Magnesium oxide has been widely used as an antacid and constipation remedy. Currently in Japan, magnesium oxide preparations manufactured by five medical companies are marketed as prescribed generic drugs. In this study, we focused on metal elemental impurities present in 330 mg magnesium oxide tablets manufactured by each of these companies. The content of such impurities was determined by atomic absorption spectrometry and inductively coupled plasma mass spectrometry. We confirmed whether the content conformed to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Guideline for Elemental Impurities (ICH-Q3D) based on the 30% control threshold. The content of these impurities varied among the five products (preparations A-E), but in all cases met the oral permitted daily exposure (PDE) criteria stipulated in ICH-Q3D. In 5 lots of preparation C and all lots of preparation D, the equivalent cadmium (Cd) intake for a daily maximum dosage of 2 g was higher than the 30% control threshold of 1.5 µg/day. By cluster analysis, preparations A-E were classified into preparations A + B and C + D + E and/or preparations A + B, C + D and E. The present study showed that all 5 preparations sold in Japan meet the PDE value standard of ICH-Q3D, and that preparations A and B meet the 30% control threshold. It is important that for preparations failing to meet the criteria, further improvements need to be sought, and impurities in magnesium oxide preparations need to be monitored to ensure their safety.

This study aimed to determine whether the placement of a peripheral intravenous catheter (PIVC) in the cephalic vein of the forearm could prevent PIVC failure in patients receiving hyperosmotic drugs through the peripheral vein. This retrospective cohort study included patients aged ≥ 20 years who had received infusion therapy via a PIVC in our institution between July and November 2017. Patients were divided into groups according to PIVC insertion into the cephalic, basilic, and medial veins. PIVCs used to administer drugs with osmotic pressure ratios > 2.0 were included. The primary outcome was survival time to catheter failure. Catheter failure was defined as accidental and unplanned catheter removal. We set the cephalic vein and other veins, including the medial and basilic veins, in the forearm as cohort groups. We used the Kaplan-Meier survival curves to compare the time until catheter failure in the cohort groups. The Cox proportional hazard models were fitted, and the hazard ratios were calculated. A total of 46 catheters with hyperosmotic agents were included in the analysis. Catheter failure was observed in 25 (54.3%) cases. Time to catheter failure in patients receiving high-dose drugs via the cephalic vein was significantly longer than that in the other two groups (p < 0.01). Thus, the cephalic vein, which has a high blood flow, is the ideal site of PIVC insertion in patients receiving high drug concentrations to prevent catheter failure.

In Japan, the increasing use of generic drugs has led to a reduction in drug prices, which affect the steady supply of drugs. A "basic drug" system was introduced to rescue these drugs by eliminating gaps in drug prices among preparations with the same constituents. "Type 1" hypotonic infusion fluids, which are potassium-free and commonly used to treat dehydration, meet the definition of a "basic drug" in Japan, and there are no drug price gaps. However, there is a lack of information on the physicochemical properties of "type 1" hypotonic infusion fluids, making it difficult to identify differences among them. Extracellular fluid-replacement solutions and "type 3" hypotonic infusion fluids have different pH and titratable acidity. Here, we measured the pH, titratable acidity, and osmolality of six different "type 1" hypotonic infusion fluids and compared the results with respect to risk avoidance considering metabolic acidosis, changes upon mixing, and vascular pain. There was a significant difference, or trend toward significance, in titratable acidity, which is a risk factor for metabolic acidosis in patients with impaired renal function, and pH, which is a risk factor for change upon mixing, among all combinations except one of the infusion fluids. Thus, the selection of "type 1" hypotonic infusion fluids for children with immature renal function, elderly patients with impaired renal function, and patients with unknown pathophysiology, considering titratable acidity and pH, is an effective strategy for risk avoidance.

Ceramides play a critical role in the skin barrier. We previously demonstrated that electrolytic-reduction ion water (ERI) improves skin integrity and enhances the protective barrier function of the epidermis. Here, we first examine the effect of ERI on the expression of ceramide synthesis–related enzymes in human skin keratinocytes. The expression of enzymes involved in the elongation of very-long-chain fatty acids protein 4 (ELOVL4) was increased after treatment with ERI-containing media. The expression of ceramide synthase 3 (CerS3), which binds ultra-long-chain fatty acids to sphingosine to produce ceramides found in the skin, was also increased. Subsequently, we examined the expression of ceramides in keratinocytes treated with ERI using thin-layer chromatography. The results showed that ERI increased the ceramide content, and these ceramides were more hydrophobic than those extracted from untreated keratinocytes. These results suggest that ERI enhances the expression of enzymes involved in the synthesis of ceramides containing ultra-long-chain fatty acid residues, which have a protective function in the skin.

Post COVID-19 sequelae are a constellation of symptoms often reported after recovering from COVID-19. There is a need to better understand the clinical spectrum and long-term course of this clinical entity. The aim of this study is to describe the clinical features and risk factors of post COVID-19 sequelae in the North Indian population. This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 and February 2021. Patients aged >18 years with laboratory-confirmed COVID-19 were recruited after at least two weeks of diagnosis, and details were captured. A total of 1234 patients were recruited and followed up for a median duration of 91 days (IQR: 45-181 days). Among them, 495 (40.1%) had persistent symptoms post-discharge or recovery. In 223 (18.1%) patients, the symptoms resolved within four weeks; 150 (12.1%) patients had symptoms till 12 weeks, and 122 (9.9%) patients had symptoms beyond 12 weeks of diagnosis/symptom-onset of COVID-19. Most common symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), insomnia (1.4%), mood disturbances (0.48%) and anxiety (0.6%). Patients who were hospitalized were more likely to report fatigue as a feature of long COVID. Hypothyroidism (OR: 4.13, 95% CI: 2.2-7.6, p-value < 0.001) and hypoxia (SpO₂ ≤ 93%) (OR: 1.7, 95% CI: 1.1-2.4, p-value 0.012) were identified as risk factors for long COVID sequelae. In conclusion, long COVID symptoms were common (22%), and 9.9% had the post COVID-19 syndrome. Myalgias, fatigue and dyspnoea were common symptoms. Patients with hypothyroidism and hypoxia during acute illness were at higher risk of long COVID.

On March 1, 2019, the Ministry of Health, Labour and Welfare added bleeding symptoms to adverse reaction package inserts as a possible adverse event for a new anti-influenza drug, baloxavir marboxil, because 13 patients with bleeding symptoms were identified among influenza patients taking the drug. Nevertheless, aspects of the epidemiology of bleeding symptoms among influenza patients remain unclear. This study elucidated bleeding symptoms among influenza patients and hospitalized patients as severe cases. A survey was administered to all physicians in Japan during the 2019-2020 season for reporting of bleeding symptoms in influenza patients. The survey elicited information about outcomes, assuming associated underlying diseases and drugs in addition to administered drugs including acetaminophen and anti-influenza (antiviral) drugs. We received reports of 63 cases with bleeding symptoms, including 5 cases of hospitalized patients. Among all patients, 54% had been administered oseltamivir; 10% had been administered baloxavir marboxil. Among hospitalized patients, all had been administered acetaminophen; 40% of them had been administered oseltamivir, and one patient had been administered baloxavir marboxil. Accumulation of bleeding symptom cases is expected to be necessary to evaluate the association.

The inhibitory activity of electrolyzed reduced water (ERW) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is the etiological agent responsible for coronavirus disease 2019 (COVID-19), was tested in vitro on Vero E6 cells using a plaque assay. Infectious virus titers of cells treated with ERW 100%, 50% and 33.3% solutions and phosphate buffered saline (PBS, negative control) and exposed to the virus suspension for 60 seconds were 2.25, 2.65, 3.21 and 7.38, respectively. ERW has a high pH and low surface tension. It is considered that the alkaline property of ERW breaks down phospholipids and proteins of envelopes. The role of pH and reducibility on the virucidal effect of ERW should be further evaluated. This study provides a foundation for utilizing ERW as an effective antiviral aqueous solution in a variety of applications.

Use of systemic corticosteroids is well-established in COVID-19 patients with hypoxia; however, there is scant data on its role in patients with mild disease and prolonged symptoms as a measure to prevent disease progression. The aim of this study is to evaluate the role of systemic corticosteroids in preventing hypoxia (SpO₂ ≤ 93% on room-air) among mild COVID-19 patients. An observational study was conducted among symptomatic COVID-19 patients taking oral corticosteroids and attending institute teleconsultation facility between 10th-30th June 2021. Patients who were already on corticosteroids for other indication or required oxygen supplementation before or within 24-hours of initiation of corticosteroids were excluded. A total of 140 consecutive symptomatic COVID-19 patients were included. Higher baseline C-reactive protein (OR: 1.03, 95% CI: 1.02-1.06, p < 0.001) and early systemic corticosteroid (within 7 days) initiation (OR: 6.5, 95% CI: 2.1-20.1, p = 0.001) were independent risk factors for developing hypoxia (SpO₂ ≤ 93%). Progression to hypoxia was significantly higher in patients who received corticosteroids before day 7 of illness (36.7%, 95% CI, 23.4-51.7%) compared to ≥ 7 of illness (14.3%, 95% CI, 7.8-23.2%) for persistent fever. Systemic corticosteroids within 7 days from symptom-onset were harmful and increased the risk of progression to hypoxia, whereas it may decrease the risk of progression when administered on or beyond 7 days in patients with mild COVID-19 and persistent symptoms. A well-designed randomised controlled trial is required to validate the findings.

To help stop the coronavirus disease 2019 (COVID-19) pandemic, vaccines are currently the most critical tool. However, the COVID-19 mRNA vaccines frequently cause systemic side effects shortly after the injection, such as fever, headache and generalized fatigue. In our survey, after receiving the second dose of the COVID-19 vaccine, 80% developed fever, 62% headache and 69% generalized fatigue. Among people who required antipyretics, the average durations of fever and headache were significantly shorter in those who took non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, loxoprofen and ibuprofen, than those who took acetaminophen. In our patch-clamp studies, NSAIDs effectively suppressed the delayed rectifier K⁺-channel (Kv1.3) currents in T-lymphocytes and thus exerted immunosuppressive effects. Because of this pharmacological property, the use of NSAIDs should be more effective in reducing the vaccine-induced systemic side effects that are caused primarily by the enhanced cellular immunity.