Drug-Induced Epistaxis: An Often-Neglected Adverse Effect.

Curr Drug Saf. 2018;13(2):74-83

Authors: Meirinho S, Relvas R, Alves G

Abstract
BACKGROUND: Epistaxis is an active nose bleeding with a population occurrence of approximately 60%. Although epistaxis is a common clinical complaint, the majority of the cases are benign and caused by local induced factors (e.g., trauma and local inflammation). Nevertheless, it is also recognised that epistaxis can be induced after some drugs intake.
AIMS: Due to the increasing use of drugs or drug combinations that potentially may induce epistaxis, this review aims to alert healthcare professionals for this often neglected adverse drug effect and its possible complications.
METHODS: A comprehensive literature search was performed on PubMed and Google Scholar databases, considering the literature published from January 1985 to December 2015, using medical terms related to drug-induced epistaxis, nosebleeds and nasal blood supply.
RESULTS AND DISCUSSION: As expected, anticoagulant and antiplatelet drugs are the main pharmacotherapeutic agents associated with epistaxis, particularly warfarin, dabigatran, rivaroxaban and aspirin. However, it was reported that some selective serotonin reuptake inhibitors, intranasal corticosteroids, certain antibiotics and other drugs or drug associations can also be responsible for nosebleeds. Although most of these epistaxis episodes are mild to moderate, being spontaneously reversed or requiring only minor medical approaches to control it, there are several case reports, as well as retrospective and prospective studies, documenting severe epistaxis episodes after specific medicines intake. In these cases, some invasive medical interventions are demanded to manage the bleeding and avoid life-threatening consequences.
CONCLUSION: This work provides an integrated and comprehensive review on drug-induced epistaxis bridging the gap in the current scientific literature addressing this topic. Therefore, the scientific information gathered and discussed will be valuable to raise awareness among doctors and pharmacists for this drug-related problem, as well as to promote their active pharmacovigilance and reinforce patient education.

PMID: 29437014 [PubMed - in process]

Monitoring for antidepressant-associated adverse events in the treatment of patients with major depressive disorder: An international consensus statement.

World J Biol Psychiatry. 2018 08;19(5):330-348

Authors: Dodd S, Mitchell PB, Bauer M, Yatham L, Young AH, Kennedy SH, Williams L, Suppes T, Lopez Jaramillo C, Trivedi MH, Fava M, Rush AJ, McIntyre RS, Thase ME, Lam RW, Severus E, Kasper S, Berk M

Abstract
OBJECTIVES: These recommendations were designed to ensure safety for patients with major depressive disorder (MDD) and to aid monitoring and management of adverse effects during treatment with approved antidepressant medications. The recommendations aim to inform prescribers about both the risks associated with these treatments and approaches for mitigating such risks.
METHODS: Expert contributors were sought internationally by contacting representatives of key stakeholder professional societies in the treatment of MDD (ASBDD, CANMAT, WFSBP and ISAD). The manuscript was drafted through iterative editing to ensure consensus.
RESULTS: Adequate risk assessment prior to commencing pharmacotherapy, and safety monitoring during pharmacotherapy are essential to mitigate adverse events, optimise the benefits of treatment, and detect and assess adverse events when they occur. Risk factors for pharmacotherapy vary with individual patient characteristics and medication regimens. Risk factors for each patient need to be carefully assessed prior to initiating pharmacotherapy, and appropriate individualised treatment choices need to be selected. Some antidepressants are associated with specific safety concerns which were addressed.
CONCLUSIONS: Risks of adverse outcomes with antidepressant treatment can be managed through appropriate assessment and monitoring to improve the risk benefit ratio and improve clinical outcomes.

PMID: 28984491 [PubMed - in process]

Impact of a pharmacist-driven pharmacovigilance system in a secondary hospital in the Gauteng Province of South Africa.

Hosp Pract (1995). 2018 Oct;46(4):221-228

Authors: Terblanche A, Meyer JC, Godman B, Summers RS

Abstract
BACKGROUND AND AIMS: Under-reporting of adverse drug reactions (ADRs) by health-care professionals (HCPs) is a worldwide problem. Spontaneous reporting in hospitals is scarce and several obstacles have been identified for this. Improved hospital-based reports could make important contributions to future care. Consequently, the objective of this study was to develop, implement and evaluate a structured pharmacist-driven pharmacovigilance (PV) system for in-patient ADR reporting in a leading public hospital in South Africa for future use in South Africa and wider.
METHOD: Descriptive, operational intervention study with a pre-post design. Pharmacist-driven interventions targeted at ADR reporting were implemented. Convenience sampling was used to recruit HCPs [medical practitioners, pharmacists, pharmacist assistants, and nurses] to complete a self-administered questionnaire. The principal outcome measures were the number of the ADRs reported for inpatients, 18 months prior to and 18 months during the intervention period, as well as an evaluation of the intervention program in terms of continuous information and training.
RESULTS: There was a significant increase in the number of HCPs reporting an ADR post-intervention (33.8% up from 12.1%; p < 0.0001). Reasons for non-reporting decreased significantly, e.g. 'How, where and when to report' an ADR (p = 0.0027) and 'Concern that the report may be wrong' (p = 0.0041). HCPs' knowledge of the ADR reporting system also improved appreciably. This was apart from pharmacists who were already knowledgeable.
CONCLUSION: The results showed the benefits of pharmacist-driven interventions on HCPs' knowledge and awareness of PV and the number of the ADRs reported. Hospital management and policy makers should consider the important role pharmacists can play in improving rational and safe use of medicines among inpatients, based on appropriate training of HCPs and proper systems. As a result, help achieve the standards established by the Department of Health in South Africa.

PMID: 30092683 [PubMed - indexed for MEDLINE]

The influence of exposome on acne.

J Eur Acad Dermatol Venereol. 2018 May;32(5):812-819

Authors: Dréno B, Bettoli V, Araviiskaia E, Sanchez Viera M, Bouloc A

Abstract
BACKGROUND: Acne vulgaris is one of the main reasons for dermatological consultations. Severity and response to treatment may be impacted by various external factors or exposome.
AIM: To assess the impact of environmental factors on acne and to provide a comprehensive overview of the acne exposome.
METHODS: Two consensus meetings of five European dermatologists and a comprehensive literature search on exposome factors triggering acne served as a basis for this review.
RESULTS: Acne exposome was defined as the sum of all environmental factors influencing the occurrence, duration and severity of acne. Exposome factors impact on the response and the frequency of relapse to treatments by interacting with the skin barrier, sebaceous gland, innate immunity and cutaneous microbiota. They may be classified into the following six main categories: nutrition, psychological and lifestyle factors, occupational factors including cosmetics, as well as pollutants, medication and climatic factors. Moreover, practical considerations for the dermatologist's clinical practice are proposed.
CONCLUSION: Exposome factors including nutrition, medication, occupational factors, pollutants, climatic factors, and psychosocial and lifestyle factors may impact on the course and severity of acne and on treatment efficacy. Identifying and reducing the impact of exposome is important for an adequate acne disease management.

PMID: 29377341 [PubMed - indexed for MEDLINE]

19 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 2018/10/16

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.

The hepatotoxic potential of protein kinase inhibitors predicted with Random Forest and Artificial Neural Networks.

Toxicol Lett. 2018 Oct 10;:

Authors: Schöning V, Krähenbühl S, Drewe J

Abstract
Protein kinases (PKs) play a role in many pivotal aspects of cellular function. Dysregulation and mutations of protein kinases are involved in the development of different diseases, which might be treated by inhibition of the corresponding kinase. Protein kinase inhibitors (PKIs) are generally well tolerated, but unexpected and serious adverse events on the heart, lung, kidney and liver were observed clinically. In this study, the structure-activity relationship of PKIs in relation to hepatotoxicity was investigated. A dataset of 165 PKIs was compiled and the probability of human hepatotoxicity with two different machine learning algorithms (Random Forest and Artificial Neural Networks) was analysed. The estimated probability of hepatotoxicity was generally high for single PKIs. However, depending on the target kinase of the PKI, a difference in hepatotoxic potential could be observed. The similarity of the PKIs to each other is caused by the conserved site of action of the protein kinases. Hepatotoxicity may therefore always be an issue in PKIs.

PMID: 30315951 [PubMed - as supplied by publisher]

Demystifying serotonin syndrome (or serotonin toxicity).

Can Fam Physician. 2018 Oct;64(10):720-727

Authors: Foong AL, Grindrod KA, Patel T, Kellar J

Abstract
OBJECTIVE: To review the symptoms of serotonin toxicity (commonly referred to as serotonin syndrome) and the causative drugs and their mechanisms of action, and to equip primary care providers with practical strategies to prevent and identify serotonin toxicity.
QUALITY OF EVIDENCE: PubMed and Google Scholar were searched for relevant articles on serotonin toxicity, the causes, and the differential diagnosis using search terms related to serotonin toxicity (serotonin syndrome, serotonin toxicity, serotonin overdose), causes (individual names of drug classes, individual drug names), and diagnosis (differential diagnosis, neuroleptic malignant syndrome, anticholinergic toxicity, discontinuation syndrome, malignant hyperthermia, serotonin symptoms). Experts in psychiatric medicine, psychiatric pharmacy, clinical pharmacology, and medical toxicology were consulted. Evidence is level II and III.
MAIN MESSAGE: Serotonin toxicity is a drug-induced condition caused by too much serotonin in synapses in the brain. Cases requiring hospitalization are rare, and mild cases caused by serotonin-mediated side effects are unlikely to be fatal. Patients present with a combination of neuromuscular, autonomic, and mental status symptoms. Serotonin-elevating drugs include monoamine oxidase inhibitors, serotonin reuptake inhibitors, and serotonin releasers. Most cases involve 2 drugs that increase serotonin in different ways; the most concerning combination is a monoamine oxidase inhibitor with a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor.
CONCLUSION: Family physicians play a key role in identifying and preventing serotonin syndrome by teaching patients to recognize symptoms and monitoring patients throughout therapy.

PMID: 30315014 [PubMed - in process]

Potential drug-drug interactions in outpatient department of a tertiary care hospital in Pakistan: a cross-sectional study.

BMC Health Serv Res. 2018 Oct 10;18(1):762

Authors: Ismail M, Noor S, Harram U, Haq I, Haider I, Khadim F, Khan Q, Ali Z, Muhammad T, Asif M

Abstract
BACKGROUND: Potential drug-drug interactions (pDDIs) are one of the preventable drug related problems having the risk of serious adverse events or therapeutic failure. In developing countries like Pakistan, this issue remains poorly addressed. The objective of this study was to explore prevalence of pDDIs in the Outpatient Department (OPD) of a tertiary care hospital in Pakistan. The secondary aim was to describe the levels of reported pDDIs and develop a list of widespread clinically relevant interactions.
METHODS: Prescriptions of 2400 OPD patients were analyzed for pDDIs through Micromedex Drug-Reax®. Prevalence, severity- and documentation-levels and widespread clinically relevant interactions were reported.
RESULTS: Of total 2400 prescriptions, pDDIs were present in 22.3%. Whereas, moderate- and major-pDDIs were found in 377 (15.7%) and 225 (9.4%), respectively. PDDIs were more prevalent in Medicine (9.2%) and Cardiology (2.6%) as compared with other OPD specialties. Total 942 pDDIs were identified, of which, the majority were either moderate- (61.9%) or major-pDDIs (32.1%). Some of the most common interactions were ibuprofen + levofloxacin (n = 50), ciprofloxacin + diclofenac (32), aspirin + atenolol (24), and diclofenac + levofloxacin (19). The potential adverse outcomes of widespread interactions were seizures, bleeding, QT-interval prolongation, arrhythmias, tendon rupture, hypoglycemia/hyperglycemia, serotonin syndrome, drug toxicity, and decreased therapeutic response.
CONCLUSIONS: OPD patients were at risk to pDDIs, particularly to major- and moderate-pDDIs. Screening of prescriptions for pDDIs and monitoring of pharmacotherapy in terms of response and associated adverse drug events will contribute to patient safety.

PMID: 30314487 [PubMed - in process]

Efficacy and safety of elbasvir/grazoprevir in participants with HCV genotype 1, 4, or 6 infection from the Asia-Pacific region and Russia: final results from the randomized C-CORAL study.

J Gastroenterol Hepatol. 2018 Oct 12;:

Authors: Wei L, Jia JD, Wang FS, Niu JQ, Zhao XM, Mu S, Liang LW, Wang Z, Hwang P, Robertson MN, Ingravallo P, Asante-Appiah E, Wei B, Evans B, Hanna GJ, Talwani R, Duan ZP, Zhdanov K, Cheng PN, Tanwandee T, Nguyen VK, Heo J, Isakov V, George J, C-CORAL Investigators

Abstract
BACKGROUND AND AIM: Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with HCV infection from Asia-Pacific countries and Russia (C-CORAL).
METHODS: C-CORAL was a phase 3, randomized, placebo-controlled study. Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferred-treatment group.
RESULTS: A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediate-treatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%).
CONCLUSIONS: Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia.

PMID: 30311701 [PubMed - as supplied by publisher]

[Liver injury induced by immune checkpoint inhibitor-therapy : Example of an immune-mediated drug side effect].

Pathologe. 2018 Oct 11;:

Authors: Straub BK, Ridder DA, Schad A, Loquai C, Schattenberg JM

Abstract
BACKGROUND: Drug-induced liver injury is increasing, especially in elderly patients with polymedication and multimorbidity.
OBJECTIVES: Clinicopathologic correlation of immune-mediated liver injury, specifically liver injury following therapy with immune checkpoint inhibitors against PD-1, PDL-1, and CTLA4.
METHODS: Histologic assessment of liver biopsies of nine patients after therapy with immune checkpoint inhibitors and correlation with clinical parameters.
RESULTS: In all nine patients, liver injury was apparent after variable administration of immune checkpoint inhibitors. Transaminase levels were increased up to a maximum of 3818 U/l. Liver histology showed liver injury resembling autoimmune hepatitis respective cholangitis. In two patients, veno-occlusive disease was seen. Corticosteroid therapy was initiated in eight patients, subsequently four patients showed decreasing transaminases and five patients died of tumor progress. In three patients, it remains unclear whether liver injury by immune checkpoint inhibitors may have ultimately contributed to the fatal course, especially in one patient with liver cirrhosis and hepatocellular carcinoma.
CONCLUSIONS: Therapy with immune checkpoint inhibitors may lead to potentially fatal immune phenomena in susceptible patients, which may affect liver and/or other organs independently. Other causes of hepatopathy need to be ruled out clinically and/or histologically.

PMID: 30310977 [PubMed - as supplied by publisher]

The use of SAMe in chemotherapy-induced liver injury.

Crit Rev Oncol Hematol. 2018 Oct;130:70-77

Authors: Vincenzi B, Russo A, Terenzio A, Galvano A, Santini D, Vorini F, Antonelli-Incalzi R, Vespasiani-Gentilucci U, Tonini G

Abstract
Drug-induced liver injury (DILI) remains the most common cause of acute liver failure in the Western world. Chemotherapy is one of the major class of drugs most frequently associated with idiosyncratic DILI. For this reason, patients who receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs may not be appropriate and which drug doses should be modified. S-adenosylmethionine (SAMe) is an endogenous agent derived from methionine. Its supplementation is effective in the treatment of liver disease, in particular intrahepatic cholestasis (IHC). The target of this review is to analyze the mechanisms of hepatotoxicity of the principal anticancer agents and the role of SAMe in the prevention of this complication.

PMID: 30196914 [PubMed - indexed for MEDLINE]

Knowledge of Adverse Drug Reaction Reporting and the Pharmacovigilance of Biological Medicines: A Survey of Healthcare Professionals in Ireland.

BioDrugs. 2018 Jun;32(3):267-280

Authors: O'Callaghan J, Griffin BT, Morris JM, Bermingham M

Abstract
BACKGROUND: In Europe, changes to pharmacovigilance legislation, which include additional monitoring of medicines, aim to optimise adverse drug reaction (ADR) reporting systems. The legislation also makes provisions related to the traceability of biological medicines.
OBJECTIVE: The objective of this study was to assess (i) knowledge and general experience of ADR reporting, (ii) knowledge, behaviours, and attitudes related to the pharmacovigilance of biologicals, and (iii) awareness of additional monitoring among healthcare professionals (HCPs) in Ireland.
METHODS: Hospital doctors (n = 88), general practitioners (GPs) (n = 197), nurses (n = 104) and pharmacists (n = 309) completed an online questionnaire.
RESULTS: There were differences in mean knowledge scores relating to ADR reporting and the pharmacovigilance of biologicals among the HCP groups. The majority of HCPs who use biological medicines in their practice generally record biologicals by brand name but practice behaviours relating to batch number recording differed between some professions. HCPs consider batch number recording to be valuable but also regard it as being more difficult than brand name recording. Most respondents were aware of the concept of additional monitoring but awareness rates differed between some groups. Among those who knew about additional monitoring, there was higher awareness of the inverted black triangle symbol among pharmacists (> 86.4%) compared with hospital doctors (35.1%), GPs (35.6%), and nurses (14.9%). Hospital pharmacists had more experience and knowledge of ADR reporting than other practising HCPs.
CONCLUSION: This study highlights the important role hospital pharmacists play in post-marketing surveillance. There is a need to increase pharmacovigilance awareness of biological medicines and improve systems to support their batch traceability.

PMID: 29721705 [PubMed - indexed for MEDLINE]

11 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 2018/10/12

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.

11 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 2018/10/12

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.

14 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 2018/10/10

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.

A 52-Week Study of Dose-Adjusted Subcutaneous Testosterone Enanthate in Oil Self-Administered via Disposable Auto-injector.

J Urol. 2018 Oct 05;:

Authors: Kaminetsky JC, McCullough A, Hwang K, Jaffe JS, Wang C, Swerdloff RS

Abstract
PURPOSE: This open-label, single-arm, dose-blinded, 52-week, registration-phase study evaluated the efficacy and safety of subcutaneous testosterone enanthate auto-injector (SCTE-AI) administered weekly to men with hypogonadism.
METHODS: Patients (N=150) were initiated on 75 mg SCTE-AI self-administered weekly. Dose adjustments were made at week 7 to 50, 75, or 100 mg testosterone enanthate (TE) based on week 6 total testosterone (TT) trough concentration. If required, dose adjustments continued through the extended treatment phase. Pharmacokinetic (PK) and clinical laboratory parameters, treatment-emergent adverse events (TEAEs), and injection site reactions were captured.
RESULTS: The primary endpoint was met: 92.7% of patients achieved an average TT concentration of 300-1100 ng/dL (553.3 ± 127.29 ng/dL, mean ± SD) at week 12. A Cmax of <1500 ng/dL was achieved by 91.3% of patients, and no patients had levels >1800 ng/dL at week 12. Mean TT Ctrough was 487.2 ± 153.33 ng/dL at week 52. Most patients (>95%) reported no injection-related pain. The most frequently-reported TEAEs were increased hematocrit, hypertension, and increased prostate-specific antigen, which led to discontinuation in 30 men. There were no study drug-related serious AEs.
DISCUSSION: Dose-adjusted SCTE-AI demonstrated a steady serum TT PK profile, with small peak and trough fluctuations. SCTE-AI was safe, well tolerated, and virtually painless, indicating that SCTE-AI offers a testosterone delivery system that is a convenient weekly option for treatment of testosterone deficiency.

PMID: 30296416 [PubMed - as supplied by publisher]

Fluoxetine-induced Stevens-Johnson syndrome and liver injury.

J Clin Pharm Ther. 2018 Oct 08;:

Authors: Agrawal R, Almoghrabi A, Attar BM, Gandhi S

Abstract
WHAT IS KNOWN AND OBJECTIVE: Drug-induced liver injuries (DILI) are overall rare and often associated with use of medications. Medications are also the most common aetiology of Stevens-Johnson syndrome (SJS), but SJS is seldom seen concomitantly with liver injury. Many common drugs can cause either one of these conditions; however, there are no reported cases of concomitant DILI and SJS secondary to fluoxetine.
CASE SUMMARY: A 41-year-old female presented with a skin rash and abnormal liver function tests after the recent initiation of fluoxetine. Skin and liver biopsies showed features of SJS and DILI, respectively. Fluoxetine was stopped, following which there was improvement in her liver function tests and skin rash, without progression to fulminant hepatic failure.
WHAT IS NEW AND CONCLUSION: Commonly used and safe pharmaceuticals such as fluoxetine have the potential for serious adverse events affecting the skin and liver.

PMID: 30296343 [PubMed - as supplied by publisher]

Patented and Approval Scenario of Nanopharmaceuticals with Relevancy to Biomedical Application, Manufacturing Procedure and Safety Aspects.

Recent Pat Drug Deliv Formul. 2018;12(1):40-52

Authors: Agarwal V, Bajpai M, Sharma A

Abstract
BACKGROUND: Nanopharmaceutical is the field that arises gradually but many challenges are also still there. This review aims to identify these challenges and give the focus on their rectification.
METHODS: In this paper, we memorize the safety issues, patented manufacturing procedure, applications and regulatory aspects of the nanopharmaceuticals by using the peer-reviewed research literatures. All the screened literatures described the quality content of nanopharmaceuticals with relevancy to biomedical and pharmaceutical field.
RESULTS: Nanopharmaceuticals have great potential to resolve the different issues such as; site specific drug delivery however, many challenges are also arising in their commercialization. In the recent years, some nanopharmaceuticals have the desired quality and safety for the public, have been approved by the regulatory agencies but this field is still a thrust area that demands a lot of attention.
CONCLUSION: The present review article confirms the importance of nanopharmaceuticals and impart the knowledge for making the significant approaches and strategies to overcome the manufacturing, safety, legal and regulatory issues related to nanopharmaceuticals.

PMID: 29303083 [PubMed - indexed for MEDLINE]

Screening for Adverse Drug Events: a Randomized Trial of Automated Calls Coupled with Phone-Based Pharmacist Counseling.

J Gen Intern Med. 2018 Oct 05;:

Authors: Schiff GD, Klinger E, Salazar A, Medoff J, Amato MG, John Orav E, Shaykevich S, Seoane EV, Walsh L, Fuller TE, Dykes PC, Bates DW, Haas JS

Abstract
BACKGROUND: Medication adverse events are important and common yet are often not identified by clinicians. We evaluated an automated telephone surveillance system coupled with transfer to a live pharmacist to screen potentially drug-related symptoms after newly starting medications for four common primary care conditions: hypertension, diabetes, depression, and insomnia.
METHODS: Cluster randomized trial with automated calls to eligible patients at 1 and 4 months after starting target drugs from intervention primary care clinics compared to propensity-matched patients from control clinics. Primary and secondary outcomes were physician documentation of any adverse effects associated with newly prescribed target medication, and whether the medication was discontinued and, if yes, whether the reason for stopping was an adverse effect.
RESULTS: Of 4876 eligible intervention clinic patients who were contacted using automated calls, 776 (15.1%) responded and participated in the automated call. Based on positive symptom responses or request to speak to a pharmacist, 320 patients were transferred to the pharmacist and discussed 1021 potentially drug-related symptoms. Of these, 188 (18.5%) were assessed as probably and 479 (47.1%) as possibly related to the medication. Compared to a propensity-matched cohort of control clinic patients, intervention patients were significantly more likely to have adverse effects documented in the medical record by a physician (277 vs. 164 adverse effects, p < 0.0001, and 177 vs. 122 patients discontinued with documented adverse effects, p < 0.0001).
DISCUSSION: Systematic automated telephone outreach monitoring coupled with real-time phone referral to a pharmacist identified a substantial number of previously unidentified potentially drug-related symptoms, many of which were validated as probably or possibly related to the drug by the pharmacist or their physicians. Multiple challenges were encountered using the interactive voice response (IVR) automated calling system, suggesting that other approaches may need to be considered and evaluated.
TRIAL REGISTRATION: ClinicalTrials.gov : NCT02087293.

PMID: 30291602 [PubMed - as supplied by publisher]

Efficacy and Safety of High-Specific-Activity I-131 MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma.

J Nucl Med. 2018 Oct 05;:

Authors: Pryma DA, Chin BB, Noto RB, Dillon JS, Perkins S, Solnes L, Kostakoglu L, Serafini AN, Pampaloni MH, Jensen J, Armor T, Lin T, White T, Stambler N, Apfel S, DiPippo V, Mahmood S, Wong V, Jimenez C

Abstract
Patients with metastatic or unresectable (advanced) pheochromocytoma or paraganglioma (PPGL) have poor prognoses and few treatment options. This multicenter, phase 2 trial evaluated the efficacy and safety of high-specific-activity I-131 meta-iodobenzylguanidine (HSA I-131 MIBG) in patients with advanced PPGL. Methods: In this open-label, single-arm study, 81 PPGL patients were screened for enrollment, and 74 received a treatment-planning dose of HSA I-131 MIBG. 68 patients with advanced PPGL received at least one therapeutic dose (~18.5 GBq) of HSA I-131 MIBG intravenously. The primary endpoint was the proportion of patients with at least a 50% reduction in baseline antihypertensive medication use lasting at least 6 months. Secondary endpoints included objective tumor response as assessed by Response Evaluation Criteria in Solid Tumors version 1.0; biochemical tumor marker response; overall survival (OS); and safety. Results: Of the 68 patients who received at least one therapeutic dose of HSA I-131 MIBG, 17 (25%; 95% CI, 16-37%) had a durable reduction in baseline antihypertensive medication use. Among 64 patients with evaluable disease, 59 (92%) had a partial response or stable disease as the best objective response within 12 months. Decreases in elevated (≥1.5 times the upper limit of normal (ULN) at baseline) serum CgA levels were observed with confirmed complete and partial responses 12 months after treatment in 19 of 28 patients (68%). The median OS duration was 36.7 months (95% CI, 29.9-49.1 months). The most common treatment-emergent adverse events were nausea, myelosuppression, and fatigue. No patients had drug-related acute hypertensive events during or after the administration of HSA I-131 MIBG. Conclusion: HSA I-131 MIBG offers multiple benefits, including sustained blood pressure control and tumor response in PPGL patients.

PMID: 30291194 [PubMed - as supplied by publisher]