study.
2. History or presence of clinically significant medical or psychiatric condition or
disease in the opinion of the Investigator or designee.
3. History of any illness that, in the opinion of the Investigator or designee, might
confound the results of the study or poses an additional risk to the participant by
their participation in the study.
4. Has a history of any of the following:
- Active infection or febrile illness within 7 days prior to first baseline
cardiodynamic measurement (Day -1), as assessed by the Investigator or designee.
- Symptoms suggestive of systemic or invasive infection requiring hospitalization
or treatment within 8 weeks prior to first baseline cardiodynamic measurement
(Day -1).
- Chronic or recurrent bacterial disease, including but not limited to chronic
pyelonephritis or cystitis, chronic bronchitis/pneumonitis, osteomyelitis, or
chronic skin ulcerations/infections or fungal infections (except superficial
nailbed mycosis).
- An infected joint prosthesis unless that prosthesis has been removed or replaced
greater than 60 days prior to first baseline cardiodynamic measurement (Day -1).
- Opportunistic infections (eg, Pneumocystis jirovecii pneumonia, histoplasmosis,
coccidiomycosis).
- Cancer or lymphoproliferative disease within 5 years prior to first baseline
cardiodynamic measurement (Day -1), with the exception of successfully treated
nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized
carcinoma in situ of the cervix is not exclusionary.
- Known or suspected condition/illness that is consistent with compromised
immunity, including but not limited to any identified congenital or acquired
immunodeficiency; splenectomy.
- Liver, kidney, heart, or other solid organ transplant.
- Myasthenia gravis.
- Peripheral neuropathy.
5. Has history or presence of alcoholism and/or drug abuse within the past 2 years prior
to first baseline cardiodynamic measurement (Day -1), as determined by the
Investigator or designee.
6. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs.
7. Allergy to band aids, adhesive dressing, or medical tape.
8. History or presence of any of the following, deemed clinically relevant by the
Investigator or designee at the screening visit or at check-in:
- Cardiac disease; arrhythmias, presyncope, or syncopal episodes; heart failure,
heart disease or risk factors for torsades de pointes (including long QT syndrome
or family history of long QT syndrome).
- Sick sinus syndrome, second or third degree atrioventricular block, myocardial
infarction, pulmonary congestion, history of cardiac arrhythmia, prolonged QTcF
interval, or conduction abnormalities.
- Ischemic heart disease, poorly controlled hypertension, or other cardiovascular
disorder
- T wave flattening or other abnormalities which in the opinion of the Investigator
or designee may interfere with the analysis of QT intervals.
- A family history of sudden cardiac death.
9. Female participant with a positive pregnancy test at the screening visit or at
check-in or who is breastfeeding and/or lactating.
10. Positive urine drug or alcohol results at the screening visit or at check-in.
11. Positive Coronavirus disease 2019 (COVID-19) result at check-in.
12. Unable to refrain from or anticipates the use of:
- Any drugs, including prescription and non-prescription medications, herbal
remedies, or vitamin supplements, including any cytochrome P450 (CYP)3A4
inhibitors, beginning 14 days prior to the first baseline cardiodynamic
measurement (Day -1).
- Any drugs known to be inducers of CYP3A4 enzymes and/or P-glycoprotein (P-gp),
including St. John's Wort, for 28 days prior to the first baseline cardiodynamic
measurement (Day -1). Appropriate sources (eg, Flockhart Table™) including the
product label for moxifloxacin (Avelox [moxifloxacin hydrochloride] tablets and
intravenous injection 2020) will be consulted to confirm lack of pharmacokinetic
ABSTRACT
Condition:
Alpha1-Antitrypsin DeficiencyIntervention:
Drug: Fazirsiran Injection;Drug: PlaceboPrimary outcome:
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs);Number of Participants With Clinically Significant Change From Baseline in Pulmonary Function Parameters;Change From Baseline in Whole Lung 15th Percentile Density as Measured by Computed Tomography (CT) Lung Densitometry;Number of Participants With Clinically Significant Changes in Vital Signs;Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Parameters;Number of Participants With Clinically Significant Changes in Clinical Laboratory ParametersCriteria:
Inclusion Criteria:
- In the opinion of the investigator, the participant is capable of understanding and
fully complying with the protocol requirements and adhering to the protocol schedule.
- The participant is able to read, understand, and complete the study questionnaires
electronically per the investigator's judgment.
- The participant signs and dates a written Informed Consent Form (ICF). Any required
privacy authorization should also be signed before the initiation of any study
procedures.
- The participant, of any sex, is aged 18 to 75 years, inclusive.
- The participant must have a diagnosis of the protease inhibitor Z mutation (PiZZ)
genotype AATD. A diagnosis of PiZZ from source-verifiable medical records is
permitted. Otherwise, participants must undergo PiZZ confirmatory testing (genotyping
for PiS and PiZ alleles) at screening. PiMZ or PiSZ genotypes are not permitted.
- The participant's liver biopsy core samples should be collected as per protocol
requirements.
- The participant has evidence of METAVIR stage F1 liver fibrosis, evaluated by a
centrally read baseline liver biopsy during the screening period; or confirmed as
meeting all the entry criteria by central reading from a previous biopsy conducted
within 1 year before the screening period using an adequate liver biopsy and slides as
defined in the study laboratory manual.
- The participant has a pulmonary status that meets the protocol requirements.
- It must be confirmed that the participant does not have hepatocellular carcinoma
(HCC).
- Participants must have a negative coronavirus disease 2019 (COVID-19) polymerase chain
reaction (PCR) test at screening.
- Any participant who is taking statins, angiotensin-converting enzyme inhibitors,
angiotensin II receptor blockers, or beta-1 selective adrenergic receptor inhibitors
must have been receiving a stable dose of these medications for at least 8 weeks
before randomization. All attempts are to be made for the participant to continue the
same dose of the medication for the duration of study participation.
- An adult participant must have a body mass index (BMI) between 18 and 39 kilogram per
meter square (kg/m^2), inclusive.
- The participant has a 12-lead electrocardiogram at screening that, in the opinion of
the investigator, has no abnormalities that could compromise the participant's safety
in this study.
- The participant is a nonsmoker.
- If the participant was being treated with any respiratory medications including
inhaled bronchodilators, inhaled anticholinergics, inhaled corticosteroids, or
low-dose systemic corticosteroids (prednisone less than or equal to (<=10) milligrams
per day (mg/d) or its equivalent), the doses of the participant's medications must
have remained unchanged for at least 14 days before screening.
- The participant must have suitable venous access for blood sampling.
- A person of childbearing potential (POCBP) must have a negative serum pregnancy test
at screening and a negative urine pregnancy test on Day 1 before dosing.
- The participant must use highly effective contraception for the entire duration of the
study and for 24 weeks after the last dose of study medication. The participant must
not donate sperm for at least 24 weeks after the last dose of study medication.
Exclusion criteria:
- The participant has evidence of greater than or equal to (>=) F2 fibrosis based on
liver biopsy during the screening period.
- The participant has a history of liver decompensating events.
- The participant has a history of varices based on a previous
esophagogastroduodenoscopy.
- The participant has portal vein thrombosis.
- The participant has undergone a prior trans-jugular portosystemic shunt procedure.
- The participant has evidence of other forms of chronic liver diseases.
- The participant has a history of malignancy within the last 5 years, except for
adequately treated basal cell carcinoma, squamous cell skin cancer, superficial
bladder tumors, or in situ cervical cancer. Participants with curatively treated
malignancies who have no evidence of metastatic disease and disease-free interval
greater than (>) 1 year may be enrolled after approval by the medical monitor.
- The participant has an abnormal finding of clinical relevance at the screening
evaluation and before administration of the first dose of study dosing that, in the
opinion of the investigator, could adversely impact participant safety during the
study or adversely impact study results.
- The participant has any laboratory abnormalities at screening and before the first
dose of the study drug that meet protocol parameters.
- The participant is expected to have severe and unavoidable high-level exposure to
inhaled pulmonary toxins during the study such as may occur with occupational exposure
to mineral dusts or metals.
- The participant has a recent lower respiratory tract infection, such as pneumonia,
within the last 24 weeks before screening.
- The participant has a history of frequent pulmonary exacerbations (>=2 moderate or
severe exacerbations within 52 weeks before screening).
- The participant is experiencing a pulmonary exacerbation at the time of screening
(participant may be rescreened after the clinical resolution of an exacerbation).
- The participant is receiving long-term, around-the-clock oxygen supplementation or
supplemental oxygen with continuous positive airway pressure (CPAP) or bilevel
positive airway pressure for acute respiratory failure. The following conditions are
allowable for the participant to enter screening: short-term use of oxygen
supplementation (example, for the management of acute chronic obstructive pulmonary
disease [COPD] exacerbation) or CPAP for obstructive sleep apnea.
- The participant has human immunodeficiency virus (HIV) infection as shown by the
presence of anti-HIV antibody (seropositive).
- The participant is seropositive for hepatitis B virus (HBV surface antigen positive
and/or HBV core antibody positive without HBV surface antibody at screening) or
hepatitis C virus (HCV) (detectable HCV Ribonucleic Acid [RNA] at screening). Cured
HCV (positive antibody test without detectable HCV RNA for at least 24 weeks after
treatment) is acceptable.
- The participant has unstable, poorly controlled, or severe hypertension. Participants
may be rescreened once their blood pressure (BP
ABSTRACT
Condition:
Healthy VolunteersIntervention:
Drug: Brigatinib;Drug: BrigatinibPrimary outcome:
Cmax: Maximum Observed Plasma Concentration for Brigatinib;AUClast: Area Under the Plasma Concentration-Time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Brigatinib;AUC8: Area Under the Plasma Concentration-Time Curve from Time 0 to Infinity for BrigatinibCriteria:
Inclusion Criteria:
1. Continuous nonsmoker who has not used nicotine-containing products for at least 3
months prior to the first dosing and throughout the study.
2. Body mass index (BMI) =18.0 and ?32.0 kilograms per meters squared (kg/m^2) at
screening.
3. Pulse rate between 60 and 100 beats per minute (bpm) and a blood pressure between 90
to 140 millimeters of mercury (mmHg) systolic and 40 to 90 mmHg diastolic at screening
and prior to dosing of Period 1.
4. Creatine phosphokinase is =1.1x upper limit of normal [ULN]; lipase, amylase, alanine
aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, glucose,
and activated partial thromboplastin time (aPTT) are =ULN at screening and check-in of
Period 1.
Exclusion Criteria:
1. Any history of major surgery.
2. History or presence of hypersensitivity or idiosyncratic reaction to the study drug or
related compounds.
3. Unable to refrain from or anticipates the use of any drug, including prescription and
nonprescription medications, herbal remedies, or vitamin supplements within 28 days
prior to the first dosing and throughout the study.
4. Positive results at screening for Human Immunodeficiency Virus (HIV), Hepatitis B
surface Antigen (HBsAg), or Hepatitis C Virus (HCV).
5. Positive coronavirus disease 2019 (COVID-19) results at first check-in.
6. Donation of blood or significant blood loss within 56 days prior to the first dosing.
7. Plasma donation within 7 days prior to the first dosing.
ABSTRACT
Condition:
Healthy VolunteersIntervention:
Drug: TAK-279;Drug: PlaceboPrimary outcome:
Area Under the Concentration Time Curve From Time 0 to the Time t (AUC0-t) of TAK-279;Area Under the Concentration-time Curve From Time 0 To Infinity (AUC0-inf) of TAK-279;Maximum Observed Plasma Concentration (Cmax) of TAK-279;Area Under the Concentration-Time Curve During a Dosing Interval (AUCtau) of TAK-279;Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of TAK-279Criteria:
Inclusion criteria:
- Participant is willing to participate and is capable of giving informed consent.
- Healthy, male or female participants of Chinese descent 18 to 45 years of age,
inclusive, at the time of informed consent.
- Female participants meets the following contraception requirements: A surgically
sterile female participant; or a female participant of nonchildbearing potential with
laboratory confirmation of postmenopausal status (that is follicle-stimulating hormone
levels greater than [>] 40 milli-international units per milliliter [mIU/mL]); or, if
sexually active with a non-sterilized male partner, a female participant who agrees to
use an effective method of contraception from the signing of informed consent
throughout the duration of the study and for 10 days after the last dose.
- Body mass index greater than or equal to (>=) 18.0 kilogram per meter square (kg/m^2)
and less than or equal to (<=) 28.0 kg/m^2 at the screening visit.
- Medically healthy with no clinically significant medical history, physical
examination, laboratory profiles, vital signs, or electrocardiograms [ECGs], as deemed
by the principal investigator (PI) or designee, including the following:
- Seated blood pressure (systolic blood pressure/diastolic blood pressure) >=90/60
millimeters of mercury (mmHg) and <=140/90 mmHg at the screening visit.
- Seated heart rate or pulse is >=50 beats per minute (bpm) and <=100 bpm at the
screening visit.
- ECG findings are considered normal or not clinically significant by the PI or
designee at the screening visit.
- Participant must be willing and able to understand and fully comply with all study
procedures and must be available for the duration of the study.
Exclusion criteria:
- Site personnel or their family.
- History or presence of clinically significant medical or psychiatric condition or
disease.
- History of any illness or condition that might confound the results of the study or
poses an additional risk to the participant by their participation in the study.
- History of allergy to study drug or any of its components.
- History of stomach or intestinal surgery or resection that would potentially alter
absorption and/or excretion of orally administered drugs (uncomplicated appendectomy
and hernia repair will be allowed).
- Clinical laboratory values at the time of screening or at check-in:
- Aspartate aminotransferase (AST) or alanine transaminase (ALT) >1.5 * the upper
limit normal (ULN).
- Creatine phosphokinase (CPK) > the ULN.
- Hemoglobin <11.0 grams per deciliter (g/dL) (<110.0 gram per liter [g/L]).
- Absolute neutrophil count <1.8*10^9/liters (L) (<1800 per cubic millimeter
[/mm^3]).
- Absolute lymphocyte count <0.8*10^9/L (<800/mm^3).
- Platelet count <100*10^9/L (<100,000/mm^3).
- A participant with out-of-range values may have the test repeated once at each time
point (screening or check-in) and the participant may be enrolled if the repeated
values are within protocol-specified ranges.
- Ingestion of Seville orange- or grapefruit-containing foods or beverages within 7 days
prior to check-in.
- History of alcohol abuse or drug/chemical abuse within 2 years prior to check-in.
- Continuous smoker who has used nicotine- or tobacco-containing products within 1 month
prior to the first dosing based on participant self-reporting.
- Female participants who have a positive pregnancy test result at the screening visit
or at check-in, are planning to become pregnant during the study or are lactating.
- Positive results for urine drug test at the screening visit or at check-in.
- Herpes infections:
- Participants has active herpes virus infection, including herpes zoster or herpes
simplex 1 and 2 (demonstrated on physical examination and/or medical history) at
screening or check-in.
- Participants has a history of serious herpetic infection that includes any
episode of disseminated disease, multi-dermatomal herpes simplex virus, herpes
encephalitis, ophthalmic herpes, or recurrent herpes zoster (defined as 2
episodes within 2 years).
- Positive results for non-herpetic viral diseases at the screening visit:
- Participant has presence of hepatitis C virus (HCV) antibody or a positive
confirmatory test result for HCV RNA (Ribonucleic acid) test or polymerase chain
reaction (PCR).
- Participant has presence of positive result for hepatitis B surface antigen,
presence of hepatitis B virus deoxyribonucleic acid, or positive anti-hepatitis B
core antibody without concurrent positive hepatitis B surface antibody.
- Participant has positive results for human immunodeficiency virus.
- Positive results for Tuberculosis (TB) at the screening visit:
- The participant has a history of active TB infection, regardless of treatment
status.
- The participant has signs or symptoms of active TB (including but not limited to
chronic fever, chronic productive cough, night sweats, or weight loss) as judged
by the investigator.
- The participant has evidence of latent TB as evidenced by a positive
QuantiFERON-TB Gold (QFT) result or tuberculosis-specific enzyme-linked
immunospot assay (T-Spot) OR 2 indeterminant QFT results or 2 borderline T-Spot
results.
- The participant has had any imaging study during or 6 months prior to screening,
including x-ray, chest computed tomography, magnetic resonance imaging, or other
chest imaging suggesting evidence of current active or a history of TB.
- Positive result for Coronavirus disease 2019 (COVID-19) PCR test at the screening
visit.
- Prior and concomitant therapy:
- Participants who received a live or live-attenuated vaccine in the 60 days prior
to study drug administration. Administration of nonlive-attenuated vaccines or
boosters for COVID-19 (for example [eg,] RNA-based vaccines, inactivated
adenovirus-based vaccines, protein-based vaccines) in the 14 days prior to first
dosing. The study site should follow local guidelines related to COVID-19.
- Use or intent to use any medications/products known to alter drug absorption,
metabolism, or elimination processes, including CYP3A4 and/or P-glyc
ABSTRACT
The number of mothers suffering from mental illness is increasing steadily, particularly under conditions of the coronavirus disease pandemic. The identification of factors that contribute to resilience in mothers is urgently needed to decrease the risks of poor physical and psychological functioning. We focused on the risk of parenting stress and psychological resilience in nonclinical mothers and conducted two studies to examine the relationships between intestinal microbiota, physical condition, and psychological state. Our results showed that alpha diversity and beta diversity of the microbiome are related to high parenting stress risk. Psychological resilience and physical conditions were associated with relative abundances of the genera Blautia, Clostridium, and Eggerthella. This study helps further understand the gut–brain axis mechanisms and supports proposals for enhancing resilience in mothers.
Subject(s)
Coronavirus Infections , Intellectual DisabilityABSTRACT
We employed publicly available user-generated content (UGC) data from the website Tripadvisor and developed an autoregressive integrated moving average (ARIMA) model using the R language to analyze the seasonality of the use of urban green space (UGS) in Okinawa under normal conditions and during the COVID-19 pandemic. The seasonality of the use of ocean-area UGS is primarily influenced by climatic factors, with the peak season occurring from April to October and the off-peak season from November to March. Conversely, the seasonality of the use of non-ocean-area UGS remains fairly stable throughout the year, with a relatively high number of visitors in January and May. The outbreak of the COVID-19 pandemic greatly impacted visitor enthusiasm for travel, resulting in significantly fewer actual postings compared with predictions. During the outbreak, use of ocean-area UGS was severely restricted, resulting in even fewer postings and a negative correlation with the number of new cases. In contrast, for non-ocean-area UGS, a positive correlation was observed between the change in postings and the number of new cases. We offer several suggestions to develop UGS management in Okinawa, considering the opportunity for a period of recovery for the tourism industry.
ABSTRACT
The effectiveness of population-wide compliance to personal precautions (mask-wearing and hand hygiene) in preventing community-acquired pneumonia has been unknown. In Japan, different types of nonpharmaceutical interventions from personal precautions to containment and closure policies (CACPs, e.g. stay-at-home requests) were sequentially introduced from late January to April 2020, allowing for separate analysis of the effects of personal precautions from other more stringent interventions. We quantified the reduction in community-acquired pneumonia hospitalizations and deaths and assessed if it coincided with the timing of increased public awareness of personal precautions before CACPs were implemented. A quasi-experimental interrupted time-series design was applied to non-COVID-19 pneumonia hospitalization and 30-day death data from April 2015 to August 2020 across Japan to identify any trend changes between February and April 2020. We also performed a comparative analysis of pyelonephritis and biliary tract infections to account for possible changes in the baseline medical attendance. These trend changes were then compared with multiple indicators of public awareness and behaviors related to personal precautions, including keyword usage in mass media coverage and sales of masks and hand hygiene products. Hospitalizations and 30-day deaths from non-COVID-19 pneumonia dropped by 24.3% (95% CI 14.8-32.8) and 16.1% (5.5-25.5), respectively, in February 2020, before the implementation of CACPs, whereas pyelonephritis and biliary tract infections did not suggest a detectable change. These changes coincided with increases in indicators related to personal precautions rather than those related to contact behavior changes. Community-acquired pneumonia could be reduced by population-wide compliance to moderate precautionary measures.
ABSTRACT
BACKGROUND: Under the state of emergency, it has been reported that the amount of physical activity among community-dwelling older adults has decreased significantly due to refraining from going out, and there are strong concerns about the Geriatric Locomotive Function Scale and deterioration of mental health. Therefore, this study aimed to investigate whether the depressive state before the coronavirus disease 2019 (COVID-19) pandemic affected the 25-Geriatric Locomotive (GLFS) score during the COVID-19 pandemic among community-dwelling older adults. METHODS: The participants were 194 community-dwelling older adults (45 men, 149 women) with an average age of 75.5 ± 5.5 years who responded to a self-administered survey conducted three times (preliminary, second, and third) from before the 2018 COVID-19 pandemic to March 2021. Individuals with a score of ≥ 10 on the Geriatric Depression Scale 15 (GDS 15) were excluded. The survey items included the 25-question Geriatric Locomotive Function Scale (GLFS25), GDS 15, and other basic attributes. Those with scores of 5 to 9 on the GDS 15 and those with scores of 0 to 4 were assigned to the depressive symptoms (DS) group and the non-DS group, respectively. Statistical analysis was performed using two-way analysis of variance. The Mann-Whitney U test was used for comparisons between the groups. RESULTS: In total, 187 patients were included in the analysis, excluding 7 patients. GLFS 25 showed a significant increase in scores at the second and third time points compared with baseline, and a main effect was confirmed in both groups, with no interaction effect. The second time, the score was 10.0 ± 8.5 and 13.7 ± 10.5 in the non-DS and DS groups, respectively. The third time, the non-DS and DS groups scored 10.8 ± 10.5 and 14.9 ± 10.1 points, respectively, indicating a significant difference. CONCLUSIONS: Our results revealed that the increase in the GLFS 25 score in community-dwelling older adults during the COVID-19 pandemic was related to their DS during normal times before the pandemic. Evaluating such individuals and providing social support may effectively reduce the deterioration of the GLFS 25 score.
Subject(s)
COVID-19 , Depression , Male , Humans , Female , Aged , Aged, 80 and over , Depression/diagnosis , Depression/epidemiology , Depression/psychology , Independent Living , Pandemics , COVID-19/epidemiology , Surveys and QuestionnairesABSTRACT
Objective We evaluated the clinical differences in coronavirus disease 2019 (COVID-19) patients between the sixth wave with the Omicron BA.1/BA.2 dominant variant (from January to April 2022) and seventh wave with the Omicron BA.5 dominant variant (from July to August 2022). Methods This retrospective, single-center, observational study included COVID-19 patients admitted to our institution in the sixth wave (sixth-wave group) and the seventh wave (seventh-wave group). Inter-group comparisons of clinical presentations, the prognosis, and proportion of nosocomial infections were performed. Results A total of 190 patients were included (93 and 97 patients in the sixth- and seventh-wave groups, respectively). While there were no significant differences in severity, significantly more patients developed pneumonia caused by COVID-19 in the sixth-wave group than in the seventh-wave group. Although there was no marked difference in in-hospital deaths, more patients died from COVID-19 in the sixth-wave group than in the seventh-wave group. There were significantly more COVID-19 inpatients with nosocomial infections in the seventh-wave group than in the sixth-wave group. Pneumonia from COVID-19 was significantly more severe in the sixth-wave group than in the seventh-wave group. Conclusions COVID-19 patients in the seventh wave are at a lower risk of pneumonia than those in the sixth wave. However, even in the seventh wave, patients with underlying diseases have a risk of death because of the exacerbation of underlying diseases triggered by COVID-19.
ABSTRACT
In this study, we examine the short-term stock price reactions of Japanese gaming companies to events related to the coronavirus disease 2019 (COVID-19) pandemic. Using the event study method, we first estimate stock price reactions to the outbreak of the pandemic and the declaration of a state of emergency. We then perform multivariate regressions to investigate the factors affecting market responses. Our results demonstrate that the stock prices of Japanese gaming companies reacted negatively to the outbreak of the COVID-19 pandemic, and the initial negative effects were greater for mobile gaming companies and for companies with small sizes or low Tobin's Q. By contrast, the market has reacted positively to the declaration of the state of emergency, which perhaps drove more people to play games at home.
ABSTRACT
The coronavirus (COVID-19) pandemic has affected society in immeasurable ways, including investment. As the pandemic has impacted society's values, it has proven to be a major turning point for environmental, social, and governance (ESG) investment. This investment approach, which evaluates a company's ESG ratings alongside traditional financial metrics, was already "coming off a banner year,” and its reach continues to expand. Although numerous studies have investigated the impact of ESG scores on financial returns and the trend in ESG investment strategies, only a limited number of studies have attempted to capture the key players in ESG investment. Therefore, to determine the most influential investors in the ESG investment field, the cumulative impacts are calculated based on the ESG scores of invested companies, the total market price of invested companies, and the investor history portfolio report. We perform an iteration of calculation to convey the impacts that the invested companies have on the ultimate investors, and we identify the major players in the field and differences in the trend by type of investor and country. Copyright © 2022 Keeley, Li, Takeda, Gloria and Managi.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), and norovirus are global threats to human health. The application of effective virucidal agents, which contribute to the inactivation of viruses on hands and environmental surfaces, is important to facilitate robust virus infection control measures. Naturally derived virucidal disinfectants have attracted attention owing to their safety and eco-friendly properties. In this study, we showed that multiple Japanese Saxifraga species-derived fractions demonstrated rapid, potent virucidal activity against the SARS-CoV-2 ancestral strain and multiple variant strains, IAV, and two human norovirus surrogates: feline calicivirus (FCV) and murine norovirus (MNV). Condensed tannins were identified as active chemical constituents that play a central role in the virucidal activities of these fractions. At a concentration of 25 µg/mL, the purified condensed tannin fraction Sst-2R induced significant reductions in the viral titers of the SARS-CoV-2 ancestral strain, IAV, and FCV (reductions of ≥3.13, ≥3.00, and 2.50 log10 50% tissue culture infective doses [TCID50]/mL, respectively) within 10 s of reaction time. Furthermore, at a concentration of 100 µg/mL, Sst-2R induced a reduction of 1.75 log10 TCID50/mL in the viral titers of MNV within 1 min. Western blotting and transmission electron microscopy analyses revealed that Sst-2R produced structural abnormalities in viral structural proteins and envelopes, resulting in the destruction of viral particles. Furthermore, Saxifraga species-derived fraction-containing cream showed virucidal activity against multiple viruses within 10 min. Our findings indicate that Saxifraga species-derived fractions containing condensed tannins can be used as disinfectants against multiple viruses on hands and environmental surfaces. IMPORTANCE SARS-CoV-2, IAV, and norovirus are highly contagious pathogens. The use of naturally derived components as novel virucidal/antiviral agents is currently attracting attention. We showed that fractions from extracts of Saxifraga species, in the form of a solution as well as a cream, exerted potent, rapid virucidal activities against SARS-CoV-2, IAV, and surrogates of human norovirus. Condensed tannins were found to play a central role in this activity. The in vitro cytotoxicity of the purified condensed tannin fraction at a concentration that exhibited some extent of virucidal activity was lower than that of 70% ethanol or 2,000 ppm sodium hypochlorite solution, which are popular virucidal disinfectants. Our study suggests that Saxifraga species-derived fractions containing condensed tannins can be used on hands and environmental surfaces as safe virucidal agents against multiple viruses.
Subject(s)
Disinfectants , Influenza A virus , Norovirus , Proanthocyanidins , SARS-CoV-2 , Saxifragaceae , Disinfectants/pharmacology , Influenza A virus/drug effects , Norovirus/drug effects , Proanthocyanidins/pharmacology , SARS-CoV-2/drug effects , Saxifragaceae/chemistry , TanninsABSTRACT
Purpose: Adolescence is a period of transition from childhood to adulthood where people are vulnerable to stress. The COVID-19 pandemic continues to cause sustained stress in the population. Since the COVID-19 pandemic, social isolation and loneliness have increased. Loneliness is associated with increased stress, psychological distress, and a higher risk of mental illnesses, such as depression. This study examined the association between loneliness, premenstrual symptoms, and other factors in the era of the COVID-19 pandemic among adolescent females in Japan. Patients and Methods: A school-based cross-sectional survey of 1450 adolescent female students in Japan was conducted in mid-December of 2021. Specifically, paper-based questionnaires were distributed in class, and the responses were collected. The Premenstrual Symptoms Questionnaire (PSQ), 6-item Kessler Psychological Distress Scale, 3-item Revised UCLA Loneliness Scale (R-UCLA), and Fear of COVID-19 Scale were used as measurement tools. The prevalence of loneliness was defined as a total R-UCLA score ≥ 6. Results: The prevalence of loneliness was 29.0%. The prevalence of serious psychological distress was also high (8.2%), especially in the lonely group (16.0%). Multivariable regression analysis identified the following factors associated with loneliness: second year (odds ratio [OR] 1.53; 95% confidence interval [CI] 1.09-2.14), longer internet use (OR, 1.11; 95% CI, 1.02-1.20), total PSQ score (OR 1.08; 95% CI 1.06-1.11), and psychological distress (OR 1.05; 95% CI 1.01-1.08). Conclusion: Adolescent females in Japan showed a high prevalence of loneliness. School year (2nd year), longer periods of internet use, premenstrual symptom severity, and psychological distress were independently associated with loneliness. For clinicians and school health professionals, special concern should be given to the psychological health of adolescent females during the COVID-19 pandemic.
ABSTRACT
Drug repurposing requires distinguishing established drug class targets from novel molecule-specific mechanisms and rapidly derisking their therapeutic potential in a time-critical manner, particularly in a pandemic scenario. In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. However, it is unknown if different statins exhibit consistent function or may have varying therapeutic benefit. A Bayesian network tool was used to predict drugs that shift the host transcriptomic response to SARS-CoV-2 infection towards a healthy state. Drugs were predicted using 14 RNA-sequencing datasets from 72 autopsy tissues and 465 COVID-19 patient samples or from cultured human cells and organoids infected with SARS-CoV-2. Top drug predictions included statins, which were then assessed using electronic medical records containing over 4,000 COVID-19 patients on statins to determine mortality risk in patients prescribed specific statins versus untreated matched controls. The same drugs were tested in Vero E6 cells infected with SARS-CoV-2 and human endothelial cells infected with a related OC43 coronavirus. Simvastatin was among the most highly predicted compounds (14/14 datasets) and five other statins, including atorvastatin, were predicted to be active in > 50% of analyses. Analysis of the clinical database revealed that reduced mortality risk was only observed in COVID-19 patients prescribed a subset of statins, including simvastatin and atorvastatin. In vitro testing of SARS-CoV-2 infected cells revealed simvastatin to be a potent direct inhibitor whereas most other statins were less effective. Simvastatin also inhibited OC43 infection and reduced cytokine production in endothelial cells. Statins may differ in their ability to sustain the lives of COVID-19 patients despite having a shared drug target and lipid-modifying mechanism of action. These findings highlight the value of target-agnostic drug prediction coupled with patient databases to identify and clinically evaluate non-obvious mechanisms and derisk and accelerate drug repurposing opportunities.
Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , SARS-CoV-2 , Atorvastatin/pharmacology , Bayes Theorem , Endothelial Cells , Simvastatin/pharmacology , Simvastatin/therapeutic use , Drug Repositioning , Medical RecordsABSTRACT
BACKGROUND: The spread of coronavirus disease 2019 (COVID-19), which began in 2020, has had a major impact on healthcare systems. The spread of COVID-19 has been reported to have affected the readiness to treat patients with burns worldwide. However, the existing reports have evaluated burn care status within a limited time period during the pandemic, and no report clarifies the change in the impact of infection status on burn care from the beginning of the pandemic to the present. METHODS: Japanese Society for Burn Injuries-accredited burn care facilities were surveyed using questionnaires on April 9-23, 2020; June 23-July 6, 2020; July 9-21, 2021; and January 21-31, 2022. Differences between groups were evaluated using Friedman's test or Bonferroni's multiple comparison test, as appropriate. RESULTS: From the 103 facilities included in the study, we received 85, 55, 56, and 58 responses in the first, second, third, and fourth surveys, respectively. We could continuously observe 34 facilities. The rate of acceptance of patients with severe burns improved significantly over time (P < 0.05). However, in the second and third surveys, there was an increase in the number of respondents who did not accept patients with burns irrespective of COVID-19 status. CONCLUSIONS: The number of facilities treating patients with burns who have COVID-19 is increasing; however, COVID-19 care may negatively impact routine burn care. It is necessary to continuously examine medical resource allocation through methods such as information sharing by academic societies.
ABSTRACT
The coronavirus disease 2019, i.e., the COVID-19 pandemic, caused by a highly virulent and transmissible pathogen, has profoundly impacted global society. One approach to combat infectious diseases caused by pathogenic microbes is using mucosal vaccines, which can induce antigen-specific immune responses at both the mucosal and systemic sites. Despite its potential, the clinical implementation of mucosal vaccination is hampered by the lack of safe and effective mucosal adjuvants. Therefore, developing safe and effective mucosal adjuvants is essential for the fight against infectious diseases and the widespread clinical use of mucosal vaccines. In this study, we demonstrated the potent mucosal adjuvant effects of intranasal administration of sodium nitroprusside (SNP), a known nitric oxide (NO) donor, in mice. The results showed that intranasal administration of ovalbumin (OVA) in combination with SNP induced the production of OVA-specific immunoglobulin A in the mucosa and increased serum immunoglobulin G1 levels, indicating a T helper-2 (Th2)-type immune response. However, an analog of SNP, sodium ferrocyanide, which does not generate NO, failed to show any adjuvant effects, suggesting the critical role of NO generation in activating an immune response. In addition, SNPs facilitated the delivery of antigens to the lamina propria, where antigen-presenting cells are located, when co-administered with antigens, and also transiently elicited the expression of interleukin-6, interleukin-1ß, granulocyte colony-stimulating factor, C-X-C motif chemokine ligand 1, and C-X-C motif chemokine ligand 2 in nasal tissue. These result suggest that SNP is a dual-functional formulation with antigen delivery capabilities to the lamina propria and the capacity to activate innate immunity. In summary, these results demonstrate the ability of SNP to induce immune responses via an antigen-specific Th2-type response, making it a promising candidate for further development as a mucosal vaccine formulation against infectious diseases.
Subject(s)
COVID-19 , Vaccines , Mice , Animals , Humans , Administration, Intranasal , Nitroprusside , Antibody Formation , Ligands , Pandemics , Mucous Membrane , Adjuvants, Immunologic , Antigens , Immunity, Innate , Chemokines , Immunity, Mucosal , Mice, Inbred BALB CABSTRACT
Obesity hypoventilation syndrome (OHS) can cause acute hypercapnic respiratory failure (AHRF). The onset of AHRF in four patients with OHS during the coronavirus disease 2019 (COVID-19) pandemic is reported in this study. Two men (23 and 45 years old) and two women (both 77 years old) presented to our hospital with AHRF. In the two elderly women, a prolonged supine position due to falls seemed to be the cause of AHRF. Treatment was started with bilevel positive airway pressure for all patients. While one patient died, the condition of the other three improved; they were discharged with continuous positive airway pressure. AHRF due to OHS was rarely reported in the rural region of Japan. It is suggested that increased rates of obesity due to lifestyle changes during the COVID-19 pandemic may be responsible for an increase in the prevalence of OHS-associated AHRF.