Search

The development of new anti-HIV drugs and advances in antiretroviral therapy (ART) regimens have enabled longer and more effective treatments in people living with HIV (PLWH). However, the aging of PLWHs is another issue that needs to be addressed. In addition to ART, many PLWHs frequently receive medications for various comorbidities. However, real-world data on the occurrence of adverse events in PLWHs and their causative drugs are rare. Therefore, this study aimed to clarify the characteristics of adverse event reports among PLWHs in Japan. PLWH cases with adverse events were comprehensively searched and analyzed using the Japanese Adverse Drug Event Report database (JADER). Despite changes in guideline-recommended ART regimens, anti-HIV drugs were the main cause of adverse events in PLWHs throughout the study period. However, considerable variations have been observed in the reporting rate of anti-HIV drug classes registered as causative drugs in JADER, especially for anchor drugs. In other words, the reporting rate of integrase strand transfer inhibitors has increased in recent years, while that of protease inhibitors and non-nucleoside reverse transcriptase inhibitors has decreased. Immune reconstitution inflammatory syndrome was the most reported adverse event and was frequently noticed by healthcare providers managing patients with HIV infections. The trends in adverse event reports for female and older patients differed from those for the overall population. This study may provide insights that can help in the establishment of optimal management strategies for PLWHs. [ABSTRACT FROM AUTHOR]

Background/Aim: Gemcitabine-induced thrombotic microangiopathy (G-TMA) is associated with a high mortality rate. However, owing to its low incidence, data on G-TMA remain limited. Therefore, a detailed review of G-TMA cases is critical to understand this adverse event. In addition, reviewing literature and pharmacovigilance analytics may be useful to characterise G-TMA. Here, time to onset of G-TMA was analysed based on available data. Patients and Methods: We collected data for a case of TMA following gemcitabine administration at the Tokyo Metropolitan Geriatric Hospital. We also reviewed the literature on G-TMA cases in Japan from April 2000 to March 2022 to provide a case series. Moreover, we performed time-to-onset analysis of G-TMA using the data from the Japanese Adverse Drug Event Report (JADER) database. Results: Our case involved a patient with pancreatic cancer who developed thrombotic thrombocytopenic purpura 13 months after starting gemcitabine treatment. From the literature reviewed, in 14 out of 17 cases, G-TMA occurred 5-8 months after treatment initiation. The analysis of data from the JADER database showed that the median time to onset of G-TMA was 161 days. Weibull shape parameter analysis showed that the pattern of onset of G-TMA represented a random failure. Conclusion: This study elucidated the time to onset of G-TMA in a Japanese population. Weibull shape parameter analysis showed that G-TMA may not necessarily develop in a dose-dependent manner. These results may be useful for monitoring G-TMA in the clinical setting. [ABSTRACT FROM AUTHOR]

We aimed to investigate the association between anaphylaxis and anti-influenza drug use using the Japanese Adverse Drug Event Report (JADER) database, a national spontaneous reporting database in Japan. We surveyed registered cases from the JADER database between April 2004 and November 2019. The target drugs were five anti-influenza drugs, namely oseltamivir, zanamivir, peramivir, laninamivir, and baloxavir. Adverse events associated with anaphylaxis, "anaphylactic reaction," "anaphylactic shock," "anaphylactoid reaction," and "anaphylactoid shock," were evaluated. The association between anaphylaxis and anti-influenza drug use was assessed by calculating the reporting odds ratio (ROR) and information component (IC) as a measure of disproportionality. Signals were considered positive if the lower limit of the 95% confidence interval (CI) of ROR was > 1, and that of IC was > 0. The number of anaphylaxis cases associated with anti-influenza drug use was 199 (0.9%). Signals were detected for inhaled laninamivir (ROR: 4.24 [95% CI: 3.06-5.88], IC: 1.83 [1.35-2.30]), intravenous peramivir (ROR: 2.97 [2.11-4.17], IC: 1.40 [0.90-1.89]), and oral baloxavir (ROR: 3.05 [2.22-4.18], IC: 1.44 [0.98-1.90]). Conversely, signals were not detected for oral oseltamivir or inhaled zanamivir. Although zanamivir and laninamivir were used as dry powder inhalers containing lactose as an additive, they differed in terms of signal detection. Our analysis indicated that the signal of anaphylaxis may varies based on the main component or dosage form of each anti-influenza drug. Appropriate use of these drugs is essential to prevent anaphylaxis and improve health status. [ABSTRACT FROM AUTHOR]

Background: To identify the clinical factors affecting activities of daily living (ADL) at baseline and after 6 months. Methods: We conducted a single-centre observational study at two time points across 6 months (baseline and after 6 months) from April 2015 to March 2017. in a 270-bed rural recuperation hospital at Hyogo prefecture in Japan. The total number of participants was 131 (male 33, female 98; mean age: 87.0 ± 7.0; mild and moderate dementia, 38; severe dementia, 93). Measurement scales used were Personal Self-Maintenance Scale (PSMS) for assessing ADL, Mini-Mental State Examination and Cognitive Test in Severe Dementia (CTSD) for cognitive function, Neuropsychiatric Inventory- Nursing Home version and Cornell Scale for Depression in Dementia (CSDD) for behavioural/psychological symptoms of dementia, Mini Nutritional Assessment Short form (MNA-SF) for nutritional status, Pain Assessment in Advanced Dementia for pain, and Charlson comorbidity index (CCI) and the number of illness categories based on Cumulative Illness Rating Scale Geriatrics for comorbidities. Multiple regression analyses identified the association between PSMS score as the dependent variable and other variables as independent variables. Results: In participants with severe dementia, the PSMS scores at baseline were significantly associated with CTSD, CCI, MNA-SF, and CSDD scores. In the longitudinal analysis, only CTSD score was significantly associated with PSMS score after 6 months. It is noteworthy that for participants with severe dementia, the only factor associated with ADL after 6 months was cognitive function, as assessed by CTSD score. Conclusions: The most important factor predicting functional decline is cognitive function, even at the severe and profound stage. [ABSTRACT FROM AUTHOR]

Berberine (BBR), an isoquinoline alkaloid, is a well-known bioactive compound contained in medicinal plants used in traditional and folk medicines. In this study, we investigated the subcellular localization and the apoptotic mechanisms of BBR were elucidated. First, we confirmed the incorporation of BBR into the cell visually. BBR showed antiproliferative activity and promptly localized to the nucleus from 5 min to 15 min after BBR treatment in HL-60 human promyelocytic leukemia cells. Next, we examined the antiproliferative activity of BBR (1) and its biosynthetically related compounds (2-7) in HL-60 cells. BBR exerted strongest antiproliferative activity among 1-7 and the results of structures and activity relation suggested that a methylenedioxyl group in ring A, an O-alkyl group at C-9 position, and the frame of isoquinoline may be necessary for antiproliferative activity. Moreover, BBR showed the most potent antiproliferative activity in HL-60 cells among human cancer and normal cell lines tested. Next, we examined the effect of BBR on molecular events known as apoptosis induction. In HL-60 cells, BBR induced chromatin condensation and DNA fragmentation, and triggered the activation of PARP, caspase-3 and caspase-8 without the activation of caspase-9. BBR-induced DNA fragmentation was abolished by pretreatment with inhibitors against caspase-3 and caspase-8, but not against caspase-9. ERK and p38 were promptly phosphorylated after 15 min of BBR treatment, and this was correlated with time of localization to the nucleus of BBR. These results demonstrated that BBR translocated into nucleus immediately after treatments and induced apoptotic cell death by activation of caspase-3 and caspase-8. [ABSTRACT FROM AUTHOR]

Background: Treatment costs for children with growth hormone (GH) deficiency are subsidized by the government in Japan if the children meet clinical criteria, including height limits (boys: 156.4 cm; girls: 145.4 cm). However, several funding programs, such as a subsidy provided by local governments, can be used by those who exceed the height limits. In this study, we explored the impacts of financial support on GH treatment using this natural allocation. Methods: A retrospective analysis of 696 adolescent patients (451 boys and 245 girls) who reached the height limits was conducted. Associations between financial support and continuing treatment were assessed using multiple logistic regression analyses adjusting for age, sex, height, growth velocity, bone age, and adverse effects. Results: Of the 696 children in the analysis, 108 (15.5%) were still eligible for financial support. The proportion of children who continued GH treatment was higher among those who were eligible for support than among those who were not (75.9% vs. 52.0%, P < 0.001). The odds ratios of financial support to continuing treatment were 4.04 (95% confidence interval [CI]: 1.86-8.78) in boys and 1.72 (95% CI: 0.80-3.70) in girls, after adjusting for demographic characteristics and clinical factors. Conclusions: Financial support affected decisions on treatment continuation for children with GH deficiency. Geographic variations in eligibility for financial support pose an ethical problem that needs policy attention. An appropriate balance between public spending on continuation of therapy and improved quality of life derived from it should be explored. [ABSTRACT FROM AUTHOR]

Objective A catecholamine-mediated mechanism has been implicated in the pathogenesis of Takotsubo cardiomyopathy (TC). However, the impact of β-blockers in acute-phase management of TC remains uncertain. This study aimed to examine whether early β-blocker use in TC was associated with lower in-hospital mortality. Methods This was a retrospective cohort study using the Diagnosis Procedure Combination nationwide inpatient database in Japan. Patients with TC aged ≥20 years who were admitted to acute-care hospitals between 2010 and 2014 were identified. Thirty-day inhospital mortality was compared between patients who started β-blocker therapy on hospitalisation day 1 or 2 (early β-blocker group) and those who did not receive a β-blocker during hospitalisation (control group) using propensity score-matching and instrumental variable analyses. Results Of 2672 eligible patients (female, 81.5%; 423 early β-blocker therapy, 2249 controls) from 615 hospitals, 1:4 propensity score-matching created a cohort of 2110 patients (422 early β-blocker therapy, 1688 controls). There was no significant difference in 30-day in-hospital mortality between the early β-blocker group and control group (2.4% vs 2.0%, p=0.703; risk difference, 0.4%; 95% CI, -1.2% to 2.0%). Logistic regression analysis did not show a significant association between early β-blocker use and 30-day in-hospital mortality (OR, 1.17; 95% CI 0.58 to 2.37). Instrumental variable analysis also found that early β-blocker use was not associated with lower 30-day in-hospital mortality (risk difference, 1.2%; 95% CI -3.1% to 5.5%). Conclusions This study found no significant association between early β-blocker use and in-hospital mortality in patients with TC. [ABSTRACT FROM AUTHOR]

Background: Swertia japonica (S. japonica) is a medicinal plant that belongs to the Gentianaceae family. Several reports confirm the biological effects of the S. japonica extract. This plant is used mainly as a digestive stimulant, appetite stimulant, and gastrointestinal disease remedy in Japan. Secoiridoid glycosides are a group of compounds related to the beneficial effects of this plant. Objective: We developed an immunochromatographic strip test for major secoiridoid glycosides, such as swertiamarin (SM) and sweroside (SS) detection. Methods: We fabricated an immunoprobe using activated carbon as a reporter molecule and a monoclonal antibody against SM and SS (MAb D2) as a detection molecule. The test and control zones of the strip test contained SM-cBSA and Goat pAb anti-mouse IgM HRP conjugate, respectively. The immunoprobe reacted competitively with free SM and/or SS and immobilized SM-cBSA. The results were read and interpreted by the black spot intensity in the test zone. Results: We succeeded in developing a strip test system with a detection limit (LOD) of 12.5 mg/mL. The selectivity and reliability evaluation revealed that the strip test is suitable for detecting SM and SS in S. japonica. The result was ready to be read in 30 min. Conclusions: This method can be a useful tool for the screening of biologically active S. japonica samples for further preparation of traditional medicine. Highlights: To the best of our knowledge, this is the first immunochromatographic strip test developed for the detection of SM and SS in S. japonica samples. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background No previous nationwide study has examined whether there is a 'weekend effect' of higher mortality after admission for acute myocardial infarction (AMI) when percutaneous coronary intervention (PCI) is easily accessible. Methods Using the Diagnosis Procedure Combination inpatient database in Japan, we identified AMI patients aged ? 20 years who were admitted to acute care hospitals between July 1, 2010 and March 31, 2013. Multivariable regression models fitted with generalized estimating equations were used to determine the association between weekend admission and in-hospital mortality. Eligible patients were also classified into subgroups according to Killip class at admission. Results Of 111,200 eligible patients, 30,847 patients were admitted on weekends and 80,353 patients on weekdays. Overall, the in-hospital mortality was significantly higher for weekend admission than for weekday admission (13.6% versus 11.4%; P < 0.001; unadjusted odds ratio [OR] 1.222; 95% confidence interval [CI] 1.172 to 1.274), despite the higher rate of PCI performed on the day of admission (68.9% versus 64.8%; P < 0.001). The association remained significant after adjusting for baseline characteristics, invasive procedures, and medications (adjusted OR 1.144, 95% CI 1.079 to 1.214). In subgroup analyses, the effect of weekend admission remained significant in the Killip II to IV subgroups, but became insignificant in the Killip I subgroup (adjusted OR 1.002, 95% CI 0.828 to 1.213). Conclusions This study showed that weekend admission for AMI was significantly associated with higher in-hospital mortality even in a setting where PCI was highly available. [ABSTRACT FROM AUTHOR]