Anatomical Therapeutic Chemical Code Research Articles

Psychotropic medication utilisation in adult cancer patients in China: A cross-sectional study based on national health insurance database

BackgroundPsychotropic medications are useful to treat psychiatric disorders which are frequently underdiagnosed and undertreated in cancer patients. Evidence on utilisation of psychotropic medications in cancer patients was absent in China. This study aimed to analyse the prevalence and the potential predictors of psychotropic medication use in adult cancer patients in China. MethodsWe analysed cross-sectional data from the China Health Insurance Association database in 2015–2017, which contained health care utilisation information for a national representative sample of basic medical insurance beneficiaries. Cancer patients aged above 18 were identified by International Classification of Disease 10th revision code C00–C97. Psychotropic medications were defined following the Anatomical Therapeutic Chemical codes: antipsychotics (N05A), anxiolytics (N05B), hypnotics and sedatives (N05C), and antidepressants (N06A, N06CA). We calculated the prevalence of psychotropic medication use in cancer patients, and applied multivariable logistic regression to identify its potential predictors. FindingsA total of 260,364 adults with cancer were identified in the database, of which 48,111 (18•5%) were prescribed at least one psychotropic medication comprising antipsychotics (3763, 1•4%), anxiolytics (15,902, 6•1%), hypnotics and sedatives (37,040, 14•2%), and antidepressants (2379, 0•9%). Patients with solid tumours had higher prevalence of psychotropic medication use than patients with lymphoid and hematopoietic malignancies (e.g. female genital organs, adjusted odds ratio (OR)=2•25, 95%CI=2•09–2•44). The prevalence of psychotropic medication use in cancer patients in the Eastern region was significantly higher than those of cancer patients in the Western regions (OR=2•33, 95%CI=2•27–2•40). Compared with the Urban Rural Resident Basic Medical Insurance beneficiaries, cancer patients covered by the Urban Employee Basic Medical Insurance were more likely to use psychotropic medications (OR=1•18, 95%CI=1•15–1•20). Midazolam was the most frequently used psychotropic (21,728, 45•2%), and flupentixol–melitracen was the most commonly used antidepressant (1176, 2•4%) among all psychotropic medication users in the sample. InterpretationThe prevalence of psychotropic medication use in Chinese adult cancer patients was inequitable. Further attention will be needed to be paid to the mental health of cancer patients in China. FundingNo funding.

A systematically collated library of prescribing safety indicators for people with chronic kidney disease

BackgroundPeople with chronic kidney disease (CKD) have high levels of co-morbidity and polypharmacy placing them at increased risk of prescribing-related harm. Tools for assessing prescribing safety in the general population using prescribing safety indicators (PSIs) have been established. However, people with CKD pose different prescribing challenges to people without kidney disease. Therefore, PSIs designed for use in the general population may not include all PSIs relevant to a CKD population.The aim of this study was to systematically collate a library of PSIs relevant to people with CKD.MethodsA systematic literature search identified papers reporting PSIs. CKD-specific PSIs were extracted and categorised by Anatomical Therapeutic Chemical (ATC) classification codes. Duplicate PSIs were removed to create a final list of CKD-specific PSIs.ResultsNine thousand, eight hundred fifty-two papers were identified by the systematic literature search, of which 511 proceeded to full text screening and 196 papers were identified as reporting PSIs. Following categorisation by ATC code and duplicate removal, 841 unique PSIs formed the final set of CKD-specific PSIs. The five ATC drug classes containing the largest proportion of CKD-specific PSIs were: Cardiovascular system (26%); Nervous system (13.4%); Blood and blood forming organs (12.4%); Alimentary and metabolism (12%); and Anti-infectives for systemic use (11.3%).ConclusionCKD-specific PSIs could be used alone or alongside general PSIs to assess the safety and quality of prescribing within a CKD population.

New prescription of antihyperglycemic agents among patients with diabetes in Germany: Moderate concordance between health insurance data and self-reports.

To analyze the concordance of new prescription of antihyperglycemic agents between two data sources: patients' self-reports and statutory health insurance (SHI) data among patients with diabetes. Within a cross-sectional study, 494 patients with diabetes were interviewed if and which new prescriptions of diabetes medication they received within the last 3 or 6 months. SHI data for 12 months were linked to cover these periods. For the agreement measurement, SHI data was set as reference, and kappa, positive predictive value (PPV), and sensitivity were calculated for single Anatomical Therapeutic Chemical (ATC) codes and cumulated code groups. The number of new prescriptions within 3 or 6 months was low, with 5.5% (n = 27) for Metformin/self-report being the highest. Contingency tables were unbalanced and showed large numbers in the no/no-cells. Regarding non-agreement, we found new prescriptions slightly more often in SHI data only than in self-reports only, with insulin and metformin representing an exception. Agreement results were moderate with large confidence intervals (CI). The values for cumulated "all drugs in diabetes" were: kappa = 0.58 (95% CI: 0.51-0.65), PPV = 62.0 (53.4-70.2), sensitivity = 55.6 (47.3-63.6). Patients reported a low number of new prescriptions within the last 3 or 6 months. In general we found moderate agreement and in case of non-agreement that self-report no/SHI yes was slightly more frequent than vice versa. These results were based on small case numbers, but could nevertheless be considered when collecting self-reported information on the prescription of antihyperglycemic agents.

Oral adverse effects: drug-induced tongue disorders.

ObjectivesDue to a worldwide increase in drug consumption, oral healthcare professionals are frequently confronted with patients using one or more drugs. A large number of drugs can be accompanied with adverse drug reactions in the orofacial region, amongst others of the tongue. This paper aims to give an overview of drugs that are known to be accompanied with tongue disorders.Materials and methodsThe national drug information database for Dutch pharmacists, composed of scientific drug information, guidelines and summaries of product characteristics, was analysed for drug‐induced tongue disorders. “MedDRA classification” and “Anatomical Therapeutic Chemical codes” were used to categorize the disorders.ResultsThe database comprises of 1645 drugs of which 121 (7.4%) are documented to be accompanied with tongue disorders as an adverse effect. Drug‐induced tongue disorders are predominantly observed in the following drug categories: “nervous systems,” “anti‐infectives for systemic use” and “alimentary tract and metabolism”. The most common drug‐induced tongue disorders are glossitis, tongue oedema, tongue discoloration and burning tongue.ConclusionHealthcare professionals are frequently confronted with drugs that can cause tongue disorders. The overview of drugs reported in this article supports clinicians in their awareness, diagnosis and treatment of drug‐induced tongue disorders.

Impact of liver disease on oral anticoagulant prescription and major adverse events in patients with atrial fibrillation: analysis from a population-based cohort study

Abstract Aims Data on the impact of liver disease (LD) in patients with atrial fibrillation (AF) and the role of oral anticoagulant (OAC) drugs for stroke prevention, are limited. We analysed the impact of LD and OAC treatment in determining stroke, major bleeding, all-cause death and secondary bleeding outcomes. Methods A retrospective observational population-based cohort study. The study cohort is derived from the administrative health databases of Lombardy region (>10 million inhabitants), Italy. All AF patients ≥40 years admitted to hospital from 2000 to 2018 were considered. AF and LD diagnosis were established using ICD9-CM codes. Use of OAC was determined with Anatomical Therapeutic Chemical (ATC) codes. Primary study outcomes were stroke, major bleeding and all-cause death. Results Among 393,507 AF patients, 16,168 (4.1%) had concomitant LD. LD AF patients were significantly less treated with OAC independent of associated clinical characteristics (OR: 0.96, 95% CI: 0.92–0.98). Concomitant LD was found associated with an increased risk in all the study outcomes (HR: 1.18, 95% CI: 1.11–1.25 for stroke; HR: 1.57, 95% CI: 1.47–1.66 for major bleeding; HR: 1.41, 95% CI: 1.39–1.44 for all-cause death. Use of OAC in patients with AF and LD resulted in a reduction in stroke (HR: 0.80, 95% CI: 0.70–0.92), major bleeding (HR: 0.86, 95% CI: 0.74–0.99) and all-cause death (HR: 0.85, 95% CI: 0.80–0.90), with similar results according to several clinically relevant subgroups. A net clinical benefit (NCB) analysis suggested a positive benefit/risk ratio in using OAC in AF patients with LD (NCB: 0.408, 95% CI: 0.375–0.472). Conclusions In AF patients, concomitant LD carries a significantly higher risk for all clinical outcomes. Use of OAC in AF patients with LD was associated with a significant benefit/risk ratio, even in high-risk patient subgroups. Funding Acknowledgement Type of funding source: None

Variability in Antimicrobial Use Among Hospitals Participating in the Canadian Nosocomial Infection Surveillance Program

Background: The association between antimicrobial use (AMU) and emergence of antimicrobial resistance is well documented. The Canadian Nosocomial Infection Surveillance Program (CNISP) has conducted sentinel surveillance of AMU at participating Canadian hospitals since 2009 resulting in the largest pan-Canadian hospital database of dispensed antimicrobials. Objectives: Describe interhospital variability of AMU across Canada. Methods: Hospitals submit annual AMU data based on patient days (PD). Antimicrobials were measured in defined daily doses (DDD) for adults using the WHO Anatomical Therapeutic Chemical (ATC) system. The AMU data among pediatric patients have been available since 2017 using days of therapy (DOT). Surveillance includes systemic antibacterial agents (J01 ATC codes), oral metronidazole, and oral vancomycin. AMU was assessed using quintiles, interquartile ranges (IQR), and relative IQRs (upper- and lower-quartile values divided by the median). Results: Between 2009 and 2018, 20–26 hospitals participated in adult surveillance each year (35 teaching hospitals and 3 nonteaching hospitals participated in ≥1 year). Over this period, overall AMU decreased by 13% at participating adult hospitals from 645 to 560 DDD per 1,000 PD. AMU varied substantially between hospitals, but this variability decreased over time (Fig. 1). In 2009, the IQRs for overall AMU spanned 309 DDD per 1,000 PD, and in 2018 it spanned only 103 DDD per 1,000 PD. This decrease in variability was due to large decreases in use among hospitals with high use in 2009–2010. Among hospitals in the highest use quintile in 2009–2010, AMU decreased, on average, 44 DDD per 1,000 PD each year. Among hospitals in the lowest use quintile in 2009–2010, AMU increased, on average, 6 DDD per 1,000 PD each year. In 2018, antibiotics with the largest absolute IQR variability were cefazolin (61–113 DDD per 1,000 PD), piperacillin-tazobactam (32–64 DDD per 1,000 PD), and vancomycin (24–49 DDD per 1,000 PD). Among antibiotics with ≥1 DDD per 1,000 PD, antibiotics with the largest relative IQR variability were tobramycin (0.3–6 DDD per 1,000 PD), cefadroxil (0.08–9 DDD per 1,000 PD), and linezolid (0.2–3 DDD per 1,000 PD). In 2018, the IQR for overall pediatric AMU (n = 7 teaching hospitals) was 426–581 DOT per 1,000 PD. Antibiotics with the largest IQRs were vancomycin (0.6–58 DOT per 1,000 PD), cefazolin (33–88 DOT per 1,000 PD), and tobramycin (3–57 DOT per 1,000 PD). Among antibiotics with ≥1 DOT per 1,000 PD in 2018, antibiotics with the largest relative IQRs were tobramycin (3–57 DOT per 1,000 PD), cefuroxime (1–6 DOT per 1,000 PD), and amoxicillin (8–42 DOT per 1,000 PD). Conclusions: There is wide variation in overall antibiotic use across hospitals. Variation between AMU at adult hospitals has decreased between 2009 and 2018; in 2018, antibiotics with the largest IQRs were cefazolin and piperacillin-tazobactam. Benchmarking AMU is crucial for informing antimicrobial stewardship efforts.Funding: CNISP is funded by the Public Health Agency of Canada.Disclosures: Allison McGeer reports funds to her institution from Pfizer and Merck for projects for which she is the principal investigator. She also reports consulting fees from Sanofi-Pasteur, Sunovion, GSK, Pfizer, and Cidara.

Effects of restrictive-prescribing stewardship on antibiotic consumption in primary care in China: an interrupted time series analysis, 2012\u20132017

BackgroundThe overuse of antibiotics has been a major public health problem worldwide, especially in low- and middle- income countries (LMIC). However, there are few policies specific to antibiotic stewardship in primary care and their effectiveness are still unclear. A restrictive-prescribing stewardship targeting antibiotic use in primary care has been implemented since December 2014 in Hubei Province, China. This study aimed to evaluate the effects of the restrictive-prescribing stewardship on antibiotic consumption in primary care so as to provide evidence-based suggestions for prudent use of antibiotics.MethodsMonthly antibiotic consumption data were extracted from Hubei Medical Procurement Administrative Agency (HMPA) system from Sept 1, 2012, to Aug 31, 2017. Quality Indictors of European Surveillance of Antimicrobial Consumption (ESAC QIs) combined with Anatomical Therapeutic Chemical (ATC) classification codes and DDD per 1000 inhabitants per day (DID) methodology were applied to measure antibiotic consumption. An interrupted time series analysis was performed to evaluate the effects of restrictive-prescribing stewardship on antibiotic consumption.ResultsOver the entire study period, a significant reduction (32.58% decrease) was observed in total antibiotic consumption, which declined immediately after intervention (coefficient = − 2.4518, P = 0.005) and showed a downward trend (coefficient = − 0.1193, P = 0.017). Specifically, the use of penicillins, cephalosporins and macrolides/lincosamides/streptogramins showed declined trends after intervention (coefficient = − 0.0553, P = 0.035; coefficient = − 0.0294, P = 0.037; coefficient = − 0.0182, P = 0.003, respectively). An immediate decline was also found in the contribution of β-lactamase-sensitive penicillins to total antibiotic use (coefficient = − 2.9126, P = 0.001). However, an immediate increase in the contribution of third and fourth-generation cephalosporins (coefficient = 5.0352, P = 0.005) and an ascending trend in the contribution of fluoroquinolones (coefficient = 0.0406, P = 0.037) were observed after intervention. The stewardship led to an immediate increase in the ratio between broad- and narrow-spectrum antibiotic use (coefficient = 1.8747, P = 0.001) though they both had a significant downward trend (coefficient = − 0.0423, P = 0.017; coefficient = − 0.0223, P = 0.006, respectively). An immediate decline (coefficient = − 1.9292, P = 0.002) and a downward trend (coefficient = − 0.0815, P = 0.018) were also found in the oral antibiotic use after intervention, but no significant changes were observed in the parenteral antibiotic use.ConclusionsRestrictive-prescribing stewardship in primary care was effective in reducing total antibiotic consumption, especially the use of penicillins, cephalosporins and macrolides/lincosamides/streptogramins. However, the intervention effects were limited regarding the use of combinations of penicillins with ß-lactamase inhibitors, the third and fourth-generation cephalosporins, fluoroquinolones and parenteral antibiotics. Stronger administrative regulations focusing on specific targeted antibiotics, especially the use of broad-spectrum antibiotics and parenteral antibiotics, are in urgent need in the future.

Psoriasis is Associated with a High Comedication Burden: A Population Based Register Study.

IntroductionA large body of evidence supports the association between psoriasis and concomitant diseases. However, the study of comedication for these diseases in patients with psoriasis is limited. The current study aimed to investigate the prescription and drug dispensation for comorbidity associated with psoriasis.MethodsWe conducted a retrospective case-control study from 9 April 2008 until 1 January 2016 using an electronic medical records database covering the entire population of the County of Jönköping and the Swedish Prescribed Drug Register. ICD-10 and Anatomical Therapeutic Chemical codes were used to identify patients with psoriasis and dispensed pharmaceutical prescriptions. Individuals without psoriasis were selected as controls. Patients receiving systemic treatment for psoriasis were considered as having moderate-severe psoriasis. Odds ratios for being dispensed pharmaceutical prescriptions and differences in mean number of dispensed prescriptions were explored.ResultsA total of 4587 patients with psoriasis were identified in the medical records, and 268,949 individuals served as controls. Patients with psoriasis had a significantly higher number of different drug dispensations compared to controls. Only 1.3% of all patients with psoriasis were without any prescription (excluding medication for psoriasis) during the study period while the number in the general population was 9.3%. Sex- and age-adjusted odds ratios for dispensation of drug groups related to comorbid disease were significantly higher among patients with psoriasis including drug groups such as anxiolytics and sedatives as well as drugs targeting COPD, migraine and erectile dysfunction. The most frequently dispensed comedications were oral antibiotics and analgesics including an increased risk for dispensation of opioids. Sex predisposed dispensation frequency for a variety of drug groups. Drugs targeting obesity, osteoporosis, psychiatric disease and anti-mycotics/-fungals were more frequent among women.ConclusionPatients with psoriasis have significantly increased numbers of different dispensed prescriptions than those without psoriasis. This underlines previous findings on increased comorbidity and health care costs for patients with psoriasis.Electronic supplementary materialThe online version of this article (10.1007/s13555-020-00442-3) contains supplementary material, which is available to authorized users.

Recognizing novel chemicals/drugs for anatomical therapeutic chemical classes with a heat diffusion algorithm

Drug Anatomical Therapeutic Chemical (ATC) classification system is a widely used and accepted drug classification system. It is recommended and maintained by World Health Organization (WHO). Each drug in this system is assigned one or more ATC codes, indicating which classes it belongs to in each of five levels. Given a chemical/drug, correct identification of its ATC codes in such system can be helpful to understand its therapeutic effects. Several computational methods have been proposed to identify the first level ATC classes for any drug. Most of them built multi-label classifiers in this regard. One previous study proposed a quite different scheme, which contained two network methods, based on shortest path (SP) and random walk with restart (RWR) algorithms, respectively, to infer novel chemicals/drugs for each first level class. However, due to the limitations of SP and RWR algorithms, there still exist lots of hidden chemicals/drugs that above two methods cannot discover. This study employed another classic network algorithm, Laplacian heat diffusion (LHD) algorithm, to construct a new computational method for recognizing novel latent chemicals/drugs of each first level ATC class. This algorithm was applied on a chemical network, which containing lots of chemical interaction information, to evaluate the associations of candidate chemicals/drugs and each ATC class. Three screening tests, which measured the specificity and association to one ATC class, followed to yield more reliable potential members for each class. Some hidden chemicals/drugs were recognized, which cannot be found out by previous methods, and they were extensively analyzed to confirm that they can be novel members in the corresponding ATC class.

Cardiovascular drug treatment, statins and biopsy-confirmed giant cell arteritis: a population-based case–control study

ObjectiveTo determine whether exposure to cardiovascular medications and statins is associated with increased risk of giant cell arteritis (GCA).DesignThe population-based case–control study comprised a cohort of patients with biopsy-confirmed GCA...

NetInfer: A Web Server for Prediction of Targets and Therapeutic and Adverse Effects via Network-Based Inference Methods.

In this study, we developed a web server named NetInfer for prediction of targets and therapeutic and adverse effects via network-based inference methods. Compared with our previously developed standalone version of NetInfer, this web server provides a user-friendly interface. With the web server, users can easily predict potential target proteins, microRNAs, Anatomical Therapeutic Chemical (ATC) classification codes, or adverse drug events for small molecules of their interests in a few steps. Most of the prediction models were constructed on the basis of our previous studies, where those models have been evaluated systematically and demonstrated high performance. The high-quality models can generate accurate predictions. As a case study, we predicted ATC codes and target proteins for several drugs. The predicted therapeutic effects of these drugs on cardiovascular diseases and their potential molecular mechanisms were validated by the literature. This successful case study demonstrated that our web server would be a powerful tool in drug repositioning and systems pharmacology. The web server of NetInfer is freely available at http://lmmd.ecust.edu.cn/netinfer/.

Prescribing patterns of vitamin D and analogues in a private healthcare patient population in South Africa

Introduction: Numerous studies show the benefits of vitamin D: in the prevention of bone disease, supporting the immune system and the prevention and mitigation of cancer. Until recently, supplementation has been deemed unnecessary. Nonetheless, in the light of emerging evidence, some practitioners are adding vitamin D and its analogues (Anatomic Therapeutic Chemical (ATC) classification code A11CC) to their prescriptions. Therefore, the aim was to determine the medical insurance prescribing patterns of vitamin D in South Africa. Methods: A retrospective, cross-sectional drug utilisation study was conducted on a South African medical insurance administrator database for 2018. Products in ATC subgroup A11CC (vitamin D and analogues) were extracted and analysed. Results: A total of 302 patients received 1 164 prescriptions for a vitamin D or analogue product during 2018. The average age of patients was 47.14 (SD = 24.03) years, and the majority were female (58.28%). Very young patients and middle-aged patients received most of the prescriptions. Ergocalciferol (A11CC01) was the most frequently prescribed (59.79%), followed by alfacalcidol (A11CC), colecalciferol (A11CC05) and calcitriol (A11CC04). Ergocalciferol 50 000 IU tablets comprised the most frequently prescribed trade name product (59.45%), followed by alfacalcidol capsules (21.31%). Conclusion: Vitamin D was used across the age range. Vitamin D supplementation was primarily prescribed in the very young and older age groups, suggesting their need for additional supplementation. As the cost of additional supplements is relatively small compared with the treatment of deficiency disorders, vitamin D supplementation could have broad and positive effects on long-term health for very little outlay.

Risk factors for drug-related problems in a general hospital: A large prospective cohort.

ObjectiveTo identify risk factors for potential Drug-Related Problems (DRP) at admission in hospitalized patients.MethodologyProspective cohort study conducted in adults patients hospitalized (May 2016 to May 2018) in a general tertiary care hospital in Brazil. Potential DRP were detected by daily review of 100% of electronic medication orders by hospital pharmacists and classified by the Pharmaceutical Care Network Europe classification system (PCNE version 6.2). For the identification of risk factors of potential DRP, backward stepwise logistic regression was used to identify the set of independent predictors among over 120 variables collected in the initial 48 hours after admission in a training set consisting of 2/3 of the study population. The model was validated in the remaining sample.ResultsThe study population consisted of 1686 patients aged 52.0+/- 18.3 years-old, 51.4% females, with a median length of stay of 3.24 days, and 4.5% in-hospital mortality. The cumulative incidence of potential DRP was 14.5%. Admission for elective surgery and main diagnosis of disease of the circulatory system were associated with reduced risk of DRP (OR 0.41 and 0.57, respectively, p<0.05). The independent risk factors of DRP are heart rate ≥ 80 bpm (OR 1.41, p = 0.05), prescription of more than seven drugs in day 2 (OR 1.63, p = 0.05), prescription in day 1 of drugs of the Anatomical Therapeutic Chemical Code (ATC) class A (alimentary tract and metabolism, OR 2.24, p = 0.003), prescription in day 2 of two or more ATC class A drugs (OR = 3.52, p<0.001), and in day 1 of ATC class J drugs (antiinfectives for systemic use, OR 1.97, p = 0.001). In the validation set, the c-statistic of the predictive model was 0.65, the sensitivity was 56.1% and the specificity was 65.2%.ConclusionThis study identified seven independent risk factors of potential DRP in patients hospitalized in a general hospital that have fair predictive performance for utilization in clinical practice.

Prescription patterns of benzodiazepine and benzodiazepine-related drugs in the peripartum period: A population-based study

Using prescription drugs during pregnancy is challenging and approached with caution. In this study, we present population-based information on prescription patterns of benzodiazepines and benzodiazepine-related drugs in the peripartum period. A population-based study of 1,154,817 pregnancies between 1997 and 2015 in Denmark, of which 205,406 (17.8%) pregnancies in women with a psychiatric history. Prescription drugs starting with Anatomical Therapeutic Chemical codes N05BA, N05CD, and N05CF from 12 months before pregnancy to 12 months following pregnancy were identified. We used generalised estimating equations to estimate the adjusted 5 year risk difference in the proportion of women redeeming benzodiazepines from 1 year to 5 years after. Logistic regression was used to analyze the association between characteristics and discontinuation of benzodiazepines during pregnancy. The prevalence of benzodiazepine prescriptions was 1.9% before pregnancy, 0.6% during pregnancy, and 1.3% after pregnancy. In women with a psychiatric history, the prevalence was 5–6 times higher. A significant decrease in prescriptions to women with a psychiatric history was observed, which was less profound among women with no psychiatric history. Approximately 90% of women discontinue benzodiazepines during pregnancy, with a higher percentage of women discontinuing from 1997 to 2015. The observed decrease is likely explained by changing treatment guidelines.

The association of dry eye syndrome and psychiatric disorders: a nationwide population-based cohort study

BackgroundSeveral previous studies reported a greater prevalence of dry eye syndrome (DES) among patients with psychiatric diseases. The aim of this study is to investigate the prevalence and risk factors of DES in patients with psychiatric disorders (PD) using nationwide population-based data in Taiwan.MethodsThis population-based cohort study retrospectively identified patients with PD from 1997 to 2011. Patients with both PD and DES served as the DES cohort, and PD patients without DES comprised the non-DES cohort. PD was defined as a diagnosis of PD (ICD-9-CM 290–319) made by psychiatrists only, with at least three consecutive outpatient visits or at least one inpatient visit. DES was defined as a diagnosis of DES (ICD-9-CM 375.15) and a prescription for an eye lubricant (anatomical therapeutic chemical code, ATC code: S01XA). The main outcome measures were the prevalence of DES in these patients and associated risk factors.ResultsA total of 75,650 patients with PD (3665 in the DES cohort and 71,985 in the non-DES cohort) were included in the final analysis. The majority of patients in the DES group were women (72.6%), compared the non-DES group (57.8%). The mean age of patients in the DES cohort was 62.2 ± 14.9, which was significantly older than those in the non-DES group (50.9 ± 17.5). The patients with DES had a significantly greater likelihood of having dementia, bipolar disorder, depression, and neurotic disorders. Conditional regression analyses revealed that patients with dry eye disease were more likely to have schizophrenia (OR = 1.34), bipolar disorder (OR = 1.9), depression (OR = 1.54), and neurotic disorders (OR = 1.62). In addition, patients with DES were more likely to use 1st generation anti-psychotics (OR = 1.28) and had a lower risk of using 2nd generation anti-psychotics (OR = 0.64).ConclusionThe study demonstrated that among PD patients, DES is highly prevalence in certain subtypes of PD, such as depression, bipolar disorder, and neurotic disorders, after adjusting for the comorbidities.

Drug repositioning by prediction of drug's anatomical therapeutic chemical code via network-based inference approaches.

Drug discovery and development is a time-consuming and costly process. Therefore, drug repositioning has become an effective approach to address the issues by identifying new therapeutic or pharmacological actions for existing drugs. The drug's anatomical therapeutic chemical (ATC) code is a hierarchical classification system categorized as five levels according to the organs or systems that drugs act and the pharmacology, therapeutic and chemical properties of drugs. The 2nd-, 3rd- and 4th-level ATC codes reserved the therapeutic and pharmacological information of drugs. With the hypothesis that drugs with similar structures or targets would possess similar ATC codes, we exploited a network-based approach to predict the 2nd-, 3rd- and 4th-level ATC codes by constructing substructure drug-ATC (SD-ATC), target drug-ATC (TD-ATC) and Substructure&Target drug-ATC (STD-ATC) networks. After 10-fold cross validation and two external validations, the STD-ATC models outperformed the SD-ATC and TD-ATC ones. Furthermore, with KR as fingerprint, the STD-ATC model was identified as the optimal model with AUC values at 0.899 ± 0.015, 0.916 and 0.893 for 10-fold cross validation, external validation set 1 and external validation set 2, respectively. To illustrate the predictive capability of the STD-ATC model with KR fingerprint, as a case study, we predicted 25 FDA-approved drugs (22 drugs were actually purchased) to have potential activities on heart failure using that model. Experiments in vitro confirmed that 8 of the 22 old drugs have shown mild to potent cardioprotective activities on both hypoxia model and oxygen-glucose deprivation model, which demonstrated that our STD-ATC prediction model would be an effective tool for drug repositioning.

Changes in incidence of severe hypoglycaemia in people with type 2 diabetes from 2006 to 2016: analysis based on health insurance data in Germany considering the anti-hyperglycaemic medication.

To investigate the incidence of severe hypoglycaemia over the past 10 years, taking into account changes in anti-hyperglycaemic therapy. This retrospective population-based study used German health insurance data. All adults diagnosed with documented type 2 diabetes (extrapolated to the German population: 6.6 million in 2006; 7.9 million in 2011; 8.86 million in 2016) were screened for severe hypoglycaemia. Anti-hyperglycaemic agents were identified by Anatomical Therapeutic Chemical (ATC) code. The event rate for severe hypoglycaemia was 460 per 100000 people in 2006, 490 per 100000 in 2011 and 360 per 100000 in 2016. The proportion of people with severe hypoglycaemia receiving sulfonylureas, as well as receiving combination therapy of metformin and sulfonylureas decreased from 2006 to 2016 (23.6% vs. 6.2%) Among those with severe hypoglycaemia in 2006, there were no prescriptions for dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose co-transporter 2 (SGLT2) agonists. The proportions of people with severe hypoglycaemia receiving DPP-4 inhibitors, GLP-1 receptor agonists or SGLT2 agonists in 2011 and 2016 were low. The proportion of people receiving human insulin also decreased (from 11.3% in 2006 to 10.3% in 2011 and 4.3% in 2016); the proportion of people receiving insulin analogues increased from 5.4% in 2006 to 11.5% in 2016. Therapy with mixed insulins was used by 19.7% of people with severe hypoglycaemia in 2006, by 14.0% in 2011 and by 7.3% in 2016. People undergoing therapy with insulin analogues have the highest risk of severe hypoglycaemia adjusted by age, gender, nephropathy diagnosis and year of survey [odds ratio (OR) 14.4, 95% confidence interval (95% CI) 13.5-15.5]. The incidence of severe hypoglycaemic events in Germany increased between 2006 and 2011, and decreased in 2016.

Impact of liver disease on oral anticoagulant prescription and major adverse events in patients with atrial fibrillation: analysis from a population-based cohort study.

Data on the impact of liver disease (LD) in patients with atrial fibrillation (AF) and the role of oral anticoagulant (OAC) drugs for stroke prevention are limited. A retrospective observational population-based cohort study on the administrative health databases of Lombardy region Italy. All AF patients ≥40 years admitted to hospital from 2000 to 2018 were considered. Atrial fibrillation and LD diagnosis were established using ICD9-CM codes. Use of OAC was determined with Anatomical Therapeutic Chemical codes. Primary study outcomes were stroke, major bleeding, and all-cause death. Among 393 507 AF patients, 16 168 (4.1%) had concomitant LD. Liver disease AF patients were significantly less treated with OAC. Concomitant LD was associated with an increased risk in all the study outcomes [hazard ratio (HR): 1.18, 95% confidence interval (CI): 1.11-1.25 for stroke; HR: 1.57, 95% CI: 1.47-1.66 for major bleeding; HR: 1.41, 95% CI: 1.39-1.44 for all-cause death]. Use of OAC in patients with AF and LD resulted in a reduction in stroke (HR: 0.80, 95% CI: 0.70-0.92), major bleeding (HR: 0.86, 95% CI: 0.74-0.99), and all-cause death (HR: 0.77, 95% CI: 0.73-0.80), with similar results according to subgroups. A net clinical benefit (NCB) analysis suggested a positive benefit/risk ratio in using OAC in AF patients with LD (NCB: 0.408, 95% CI: 0.375-0.472). In AF patients, concomitant LD carries a significantly higher risk for all clinical outcomes. Use of OAC in AF patients with LD was associated with a significant favourablebenefit/risk ratio, even in high-risk patient subgroups.

A Pediatrics Utilization Study in The Netherlands to Identify Active Pharmaceutical Ingredients Suitable for Inkjet Printing on Orodispersible Films.

Background: The use of medication in pediatrics, children aged 0–5 years, was explored so as to identify active pharmaceutical ingredients (APIs) suitable for inkjet printing on a plain orodispersible film (ODF) formulation in a pharmacy. Methods: The database IADB.nl, containing pharmacy dispensing data from community pharmacies in the Netherlands, was used to explore medication use in the age group of 0–5 years old, based on the Anatomical Therapeutic Chemical classification code (ATC code). Subsequently, a stepwise approach with four exclusion steps was used to identify the drug candidates for ODF formulation development. Results: there were 612 Active Pharmaceutical Ingredients (APIs) that were dispensed to the target group, mostly antibiotics. Of the APIs, 221 were not registered for pediatrics, but were used off-label. After the exclusion steps, 34 APIs were examined regarding their suitability for inkjet printing. Almost all of the APIs were sparingly water soluble to practically insoluble. Conclusion: Pharmaceutical inkjet printing is a suitable new technique for ODF manufacturing for pediatric application, however the maximal printed dose as found in the literature remained low. From the selected candidates, only montelukast shows a sufficiently high water-solubility to prepare a water-based solution. To achieve higher drug loads per ODF is ambitious, but is theoretically possible by printing multiple layers, using highly water-soluble APIs or highly loaded suspensions.

Non-Adherence to Pharmacotherapy: A Prospective Multicentre Study About Its Incidence and Its Causes Perceived by Chronic Pain Patients.

ObjectivePharmacological interventions remain the cornerstone of chronic pain treatment; however, nearly 40% of the prescription medicines are not taken as prescribed. The present study aims at understanding and describing non-adherence from the perspective of chronic pain patients during a 1-year follow-up study.MethodsA cohort of 950 consecutive patients referred to a first consultation in Multidisciplinary Chronic Pain Clinics was followed with a standardized protocol for 1 year. This included assessment of pain characteristics; prescribed medication; therapeutic adherence; effectiveness of treatment, non-adherence and its perceived reasons; clinical outcomes and quality of life. We used a mixed methods approach, including qualitative and quantitative analyses.ResultsForty-nine percent of the 562 patients who responded to all assessments during follow-up were adherent after 1 year of chronic pain treatment. The core associations between each “non-adherence reason” and Anatomical Therapeutic Chemical Code (ATC) group were perceived side effects (p=0.019) and delayed start (p=0.022) for narcotic analgesics (opioids); perceived non-efficacy (p=0.017) and delayed start (p=0.004) for antiepileptics and anticonvulsants; perceived low necessity (p=0.041) and delayed start (p=0.036) for analgesics antipyretics; change in prescriptions because of a new clinical condition for antidepressants (p=0.024); high concerns (p=0.045) and change in prescriptions because of a new clinical condition (p<0.001) for non-steroidal anti-inflammatory drugs; delayed start (p=0.016) and financial constraints (p=0.018) for other medications.DiscussionThis study emphasizes the patient’s perspective regarding non-adherence to pharmacological treatment of chronic pain, providing valuable and novel information to be used in future interventions to help patients make an informed choice about their adherence behavior.