[Recommendation of ICD-10 codes for surveillance of adverse drug reactions and drug intoxication].

Cien Saude Colet. 2018 Sep;23(9):3041-3054

Authors: Mota DM, Vigo Á, Kuchenbecker RS

Abstract
ICD-10 is the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD), a medical classification list by the World Health Organization. It contains codes for diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases. Associations between variables were evaluated using Pearson's chi-squared test and multiple correspondence analysis. Six hundred and ninety-one (691) codes were identified related to adverse drug reactions (52.1%) and drug poisoning (47.9%). A total of 687 (99.4%) and 511 (73.9%) codes were validated in 1st and 2nd validation, respectively. There were statistically significant differences (p <0.05) between adverse reactions and drug poisoning in the variables used to characterize the reference list. The association between drug and hospital admission and death was statistically significant when stratified by type of adverse event (p <0.001). Three groupings of codes were identified in multiple correspondence analysis where there are associations between categories of response assessed. The reference list can be a useful tool in pharmacovigilance actions in Brazil.

PMID: 30281741 [PubMed - indexed for MEDLINE]

Modeling effects of side-effect probability, side-effect severity, and medication efficacy on patients with multiple sclerosis medication choice.

Exp Clin Psychopharmacol. 2018 Dec;26(6):599-607

Authors: Jarmolowicz DP, Reed DD, Bruce AS, Lynch S, Smith J, Bruce JM

Abstract
Multiple sclerosis (MS) is an autoimmune disease that causes a range of problematic symptoms. These symptoms tend to get worse over time, causing substantial impairment in patient quality of life. Although many effective disease-modifying therapies (DMTs) exist that slow the course of MS, patients often do not choose to take them, which may be because these medications carry substantial risks of side effects, varying from mild to severe, while only decreasing the probability of future symptoms. In the current study, we examined MS patients' self-reported likelihood of taking medications with a range of efficacies (11 values, ranging from 0.1% to 99.9%), side-effect probabilities (11 values, ranging from 0.1% to 99.9%), and side-effect severities (mild, moderate, or severe). These data were well-described by a three-dimensional probability-discounting model that isolated patients' undiscounted likelihood of taking DMTs, as well as their discounting and psychophysical scaling/weighting of side-effect probabilities and efficacy. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID: 30148403 [PubMed - indexed for MEDLINE]

Impact of medication reconciliation for improving transitions of care.

Cochrane Database Syst Rev. 2018 08 23;8:CD010791

Authors: Redmond P, Grimes TC, McDonnell R, Boland F, Hughes C, Fahey T

Abstract
BACKGROUND: Transitional care provides for the continuity of care as patients move between different stages and settings of care. Medication discrepancies arising at care transitions have been reported as prevalent and are linked with adverse drug events (ADEs) (e.g. rehospitalisation).Medication reconciliation is a process to prevent medication errors at transitions. Reconciliation involves building a complete list of a person's medications, checking them for accuracy, reconciling and documenting any changes. Despite reconciliation being recognised as a key aspect of patient safety, there remains a lack of consensus and evidence about the most effective methods of implementing reconciliation and calls have been made to strengthen the evidence base prior to widespread adoption.
OBJECTIVES: To assess the effect of medication reconciliation on medication discrepancies, patient-related outcomes and healthcare utilisation in people receiving this intervention during care transitions compared to people not receiving medication reconciliation.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, seven other databases and two trials registers on 18 January 2018 together with reference checking, citation searching, grey literature searches and contact with study authors to identify additional studies.
SELECTION CRITERIA: We included only randomised trials. Eligible studies described interventions fulfilling the Institute for Healthcare Improvement definition of medication reconciliation aimed at all patients experiencing a transition of care as compared to standard care in that institution. Included studies had to report on medication discrepancies as an outcome.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts, assessed studies for eligibility, assessed risk of bias and extracted data. Study-specific estimates were pooled, using a random-effects model to yield summary estimates of effect and 95% confidence intervals (CI). We used the GRADE approach to assess the overall certainty of evidence for each pooled outcome.
MAIN RESULTS: We identified 25 randomised trials involving 6995 participants. All studies were conducted in hospital or immediately related settings in eight countries. Twenty-three studies were provider orientated (pharmacist mediated) and two were structural (an electronic reconciliation tool and medical record changes). A pooled result of 20 studies comparing medication reconciliation interventions to standard care of participants with at least one medication discrepancy showed a risk ratio (RR) of 0.53 (95% CI 0.42 to 0.67; 4629 participants). The certainty of the evidence on this outcome was very low and therefore the effect of medication reconciliation to reduce discrepancies was uncertain. Similarly, reconciliation's effect on the number of reported discrepancies per participant was also uncertain (mean difference (MD) -1.18, 95% CI -2.58 to 0.23; 4 studies; 1963 participants), as well as its effect on the number of medication discrepancies per participant medication (RR 0.13, 95% CI 0.01 to 1.29; 2 studies; 3595 participants) as the certainty of the evidence for both outcomes was very low.Reconciliation may also have had little or no effect on preventable adverse drug events (PADEs) due to the very low certainty of the available evidence (RR 0.37. 95% CI 0.09 to 1.57; 3 studies; 1253 participants), with again uncertainty on its effect on ADE (RR 1.09, 95% CI 0.91 to 1.30; 4 studies; 1363 participants; low-certainty evidence). Evidence of the effect of the interventions on healthcare utilisation was conflicting; it probably made little or no difference on unplanned rehospitalisation when reported alone (RR 0.72, 95% CI 0.44 to 1.18; 5 studies; 1206 participants; moderate-certainty evidence), and had an uncertain effect on a composite measure of hospital utilisation (emergency department, rehospitalisation RR 0.78, 95% CI 0.50 to 1.22; 4 studies; 597 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS: The impact of medication reconciliation interventions, in particular pharmacist-mediated interventions, on medication discrepancies is uncertain due to the certainty of the evidence being very low. There was also no certainty of the effect of the interventions on the secondary clinical outcomes of ADEs, PADEs and healthcare utilisation.

PMID: 30136718 [PubMed - indexed for MEDLINE]

Prevention of potentially inappropriate medication in internal medicine patients: A prospective study using the electronic application PIM-Check.

J Clin Pharm Ther. 2018 Dec;43(6):860-866

Authors: Blanc AL, Guignard B, Desnoyer A, Grosgurin O, Marti C, Samer C, Bonnabry P

Abstract
WHAT IS KNOWN: Potentially inappropriate medication (PIM) is a risk factor for drug-related problems (DRPs) and an important inpatient safety issue. PIM-Check is a screening tool designed to detect PIM in internal medicine patients.
OBJECTIVE: This study aimed to determine whether PIM-Check could help to identify and reduce DRPs.
METHOD: Prospective interventional study conducted on patients admitted to internal medicine wards in a university hospital between 1 September 2015 and 30 October 2015. Adult patients were included if they were hospitalized for more than 48 hours. Patients received either usual care (period 1 = control) or usual care plus medication screening by the wards' chief residents using PIM-Check (period 2 = intervention). An expert panel, composed of a clinical pharmacist, a clinical pharmacologist and two attending physicians in internal medicine, blinded to patient groups, identified DRPs.
RESULTS: A total of 297 patients were included (intervention: 109). The groups' demographic parameters were similar. The expert panel identified 909 DRPs (598: control; 311: intervention). The mean number of DRPs per patient was similar in the control (3.2; 95% CI: 2.9-3.5) and intervention groups (2.9; 95% CI: 2.4-3.3) (P = .12). PIM-Check displayed 33.4% of the 311 DRPs identified in the intervention group.
WHAT IS NEW AND CONCLUSION: In this study, PIM-Check had limited value, as the average number of DRPs per person was similar in both groups. Although one-third of DRPs counted in intervention group had been identified by PIM-Check, this did not lead to a reduction in DRPs. This lack of impact of PIM-Check on drug prescription may be explained by the number of alerts displayed by the application and hospital physicians' reluctance to modify the treatments for chronic conditions previously prescribed by general practitioners.

PMID: 29978537 [PubMed - indexed for MEDLINE]

Mortality from adverse drug reaction-related hospitalizations in south-west Ethiopia: A cross-sectional study.

J Clin Pharm Ther. 2018 Dec;43(6):790-798

Authors: Angamo MT, Chalmers L, Curtain CM, Yilma D, Bereznicki L

Abstract
WHAT IS KNOWN AND OBJECTIVE: Adverse drug reactions (ADRs) are an important cause of mortality during medical care. To our knowledge, no Ethiopian studies have reported on mortality due to ADRs in patients presenting to hospital from the community setting. The aim of this study was to determine the mortality rate attributable to ADRs in patients presenting to hospital, identify drugs implicated in the ADR-related deaths and identify factors contributing to ADR-related mortality at Jimma University Specialised Hospital (JUSH), south-west Ethiopia METHODS: This cross-sectional study included 1001 patients aged ≥18 years consecutively admitted to medical wards from May 2015 to August 2016. ADR-related mortality was determined through detailed review of medical records, laboratory tests and patient interviews followed by causality assessment by the Naranjo algorithm and expert consensus.
RESULTS: Of 1001 patients, 15, 1.5% (95% confidence interval [CI]: 0.80%-2.30%) died with an ADR. The primary suspected causes of death were drug-induced hepatotoxicity (7, 43.8%) followed by acute kidney injury (4, 25.0%). Isoniazid (6, 33.3%), pyrazinamide (3, 16.7%), efavirenz (2, 11.1%) and tenofovir (2, 11.1%) were commonly implicated drugs. The majority of ADRs (14, 93.8%) were preventable. Unadjusted bivariate comparisons suggested patients who died with ADRs were more likely to have pre-existing liver disease (40.0% vs 7.0%; 95% confidence interval [CI]: 8.1%-57.8%), a history of ADRs (40% vs 1.4%; 95% CI: 13.8%-63.4%), a lower mean (±SD) body mass index (BMI, 17.6 ± 2.1 vs 20.0 ± 2.9 kg/m2 ; 95% CI = 0.9-3.9), exposure to antitubercular (46.7% vs 18.9%; 95% CI: 2.3%-53.1%) and antiretroviral (40.0% vs 7.7%; 95% CI: 7.5%-57.2%) therapies, and a higher mean number of medications (7.1 ± 3.3 vs 3.8 ± 2.1; 95% CI: 2.2-4.4) and Charlson Comorbidity Index (3.9 ± 2.9 vs 1.6 ± 1.8; 95% CI: 1.4-3.2) than surviving patients without ADRs.
WHAT IS NEW AND CONCLUSION: Fatal ADRs were common in patients presenting to hospital. The drugs implicated were mostly antitubercular and antiretroviral therapies, reflecting the high burden of HIV and tuberculosis in the study population. ADR-related deaths were significantly associated with poor nutritional status. The majority of ADR-related deaths were preventable, highlighting the need to develop a multidisciplinary approach to closely monitor patients who are prescribed antitubercular and antiretroviral therapies, particularly in patients with hepatic disease, a history of ADRs, who are malnourished and who are exposed to multiple medications.

PMID: 29722039 [PubMed - indexed for MEDLINE]

[Immunotherapy is cancer treatment with a novel side-effect profile].

Ugeskr Laeger. 2017 Oct 02;179(40):

Authors: Kondrup M, Raunkilde L, Svane IM, Schmidt H, Bastholt L

Abstract
Within the last few years we have treated still more types of cancer with immune checkpoint inhibitors - anti-cytotoxic T-lymphocyte-associated-4 antibodies and anti-program-med cell death 1/anti-programmed cell death ligand 1 antibodies. A unique set of side effects called immune related adverse events irAEs may occur during treatment. Although severe irAEs remain rare they can become life-threatening. Early detection of irAEs and initiation of relevant treatment are therefore crucial to reduce the risk of long-term seque-lae. We provide a detailed overview of irAEs and recommendations for treatment according to established guidelines.

PMID: 28992844 [PubMed - indexed for MEDLINE]

A single center retrospective analysis of a protocol for high-dose methotrexate and leucovorin rescue administration.

J Oncol Pharm Pract. 2019 Jan;25(1):76-84

Authors: Cerminara Z, Duffy A, Nishioka J, Trovato J, Gilmore S

Abstract
BACKGROUND: Methotrexate has a wide dosing range. High-dose methotrexate is a dose of 1000 mg/m2 or greater. In the 1970s, the incidence of mortality associated with High-dose methotrexate ranged from 4.6 to 6%. In 2012, the University of Maryland Medical Center implemented a standardized high-dose methotrexate protocol. The purpose of this study was to evaluate whether the institution followed recommendations based on the Bleyer nomogram for the administration of high-dose methotrexate more closely after the implementation of the protocol.
METHODS: In this retrospective chart review, 37 patients received 119 cycles of high-dose methotrexate before the protocol implementation (1 January 2009 through 31 December 2010) and 45 patients received 106 cycles of high-dose methotrexate after protocol implementation (1 January 2013 through 31 December 2014). Patient characteristics, protocol data, and complications were analyzed.
RESULTS: Protocol implementation significantly reduced the deviation of methotrexate level timing at 24, 48, and 72 h: median 7.47 vs. 1.46 h, 7.23 vs. 1.35 h, and 7.00 vs. 1.52 h before and after implementation, respectively (p < 0.0001 for each). The protocol significantly reduced deviation of the first dose of leucovorin administration: median 5.2 vs. 0.675 h before and after implementation, respectively (p<0.0001). After protocol implementation, there was an increase in the use of leucovorin prescriptions written appropriately for patients discharged before methotrexate levels reached a value of ≤0.05 µmol/L.
CONCLUSIONS: Implementation of a protocol for the administration of high-dose methotrexate improved the adherence to consensus recommendations. Further analysis is needed to assess clinical pharmacist involvement and the cost savings implications within this protocol.

PMID: 28942720 [PubMed - indexed for MEDLINE]

Implementation and evaluation of medicine and therapeutic information service by clinical pharmacists in oncology care setting.

J Oncol Pharm Pract. 2019 Jan;25(1):60-67

Authors: Patel H, Gurumurthy P

Abstract
BACKGROUND: This study was conducted to explore the role of clinical pharmacists in providing medicine and therapeutic information service in oncology care setting.
METHODS: It was a prospective study conducted for a period of three years after implementation of medicine and therapeutic information service as an integral part of oncology pharmacy services. The medicine and therapeutic information queries were received during ward rounds, at ambulatory care and via telephone by clinical pharmacists. All the medicine and therapeutic information requests were reviewed and answered to the concerned requester(s). Answered medicine and therapeutic information requests were electronically documented in the hospital drug information database and analyzed further.
RESULTS: A total of 484 medicine and therapeutic information requests were received by clinical pharmacists during period of August 2013 to June 2016. Majority of medicine and therapeutic information queries were requested by radiation oncologists (27.2%) followed by medical oncologists (26.4%), general physicians (14.04%), resident medical officers (11.7%), ambulatory care nurses (8.6%), in-patient nurses (5.1%) and patients and care takers (6.6%). Majority of the medicine and therapeutic information queries were asked for the purpose of improving patient care (48.3%) followed by to update knowledge (30.9%) and training sessions to nurses (6.6%). The most common categories of medicine and therapeutic information were adverse drug reactions and its management (21.4%) followed by dosage adjustments of chemotherapy and biologicals (15.5%), supportive care related (14.6%), contraindications (14%), drug-drug interactions (11.9%), management of co-morbidities (7.8%), chemotherapy selection in special populations (4.5%).
CONCLUSION: The provision of medicine and therapeutic information was found to be useful in providing medicine information to improve patient care and to update knowledge of health care professionals at the study hospital.

PMID: 28841101 [PubMed - indexed for MEDLINE]

[Vaccinovigilance: Reports of adverse reactions in the year 2017].

Schweiz Arch Tierheilkd. 2018 Oct;160(10):607-611

Authors: Albrecht N, Ottiger H

Abstract
INTRODUCTION: The aim of the Vaccinovigilance system is the identification of adverse reactions and rare events after the use of immunological veterinary medicinal products. In the year 2017, 128 reports of adverse reactions following the application of various authorized vaccines were received and evaluated. The notifications were submitted primarily by marketing authorization holders (96) or veterinarians (27) and private persons (5). As in previous years, dogs were involved in most of the adverse effects (55%), followed by cattle (18%) and swine (10%). Unlike the previous years, significantly fewer reports were submitted on cats (8%). The correlation between reaction and vaccination was considered probable in 43% of the - cases.

PMID: 30301714 [PubMed - indexed for MEDLINE]

Commentary: Improving Care through Innovations in Infusion Systems.

Biomed Instrum Technol. 2018 Sep/Oct;52(5):366-371

Authors: Gray G

PMID: 30260667 [PubMed - indexed for MEDLINE]

Consumer Healthcare Products Association response to Major et al., "Trends in rates of acetaminophen-related adverse events in the United States", Pharmacoepidemiology & Drug Safety, May 2016, 25: 590-8.

Pharmacoepidemiol Drug Saf. 2017 03;26(3):353-354

Authors: Sirois JE

PMID: 28247547 [PubMed - indexed for MEDLINE]

Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of ELX-02, a Potential Treatment for Genetic Disorders Caused by Nonsense Mutations, in Healthy Volunteers.

Clin Pharmacol Drug Dev. 2019 Jan 16;:

Authors: Leubitz A, Frydman-Marom A, Sharpe N, van Duzer J, Campbell KCM, Vanhoutte F

Abstract
ELX-02 is an investigational synthetic eukaryotic ribosome-selective glycoside optimized as a translational read-through molecule that induces read through of nonsense mutations, resulting in normally localized full-length functional proteins. ELX-02 is being developed as a therapy for genetic diseases caused by nonsense mutations. Two phase 1a, randomized, double-blind placebo-controlled, single-ascending-dose studies were conducted in healthy human subjects to evaluate the safety and pharmacokinetics of ELX-02. Single subcutaneously injected doses of ELX-02 between 0.3 mg/kg and 7.5 mg/kg showed an acceptable safety profile without severe or serious drug-related adverse events, including a lack of renal and ototoxicity events. Injection of ELX-02 resulted in a rapid time to peak concentration and elimination phase, with complete elimination from the vascular compartment within 10 hours. ELX-02 area under the concentration-time curve to infinity showed dose-exposure linearity (24-fold increase for a 25-fold dose increase), and the maximum concentration showed dose proportionality (17-fold increase for a 25-fold increase). The mean apparent volume of distribution was dose dependent, suggesting an increased distribution and tissue uptake of ELX-02 at higher doses. The primary route of excretion was in the urine, with the majority of the compound excreted unchanged. These results support the evaluation of the safety, pharmacokinetics, and efficacy of repeat dosing in future studies.

PMID: 30650260 [PubMed - as supplied by publisher]

Drug-induced diabetes type 2: In silico study involving class B GPCRs.

PLoS One. 2019;14(1):e0208892

Authors: Latek D, Rutkowska E, Niewieczerzal S, Cielecka-Piontek J

Abstract
A disturbance of glucose homeostasis leading to type 2 diabetes mellitus (T2DM) is one of the severe side effects that may occur during a prolonged use of many drugs currently available on the market. In this manuscript we describe the most common cases of drug-induced T2DM, discuss available pharmacotherapies and propose new ones. Among various pharmacotherapies of T2DM, incretin therapies have recently focused attention due to the newly determined crystal structure of incretin hormone receptor GLP1R. Incretin hormone receptors: GLP1R and GIPR together with the glucagon receptor GCGR regulate food intake and insulin and glucose secretion. Our study showed that incretin hormone receptors, named also gut hormone receptors as they are expressed in the gastrointestinal tract, could potentially act as unintended targets (off-targets) for orally administrated drugs. Such off-target interactions, depending on their effect on the receptor (stimulation or inhibition), could be beneficial, like in the case of incretin mimetics, or unwanted if they cause, e.g., decreased insulin secretion. In this in silico study we examined which well-known pharmaceuticals could potentially interact with gut hormone receptors in the off-target way. We observed that drugs with the strongest binding affinity for gut hormone receptors were also reported in the medical information resources as the least disturbing the glucose homeostasis among all drugs in their class. We suggested that those strongly binding molecules could potentially stimulate GIPR and GLP1R and/or inhibit GCGR which could lead to increased insulin secretion and decreased hepatic glucose production. Such positive effect on the glucose homeostasis could compensate for other, adverse effects of pharmacotherapy which lead to drug-induced T2DM. In addition, we also described several top hits as potential substitutes of peptidic incretin mimetics which were discovered in the drug repositioning screen using gut hormone receptors structures against the ZINC15 compounds subset.

PMID: 30650080 [PubMed - in process]

Enhanced passive surveillance of influenza vaccination in England, 2016-2017 - an observational study using an adverse events reporting card.

Hum Vaccin Immunother. 2019 Jan 16;:

Authors: de Lusignan S, Ferreira F, Damaso S, Byford R, Pathirannehelage S, Yeakey A, Yonova I, Schuind A, Dos Santos G

Abstract
Influenza is a major public health burden, mainly prevented by vaccination. Recommendations on influenza vaccine composition are updated annually and constant benefit-risk monitoring is therefore needed. We conducted near-real-time enhanced passive surveillance (EPS) for the influenza vaccine, Fluarix Tetra, according to European Medicines Agency guidance, in 10 volunteer general practices in England using Fluarix Tetra as their principal influenza vaccine brand, from 1-Sep to 30-Nov-2016. The EPS method used a combination of routinely collected data from electronic health records (EHR) and a customized adverse events reporting card (AERC) distributed to participants vaccinated with Fluarix Tetra. For participants vaccinated with a different influenza vaccine, data were derived exclusively from the EHR. We reported weekly and cumulative incidence of pre-defined adverse events of interest (AEI) occurring within 7 days post-vaccination, adjusted for clustering effect. Of the 97,754 eligible participants, 19,334 (19.8%) received influenza vaccination, of whom 13,861 (71.7%) received Fluarix Tetra. A total of 1,049 participants receiving Fluarix Tetra reported AEIs; 703 (67%) used the AERC (adjusted cumulative incidence rate 4.96% [95% CI: 3.92-6.25]). Analysis by individual pre-specified AEI categories identified no safety signal for Fluarix Tetra. A total of 62 individuals reported an AEI with a known brand of non-GSK influenza vaccine and 54 with an unknown brand (adjusted cumulative incidence rate 2.59% [1.93-3.47] and 1.77% [1.42-2.20], respectively). In conclusion, the study identified no safety signal for Fluarix Tetra and showed that the AERC was a useful tool that complemented routine pharmacovigilance by allowing more comprehensive capture of AEIs.

PMID: 30648923 [PubMed - as supplied by publisher]

Ameliorative and protective effects of ginger and its main constituents against natural, chemical and radiation-induced toxicities: A comprehensive review.

Food Chem Toxicol. 2019 Jan;123:72-97

Authors: Alsherbiny MA, Abd-Elsalam WH, El Badawy SA, Taher E, Fares M, Torres A, Chang D, Li CG

Abstract
Fatal unintentional poisoning is widespread upon human exposure to toxic agents such as pesticides, heavy metals, environmental pollutants, bacterial and fungal toxins or even some medications and cosmetic products. In this regards, the application of the natural dietary agents as antidotes has engrossed a substantial attention. One of the ancient known traditional medicines and spices with an arsenal of metabolites of several reported health benefits is ginger. This extended literature review serves to demonstrate the protective effects and mechanisms of ginger and its phytochemicals against natural, chemical and radiation-induced toxicities. Collected data obtained from the in-vivo and in-vitro experimental studies in this overview detail the designation of the protective effects to ginger's antioxidant, anti-inflammatory, and anti-apoptotic properties. Ginger's armoury of phytochemicals exerted its protective function via different mechanisms and cell signalling pathways, including Nrf2/ARE, MAPK, NF-ƙB, Wnt/β-catenin, TGF-β1/Smad3, and ERK/CREB. The outcomes of this review could encourage further clinical trials of ginger applications in radiotherapy and chemotherapy regime for cancer treatments or its implementation to counteract the chemical toxicity induced by industrial pollutants, alcohol, smoking or administered drugs.

PMID: 30352300 [PubMed - indexed for MEDLINE]

Factors associated with potentially harmful drug-drug interactions in older Korean people: A population-based study.

Geriatr Gerontol Int. 2018 Sep;18(9):1378-1382

Authors: Yoon SJ, Kim JS, Jung JG, Ahn SK, Song YS, Bae NK, Seon JY, Kim JH

Abstract
AIM: The present study investigated the status of potentially harmful drug-drug interactions (PHDI) in older adults, to obtain insight into factors that influence the risk of PHDI.
METHODS: The present study included Korean people aged ≥65 years who were prescribed one or more drugs included in the list of PHDI under the Beers Criteria 2015 from January to December, 2016 (n = 1 257 317). PHDI were defined based on the Beers Criteria 2015. Among 10 PHDI, a prevalence of >5% was taken to be clinically significant, and the relationships between multiple variables and PHDI were examined.
RESULTS: The most frequent PHDI was corticosteroids and non-steroidal anti-inflammatory drugs (n = 259 499, 20.64%), followed by a combination of two or more anticholinergic drugs (n = 139 622, 11.1%), and three or more drugs acting on the central nervous system (n = 86 023, 6.84%). These three types of PHDI were more frequent in women (OR 1.066-1.141) and medical aid beneficiaries (OR 1.095-1.510). The risk of PHDI increased in proportion to the number of healthcare institutions used by the participants and their outpatient visits during the year (OR 1.043-1.079, 1.008-1.010, respectively). The risk of PHDI was low when patients took no more than five medications in a single prescription (OR 0.017-0.791).
CONCLUSIONS: The findings of the present study highlight the three most frequent PHDI in Korea according to the Beers Criteria 2015. Healthcare providers should take PHDI into account when treating female patients, medical aid beneficiaries, patients using multiple healthcare institutions, frequent outpatient visitors and patients prescribed more than six medications in a single prescription. Geriatr Gerontol Int 2018; 18: 1378-1382.

PMID: 30094910 [PubMed - indexed for MEDLINE]

Tolerability of trivalent inactivated influenza vaccine among pregnant women, 2015.

BMC Pregnancy Childbirth. 2018 04 23;18(1):110

Authors: Asavapiriyanont S, Kittikraisak W, Suntarattiwong P, Ditsungnoen D, Kaoiean S, Phadungkiatwatana P, Srisantiroj N, Chotpitayasunondh T, Dawood FS, Lindblade KA

Abstract
BACKGROUND: Thailand recommends influenza vaccination among pregnant women. We conducted a cohort study to determine if the prevalence of adverse events following immunization (AEFIs) with influenza vaccine among Thai pregnant women was similar to that often cited among healthy adults.
METHODS: Women who were ≥17 gestational weeks and ≥18 years of age were recruited. Demographic and health history data were collected using structured questionnaires. Women were provided with symptom diary, ruler to measure local reaction(s), and thermometer to measure body temperature. AEFIs were defined as any new symptom/abnormality occurring within four weeks after vaccination. The diaries were abstracted for frequency, duration, and level of discomfort/inconvenience of the AEFIs. Serious adverse events (SAEs) and the likelihood of AEFIs being associated with vaccination were determined using standard definitions.
RESULTS: Among 305 women enrolled between July-November 2015, median age was 29 years. Of these, 223 (73%) were in their third trimester, 271 (89%) had completed secondary school or higher, and 20 (7%) reported ≥1 pre-existing conditions. AEFIs were reported in 134 women (44%; 95% confidence interval [CI] 38-50%). Soreness at the injection site (74, 24%; CI 19-29%), general weakness (50, 16%; CI 12-21%), muscle ache (49, 16%; CI 12-21%), and headache (45, 15%; CI 1-19%) were most common. Of those with AEFIs, 120 (89%) reported symptom/abnormality occurred on day 0 or day 1 following vaccination. Ten women (7%) reported the AEFIs affected daily activities. The AEFIs generally spontaneously resolved within 24 h of onset. There were two vaccine-unrelated SAEs. Of 294 women with complete follow-up, 279 (95%) had term deliveries, 12 (4%) had preterm deliveries, and 3 (1%) had miscarriage or stillbirth.
CONCLUSION: In our cohort, AEFIs with influenza vaccine occurred with similar frequency to those reported among healthy adults in other studies, and were generally mild and self-limited. No influenza vaccine-associated SAEs were identified.

PMID: 29685106 [PubMed - indexed for MEDLINE]

Efficacy and safety of taxane-based systemic chemotherapy of advanced gastric cancer: A systematic review and meta-analysis.

Sci Rep. 2017 07 13;7(1):5319

Authors: Shi J, Gao P, Song Y, Chen X, Li Y, Zhang C, Wang H, Wang Z

Abstract
Taxanes are chemotherapeutic agents commonly used to treat several cancers. However, the effects of taxanes on advanced gastric cancer (AGC) are still not clear, especially when used as a first-line treatment. This systematic review and meta-analysis aims to investigate the efficacy and safety of taxanes as a first-line treatment of AGC. The quality of our included studies was assessed using the Cochrane risk of bias tool for RCTs and NOS scale for nRCTs, and the data of the included studies was of satisfactory quality to analyze. The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity. Taxanes significantly improved OS (HR = 0.84, 95% CI 0.76-0.92, P = 0.0004) and had a slight effect on ORR (RR = 1.23, 95% CI 1.00-1.51, P = 0.05). However, taxanes may also increase the risks of neutropenia and leucopenia, similar to effects observed in other conventional chemotherapeutic treatments such as oxaliplatin and epirubicin. Therefore, patient characteristics including concomitant diseases, physical condition, and prior therapies should be considered before selecting taxane-based treatments for AGC.

PMID: 28706257 [PubMed - indexed for MEDLINE]

Switching to anastrozole plus goserelin vs continued tamoxifen for adjuvant therapy of premenopausal early-stage breast cancer: preliminary results from a randomized trial.

Cancer Manag Res. 2019;11:299-307

Authors: Li JW, Liu GY, Ji YJ, Yan X, Pang D, Jiang ZF, Chen DD, Zhang B, Xu BH, Shao ZM

Abstract
Purpose: To assess the efficacy, safety, and quality-of-life impact of switching adjuvant treatment in hormone receptor-positive primary breast cancer patients who are still premenopausal after 2-3 years of tamoxifen therapy to anastrozole plus goserelin as compared with continuing tamoxifen over a total period of 5 years.
Patients and methods: Hormone receptor-positive, premenopausal, lymph node-positive, or tumor size ≥4 cm breast cancer patients who had received tamoxifen for 2-3 years were randomly assigned to continue tamoxifen treatment (TAM group) or switch to adjuvant anastrozole plus goserelin (ADD group) and continue treatment for another 2-3 years (total treatment duration 5 years). Endpoints evaluated were adverse events (AEs), changes in bone mineral density, quality of life, and disease-free survival-related events.
Results: A total of 62 patients (33 in the ADD group and 29 in the TAM group) were evaluated. Grade 3-4 drug-related AEs occurred in five patients (15.2%) in the ADD group vs none in the TAM group. In the ADD group, arthralgias were the most common AEs (5/33 patients; 15.2%), and three patients in this group were discontinued because of AEs. Treatment was temporarily suspended due to AEs in three patients (9.1%) in the ADD group and one patient (3.4%) in the TAM group. Compared with continuing TAM therapy, switching to anastrozole plus goserelin did not result in any worsening of bone mineral density or quality of life. During a median follow-up of 34 months, five patients (15.2%) in the ADD group had disease-free survival events vs four patients (13.8%) in the TAM group.
Conclusion: For early-stage breast cancer patients who remain premenopausal following 2-3 years of adjuvant tamoxifen therapy, switching to anastrozole plus goserelin therapy was safe with tolerable adverse effects. However, it did not show superior efficacy compared to remaining on tamoxifen treatment.
Trial Registration: ClinicalTrials.gov (identifier NCT01352091).

PMID: 30643455 [PubMed]

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study.

Lancet Haematol. 2019 Jan 11;:

Authors: Younes A, Brody J, Carpio C, Lopez-Guillermo A, Ben-Yehuda D, Ferhanoglu B, Nagler A, Ozcan M, Avivi I, Bosch F, Caballero Barrigón MD, Hellmann A, Kuss B, Ma DDF, Demirkan F, Yağci M, Horowitz NA, Marlton P, Cordoba R, Wrobel T, Buglio D, Streit M, Hodkinson BP, Schaffer M, Alvarez J, Ceulemans R, Balasubramanian S, de Jong J, Wang SS, Fourneau N, Jurczak W

Abstract
BACKGROUND: Preclinical studies have shown synergistic antitumour effects between ibrutinib and immune-checkpoint blockade. The aim of this study was to assess the safety and activity of ibrutinib in combination with nivolumab in patients with relapsed or refractory B-cell malignant diseases.
METHODS: We did a two-part, open-label, phase 1/2a study at 21 hospitals in Australia, Israel, Poland, Spain, Turkey, and the USA. The primary objective of part A (dose escalation) was to assess the safety of daily oral ibrutinib (420 mg or 560 mg) in combination with intravenous nivolumab (3 mg/kg every 2 weeks) to ascertain a recommended phase 2 dose in patients with relapsed or refractory high-risk chronic lymphocytic leukaemia or small lymphocytic lymphoma (del17p or del11q), follicular lymphoma, or diffuse large B-cell lymphoma. Dose optimisation was investigated using a modified toxicity probability interval design. The primary objective of the part B expansion phase was to establish the preliminary activity (the proportion of patients who achieved an overall response) of the combination of ibrutinib and nivolumab in four cohorts: relapsed or refractory high-risk chronic lymphocytic leukaemia or small lymphocytic lymphoma (del17p or del11q), follicular lymphoma, diffuse large B-cell lymphoma, and Richter's transformation. All participants who received at least one dose of treatment were included in the primary analysis and analyses were done by disease cohort. This trial is registered with ClinicalTrials.gov, number NCT02329847. The trial is ongoing.
FINDINGS: Between March 12, 2015, and April 11, 2017, 144 patients were enrolled in the study. Three patients died before receiving study treatment; thus, 141 patients were included in the analysis, 14 in part A and 127 in part B. One dose-limiting toxicity (grade 3 hyperbilirubinaemia) was reported at the 420 mg dose in the diffuse large B-cell lymphoma cohort, which resolved after 5 days. The combination of ibrutinib and nivolumab led to overall responses in 22 (61%) of 36 patients with high-risk chronic lymphocytic leukaemia or small lymphocytic lymphoma, 13 (33%) of 40 patients with follicular lymphoma, 16 (36%) of 45 patients with diffuse large B-cell lymphoma, and 13 (65%) of 20 patients with Richter's transformation. The most common all-grade adverse events were diarrhoea (47 [33%] of 141 patients), neutropenia (44 [31%]), and fatigue (37 [26%]). 11 (8%) of 141 patients had adverse events leading to death; none were reported as drug-related. The most common grade 3-4 adverse events were neutropenia (40 [28%] of 141 patients) and anaemia (32 [23%]). The incidence of grade 3-4 neutropenia ranged from eight (18%) of 45 patients with diffuse large B-cell lymphoma to 19 (53%) of 36 patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma; incidence of grade 3-4 anaemia ranged from five (13%) of 40 patients with follicular lymphoma to seven (35%) of 20 patients with Richter's transformation. The most common serious adverse events included anaemia (six [4%] of 141 patients) and pneumonia (five [4%]). The most common grade 3-4 immune-related adverse events were rash (11 [8%] of 141 patients) and increased alanine aminotransferase (three [2%]).
INTERPRETATION: The combination of ibrutinib and nivolumab had an acceptable safety profile and preliminary activity was similar to that reported with single-agent ibrutinib in chronic lymphocytic leukaemia or small lymphocytic lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma. The clinical response in patients with Richter's transformation was promising and supports further clinical assessment.
FUNDING: Janssen R&D.

PMID: 30642819 [PubMed - as supplied by publisher]