Development of a decision flowchart to identify the patients need high-dose vancomycin in early phase of treatment

Background The standard dose of vancomycin (VCM, 2 g/day) sometimes fails to achieve therapeutic concentration in patients with normal renal function. In this study, we aimed to identify factors to predict patients who require high-dose vancomycin (> 2 g/day) to achieve a therapeutic concentration and to develop a decision flowchart to select these patients prior to VCM administration. Methods Patients who had an estimated creatinine clearance using the Cockcroft–Gault equation (eCCr) of ≥50 mL/min and received intravenous VCM were divided into 2 cohorts: an estimation set (n = 146, from April to September 2016) and a validation set (n = 126, from October 2016 to March 2017). In each set, patients requiring ≤2 g/day of VCM to maintain the therapeutic trough concentration (10–20 μg/mL) were defined as standard-dose patients, while those who needed > 2 g/day were defined as high-dose patients. Univariate and multivariate logistic regression analysis was performed to identify the predictive factors for high-dose patients and decision tree analysis was performed to develop decision flowchart to identify high-dose patients. Results Among the covariates analyzed, age and eCCr were identified as independent predictors for high-dose patients. Further, the decision tree analysis revealed that eCCr (cut off value = 81.3 mL/min) is the top predictive factor and is followed by age (cut off value = 58 years). Based on these findings, a decision flowchart was constructed, in which patients with eCCr ≥81.3 mL/min and age < 58 years were designated as high-dose patients and other patients were designated as standard-dose patients. Subsequently, we applied this decision flowchart to the validation set and obtained good predictive performance (positive and negative predictive values are 77.6 and 84.4%, respectively). Conclusion These results suggest that the decision flowchart constructed in this study provides an important contribution for avoiding underdosing of VCM in patients with eCCr of ≥50 mL/min.

Relationship between tracheal intubation and the drugs used by patients with drug overdose due to self-harm

Background Tracheal intubation may be performed in patients with drug overdose due to self-harm; however, the details of the causative drug are unknown. The purpose of this study was to clarify the relationship between drugs or its blood levels of patients with drug overdose and the need for tracheal intubation based on the actual measurement results. Methods From October 2018 to March 2020, 132 patients with drug overdose due to self-harm who were transported to the emergency department (ED) were studied. Patient drugs were measured using gas chromatography–mass spectrometry (GC-MS) and were analyzed on the basis of the GC/MS Forensic Toxicological Database. Logistic analysis was performed by combining patient information and GC-MS information. Results The Glasgow Coma Scale (GCS) and Japan Coma Scale (JCS) efficiently predicted tracheal intubation in patients with drug overdose during transport triage; GCS (cut-off value: 12, area under the curve (AUC): 0.81, 95% confidence interval (CI): 0.71–0.88, sensitivity: 0.85, specificity: 0.71, P < 0.05) and JCS (cut-off value: 3, AUC: 0.74, 95% CI: 0.60–0.84, sensitivity: 0.60, specificity: 0.84, P < 0.05). The drugs detected in all patients with drug overdose in order were benzodiazepine receptor agonists (BZs; 43.9%), anticonvulsants (38.6%), antipsychotics (25.0%), and antidepressants (9.8%). In univariate logistic analysis, antipsychotics (odds ratio (OR) 2.46, 95% CI 1.19–5.20, P < 0.05), anticonvulsants (OR 2.71, 95% CI 1.26–5.98, P < 0.05), and anticonvulsants above alert blood levels (OR 27.8, 95% CI 2.92–264.1, P < 0.05) were significantly associated with tracheal intubation in patients with drug overdose, but not BZs and antidepressants. Also, in multivariate logistic analysis, antipsychotics (OR 2.27, 95% CI 1.07–4.83, P < 0.05), anticonvulsants (OR 2.50, 95% CI 1.14–5.64, P < 0.05) and in multivariate logistic analysis of blood levels, anticonvulsants above the alert blood levels (OR 24.9, 95% CI 2.56–241.6, P < 0.05) were significantly associated with tracheal intubation in patients with drug overdose respectively. Conclusions Logistic analysis revealed that the use of anticonvulsants and antipsychotics were significantly associated with an increased OR in the tracheal intubation of patients with drug overdose due to self-harm.

Casirivimab-imdevimab neutralizing SARS-CoV-2: post-infusion clinical events and their risk factors

Background Casirivimab-imdevimab has been developed to neutralize SARS-CoV-2. The global clinical trials in outpatients documented several adverse effects (AE), which mandate caution in Japan where part of patients return home. To investigate post-infusion clinical events and their risk factors, we attempted a retrospective study. Main body Subjects were a consecutive series of inpatients with COVID-19 undergoing an infusion of casirivimab-imdevimab in our institute. The criteria for administration were in accordance with previous clinical trials, e.g., exclusion of patients necessitating oxygen supply. In Japan, however, SARS-CoV-2 vaccinees were eligible. Methods were review of background factors of status, imaging, and laboratory findings for the outcome of post-infusion events such as temperature increase (Temp+), pulse oximetry below 94%, and other events. Also, we documented the drug efficacy. Of a total of 96 patients with a median follow-up of 54 days, one (1.0%) died who alone was an exception demanding oxygen supply. Other 95 patients (99.0%) recovered from fever and hypoxia by Day 4 and later had no worsening of COVID-19. Median increase of body temperature was 1.0 degrees Celsius, which was used for computation of Temp+. Multivariate analysis showed that for Temp+ (n = 47), white blood cell counts more than 4.3 × 103/microliter (Odds Ratio [OR] 2.593, 95% Confidence Interval [CI] 1.060–6.338, P = 0.037) was at risk, whereas 2-time vaccination for SARS-CoV-2 (OR 0.128, 95% CI 0.026–0.636, P = 0.012) was a preventing factor. Likewise for lowered oximetry (n = 21), CT showing bilateral ground glass attenuation (OR 5.544, CI 1.599–19.228, P = 0.007) was a significant risk factor. Two patients (2.1%) showed bradycardia (asymptomatic, intervention not indicated) on Day 3 and recovery on Day 5. Limitations for this study included the difficulty distinguishing AE from worsening of COVID-19, thus we documented as clinical events. Conclusions For 24 h after infusion of casirivimab-imdevimab, COVID-19 patients with increased white blood cell counts may be predisposed to temperature elevation more than 1.0 degrees centigrade, as may bilateral ground glass opacity to lowered oximetry. Thus, patients with leukocytosis and bilateral ground glass attenuation may need precaution for transient fever and hypoxia, respectively.

Potential drug–drug interactions in the era of integrase strand transfer inhibitors: a cross-sectional single-center study in Japan

Background Potential drug–drug interactions (PDDIs) commonly occur because of aging and comorbidities in people living with human immunodeficiency virus (HIV; PLWH). Protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been reported to cause PDDIs in these patients. However, there are few reports of PDDIs in the era of treatment using integrase strand transfer inhibitors. Therefore, we investigated PDDIs in Japanese PLWH receiving antiretroviral drugs (ARVs). Methods This was a cross-sectional observational study conducted in Japanese outpatients. All eligible patients who had received ARV therapy for at least 48 weeks were enrolled. The primary endpoint was the incidence of PDDIs detected using the Lexicomp® interface. Results Of the 71 eligible patients, 51 (71.8%) were prescribed concomitant non-ARV medications. In 21 patients (29.6%), PDDIs with the potential to reduce the effects of ARVs occurred, although the HIV load was suppressed in all cases. Polypharmacy (the use of ≥5 non-ARVs) was observed in 25 patients (35.2%). There was a significantly higher median number of non-ARV medications in the PDDI group than in the non-PDDI group (6 vs. 3, P < 0.001). Furthermore, the proportion of patients on polypharmacy was significantly higher in those with PDDIs than in those without PDDIs (81.0% vs. 26.7%, P < 0.001). Conclusions The incidence of PDDIs is relatively high in Japanese PLWH, even in the era of treatment using integrase strand transfer inhibitors. Therefore, it is important for patients and health care providers to be constantly aware of PDDIs associated with ARV treatment.

A case of complete atrioventricular block with extremely high blood concentration of azelnidipine

Background Azelnidipine, a dihydropyridine calcium channel blocker (CCB), has less adverse effects (e.g. hot flushes and reflex tachycardia) compared to other dihydropyridine CCBs. Azelnidipine has been reported to reduce heart rate as opposed to inducing tachycardia. No evidence of bradycardia or complete atrioventricular block (CAVB) with azelnidipine treatment has been reported. Case presentation In the present study, a 92-year-old woman was diagnosed with CAVB while taking azelnidipine and simvastatin for an extended period of time, and referred to our medical center. It was thought that the CAVB may have been an adverse effect of azelnidipine treatment. Specifically, it was considered that in this patient, one of the causes might be the concomitant use of simvastatin inhibiting the metabolism of azelnidipine by cytochrome P450 enzyme 3A4. Consequently, it was suggested to the patient’s physician that the patient’s serum azelnidipine levels be measured and treatment with azelnidipine and simvastatin be discontinued. The patient’s serum concentration of azelnidipine at the time of her visit to our center was 63.4 ng/mL, higher than the normal acceptable level. There was no occurrence of CAVB for 4 weeks, to present, following discontinuation of azelnidipine and simvastatin treatment. Conclusions Azelnidipine has a different mechanism of action that other CCBs. In very rare cases, it may cause CAVB when combined with CYP3A4 inhibitors. If a patient taking azelnidipine is diagnosed with CAVB, physicians should suspect that the condition may be an adverse effect of azelnidipine and should consider discontinuing azelnidipine. And, in the elderly, it is necessary to avoid concomitant use of CYP3A4 inhibitors.

Administration of zinc to preterm infants with hypozincemia does not reduce serum copper concentrations in most cases: a single-center retrospective observational study

Background Zinc is an essential trace element involved in various physiological functions. In Japan, zinc acetate dihydrate is administered to neonates and infants with hypozincemia. Since serum copper concentrations are reduced by the administration of zinc, we retrospectively investigated changes in serum zinc and copper concentrations in preterm infants with hypozincemia receiving zinc acetate dihydrate. Methods Sixty-three preterm infants were included in the present study. Serum zinc and copper concentrations, doses, and other clinical characteristics were retrieved from electronic medical records. Results The medians and interquartile ranges of the dosage and duration of zinc acetate dihydrate were 2.1 (1.8–2.5) mg/kg/day and 12.0 (10.0–13.0) days, respectively. Its administration increased serum zinc concentrations in 39 patients (61.9%) and to more than 70 μg/dL in 16 patients (25.4%). The group with a serum zinc concentration of 70 μg/dL or higher after administration had a significantly higher zinc dose of 2.5 mg/kg/day than the group with a serum zinc concentration of less than 70 μg/dL. Serum copper concentrations did not decrease in 44 patients (69.8%). In the group with a decreased serum copper concentration, postmenstrual age and body weight were significantly lower, while serum zinc concentrations were significantly higher at the start of administration. Conclusion The present results showed that when zinc acetate dihydrate was administered to preterm infants with hypozincemia, it was possible to increase serum zinc concentrations without decreasing serum copper concentrations in many cases. However, caution may be required when administering zinc to preterm infants with a lower postmenstrual age or milder hypozincemia because serum copper concentrations may decrease.

Active TB infection and its associated factors among HIV-1 infected patients at Jimma medical center, Southwest Ethiopia

Background Human immune deficiency virus (HIV) increases the susceptibility to primary infection or reinfection and the risk of tuberculosis (TB) reactivation for patients with latent TB. There was no current report on the rate of active TB infection among HIV-1 infected patients in our teaching and referral hospital. Therefore, this study was aimed to determine the prevalence and factors associated with active TB infection among HIV-1 infected patients. Methods Hospital-based retrospective cross-sectional study was conducted at the Anti-Retroviral Therapy (ART) chronic follow-up clinic. Systematic random sampling was used to include the patients. A structured questionnaire was used to collect data. Data were analyzed using SPSS version 25. Descriptive statistics were used to describe the findings and multivariate logistic regression was performed to identify factors associated with active TB infection. Result 150 HIV-1 infected patients (female 54.7%) were included. The median (interquartile range, IQR) age of the patients was 33.5 (25.7, 40.0) years. Twenty-six (17.3%) of the patients had developed active TB infection, which was independently associated with the WHO clinical stage III and IV (AOR: 9.67, 95% confidence interval (CI); 2.21–42.37), p = 0.003). The use of isoniazid preventive therapy (IPT) (AOR: 0.123, 95CI; 0.034–0.44, p = 0.001) and having good adherence to ART medications (AOR: 0.076, 95CI; 0.007–0.80, p = 0.032) was associated with the reduced risk of active TB infection among HIV-1 infected patients. Conclusions Advanced WHO clinical stages increased the risk of active TB infection, while the use of IPT and good adherence to ART medications reduced the risk of active TB infection. Therefore, patients with advanced WHO clinical stage should be screened for TB infection, and starting IPT for the candidate patients should be strengthened to reduce the burden of active TB incidence. ART medication adherence should also be supported.

Assessment of the potential impact of resolving drug-related problems by clinical pharmacists in Japan: a retrospective observational study

Background Clinical pharmacists play a role in limiting the disadvantages of pharmacotherapy for patients by detecting and resolving drug-related problems (DRPs) through medication reviews. Although their contributions to patient care have been analyzed and understood in various countries, the role of Japanese clinical pharmacists in this context remains to be clearly elucidated. Thus, in this study, we aimed to elucidate the detection of DRPs by clinical pharmacists and determine the potential impact of pharmacist interventions in Japan. Methods This study was conducted in a 273-bed hospital and targeted hospitalized patients over a period of 6 months. DRPs detected by clinical pharmacists during the study period were investigated and classified into 10 types. Furthermore, medications were categorized according to the Anatomical Therapeutic Chemical classification. A review committee consisting of two pharmacists independently reviewed the pharmacist interventions on a six-point scale (extremely significant, very significant, significant, somewhat significant, no significance, adverse significance) according to the potential impact on patient care. Results During the study period, 1711 patients (mean age: 71.2 years, 54.1% male) were included, and 2149 DRPs were detected (1.26 DRPs/patient). Pharmacists intervened in all the DRPs detected. The most common DRP was supratherapeutic dosage (19.3%), followed by untreated indication (18.1%). The most common medication classification causing DRPs was “Antiinfectives for Systemic Use” (25.1%), followed by “Alimentary Tract and Metabolism” (19.9%). Most of the pharmacist interventions (99.6%) were rated “somewhat significant” or more significant, of which 1.1% were rated “extremely significant,” and none were rated as “adverse significance.” Conclusions Our results show that in Japan, as in other countries, clinical pharmacists detect and resolve DRPs in hospitalized patients through medication review. Our findings also show that clinical pharmacists have a positive impact on patient care and suggest the need for their involvement.

A case of improvement of clozapine-induced low leukocyte counts by adenine, cepharanthin and ninjin-yoei-to in a patient with treatment-resistant schizophrenia

Background Although clozapine is the optimal drug for patients with treatment-resistant schizophrenia, the drug has harmful adverse effects such as leukopenia. Adenine and cepharanthine are known to be effective for radiation- or drug-induced leukopenia. Furthermore, ninjin-yoei-to, a Chinese herbal medicine, augments the production of granulocyte-macrophage colony-stimulating factor. Thus, these drugs may be useful for clozapine-induced leukopenia. Case presentation A 21 years-old woman with schizophrenia was hospitalized for initiation of clozapine treatment. Despite concomitant use of adenine, cepharanthine, and lithium carbonate having activities of increasing leukocytes, a decrease in leukocyte counts occurred after the initiation of clozapine. Additional administration of ninjin-yoei-to increased leukocyte counts, which prevented the development of leukopenia. Conclusions This is the first case that concomitant use of adenine, cepharanthin, and ninjin-yoei-to exhibited the effectiveness of reversing the decrease in leukocytes caused by clozapine. Monitoring leukocyte counts and preventing leukopenia are essential for successful treatment with clozapine for refractory schizophrenia. These medicines may be a potential option for preventing clozapine-induced leukopenia.

Treatment outcome and associated factors of bacterial meningitis at pediatric wards of southwestern Ethiopian hospital: a prospective observational study

Background Meningitis is a common infectious cause of morbidity and mortality in pediatric age-groups. Acute bacterial meningitis is considered a medical emergency, because it is a life-threatening infection that requires immediate treatment. Therefore the study was aimed to assess the magnitude and predictors of poor treatment outcome among pediatric patients admitted to Bedele General Hospital. Methods A prospective observational study was conducted at pediatric wards of Bedele General Hospital from February 12, 2020 to August 11, 2020. Lumbar puncture, in the absence of contraindications, was performed under aseptic conditions for all patients with suspected bacterial meningitis to collect cerebrospinal fluid specimen. Multivariable logistic regression was used to determine the predictors of poor treatment outcome. Result Of the 196 pediatric patients involved, 112(57.1%) were male and the mean and standard deviation of their age was 6.09 ± 4.46. Regarding to their clinical profile, a total of 101(51.5%) were completely immunized and 115(58.7%) were given corticosteroid during their treatment. In our study the most frequently occurred clinical manifestation of meningitis was fever 164(83.67%), neck rigidity149 (76.02%), and irritability 122(62.24%). Regarding to their pharmacotherapy, the most commonly prescribed antibiotics were Ampicillin 104(24.82%), and Gentamycin 102(24.34%). The magnitude of good treatment outcome was 132(67.35%) whereas 64(32.65%) were poorly controlled. The presence of comorbidity (AOR = 3.64, 95CI%:1.83–7.23,P = < 0.001),corticosteroid use (AOR = 2.37, 95CI%:1.17–4.81,P = 0.017) and oxygen administration (AOR = 3.12, 95CI%: 1.34–7.25, P = 0.008) was a predictor of meningitis treatment outcome. Conclusion The treatment outcome of meningitis was good in of two-third of the patients. It was found that the presence of comorbidity, the administration of oxygen and use of corticosteroid was predictors of the treatment outcomes of bacterial meningitis in children. Therefore, in patients with these factors, appropriate meningitis treatment should be encouraged and locally applicable treatment guidelines should be prepared to improve patient outcome. Finally, the meningitis patients should be given corticosteroid and oxygen as treatment and special attention should be given for patients having co-morbidities.