Increasing tramadol utilisation under strict regulatory control of opioid prescribing - A cross-sectional study in Taiwan from 2002 through 2016.

BACKGROUND/PURPOSE: Prescribing of opioids to patients with non-cancer pain is strictly regulated in Taiwan, but tramadol is not included in the regulation on chronic opioid prescribing. This study aims to identify the utilization trend of prescribing tramadol and other opioid analgesics and investigate the influence of government regulation on opioid prescribing in Taiwan. METHODS: This cross-sectional study used the Taiwan National Health Insurance claims database and the cancer registry from 2001 through 2016. The annual number of adult opioid users, opioid utilization (Defined Daily Doses [DDDs]/1000 registrants) and the number of supply days were enumerated for each calendar year and stratified by cancer or non-cancer patients. Descriptive statistics were used to report the trends in utilization for each calendar year. RESULTS: The regulation strictly limited persistent use of opioids for patients with non-cancer pain, of which only a small proportion of fentanyl (20%) and morphine (<2%) users were prescribed with an annual number of supply days greater than 28 days. The annual utilization of morphine (6.4-53.5 vs. 1.1 to 9.6 DDD/1000 registrants) and fentanyl (8.3-37.0 vs. 0.16 to 1.8 DDD/1000 registrants) to patients with cancer was consistently higher than patients without cancer. In contrast to morphine and fentanyl, the utilization of tramadol prescribed to patients without cancer increased 92.2-fold (3.7-341.2 DDD/1000 registrants) from 2002 to 2016. CONCLUSION: The regulation in Taiwan limited the prescribing of selective opioids for patients with non-cancer pain and the substitution of tramadol for other opioids may have safety implications.

Age assessment in the living using modified Gustafson's criteria in a northern Chinese population.

Regressive dental changes appear to be suitable for age assessment in living adults. In 2012, Olze et al. showed that several criteria presented by Gustafson for extracted teeth can also be applied to orthopantomograms. The objective of this study was to test the applicability and reliability of this method in a Chinese population. For this purpose, 1300 orthopantomograms of 650 female and 650 male Chinese aged between 15 and 40 years were evaluated. The characteristics of secondary dentin formation, periodontal recession, attrition, and cementum apposition were reviewed in all the mandibular premolars. The sample was split into a training and test dataset. Based on the training set, the correlation of the individual characteristics with chronological age was studied with a stepwise multiple regression analysis, in which individual characteristics formed the independent variable. According to the results, the R values amounted to 0.80 to 0.83; the standard error of estimate was 4.29 to 4.75 years. By analyzing the test dataset, the accuracy of the present study, Olze's and Timme's formulas were determined by the difference between the estimated dental age (DA) and chronological age (CA). Taking both mean differences and mean absolute differences into account, the Chinese age estimation formula did not always perform better compared with Olze's and Timme's formulas for both males and females. It was concluded that this method can be used in Chinese individuals for age assessment. However, the applicability of the method is limited by the quality of the X-ray images, and the method should only be applied by experienced forensic odontologists.

Application of age assessment based on the radiographic visibility of the root pulp of lower third molars in a northern Chinese population.

The purpose of the present study was to explore the potential application of radiographic visibility of the root pulp in lower third molars in a northern Chinese population, in order to determine if this methodology can be used to prove whether a person has surpassed the thresholds of 18 and 21 years of age. A total of 1300 orthopantomograms comprising equal numbers of females and males evenly distributed between the ages of 15 and 40 years were analyzed. The radiographic visibility of the root pulp of the lower third molars was assessed using the stages described by Olze et al. (2010). Stage 1 first appeared at 19.25 years in males and at 20.73 years in females. The earliest appearance of stage 2 happened at 22.33 years in males and at 22.41 years in females. Stage 3 was achieved first at 26.45 years in males and at 27.66 years in females. It was concluded that stages 1, 2, and 3 can be used to show that a person is over 18 years of age. If stages 2 or 3 are determined, it is possible to prove that an individual has already attained the age of 21 years.

A 15-year overview of increasing tramadol utilisation and associated mortality and the impact of tramadol classification in the United Kingdom.

PURPOSE: This study aimed to develop hypotheses to explain the increasing tramadol utilisation, evaluate the impact of tramadol classification, and explore the trend between tramadol utilisation and related deaths in the United Kingdom. METHODS: This cross-sectional study used individual patient data, the Clinical Practice Research Datalink from 1993 to 2015, to calculate monthly defined daily dose (DDD)/1000 registrants, monthly prevalence and incidence of tramadol users, annual supply days, and mean daily dose of tramadol. Aggregated-level national statistics and reimbursement data from 2004 to 2015 were also used to quantify annual and monthly tramadol DDD/1000 inhabitants and rate of tramadol-related deaths in England and Wales. Interrupted time-series analysis was used to evaluate the impact of tramadol classification in June 2014. RESULTS: Prevalence of tramadol users increased from 23 to 97.6/10 000 registrants from 2000 to 2015. Both annual dose and annual supply days of existing tramadol users were higher than new users. Level and trend of monthly utilisation (ß2 : -12.9, ß3 : -1.6) and prevalence of tramadol users (ß2 : -6.4, ß3 : -0.37) significantly reduced after classification. Both annual tramadol utilisation and rate of tramadol-related deaths increased before tramadol classification and decreased thereafter. CONCLUSIONS: Increasing tramadol utilisation was influenced by the increase in prevalence and incidence of tramadol users, mean daily dose, and day of supply. Prevalence of tramadol users, tramadol utilisation, and reported deaths declined after tramadol classification. Future studies need to evaluate the influencing factors to ensure the safety of long-term tramadol use.

Comprehensive risk assessment for early neurologic complications after liver transplantation.

AIM: To determine risk factors for early neurologic complications (NCs) after liver transplantation from perspective of recipient, donor, and surgeon. METHODS: In all, 295 adult recipients were enrolled consecutively between August 2001 and February 2014 from a single medical center in Taiwan. Any NC in the first 30 d post-liver transplantation, and perioperative variables from multiple perspectives were collected and analyzed. The main outcome was a 30-d NC. Generalized additive models were used to detect the non-linear effect of continuous variables on outcome, and to determine cut-off values for categorizing risk. Risk factors were identified using multiple logistic regression analysis. RESULTS: In all, 288 recipients were included, of whom 142 (49.3%) experienced at least one NC, with encephalopathy being the most common 106 (73%). NCs prolonged hospital stay (35.15 ± 43.80 d vs 20.88 ± 13.58 d, P < 0.001). Liver recipients' age < 29 or ≥ 60 years, body mass index < 21.6 or > 27.6 kg/m(2), Child-Pugh class C, history of preoperative hepatoencephalopathy or mental disorders, day 7 tacrolimus level > 8.9 ng/mL, and postoperative intra-abdominal infection were more likely associated with NCs. Novel risk factors for NCs were donor age < 22 or ≥ 40 years, male-to-male gender matching, graft-recipient weight ratio 0.9%-1.9%, and sequence of transplantation between 31 and 174. CONCLUSION: NCs post- liver transplantation occurs because of factors related to recipient, donor, and surgeon. Our results provide a basis of risk stratification for surgeon to minimize neurotoxic factors during transplantation.

[Development of CBCT technique and its application on dental age assessment].

Teeth are the hardest organs in the human body. They are not easily affected by external physical and chemical factors to degrade or deform. Dental age assessment has been widely used in forensic practice. Dental image is one of the most common methods in the age estimation. The emergence of cone beam computed tomography (CBCT) technology provides a new way to obtain three-dimensional image of teeth. It has many advantages such as low-dose radiation, short-time scanning, high-precision image, and finical convenience. Recent development of CBCT technology and its application on age estimation are reviewed in this paper.

Direct analysis in real time mass spectrometry and multivariate data analysis: a novel approach to rapid identification of analytical markers for quality control of traditional Chinese medicine preparation.

The paper presents a novel strategy to identify analytical markers of traditional Chinese medicine preparation (TCMP) rapidly via direct analysis in real time mass spectrometry (DART-MS). A commonly used TCMP, Danshen injection, was employed as a model. The optimal analysis conditions were achieved by measuring the contribution of various experimental parameters to the mass spectra. Salvianolic acids and saccharides were simultaneously determined within a single 1-min DART-MS run. Furthermore, spectra of Danshen injections supplied by five manufacturers were processed with principal component analysis (PCA). Obvious clustering was observed in the PCA score plot, and candidate markers were recognized from the contribution plots of PCA. The suitability of potential markers was then confirmed by contrasting with the results of traditional analysis methods. Using this strategy, fructose, glucose, sucrose, protocatechuic aldehyde and salvianolic acid A were rapidly identified as the markers of Danshen injections. The combination of DART-MS with PCA provides a reliable approach to the identification of analytical markers for quality control of TCMP.

[Adverse drug events and its forensic medical identification].

OBJECTIVE: To investigate the basic principles and important rules of forensic identification of adverse drug events and to accumulate basic data and to provide references for forensic identification of similar cases. METHODS: Thirty-three cases of adverse drug events in our forensic identification files were retrospectively reviewed, analyzed, and summarized. RESULTS: There were 27 live and 6 dead victims included in this study. Our study showed a gradually increasing numbers of adverse drug cases in forensic identification year by year with a slight female predominance (20/33 cases, 60.6%). Of the 33 victims, nearly two-thirds (21/33, 63.6%) were due to hospital errors including only one case of drug overdose (1/21, 4.8%), whereas the rest were not related to the hospital errors. Eight cases (8/33, 24.2%) were caused by illegal medical practitioners due to improper use of medication. CONCLUSION: Investigators need to pay more attention to the characteristics and complexities of adverse drug events on a case by case basis encountered in increasing numbers of more and more such forensic identification.