Internet-Based Inquiries From Users With the Intention to Overdose With Over-the-Counter Drugs: Qualitative Analysis of Yahoo! Chiebukuro.

BACKGROUND: Public concern with regard to over-the-counter (OTC) drug abuse is growing rapidly across countries. OTC drug abuse has serious effects on the mind and body, such as poisoning symptoms, and often requires specialized treatments. In contrast, there is concern about people who potentially abuse OTC drugs whose symptoms are not serious enough to consult medical institutions or drug addiction rehabilitation centers yet are at high risk of becoming drug dependent in the future. OBJECTIVE: Consumer-generated media (CGM), which allows users to disseminate information, is being used by people who abuse (and those who are trying to abuse) OTC drugs to obtain information about OTC drug abuse. This study aims to analyze the content of CGM to explore the questions of people who potentially abuse OTC drugs. METHODS: The subject of this research was Yahoo! Chiebukuro, the largest question and answer website in Japan. A search was performed using the names of drugs commonly used in OTC drug abuse and the keywords overdose and OD, and the number of questions posted on the content of OTC drug abuse was counted. Furthermore, a thematic analysis was conducted by extracting text data on the most abused antitussive and expectorant drug, BRON. RESULTS: The number of questions about the content of overdose medications containing the keyword BRON has increased sharply as compared with other product names. Furthermore, 467 items of question data that met the eligibility criteria were obtained from 528 items of text data on BRON; 26 codes, 6 categories, and 3 themes were generated from the 578 questions contained in these items. Questions were asked about the effects they would gain from abusing OTC drugs and the information they needed to obtain the effects they sought, as well as about the effects of abuse on their bodies. Moreover, there were questions on how to stop abusing and what is needed when seeking help from a health care provider if they become dependent. It has become clear that people who abuse OTC drugs have difficulty in consulting face-to-face with others, and CGM is used as a means to obtain the necessary information anonymously. CONCLUSIONS: On CGM, people who abused or tried to abuse OTC drugs were asking questions about their abuse expectations and anxieties. In addition, when they became dependent, they sought advice to quit their abuse. CGM was used to exchange information about OTC drug abuse, and many questions on anxieties and hesitations were posted. This study suggests that it is necessary to produce and disseminate information on OTC drug abuse, considering the situation of those who abuse or are willing to abuse OTC drugs. Support from pharmacies and drugstores would also be essential to reduce opportunities for OTC drug abuse.

Impact of prior bevacizumab therapy on the incidence of ramucirumab-induced proteinuria in colorectal cancer: a multi-institutional cohort study.

BACKGROUND: The association between prior bevacizumab (BEV) therapy and ramucirumab (RAM)-induced proteinuria is not known. We aimed to investigate this association in patients with metastatic colorectal cancer (mCRC). METHODS: mCRC patients who received folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus RAM were divided into with and without prior BEV treatment groups. The cumulative incidence of grade 2-3 proteinuria and rate of RAM discontinuation within 6 months (6M) after RAM initiation were compared between the two groups. RESULTS: We evaluated 245 patients. In the Fine-Gray subdistribution hazard model including prior BEV, age, sex, comorbidities, eGFR, proteinuria ≥ 2 + at baseline, and later line of RAM, prior BEV treatment contributed to proteinuria onset (P < 0.01). A shorter interval between final BEV and initial RAM increased the proteinuria risk; the adjusted odds ratios (95% confidence intervals) for the intervals of < 28 days, 28-55 days, and > 55 days (referring to prior BEV absence) were 2.60 (1.23-5.51), 1.51 (1.01-2.27), and 1.04 (0.76-1.44), respectively. The rate of RAM discontinuation for ≤ 6M due to anti-VEGF toxicities was significantly higher in the prior BEV treatment group compared with that in the no prior BEV treatment group (18% vs. 6%, P = 0.02). Second-line RAM discontinuation for ≤ 6M without progression resulted in shorter overall survival of 132 patients with prior BEV treatment (P < 0.01). CONCLUSION: Sequential FOLFIRI plus RAM after BEV failure, especially within 55 days, may exacerbate proteinuria. Its escalated anti-VEGF toxicity may negatively impact the overall survival.

Risk of a second cancer and infection in patients with indolent B-cell lymphoma exposed to first-line bendamustine plus rituximab: A retrospective analysis of an administrative claims database.

Bendamustine has a potent immunosuppressive effect because it causes T-cell lymphopenia, which might lead to a second primary malignancy (SPM) and would increase the risk of infection. Using the Medical Data Vision administrative claims database, we compared the cumulative incidence of SPM, infections within 6 months, and overall survival (OS) among untreated patients with indolent B-cell lymphomas (iBCL) who received rituximab-based chemotherapy between 2009 and 2020. Patients with grade 3b follicular lymphoma or a previous history of malignancy were excluded. Eligible 5234 patients were assigned to three cohorts: rituximab monotherapy (N = 780), RCHOP/RCVP/RTHPCOP (doxorubicin replaced with pirarubicin) (N = 2298), or bendamustine/rituximab (BR) (N = 2156). There were 589 recorded SPMs, of which myelodysplastic syndromes were the most common (1.7%). The cumulative incidence of SPM was significantly higher in patients treated with BR than in those treated with rituximab monotherapy (p < 0.01) or RCHOP/RCVP/RTHPCOP (p < 0.0001): the 5-year cumulative incidence function was 18.1%, 12.5%, and 12.9%, respectively. In the Fine-Gray subdistribution hazards model, BR showed a significantly higher cumulative incidence of SPM than RCHOP/RCVP/RTHPCOP (subhazard ratio, 1.33; 95% confidence interval [CI], 1.10-1.61). Furthermore, in sensitivity analysis, a nested case-control study using an entire cohort showed consistent results: the SPM odds ratios (95% CI) of first-line bendamustine, bendamustine after first-line, and any-line bendamustine were 1.43 (1.14-1.78), 1.26 (0.96-1.64), and 1.33 (1.09-1.62), respectively. Regarding infections, adjusted odds ratios (95% CI) of BR compared to RCHOP/RCVP/RTHPCOP were as follows: cytomegalovirus infection, 13.7 (4.88-38.4); bacterial pneumonia, 0.63 (0.50-0.78); and pneumocystis pneumonia, 0.24 (0.11-0.53). There was no significant difference in OS between RCHOP/RCVP/RTHPCOP and BR in patients with follicular, mantle cell, marginal zone, or lymphoplasmacytic lymphomas. In conclusion, treatment strategies that consider the risk of SPM and infections after chemotherapy are warranted in patients with iBCL.

Incidence of acute kidney injury after teicoplanin- or vancomycin- and piperacillin/tazobactam combination therapy: A comparative study using propensity score matching analysis.

INTRODUCTION: Combination therapy with vancomycin (VCM) and piperacillin/tazobactam (PIPC/TAZ) increases the risk of acute kidney injury (AKI). Teicoplanin (TEIC) has a lower risk of AKI than VCM. Currently, the difference in AKI risk after TEIC-PIPC/TAZ combination therapy and VCM-PIPC/TAZ combination therapy is controversial. This study aimed to compare AKI incidence after treatment with these two drug combinations using propensity score matching analysis. METHODS: This single-center cohort study used data extracted from patients' medical records. We included patients who received TEIC-PIPC/TAZ therapy (TEIC group) or VCM-PIPC/TAZ therapy (VCM group). After propensity score matching, AKI incidence, AKI stage, 30-day mortality, and time to AKI incidence were compared between the groups. RESULTS: After propensity score matching, 94 patients were matched in each group. AKI incidence was significantly lower in the TEIC group than in the VCM group (10.6% vs. 23.4%, odds ratio [95% confidence interval]: 0.39 [0.17-0.88], p = 0.03). AKI stage, 30-day mortality, and time to AKI incidence were not significantly different between the groups. CONCLUSIONS: This study suggested that AKI incidence may be lower in patients undergoing combination therapy with TEIC-PIPC/TAZ than in those receiving therapy with VCM-PIPC/TAZ. To prevent the occurrence of AKI, clinicians may need to choose TEIC instead of VCM for patients receiving PIPC/TAZ.

Pharmacist involvement in the inhaler choice improves lung function in patients with COPD: a prospective single-arm study.

BACKGROUND: Currently, in Japan, shifting tasks from physician to hospital pharmacist is being developed to reduce physician workload and improve the quality of pharmacotherapy. This study aimed to investigate the effects of pharmacist involvement in the choice of inhaler as the task on the clinical outcomes of patients with chronic obstructive pulmonary disease (COPD). METHODS: This prospective, single-center, single-arm study included 36 outpatients with newly diagnosed COPD indicating inhaler therapy. Eligible patients were immediately interviewed by pharmacist. Then, pharmacist assessed patient's inhalation flow rate, physical function to handle an inhaler, comprehension, and value, and finally recommended a personalized inhaler based on originally developed inhaler choice protocol, and pulmonologist prescribed a pharmacist-selected inhaler. The primary endpoint was the improvement in trough forced expiratory volume in 1 s (FEV1) between baseline and week 26. The secondary endpoints were safety, and improvements at week 26 in scores for the COPD Assessment Test (CAT), modified British Medical Research Council Dyspnea Scale (mMRC), and Adherence Starts with Knowledge-20 (ASK-20). RESULTS: The pneumonologists completely agreed with the pharmacist-recommended inhaler. Mean FEV1 significantly increased from baseline to week 26 (1.60, SD 0.54 L vs. 1.98, SD 0.56 L; p < 0.0001). Significant improvements in CAT, mMRC, and ASK-20 scores were also observed. The prevalence of CAT responders as a negative predictor of acute exacerbation, defined as those with a decrease in CAT score of ≥2 points from baseline, was 86%. None of the patients experienced exacerbation during the study period. CONCLUSIONS: Pharmacist involvement in the choice of inhaler for patients with newly diagnosed COPD was associated with improved lung function, health status, clinical symptoms, and adherence to inhaler therapy. Shifting task of choosing appropriate inhaler from physician to hospital pharmacist may be performed effectively and safely with an inhaler choice protocol. TRIAL REGISTRATION NUMBER: UMIN000039722 , retrospectively registered on March 10, 2020.

Thyroid Dysfunction Related to the Antiangiogenic VEGFR2-Binding Monoclonal Antibody Ramucirumab: A Series of 14 Cases and a Descriptive Study.

Hypothyroidism is a well-established toxicity of small-molecule anti-vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors. However, its association with anti-VEGF biologics is uncertain. The aim of this study was to investigate the incidence, time course, clinical features, and severity of thyroid dysfunction in patients receiving ramucirumab (an antiangiogenic VEGF receptor 2-binding monoclonal antibody). After retrospectively reviewing electronic medical records from September 2015 to December 2018 at Kyoto-Katsura Hospital, we identified 38 patients who received ramucirumab and had thyroid function testing available to review (case series). We also evaluated the change of thyroid-stimulating hormone (TSH) level during ramucirumab chemotherapy in 16 out of 38 patients who were regularly confirmed TSH (descriptive study). A total of 14 (36.8%) patients developed thyroid dysfunction (TSH >10 mU/L) after ramucirumab chemotherapy. Thyroid autoantibodies were detected in one of the 10 patients (10.0%) who were tested for thyroid autoantibodies. The median time to onset of thyroid dysfunction after ramucirumab initiation was 275 (range, 63-553) days. Levothyroxine replacement was needed in 10 (71.4%) patients. Sixteen patients had thyroid function regularly monitored; the mean TSH level was significantly increased after ramucirumab chemotherapy compared with that at baseline (10.7 ± 10.0 mU/L vs. 4.1 ± 2.8 mU/L; p < 0.01). Our findings indicate that ramucirumab can result in thyroid dysfunction. We propose that thyroid function testing should be performed regularly to detect hypothyroidism and guide its management in patients receiving ramucirumab chemotherapy.

Impact of prior bortezomib therapy on the incidence of lenalidomide-induced skin rash in multiple myeloma: a propensity score-matched multi-institutional cohort study.

This retrospective cohort study was conducted to investigate the association between prior bortezomib (BOR) therapy and lenalidomide (LEN)-induced rash in multiple myeloma (MM) patients. Eligible MM patients initially treated with LEN were divided into two propensity score-matched cohorts according to the presence or absence of prior BOR therapy. The primary endpoint of the study was rash incidence. We evaluated 144 patients and each cohort contained 43 patients after matching propensity-score. Rash incidence significantly decreased in patients with prior BOR therapy than in those without (30% vs. 53%, p < .05). Moreover, patients with rash showed a significantly higher incidence of eosinophilia within 1 month after LEN initiation than those without rash. Our findings indicate that prior BOR therapy may reduce the incidence of LEN-induced rash, which may be characterized by eosinophilia. Accordingly, in patients who discontinued LEN therapy due to rash, LEN re-treatment may be successful after BOR therapy.

Oral mucositis associated with anti-EGFR therapy in colorectal cancer: single institutional retrospective cohort study.

BACKGROUND: Chemotherapy-induced oral mucositis impairs the quality of life. The difference in severity of oral mucositis between different anti-epidermal growth factor receptor (EGFR) antibodies combined with cytotoxic drugs in colorectal cancer is unclear. The aim of this study was to investigate the differences in oral mucositis between panitumumab (Pmab) and cetuximab (Cmab) combined with 5-fluorouracil (5-FU). METHODS: We conducted a retrospective cohort study. A total of 75 colorectal cancer outpatients treated with an anti-EGFR antibody combined with FOLFOX, FOLFIRI, or 5-FU/leucovorin as the first- to third-line treatment were included. The primary endpoint was the incidence of grade 2-3 oral mucositis. The secondary endpoint was the time to onset of oral mucositis. We also compared the incidence of toxicities of interest, skin toxicity, hypomagnesaemia and neutropenia, and time to treatment failure (TTF) between the two groups. RESULTS: Thirty-two patients treated with Pmab and 43 patients treated with Cmab were evaluated. Patient characteristics were similar between the two groups. The incidence of grade 2-3 oral mucositis was significantly higher with Pmab than with Cmab (31.3% vs 9.3%, P < 0.05). Moreover, the incidence of grade 3 oral mucositis was significantly higher in patients treated with Pmab (18.8% vs 0%, P < 0.01). The mean (SD) cycles to onset of the worst oral mucositis was 3.0 (2.9) in the Pmab group and 2.3 (1.7) in the Cmab group (P = 0.29). Oral mucositis was characterized by glossitis and cheilitis. The incidences of other toxicities were the following (Pmab vs Cmab): grade 2-3 skin toxicity: 68.8% vs 74.4% (P = 0.61), grade 2-3 hypomagnesaemia: 9.3% vs 7.0% (P = 1.00), grade 3-4 neutropenia: 28.1% vs 37.2% (P = 0.46). The median TTF was not significantly different, i.e., 223 days vs 200 days (P = 0.39) for Pmab vs Cmab. CONCLUSIONS: Pmab-based chemotherapy resulted in significantly higher grades of oral mucositis compared with Cmab-based chemotherapy. The oral condition should be monitored carefully and early supportive care should be provided for patients treated with Pmab-based chemotherapy.

A retrospective analysis of patient-specific factors on voriconazole clearance.

BACKGROUND: Voriconazole concentrations display a large variability, which cannot completely be explained by known factors. We investigated the relationships of voriconazole concentration with patient-specific variables and concomitant medication to identify clinical factors affecting voriconazole clearance. METHODS: A retrospective chart review of voriconazole trough concentration, laboratory data, and concomitant medication in patients was performed. The concentration/dose ratio (C/D-ratio) was assessed as a surrogate marker of total clearance by dividing voriconazole concentration by daily dose per kg of body weight. RESULTS: A total of 77 samples from 63 patients were obtained. In multiple linear regression analysis, increased C-reactive protein (CRP) level (p < 0.05) and decreased albumin (Alb) level (p < 0.05) were associated with significantly increased C/D-ratio of voriconazole, and coadministration with a glucocorticoid was associated with significantly (p < 0.05) decreased C/D-ratio of voriconazole (adjusted r (2) = 0.31). Regarding CRP and Alb, receiver operating characteristic curve analysis indicated that increased CRP level and decreased Alb level were significant predictors of toxic trough concentration of voriconazole. For CRP, area under the curve (AUC) and cutoff value were 0.71 (95 % confidence interval (CI), 0.57-0.86, p < 0.01) and 4.7 mg/dl, respectively. For Alb, AUC and cutoff value were 0.68 (95 % CI, 0.53-0.82, p < 0.05) and 2.7 g/dl, respectively. A significant difference was seen in voriconazole trough concentration between patients with hepatotoxicity and those without (5.69 µg/ml vs 3.0 µg/ml, p < 0.001). CONCLUSION: Coadministration of glucocorticoid and inflammation, reflected by elevated CRP level and hypoalbuminemia, are associated with voriconazole clearance. We propose that early measurement of voriconazole concentration before the plateau phase will lead to avoidance of a toxic voriconazole level in patients with elevated CRP level and hypoalbuminemia, although further studies are needed to confirm our findings.