HOW “KHMER PRODUCT” IS MADE THROUGH DEVELOPMENT PROCESS: FOCUSING ON CHANGING THE VALUE OF AGRICULTURAL PRODUCTS IN CONTEMPORARY CAMBODIA

This study investigates some aspects of the socio-cultural changes that took place in contemporary rural Cambodia by focusing on production and marketing practices. It explores both the changing value crops and the transformation in agricultural production and trade among Khmer farmers after a new farming technology was introduced by a local NGO.  The case study presented in this paper is a local NGO operating since 2001 in the rural area where the author has conducted fieldwork from 2005 to 2016. The NGO has introduced a new agricultural technique and tried to establish farmer organizations in village and national level.  The yield crops produced with new technology was authorized by NGOs and given the new commodity value of ‘Khmer organic products. This signifies that dissemination of new agricultural techniques brings not only change in the production itself but imposes a new system for marketing crops and images of Khmer products. Therefore, dynamically transformed the social relationship patterns not only among the farmers, but with outsiders as well, including development promoter

Adverse events of smoking cessation treatments (nicotine replacement therapy and non-nicotine prescription medication) and electronic cigarettes in the Food and Drug Administration Adverse Event Reporting System, 2004−2016

Objectives: Several smoking cessation treatments (nicotine replacement therapy and non-nicotine prescription medication) and electronic cigarettes are widely used. We evaluated the adverse events related to smoking cessation treatments and electronic cigarettes in the US Food and Drug Administration Adverse Event Reporting System database. Methods: We analyzed reports of adverse events associated with smoking cessation treatment and electronic cigarettes terms dated between January 2004 and December 2016. We used the reporting odds ratio with 95% confidence intervals to detect a signal for each adverse event. Results: In total, 8,867,135 reports in the Food and Drug Administration Adverse Event Reporting System database were analyzed. The numbers of adverse events for nicotine replacement therapy (transdermal, buccal, oral, and respiratory administration) were 1673, 1016, 425, and 56, respectively. Nicotine replacement therapy (transdermal, buccal, and oral) demonstrated adverse events of nausea, nicotine dependence, and dizziness. For nicotine (transdermal) exposure, the top 5 adverse events reported were nausea (149 cases, reporting odds ratio: 2.28 (95% confidence interval: 1.92–2.69)), dizziness (132 cases, reporting odds ratio: 3.04 (95% confidence interval: 2.54–3.63)), application site erythema (108 cases, reporting odds ratio: 32.52 (95% confidence interval: 26.74–39.55)), headache (98 cases, reporting odds ratio: 1.84 (95% confidence interval: 1.50–2.25)), and dyspnea (94 cases, reporting odds ratio: 1.93 (95% confidence interval: 1.57–2.38)). Many cases of improper use of nicotine replacement therapies were reported. Nausea, depression, abnormal dreams, insomnia, and other adverse events were reported for varenicline. Insomnia, rash, anxiety, and dizziness were reported for bupropion. We observed electronic cigarettes–related adverse events such as dizziness, dyspnea, nausea, heart rate increased, and tremor. Conclusion: Our findings suggest that an association exists between nicotine-related adverse events and nicotine replacement therapy. Healthcare professionals should closely monitor smokers trying to quit nicotine use for the misuse of nicotine replacement therapy. These findings may be informative to healthcare professionals in order to improve the management of smoking cessation treatment

Time-to-Onset Analysis of Drug-Induced Long QT Syndrome Based on a Spontaneous Reporting System for Adverse Drug Events.

Long QT syndrome (LQTS) is a disorder of the heart's electrical activity that infrequently causes severe ventricular arrhythmias such as a type of ventricular tachycardia called torsade de pointes (TdP) and ventricular fibrillation, which can be fatal. There have been no previous reports on the time-to-onset for LQTS based on data from spontaneous reporting systems. The aim of this study was to assess the time-to-onset of LQTS according to drug treatment. We analyzed the association between 113 drugs in 37 therapeutic categories and LQTS including TdP using data obtained from the Japanese Adverse Drug Event Report database. For signal detection, we used the reporting odds ratio (ROR). Furthermore, we analyzed the time-to-onset data and assessed the hazard type using the Weibull shape parameter. The RORs (95% confidence interval) for bepridil, amiodarone, pilsicainide, nilotinib, disopyramide, arsenic trioxide, clarithromycin, cibenzoline, donepezil, famotidine, sulpiride, and nifekalant were 174.4 (148.6-204.6), 17.3 (14.7-20.4), 52.0 (43.4-62.4), 13.9 (11.5-16.7), 69.3 (55.3-86.8), 54.2 (43.2-68.0), 4.7 (3.8-5.8), 19.9 (15.9-25.0), 8.1 (6.5-10.1), 3.2 (2.5-4.1), 7.1 (5.5-9.2), and 254.8 (168.5-385.4), respectively. The medians and quartiles of time-to-onset for aprindine (oral) and bepridil were 20.0 (11.0-35.8) and 18.0 (6.0-43.0) days, respectively. The lower 95% confidence interval of the shape parameter β of bepridil was over 1 and the hazard was considered to increase over time.Our study indicated that the pattern of LQTS onset might differ among drugs. Based on these results, careful long-term observation is recommended, especially for specific drugs such as bepridil and aprindine. This information may be useful for the prevention of sudden death following LQTS and for efficient therapeutic planning

Drug-induced gingival hyperplasia: a retrospective study using spontaneous reporting system databases

Abstract Background Drug-induced gingival hyperplasia (DIGH) causes problems with chewing, aesthetics, and pronunciation, and leads to the deterioration of the patient’s quality of life (QOL). Thus, the aim of this study was to evaluate the incidence of DIGH using spontaneous reporting system (SRS) databases. Methods We analyzed reports of DIGH from SRS databases and calculated the reporting odds ratios (RORs) of suspected drugs (immunosuppressants, calcium channel blockers, and anticonvulsants). The SRS databases used were the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) database. With the data, we evaluated the time-to-onset profile and the hazard type using the Weibull shape parameter (WSP). Furthermore, we used the association rule mining technique to discover undetected relationships such as possible risk factors. Results The FAERS contained 5,821,716 reports. The RORs (95% confidence interval: CI) for cyclosporine, everolimus, sirolimus, mycophenolate mofetil, amlodipine, nifedipine, carbamazepine, clobazam, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, and valproic acid, were 39.4 (95% CI: 30.3–51.2), 4.2 (1.7–10.0), 6.6 (2.5–17.7), 13.1 (7.2–23.2), 94.8 (80.0–112.9), 57.9 (35.7–94.0), 15.1 (10.3–22.3), 65.4 (33.8–126.7), 6.5 (3.6–11.8), 19.7 (8.8–44.0), 65.4 (52.4–82.9), 56.5 (21.1–151.7), 2.9 (1.1–7.7), and 17.5 (12.6–24.4), respectively. The JADER database contained 430,587 reports. The median time-to-onset of gingival hyperplasia values for immunosuppressants, calcium channel blockers, and anticonvulsants use were 71, 262, and 37 days, respectively. Furthermore, the 95% CI of the WSP β for anticonvulsants was over and excluded 1, which meant that they were wear-out failure type. Conclusions Our results suggest that DIGH monitoring of patients administered immunosuppressants, calcium channel blockers, or anticonvulsants is important. We demonstrated the potential risk of DIGH following the long-term use of calcium channel blocker over approximately 260 days. Based on the results of the association rule mining approach, patients with intellectual disability who are administered phenytoin should be monitored carefully. We recommend that patients who experience symptoms related to DIGH should be closely monitored

Analysis of adverse events of renal impairment related to platinum-based compounds using the Japanese Adverse Drug Event Report database

Objectives: Platinum compounds cause several adverse events, such as nephrotoxicity, gastrointestinal toxicity, myelosuppression, ototoxicity, and neurotoxicity. We evaluated the incidence of renal impairment as adverse events are related to the administration of platinum compounds using the Japanese Adverse Drug Event Report database. Methods: We analyzed adverse events associated with the use of platinum compounds reported from April 2004 to November 2016. The reporting odds ratio at 95% confidence interval was used to detect the signal for each renal impairment incidence. We evaluated the time-to-onset profile of renal impairment and assessed the hazard type using Weibull shape parameter and used the applied association rule mining technique to discover undetected relationships such as possible risk factor. Results: In total, 430,587 reports in the Japanese Adverse Drug Event Report database were analyzed. The reporting odds ratios (95% confidence interval) for renal impairment resulting from the use of cisplatin, oxaliplatin, carboplatin, and nedaplatin were 2.7 (2.5–3.0), 0.6 (0.5–0.7), 0.8 (0.7–1.0), and 1.3 (0.8–2.1), respectively. The lower limit of the reporting odds ratio (95% confidence interval) for cisplatin was >1. The median (lower–upper quartile) onset time of renal impairment following the use of platinum-based compounds was 6.0–8.0 days. The Weibull shape parameter β and 95% confidence interval upper limit of oxaliplatin were <1. In the association rule mining, the score of lift for patients who were treated with cisplatin and co-administered furosemide, loxoprofen, or pemetrexed was high. Similarly, the scores for patients with hypertension or diabetes mellitus were high. Conclusion: Our findings suggest a potential risk of renal impairment during cisplatin use in real-world setting. The present findings demonstrate that the incidence of renal impairment following cisplatin use should be closely monitored when patients are hypertensive or diabetic, or when they are co-administered furosemide, loxoprofen, or pemetrexed. In addition, healthcare professionals should closely assess a patient’s background prior to treatment

Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system.

Doxorubicin (DOX) is an anthracycline widely used for the treatment of solid and hematological tumors. The aim of this study was to assess the adverse event profiles of conventional DOX and liposomal DOX. This is the first study to evaluate the effect of a liposomal formulation of DOX using spontaneous reporting system (SRS) databases. The SRS used was the US Food and Drug Administration Adverse Event Reporting System (FAERS). This study relied on definitions of preferred terms provided by the Medical Dictionary for Regulatory Activities (MedDRA) and the standardized MedDRA Queries (SMQ) database. We also calculated the reporting odds ratios (RORs) of suspected drugs (conventional DOX; PEGylated-liposome DOX; non-PEGylated-liposome DOX). The FAERS database contained 7,561,254 reports from January 2004 to December 2015. The number of reported AE cases for conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX was 5039, 3780, and 349, respectively. Conventional DOX and liposomal DOX have potential risks of causing myelosuppression, cardiotoxicity, alopecia, nausea, and vomiting, among other effects. The RORs (95% CI) from SMQ for haematopoietic leucopenia associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 12.75 (11.89-13.68), 6.43 (5.81-7.13), and 14.73 (11.42-18.99), respectively. Liposomal DOX formulations were associated with lower RORs with regard to myelosuppression, cardiotoxicity, and alopecia than the conventional DOX was. The RORs (95% CI) for palmar-plantar erythrodysesthesia (PPE) associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 6.56 (4.74-9.07), 64.77 (56.84-73.80), and 28.76 (15.77-52.45), respectively. This study is the first to evaluate the relationship between DOX liposomal formulations and their adverse event profiles. The results indicate that careful observation for PPE is recommended with the use of liposomal DOX, especially PEGylated-liposome DOX formulations

Adverse event profiles of solvent-based and nanoparticle albumin-bound paclitaxel formulations using the Food and Drug Administration Adverse Event Reporting System

Objectives: Paclitaxel is a highly effective antitumor agent with notable adverse events, including hypersensitivity reactions, peripheral neuropathy, arthralgia, myalgias, and neutropenia. Solvent-based paclitaxel causes severe allergic, hypersensitivity, and anaphylactic reactions. Nanoparticle albumin-bound paclitaxel was recently developed and provides an advantage over solvent-based paclitaxel in avoiding solvent/surfactant-related adverse events. The aim of this study was to assess the adverse event profiles of solvent-based paclitaxel and nanoparticle albumin-bound paclitaxel formulations using data from the spontaneous adverse event reporting system of the US Food and Drug Administration Adverse Event Reporting System database. Methods: This study relied on Medical Dictionary for Regulatory Activities preferred terms and standardized queries, and calculated the reporting ratio and reporting odds ratios of paclitaxel formulations. Results: Of 8,867,135 reports recorded in the US Food and Drug Administration Adverse Event Reporting System database from January 2004 to December 2016, 3469 and 4447 adverse events corresponded to solvent-based paclitaxel and nanoparticle albumin-bound paclitaxel, respectively. Reporting odds ratios (95% confidence interval) for anaphylactic reaction (standardized MedDRA query code: 20000021) associated with the use of solvent-based paclitaxel and nanoparticle albumin-bound paclitaxel were 1.69 (1.56–1.84) and 0.75 (0.68–0.83), respectively. Reporting odds ratio signal for anaphylactic reaction was not detected for nanoparticle albumin-bound paclitaxel. Reporting odds ratios (95% confidence interval) for acute renal failure (standardized MedDRA query code: 20000003) associated with the use of solvent-based paclitaxel and nanoparticle albumin-bound paclitaxel were 0.75 (0.58–0.98) and 1.60 (1.37–1.89), respectively. Conclusion: This is the first study to evaluate the adverse event profile of nanoparticle albumin-bound paclitaxel using US Food and Drug Administration Adverse Event Reporting System data. Considering that the US Food and Drug Administration Adverse Event Reporting System database does not allow to infer causality or risk ranking, the different reporting frequencies of anaphylactic reaction and acute renal failure between solvent-based paclitaxel and nanoparticle albumin-bound paclitaxel must be further investigated via analytical observational research