Patient, Treatment, and Health Care Utilization Variables Associated with Adherence to Metabolic Monitoring Practices in Children and Adolescents Taking Second-Generation Antipsychotics.

Can J Psychiatry. 2018 04;63(4):240-249

Authors: Coughlin M, Goldie CL, Tranmer J, Khalid-Khan S, Tregunno D

Abstract
OBJECTIVE: Children and adolescents with a range of psychiatric disorders are increasingly being prescribed atypical or second-generation antipsychotics (SGAs). While SGAs are effective at treating conduct and behavioural symptoms, they infer significant cardiometabolic risk. This study aims to explore what patient, treatment, and health care utilization variables are associated with adherence to Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) metabolic monitoring guidelines.
METHOD: A retrospective chart review of 294 children and adolescents accessing a large outpatient psychiatry setting within a 2-year study period (2014-2016) was conducted. Baseline and follow-up metabolic monitoring, demographic, treatment, and health care utilization variables were then assessed over a 1-year period of interest.
RESULTS: Metabolic monitoring practices did not adhere to CAMESA guidelines and were very poor over the 1-year observation period. There were significant differences between children (ages 4-12 years, n = 99) and adolescents (ages 13-18 years, n = 195). In adolescents, factors associated with any baseline metabolic monitoring were a higher number of psychiatry visits (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.10 to 1.41), longer duration of contact (OR, 14; 95% CI, 2.31 to 82.4), and use of other non-SGA medications (OR, 3.2; 95% CI, 1.17 to 8.94). Among children, having an emergency room visit (OR, 3.4; 95% CI, 1.01 to 11.71) and taking aripiprazole (OR, 7.4; 95% CI, 2.02 to 27.45) increased the odds of receiving baseline metabolic monitoring.
CONCLUSION: Findings from this study highlight the need for better metabolic monitoring for children and adolescents taking SGAs. Enhanced focus on opportunities for multidisciplinary collaboration is needed to improve the quality of care offered to this population.

PMID: 29528720 [PubMed - indexed for MEDLINE]

Incidence and Management of Immune-Related Adverse Events in Patients Undergoing Treatment with Immune Checkpoint Inhibitors.

Curr Oncol Rep. 2018 03 06;20(3):24

Authors: Kottschade LA

Abstract
PURPOSE OF REVIEW: The unleashing of the immune system in an effort to fight cancer has proven to be an incredible advance in the war on cancer. However that breakthrough has come with a price in the form of serious and potentially fatal immune-related adverse events (irAEs).
RECENT FINDINGS: Rapid recognition and early intervention is imperative to avoid significant morbidity and mortality. Additionally, providers need to be aware that there are still new, rare, and long-term emerging irAEs that were not previously reported in clinical trials. Because of the significant difference between irAEs and those caused by chemotherapy and/or targeted therapy, providers must have a thorough understanding of which events would be considered immune related and require treatment. This review will cover descriptions of the most common and uncommon but serious irAEs experienced by patients on immunotherapy, as well as management of these irAEs.

PMID: 29511902 [PubMed - indexed for MEDLINE]

Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: Practical experiences in a tertiary medical center.

Epilepsy Behav. 2018 03;80:240-246

Authors: Porcari GS, Fu C, Doll ED, Carter EG, Carson RP

Abstract
Medically refractory epilepsy continues to be a challenge worldwide, and despite an increasing number of medical therapies, approximately 1 in 3 patients continues to have seizures. Cannabidiol (CBD), one of many constituents of the Cannabis sativa or marijuana plant, has received renewed interest in the treatment of epilepsy. While highly purified CBD awaits Food and Drug Administration (FDA) approval, artisanal formulations of CBD are readily available and are seeing increased use in our patient population. Although randomized controlled trials of CBD are ongoing and promising, data regarding artisanal formulations of CBD are minimal and largely anecdotal. Here, we report a retrospective study to define the efficacy of artisanal CBD preparations in children with epilepsy. Given the known interaction between CBD and clobazam, we also conducted a subgroup comparison to determine if clobazam use was related to any beneficial effects of CBD. Additionally, we compared response rates with CBD and with clobazam alone within an overlapping patient cohort. A pediatric cohort with epilepsy of 108 patients was identified through a medical record search for patients using CBD oil. The addition of CBD resulted in 39% of patients having a >50% reduction in seizures, with 10% becoming seizure-free. The responder rate for clobazam was similar. No patients achieved CBD monotherapy, although the weaning of other antiepileptic drugs (AEDs) became possible in 22% of patients. A comparable proportion had AED additions during CBD therapy. With concomitant use of clobazam, 44% of patients had a 50% reduction in seizures upon addition of CBD compared with 33% in the population not taking clobazam; this difference was not statistically significant. The most common reported side effect of CBD was sedation in less than 4% of patients, all of whom were also taking clobazam. Increased alertness and improved verbal interactions were reported in 14% of patients in the CBD group and 8% of patients in the CBD and clobazam group. Benefits were more marked in the CBD alone group, in contrast to the CBD and clobazam group, but this difference was not statistically significant. In summary, these findings support efficacy of artisanal CBD preparations in seizure reduction with few significant side effects. The response to CBD was independent of concurrent clobazam use, although clobazam may contribute to the sedation seen with concurrent CBD use.

PMID: 29429908 [PubMed - indexed for MEDLINE]

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/03/21

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/03/20

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/03/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/03/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Three-year follow-up of a phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer and bone metastases.

Int J Clin Oncol. 2019 Mar 14;:

Authors: Uemura H, Uemura H, Nagamori S, Wakumoto Y, Kimura G, Kikukawa H, Yokomizo A, Mizokami A, Kosaka T, Masumori N, Kawasaki Y, Yonese J, Nasu Y, Fukasawa S, Sugiyama T, Kinuya S, Hosono M, Yamaguchi I, Akagawa T, Matsubara N

Abstract
BACKGROUND: Radium-223 is a first-in-class targeted alpha therapy to prolong overall survival (OS) in castration-resistant prostate cancer with bone metastases (mCRPC). The aim of the present analysis was to assess the long-term safety with radium-223 in Japanese patients with mCRPC.
METHODS: Patients with symptomatic mCRPC, ≥ 2 bone metastases and no known visceral metastases received up to 6 injections of radium-223 (55 kBq/kg), one every 4 weeks. Adverse events (AEs) considered to be related to radium-223 were reported until 3 years after the first injection. Pre-specified conditions, such as acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, primary bone cancer, or other primary malignancies, were reported regardless of causality.
RESULTS: Of the 49 patients enrolled in the study, 44 (89.8%) entered the survival follow-up period and 33 (67.3%) died. Throughout the entire study, there were no reports of second primary malignancy or other pre-specified conditions. Eight patients (16.3%) experienced post-treatment drug-related AEs, which were all hematological (anemia and decreased lymphocyte, platelet, and white blood cell counts). No serious post-treatment drug-related AEs were reported. Updated median OS was 19.3 months (95% CI: 14.2, 28.5).
CONCLUSIONS: In Japanese patients with symptomatic mCRPC and bone metastases, radium-223 had a favorable long-term safety profile with no second primary malignancies reported. Taken together with median OS, which was comparable to that in the pivotal phase III ALSYMPCA study, these results support continued benefit from radium-223 in Japanese patients with mCRPC.

PMID: 30875000 [PubMed - as supplied by publisher]

Betaine anhydrous in homocystinuria: results from the RoCH registry.

Orphanet J Rare Dis. 2019 Mar 14;14(1):66

Authors: Valayannopoulos V, Schiff M, Guffon N, Nadjar Y, García-Cazorla A, Martinez-Pardo Casanova M, Cano A, Couce ML, Dalmau J, Peña-Quintana L, Rigalleau V, Touati G, Aldamiz-Echevarria L, Cathebras P, Eyer D, Brunet D, Damaj L, Dobbelaere D, Gay C, Hiéronimus S, Levrat V, Maillot F

Abstract
BACKGROUND: The Registry of Adult and Paediatric Patients Treated with Cystadane® - Homocystinuria (RoCH) is a non-interventional, observational, multi-centre, post-authorization safety study that aimed to identify safety of betaine anhydrous (Cystadane®) in the treatment of patients with inborn errors of homocysteine metabolism (homocystinuria) in order to minimise the treatment associated risks and establish better knowledge on its clinical use. The registry included patients of all ages with homocystinuria who were treated with betaine anhydrous in conjunction with other therapies. Clinical data were collected retrospectively from 2007 to 2013, then prospectively up to February 2014. All adverse events (AEs) reported during the study were recorded. The clinical and biological status of patients was monitored at least once a year.
RESULTS: A total of 125 patients with homocystinuria (adults [> 18 years]: 50; paediatric [≤18 years]: 75) were enrolled at 29 centres in France and Spain. Patients were treated with betaine anhydrous for a mean duration of 7.4 ± 4.3 years. The median total daily dose of betaine anhydrous at the first and last study visits was 6 g/day for cystathionine β-synthase (CBS)-deficient vitamin B6 responders and 9 g/day for methylenetetrahydrofolate reductase-deficient patients, while the median daily dose increased in CBS-deficient B6 non-responders (from 6 to 9 g/day) and cobalamin metabolism-defective patients (from 3 to 6 g/day) between the first and last visits. Treatment caused a mean overall reduction of 29% in plasma homocysteine levels in the study population. A total of 277 AEs were reported during the study, of which two non-serious AEs (bad taste and headache) and one serious AE (interstitial lung disease) were considered to be drug related. Overall, betaine anhydrous was well tolerated with no major safety concerns.
CONCLUSIONS: Data from the RoCH registry provided real-world evidence on the clinical safety and efficacy of betaine anhydrous in the management of homocystinuria in paediatric and adult patients.

PMID: 30871635 [PubMed - in process]

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/03/15

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Single-Dose Pharmacokinetics and Safety of Solriamfetol in Participants With Normal or Impaired Renal Function and With End-Stage Renal Disease Requiring Hemodialysis.

J Clin Pharmacol. 2019 Mar 13;:

Authors: Zomorodi K, Chen D, Lee L, Lasseter K, Marbury T

Abstract
Solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with wake-promoting effects, is renally excreted ∼90% unchanged within 48 hours. Effects of renal impairment and hemodialysis on the pharmacokinetics and safety of 75-mg single-dose solriamfetol were evaluated in adults with normal renal function (n = 6); mild (n = 6), moderate (n = 6), or severe (n = 6) renal impairment; and end-stage renal disease (ESRD) with and without hemodialysis (n = 7). Relative to normal renal function, geometric mean area under the plasma concentration-time curve from time zero to infinity increased 53%, 129%, and 339%, and mean half-life was 1.2-, 1.9-, and 3.9-fold higher with mild, moderate, and severe renal impairment, respectively. Renal excretion of unchanged solriamfetol over 48 hours was 85.8%, 80.0%, 66.4%, and 57.1% in normal, mild, moderate, and severe renal impairment groups, respectively; mean maximum concentration and time to maximum concentration did not vary substantially. Decreases in solriamfetol clearance were proportional to decreases in estimated glomerular filtration rate. Geometric mean area under the plasma concentration-time curve from time zero to time of last quantifiable concentration increased 357% and 518% vs normal in ESRD with and without hemodialysis, respectively, with half-life >100 hours in both groups. Over the 4-hour hemodialysis period, ∼21% of solriamfetol dose was removed. Adverse events included headache (n = 1) and nausea (n = 1). Six days after dosing, 1 participant had increased alanine and aspartate aminotransferase, leading to study discontinuation. While these adverse events were deemed study-drug related, they were mild and resolved. Results from this study combined with population pharmacokinetic modeling/simulation suggest that solriamfetol dosage adjustments are necessary in patients with moderate or severe but not with mild renal impairment. Due to significant exposure increase/prolonged half-life, dosing is not recommended in patients with ESRD.

PMID: 30865315 [PubMed - as supplied by publisher]

Drug repositioning through integration of prior knowledge and projections of drugs and diseases.

Bioinformatics. 2019 Mar 13;:

Authors: Xuan P, Cao Y, Zhang T, Wang X, Pan S, Shen T

Abstract
MOTIVATION: Identifying and developing novel therapeutic effects for existing drugs contributes to reduction of drug development costs. Most of the previous methods focus on integration of the heterogeneous data of drugs and diseases frommultiple sources for predicting the candidate drug-disease associations. However, they fail to take the prior knowledge of drugs and diseases and their sparse characteristic into account. It is essential to develop a method that exploits the more useful information to predict the reliable candidate associations.
RESULTS: We present a method based on non-negative matrix factorization, DisDrugPred, to predict the drug-related candidate disease indications. A new type of drug similarity is firstly calculated based on their associated diseases. DisDrugPred completely integrates two types of disease similarities, the associations between drugs and diseases, and the various similarities between drugs from different levels including the chemical structures of drugs, the target proteins of drugs, the diseases associated with drugs, and the side effects of drugs. The prior knowledge of drugs and diseases and the sparse characteristic of drug-disease associations provide a deep biological perspective for capturing the relationships between drugs and diseases. Simultaneously, the possibility that a drug is associated with a disease is also dependant on their projections in the low-dimension feature space. Therefore, DisDrugPred deeply integrates the diverse prior knowledge, the sparse characteristic of associations, and the projections of drugs and diseases. DisDrugPred achieves superior prediction performance than several state-of-the-art methods for drug-disease association prediction. During the validation process, DisDrugPred also can retrieve more actual drug-disease associations in the top part of prediction result which often attracts more attention from the biologists. Moreover, case studies on 5 drugs further confirm DisDrugPred's ability to discover potential candidate disease indications for drugs.

PMID: 30865257 [PubMed - as supplied by publisher]

Long-term efficacy and tolerability of TNFα inhibitors in the treatment of non-infectious ocular inflammation: an 8-year prospective surveillance study.

Br J Ophthalmol. 2019 Mar 12;:

Authors: Sharma SM, Damato E, Hinchcliffe AE, Andrews CD, Myint K, Lee R, Dick AD

Abstract
BACKGROUND/AIM: To report the efficacy and tolerability of antitumour necrosis factor-alpha therapy (TNF inhibitors [TNFi]) in the management of non-infectious ocular inflammation, including uveitis and scleritis, in adult patients over an 8-year period.
MATERIALS AND METHODS: This is a prospective cohort study of infliximab and adalimumab in the treatment of non-infectious ocular inflammatory disease. 43 of 85 adult patients on TNFi (34 infliximab, 9 adalimumab) for ≥1 year with non-infectious uveitis or scleritis were followed from 2006 to 2014. Clinical assessments, medication, adverse events and history of steroid rescues were collected at 6 monthly intervals. General quality of life (Short Form Health Survey (SF-36)) and visual quality of life (Vision-related quality of life Core Measure (VCM1)) were assessed annually. Outcome measures included rate of sustained remission, rate of relapse, systemic corticosteroid reduction, adverse events, and VCM1 and SF-36 scores.
RESULTS: The median time on infliximab was 3.2 years (IQR 4.3) and on adalimumab was 2.4 years (IQR 1.8). Sustained remission was induced in 39 patients (91%) (0.5 per patient year) after a median of 1.2 years on a TNFi. 22 (51%) experienced one relapse, and 5 (12%) had two relapses. 23 (54%) had at least one adverse event; serious adverse events necessitating hospitalisation or cessation of medication occurred in four (9%) patients. 10 patients (23%) switched from the initiation of TNFi, at 1.7 years after starting, to another TNFi or another class of biologic therapy.
CONCLUSION: TNFi treatment is associated with long-term drug-induced remission of ocular inflammation, visual stability and corticosteroid reduction. Adverse events were common and no new safety signals occurred. Relapse of inflammation occurs in half of the treated population.

PMID: 30862619 [PubMed - as supplied by publisher]

Can lifecycle management safeguard innovation in the pharmaceutical industry?

Drug Discov Today. 2018 12;23(12):1962-1973

Authors: Hering S, Loretz B, Friedli T, Lehr CM, Stieneker F

Abstract
The pharmaceutical industry invests enormous amounts of resources (>€1 billion and >10years) in the development of new products. External factors such as intensifying foreign competition and greater regulatory demands can negatively affect the profit margin, whereas the R&D productivity diminishes. To stay competitive and to maintain high R&D capabilities for developing new medicinal products, companies must make smart investment decisions to maximize their return on investment. Consequently, the entire lifecycle of a medicinal product must be effectively managed to ensure a sustained development through commercialization. This review critically assesses the current situation and the associated management strategies throughout the lifecycle of a medicinal product.

PMID: 30342247 [PubMed - indexed for MEDLINE]

Coadministration of cytotoxic chemotherapeutic agents with irinotecan is a risk factor for irinotecan-induced cholinergic syndrome in Japanese patients with cancer.

Int J Clin Oncol. 2019 Feb;24(2):222-230

Authors: Tsuboya A, Fujita KI, Kubota Y, Ishida H, Taki-Takemoto I, Kamei D, Iwai S, Sasaki Y

Abstract
BACKGROUND: Cholinergic syndrome is an acute adverse event frequently observed in patients administered irinotecan, and can sometimes negatively affect their quality of life. In some manifestations of the syndrome such as bradycardia, careful monitoring of patients is advised. In this study, we retrospectively investigated the risk factors associated with irinotecan-induced cholinergic syndrome in Japanese patients with cancer.
METHODS: Patients who received irinotecan-based chemotherapy between April 2014 and June 2018 were examined. Patient backgrounds and clinical data during the first cycle of an irinotecan-containing regimen, including cholinergic syndrome manifestation within 24 h after the start of treatment, were collected from medical records. Univariate and multivariate analyses were performed to assess the risk of irinotecan-induced cholinergic syndrome.
RESULTS: Among 179 patients administered an irinotecan-containing regimen, 51 experienced cholinergic syndrome after the initiation of treatment. The most common symptom was sweating followed by diarrhea, abdominal pain, lacrimation, and nasal discharge. 42 patients developed symptoms of cholinergic syndrome during their first treatment with irinotecan. Multivariate analyses revealed that the incidences of cholinergic syndrome in patients administered 2 or 3 chemotherapeutic agents; i.e., irinotecan plus 1 or 2 other cytotoxic anticancer drug(s), were significantly higher than that in patients administered irinotecan alone [odds ratio (OR) 4.35, 95% confidence interval (CI) 1.5-12, p = 0.0053 and OR 4.50, 95% CI 1.5-14, p = 0.0093, respectively]. The addition of a molecularly targeted drug did not affect the incidence of cholinergic syndrome.
CONCLUSION: The incidence rate of irinotecan-induced cholinergic syndrome increased concomitantly with the addition of cytotoxic chemotherapeutic agents administered.

PMID: 30244364 [PubMed - indexed for MEDLINE]

Nonmedical prescriber experiences of training and competence to report adverse drug reactions in the UK.

J Clin Pharm Ther. 2019 Feb;44(1):78-83

Authors: Thompson A, Randall C, Howard J, Barker C, Bowden D, Mooney P, Munyika A, Smith S, Pirmohamed M

Abstract
WHAT IS KNOWN AND OBJECTIVE: Adverse drug reaction reporting in the UK is lower than expected based on epidemiological data. This study aims to explore (a) nonmedical prescribers' (NMP) confidence in identifying and reporting ADRs, (b) NMP prescribing habits and engagement with the Yellow Card Scheme (YCS) and (c) NMP desire for future training in the identification and reporting of ADRs.
METHODS: A survey was distributed across NMP networks in the north-west of England using Survey Monkey. Univariate analyses were performed to compare the features of reporters and nonreporters, Kruskal-Wallis H tests for comparisons within multiple subgroups and Spearman's rank correlation coefficient for response associations between answers to ordered-category questions.
RESULTS AND DISCUSSION: A total of 570 responses were available for analysis, an estimated response rate of 20%. Less than half (n = 219; 38.4%) reported submitting a Yellow Card to the YCS, and the majority of those individuals have submitted five or less Yellow Cards; 28 responders reported more than five submissions. Being professionally qualified for more years (linear regression: B = 0.30, P < 0.0005; 95% CI 1.01 to 1.05) and receiving additional training support about the YCS (chi-squared: χ2  = 14.7, P < 0.0005) were associated with an increased likelihood of submitting to the YCS. There was a positive linear relationship between confidence in identifying ADRs and likelihood of reporting to YCS. The most common reason given (n = 261) for never having reported to the YCS was "I have never seen an adverse drug reaction." Training appears to give NMPs confidence in reporting ADRs, but there seems to be a gap in actually identifying ADRs given the comment that most had never seen an ADR.
WHAT IS NEW AND CONCLUSION: Strategies for improving the translation of theoretical knowledge about ADRs into practical skills in identifying ADRs, and subsequently reporting them, will be important for improving pharmacovigilance practice.

PMID: 30206951 [PubMed - indexed for MEDLINE]

Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in vietnamese spontaneous adverse drug reaction database: A subgroup approach to disproportionality analysis.

J Clin Pharm Ther. 2019 Feb;44(1):69-77

Authors: Nguyen KD, Tran TN, Nguyen MT, Nguyen HA, Nguyen HA, Vu DH, Nguyen VD, Bagheri H

Abstract
WHAT IS KNOWN AND OBJECTIVE: Despite the numerous studies investigating drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), the understanding and quantitative data in developing countries remain limited. The study aimed to describe and quantify the drug-related risk of SJS/TEN in a resource-limited context using the Vietnamese spontaneous reporting database (VSRD) of adverse drug reactions.
METHODS: Spontaneous reports relating to medium- and late-onset severe cutaneous adverse reactions (MLOSCAR) and SJS/TEN recorded in the VSRD from 2010 to 2015 were retrospectively analysed. The demographic characteristics and drug information were described and compared between SJS/TEN and other MLOSCAR reports. The drug-induced SJS/TEN signals were estimated using subgrouped disproportionality analysis with calculation of the reporting odds ratio (ROR) and the respective 95% confidence interval (CI).
RESULTS: The VSRD received 2,849 MLOSCAR reports, 136 of which focus on SJS/TEN over a 6-year period. About 60% of SJS/TEN patients were male, and the majority of them were adults (mean age 42.5 ± 22.9). Up to 91.8% of drugs induced SJS/TEN within 1-28 days, and 45% SJS/TEN cases were evaluated as life-threatening. Positive signals were generated with carbamazepine (n = 25, ROR [95% CI] = 11.99 [7.07-19.92]), allopurinol (n = 15, ROR [95% CI] = 4.2 [2.20-7.59]), traditional/herbal medicines (n = 7, ROR [95% CI] = 2.76 [1.12-5.86]), colchicine (n = 4, ROR [95% CI] = 6.22 [1.69-18.72]), valproic acid (n = 3, ROR [95% CI] = 8.71 [1.89-30.19]) and meloxicam (n = 3, ROR [95% CI] = 7.09 [1.55-24.29]), which are well known for SJS/TEN. Cefixime (n = 5, ROR [95% CI] = 3.34 [1.13-8.00]) and paracetamol (n = 22, ROR [95% CI] = 5.23 [3.10-8.49]) also generated positive signals despite their popularity in Vietnam.
WHAT IS NEW AND CONCLUSION: This first Vietnamese population-based study has highlighted original characteristics and signals of drug-induced SJS/TEN, which are relatively consistent with other worldwide data and typical for a developing country.

PMID: 30129156 [PubMed - indexed for MEDLINE]

Next-Generation Machine Learning for Biological Networks.

Cell. 2018 06 14;173(7):1581-1592

Authors: Camacho DM, Collins KM, Powers RK, Costello JC, Collins JJ

Abstract
Machine learning, a collection of data-analytical techniques aimed at building predictive models from multi-dimensional datasets, is becoming integral to modern biological research. By enabling one to generate models that learn from large datasets and make predictions on likely outcomes, machine learning can be used to study complex cellular systems such as biological networks. Here, we provide a primer on machine learning for life scientists, including an introduction to deep learning. We discuss opportunities and challenges at the intersection of machine learning and network biology, which could impact disease biology, drug discovery, microbiome research, and synthetic biology.

PMID: 29887378 [PubMed - indexed for MEDLINE]

Understanding drug targets: no such thing as bad news.

Drug Discov Today. 2018 12;23(12):1925-1928

Authors: Roberts RA

Abstract
How can small-to-medium pharma and biotech companies enhance the chances of running a successful drug project and maximise the return on a limited number of assets? Having a full appreciation of the safety risks associated with proposed drug targets is a crucial element in understanding the unwanted side-effects that might stop a project in its tracks. Having this information is necessary to complement knowledge about the probable efficacy of a future drug. However, the lack of data-rich insight into drug-target safety is one of the major causes of drug-project failure today. Conducting comprehensive target-safety reviews early in the drug discovery process enables project teams to make the right decisions about which drug targets to take forward.

PMID: 29803936 [PubMed - indexed for MEDLINE]

Systems Pharmacology Model of Gastrointestinal Damage Predicts Species Differences and Optimizes Clinical Dosing Schedules.

CPT Pharmacometrics Syst Pharmacol. 2018 01;7(1):26-33

Authors: Shankaran H, Cronin A, Barnes J, Sharma P, Tolsma J, Jasper P, Mettetal JT

Abstract
Gastrointestinal (GI) adverse events (AEs) are frequently dose limiting for oncology agents, requiring extensive clinical testing of alternative schedules to identify optimal dosing regimens. Here, we develop a translational mathematical model to predict these clinical AEs starting from preclinical GI toxicity data. The model structure incorporates known biology and includes stem cells, daughter cells, and enterocytes. Published data, including cellular numbers and division times, informed the system parameters for humans and rats. The drug-specific parameters were informed with preclinical histopathology data from rats treated with irinotecan. The model fit the rodent irinotecan-induced pathology changes well. The predicted time course of enterocyte loss in patients treated with weekly doses matched observed AE profiles. The model also correctly predicts a lower level of AEs for every 3 weeks (Q3W), as compared to the weekly schedule.

PMID: 28941225 [PubMed - indexed for MEDLINE]