[Systematic review on safety of Salvianolate injection].

Zhongguo Zhong Yao Za Zhi. 2016 Oct;41(19):3686-3695

Authors: Chen ZW, Xie YM, Liao X, Wang GQ

Abstract
To systematically evaluate the safety of salvianolate injection in clinical medication. A systematic literature search was performed in the databases of Cochrane Library, Medline, Embase, the Web of Science, Clinical Trials, CNKI, VIP, WanFang Data and CBM. Literature screening was done according to inclusion and exclusion criteria, and quality was assessed according to internationally recognized quality evaluation criteria. Then the data were reviewed for analysis. 148 papers were included, consisting of 122 randomized controlled trials(RCTs), 10 non-randomized controlled trials(NRCTs), 4 case series studies, and 12 case reports. In the analysis of 135 studies, totally 7 300 patients used salvianolate injection. There were a total of 419 adverse drug reactions(ADRs), and 12 cases of serious adverse drug reactions. In the patients with Salvianolate injection, there were 176 cases of adverse drug reactions(ADRs) and 1 case of adverse cardiac event. The ADRs included 17 cases of rash, 9 cases of gastrointestinal reaction, 38 cases of headache, dizziness, heaviness in head, 1 case each of drug fever, hypotension, bleeding gums, chills, lip numbness, body jitter, slightly elevated ALT, 3 cases of palpitation, 4 cases of breath shortness, and 25 cases of other unkonwn ADRs. In the present study, a large number of rare, serious adverse events were not seen in clinical application of Salvianolate injection, but future long-term monitoring is needed to obtain evidence for the safety of the drug. In addition, the clinical application of Salvianolate injection is seriously beyond the instruction, so relevant departments shall urgently develop the medication specifications for salvianolate injection to provide better guidance for its clinical medication.

PMID: 28925169 [PubMed - indexed for MEDLINE]

[Systematic review of medication safety of Xiyanping injection in conformity with indications of package inserts].

Zhongguo Zhong Yao Za Zhi. 2016 Sep;41(18):3463-3472

Authors: Chen YY, Xie YM, Liao X, Chen HY

Abstract
To systematically review the medication safety of Xiyanping injection in conformity with indications of package inserts. Eight databases at home and abroad were searched for studies on the safety of Xiyanping injection. Literature screening, quality assessment, data extraction and analysis were performed according to internationally recognized inclusion and exclusion criteria. There were 118 clinical studies included, and 94 studies were finally studied, including 70 randomized controlled trials and eight non-randomized controlled trials, involving 16 case reports, and 4 716 patients treated with Xiyanping injection, with 148 adverse drug reactions(ADR) and no adverse event(AE). Among them, 15 cases reported serious adverse drug reactions, including 1 vegetative state, 4 allergic shock and other general cardiovascular damages. Diarrhea was the most commonly reported ADR among the 133 general adverse reactions, accounting for 30.12%, which was followed by rash. Most of the studies adopted the dosage set forth in package inserts. Some current evidences showed that irrational combined administration and use of Xiyanping may cause some ADRs. Because the most of studies didn't report the medication process and patient conditions, we can't infer the relations between the ADR and the age or solvent. Clinicians shall judge the causality according to relevant provisions and standards, and report ADRs, so as to provide more evidences for evaluating the safety of the drug.

PMID: 28925133 [PubMed - indexed for MEDLINE]

Elderly users of fall-risk-increasing drug perceptions of fall risk and the relation to their drug use - a qualitative study.

Scand J Prim Health Care. 2017 Sep;35(3):247-255

Authors: Bell HT, Steinsbekk A, Granas AG

Abstract
OBJECTIVE: The aim of the study was to explore how home-dwelling elderly who use fall-risk-increasing drugs (FRIDs) perceive their fall risk and how they relate this to their drug use.
DESIGN, SETTING AND SUBJECTS: A qualitative study with 14 home-dwelling elderly FRID users between 65 and 97 years in Central Norway participating in semi-structured individual interviews. The data were analyzed thematically by using systematic text condensation.
RESULTS: The main finding was that the informants did not necessarily perceive the use of FRIDs to be a prominent risk factor for falls. Some informants said they did not reflect upon drug use whatsoever and said they fully trusted their physician's choices. When either experiencing dizziness, fall episodes or by reading the patient information leaflet the informants said to either adjust their drug use or to contact their physician. Some felt rejected due to not getting their point across or their wish to alter the drug was not granted by the physician.
CONCLUSIONS: Elderly FRID users did not necessarily relate their drug use to fall risk or struggled to present their perceived drug-related problems. Physicians need to regularly inform, monitor and assess the drug treatment when treating elderly with FRIDs.

PMID: 28793815 [PubMed - indexed for MEDLINE]

Acute memory deficits in chemotherapy-treated adults.

Memory. 2017 Nov;25(10):1327-1339

Authors: Lindner OC, Mayes A, McCabe MG, Talmi D

Abstract
Data from research on amnesia and epilepsy are equivocal with regards to the dissociation, shown in animal models, between rapid and slow long-term memory consolidation. Cancer treatments have lasting disruptive effects on memory and on brain structures associated with memory, but their acute effects on synaptic consolidation are unknown. We investigated the hypothesis that cancer treatment selectively impairs slow synaptic consolidation. Cancer patients and their matched controls were administered a novel list-learning task modelled on the Rey Auditory Verbal Learning Test. Learning, forgetting, and retrieval were tested before, and one day after patients' first chemotherapy treatment. Due to difficulties recruiting cancer patients at that sensitive time, we were only able to study 10 patients and their matched controls. Patients exhibited treatment-dependent accelerated forgetting over 24 hours compared to their own pre-treatment performance and to the performance of control participants, in agreement with our hypothesis. The number of intrusions increased after treatment, suggesting retrieval deficits. Future research with larger samples should adapt our methods to distinguish between consolidation and retrieval causes for treatment-dependent accelerated forgetting. The presence of significant accelerated forgetting in our small sample is indicative of a potentially large acute effect of chemotherapy treatment on forgetting, with potentially clinically relevant implications.

PMID: 28285570 [PubMed - indexed for MEDLINE]

WITH AGE COMES A guide to helping older adults avoid harmful drug effects.

Diabetes Forecast. 2016 Nov;69(6):60-63

Authors: Holten J

PMID: 29693917 [PubMed - indexed for MEDLINE]

Models of Drug Induced Liver Injury (DILI) - Current Issues and Future Perspectives.

Curr Drug Metab. 2018 May 22;:

Authors: Kuna L, Bozic I, Kizivat T, Bojanic K, Mrso M, Kralj E, Smolic R, Wu GY, Smolic M

Abstract
Drug-induced liver injury (DILI) is an important cause of acute liver failure cases in the United States, and remains a common cause of withdrawal of drugs in both preclinical and clinical phases. In this article, we review the existing knowledge of appropriate models to study DILI in vitro and in vivo with special focus on hepatic cell models, variations of 3D co-cultures, animal models, databases and predictive modeling and translational biomarkers developed to understand the mechanisms and pathophysiology of DILI. Besides descriptions of current applications of existing modeling systems, associated advantages and limitations of each modeling system and future directions for research development are discussed as well.

PMID: 29788883 [PubMed - as supplied by publisher]

Gamma-aminobutyric acid agonists for antipsychotic-induced tardive dyskinesia.

Cochrane Database Syst Rev. 2018 04 17;4:CD000203

Authors: Alabed S, Latifeh Y, Mohammad HA, Bergman H

Abstract
BACKGROUND: Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. Gamma-aminobutyric acid (GABA) agonist drugs, which have intense sedative properties and may exacerbate psychotic symptoms, have been used to treat TD.
OBJECTIVES: 1. Primary objectiveThe primary objective was to determine whether using non-benzodiazepine GABA agonist drugs for at least six weeks was clinically effective for the treatment of antipsychotic-induced TD in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses.2. Secondary objectivesThe secondary objectives were as follows.To examine whether any improvement occurred with short periods of intervention (less than six weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.To examine whether there was a differential effect between the various compounds.To test the hypothesis that GABA agonist drugs are most effective for a younger age group (less than 40 years old).
SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (last searched April 2017), inspected references of all identified studies for further trials, and, when necessary, contacted authors of trials for additional information.
SELECTION CRITERIA: We included randomised controlled trials of non-benzodiazepine GABA agonist drugs in people with antipsychotic-induced TD and schizophrenia or other chronic mental illness.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected and critically appraised studies, extracted and analysed data on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous data we calculated mean differences (MD). We assumed that people who left early had no improvement. We contacted investigators to obtain missing information. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS: We included 11 studies that randomised 343 people. Overall, the risk of bias in the included studies was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, participants and outcome assessors were not clearly blinded. For some studies we were unsure if data were complete, and data were often poorly or selectively reported.Data from six trials showed that there may be a clinically important improvement in TD symptoms after GABA agonist treatment compared with placebo at six to eight weeks follow-up (6 RCTs, n = 258, RR 0.83, CI 0.74 to 0.92; low-quality evidence). Data from five studies showed no difference between GABA agonist treatment and placebo for deterioration of TD symptoms (5 RCTs, n = 136, RR 1.90, CI 0.70 to 5.16; very low-quality evidence). Studies reporting adverse events found a significant effect favouring placebo compared with baclofen, sodium valproate or progabide for dizziness/confusion (3 RCTs, n = 62 RR 4.54, CI 1.14 to 18.11; very low-quality evidence) and sedation/drowsiness (4 RCTS, n = 144, RR 2.29, CI 1.08 to 4.86; very low-quality evidence). Studies reporting on akathisia (RR 1.05, CI 0.32 to 3.49, 2 RCTs, 80 participants), ataxia (RR 3.25, CI 0.36 to 29.73, 2 RCTs, 95 participants), nausea/vomiting (RR 2.61, CI 0.79 to 8.67, 2 RCTs, 64 participants), loss of muscle tone (RR 3.00, CI 0.15 to 59.89, 1 RCT, 10 participants), seizures (RR 3.00, CI 0.24 to 37.67, 1 RCT, 2 participants), hypotension (RR 3.04, CI 0.33 to 28.31, 2 RCTs, 119 participants) found no significant difference between GABA drug and placebo (very low-quality evidence). Evidence on mental state also showed no effect between treatment groups (6 RCTS, n = 121, RR 2.65, CI 0.71 to 9.86; very low-quality evidence) as did data for leaving the study early (around 10% in both groups, 6 RCTS, n = 218, RR 1.47, CI 0.69 to 3.15; very low-quality evidence). No study reported on social confidence, social inclusion, social networks, or personalised quality of life, a group of outcomes selected as being of particular importance to patients.
AUTHORS' CONCLUSIONS: We are uncertain about the evidence of the effects of baclofen, progabide, sodium valproate or tetrahydroisoxazolopyridinol (THIP) for people with antipsychotic-induced TD. Evidence is inconclusive and unconvincing. The quality of data available for main outcomes ranges from very low to low. Any possible benefits are likely to be outweighed by the adverse effects associated with their use.

PMID: 29663328 [PubMed - indexed for MEDLINE]

Methionine and vitamin B-complex ameliorate antitubercular drugs-induced toxicity in exposed patients.

Pharmacol Res Perspect. 2017 Oct;5(5):

Authors: Amagon KI, Awodele O, Akindele AJ

Abstract
Tuberculosis therapy utilizes drugs that while effective cause treatment-related toxicity. Modulation of antitubercular drugs-induced toxicity by methionine and vitamin B-complex in patients was evaluated. 285 treatment-naïve tuberculosis patients at the Chest Clinics of Infectious Diseases Hospital, Yaba and General Hospital, Lagos in Lagos, Nigeria was prospectively recruited and allotted into test (antitubercular medicines, methionine and vitamin B-complex) and control groups (antitubercular medicines). Data on adverse drug reactions and blood samples were collected at initiation, 2 months and 6 months, and then analyzed. Red blood cells and packed cell volume were significantly higher (P < 0.05) in the test group compared to control at 6 months of therapy. At the end of 2 months, results showed a significant decrease (P < 0.001) in aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, urea, creatinine and total bilirubin in the test group compared to control. Reduced glutathione and superoxide dismutase were significantly increased (P < 0.001) and malondialdehyde significantly decreased (P < 0.001) in the test versus control groups at the end of 2 and 6 months. Adverse drug reactions were significantly lower (P < 0.001) in the test group (32.4%) compared to control group (56.2%), with 1 death. Hepatotoxicity was significantly higher (P = 0.026) in control (6.9%), compared to test group (0%). Alcohol and cigarette smoking were significantly (P = 0.019 and P = 0.027) associated with the occurrence of adverse drug reactions. Methionine and vitamin B-complex modulated hepatic, renal, hematological, antioxidant indices and adverse effects in patients administered antitubercular medicines. Such interventions can enhance compliance and better treatment outcomes in tuberculosis patients.

PMID: 28971606 [PubMed - indexed for MEDLINE]

Severe Delayed Drug Reactions: Role of Genetics and Viral Infections.

Immunol Allergy Clin North Am. 2017 Nov;37(4):785-815

Authors: Pavlos R, White KD, Wanjalla C, Mallal SA, Phillips EJ

Abstract
Adverse drug reactions (ADRs) are a significant source of patient morbidity and mortality and represent a major burden to health care systems and drug development. Up to 50% of such reactions are preventable. Although many ADRs can be predicted based on the on-target pharmacologic activity, ADRs arising from drug interactions with off-target receptors are recognized. Off-target ADRs include the immune-mediated ADRs (IM-ADRs) and pharmacologic drug effects. In this review, we discuss what is known about the immunogenetics and pathogenesis of IM-ADRs and the hypothesized role of heterologous immunity in the development of IM-ADRs.

PMID: 28965641 [PubMed - indexed for MEDLINE]

[Research progress on potential liver toxic components in traditional Chinese medicine].

Zhongguo Zhong Yao Za Zhi. 2016 Sep;41(17):3209-3217

Authors: Wu H, Zhong RL, Xia Z, Huang HC, Zhong QX, Feng L, Song J, Jia XB

Abstract
In recent years, the proportion of traditional Chinese medicine in scientific research and its clinical use increased gradually. The research result also becomes more and more valuable, but in the process of using traditional Chinese medicine, it also needs to pay more attention. With the gradual deepening of the toxicity of traditional Chinese medicine, some traditional Chinese medicines have also been found to have the potential toxicity, with the exception of some traditional toxicity Chinese medicine. Traditional Chinese medicine in the growth, processing, processing, transportation and other aspects of pollution or deterioration will also cause the side effects to the body. Clinical practice should be based on the theory of traditional Chinese medicine to guide rational drug use and follow the symptomatic medication, the principle of proper compatibility. The constitution of the patients are different, except for a few varieties of traditional Chinese medicines are natural herbs with hepatotoxicity, liver toxicity of most of the traditional Chinese medicine has idiosyncratic features. The liver plays an important role in drug metabolism. It is easy to be damaged by drugs. Therefore, the study of traditional Chinese medicine potential liver toxicity and its toxic components has become one of the basic areas of traditional Chinese medicine research. Based on the review of the literatures, this paper summarizes the clinical classification of liver toxicity, the pathogenesis of target cell injury, and systematically summarizes the mechanism of liver toxicity and toxic mechanism of traditional Chinese medicine. This paper provided ideas for the study of potential liver toxicity of traditional Chinese medicine and protection for clinical safety of traditional Chinese medicine.

PMID: 28920372 [PubMed - indexed for MEDLINE]

Effects of antipsychotic drugs on neurites relevant to schizophrenia treatment.

Med Res Rev. 2018 May 22;:

Authors: Huang XF, Song X

Abstract
Although antipsychotic drugs are mainly used for treating schizophrenia, they are widely used for treating various psychiatric diseases in adults, the elderly, adolescents and even children. Today, about 1.2% of the worldwide population suffers from psychosis and related disorders, which translates to about 7.5 million subjects potentially targeted by antipsychotic drugs. Neurites project from the cell body of neurons and connect neurons to each other to form neural networks. Deficits in neurite outgrowth and integrity are implicated in psychiatric diseases including schizophrenia. Neurite deficits contribute to altered brain development, neural networking and connectivity as well as symptoms including psychosis and altered cognitive function. This review revealed that (1) antipsychotic drugs could have profound effects on neurites, synaptic spines and synapse, by which they may influence and regulate neural networking and plasticity; (2) antipsychotic drugs target not only neurotransmitter receptors but also intracellular signaling molecules regulating the signaling pathways responsible for neurite outgrowth and maintenance; (3) high doses and chronic administration of antipsychotic drugs may cause some loss of neurites, synaptic spines, or synapsis in the cortical structures. In addition, confounding effects causing neurite deficits may include elevated inflammatory cytokines and antipsychotic drug-induced metabolic side effects in patients on chronic antipsychotic therapy. Unraveling how antipsychotic drugs affect neurites and neural connectivity is essential for improving therapeutic outcomes and preventing aversive effects for patients on antipsychotic drug treatment.

PMID: 29785841 [PubMed - as supplied by publisher]

[Relationship between hepatic drug-metabolizing enzymes CYP450 and traditional Chinese medicine-induced hepatotoxicity].

Zhongguo Zhong Yao Za Zhi. 2016 Aug;41(15):2774-2780

Authors: Hou J, Sun E, Song J, Yang L, Zhang ZH, Ning Q, Jia XB

Abstract
In recent years, with the emergence of new methods and technologies in traditional Chinese medicines metabolism, the relationship between medicine metabolism and cytochrome P450 has gradually been revealed. The research on P450 drug metabolizing enzymes can be used to predict the side effects of traditional Chinese medicines and explore the relationship between compatibility of medicines and toxicity reducing and efficacy enhancing. This paper aims to summarize the progress of CYP450 research, the mechanism of hepatic drug-metabolizing enzymes in the process of drug-metabolism and the relationship between CYP450 and medicine hepatotoxicity. Furthermore, we set out the regulation effects of typical traditional Chinese medicines on CYP450 to provide a reliable basis for the rational use of Chinese medicines.

PMID: 28914015 [PubMed - indexed for MEDLINE]

Deaths from acute drug reactions in Galician (Spain) Prisons (2001-2010).

Rev Esp Sanid Penit. 2017 Dec;19(2):49-56

Authors: Miguel-Arias D, Pereiro-Gómez C, Bermejo-Barrera AM, Vázquez-Ventoso C, Rodríguez-Barca T

Abstract
INTRODUCTION AND OBJECTIVES: drug use is associated with multiple complications with an increase in morbidity, with death by acute drugs reactions (ADR) being the most serious. A large percentage of the prison population has problems associated with drug additions, and substance abuse is also a common internal problem of penal institutions, despite their control measures. The goal of this study is to analyse the prevalence of ADR in penitentiaries, deceased sociodemographic characteristics as well as the circumstances in which they are produced.
MATERIAL AND METHODS: All deaths by ADR between 2001-2010 in Galicia are studied, in particular, those deaths that took place inside prisons.
RESULTS: In the whole sample (n=510) male (90.6%), single (46.1%) with an average age of 35.8 and with a prevalent factor of long experience in drug abuse. Thirty seven of them died in Penal/Correctional Institutions, representing 7.3% of the total sample. The characteristics of this population subtype were similar to the total sample (average age: 34.7 years; 89.2% were males) but we found significant differences regarding the substances detected.
DISCUSSION: ADR is the most frequent cause of death among drug addict convicts in prisons. The pattern of the detected substances in the toxicological analysis as well as the socio-demographic characteristics can help to establish a higher risk profile and preventive measures.

PMID: 28748984 [PubMed - indexed for MEDLINE]

[Direct mechanism of action in toxic myopathies].

Ann Pharm Fr. 2017 Sep;75(5):323-343

Authors: Khelfi A, Azzouz M, Abtroun R, Reggabi M, Alamir B

Abstract
Toxic myopathies are a large group of disorders generated by surrounding agents and characterized by structural and/or functional disturbances of muscles. The most recurrent are those induced by commonly used medications. Illicit drugs, environmental toxins from animals, vegetables, or produced by micro-organisms as well as chemical products commonly used are significant causes of such disorders. The muscle toxicity results from multiple mechanisms at different biological levels. Many agents can induce myotoxicity through a direct mechanism in which statins, glucocorticoids and ethyl alcohol are the most representative. Diverse mechanisms were highlighted as interaction with macromolecules and induction of metabolic and cellular dysfunctions. Muscle damage can be related to amphiphilic properties of some drugs (chloroquine, hydroxychloroquine, etc.) leading to specific lysosomal disruptions and autophagic dysfunctions. Some agents affect the whole muscle fiber by inducing oxidative stress (ethyl alcohol and some statins) or triggering cell death pathways (apoptosis or necrosis) resulting in extensive alterations. More studies on these mechanisms are needed. They would allow a better knowledge of the intracellular mediators involved in these pathologies in order to develop targeted therapies of high efficiency.

PMID: 28526123 [PubMed - indexed for MEDLINE]

An Evaluation of Indian Consumers' Reporting of Suspected Adverse Drug Reactions with a Designated Reporting Form.

Curr Drug Saf. 2017;12(1):51-56

Authors: Rehan HS, Sah R, Gupta A, Nagar P

Abstract
BACKGROUND: The Pharmacovigilance Program of India recently initiated a process for direct patient reporting of Adverse Drug Reactions (ADRs) with a designated form.
PATIENTS AND METHODS: A survey of 200 patients reporting ADRs filling the form. Forms were analysed for patient data, the suspected medication(s), ADRs and possible causality.
RESULTS: 54.3% of respondents provided their contact information; the implicated medicine was mentioned in 60% and the description of ADRs in 80% although 46.2% were not interpretable. The severity of ADRs was mentioned in 73.5%. No responder filled the expiry date component of the implicated modification and a causality assessment from most forms was unclassifiable (57%) or unclassified (26%). Details of concomitant drugs were missing.
CONCLUSION: Missing information was a deterrent in analysing the consumer ADR reports for signal detection. It is recommended that the following fields are highlighted in the form: consumer's initials, address, date suspected reaction started, description of event, name, dose, and the reason for the use the medication as well as its expiry date. These should be mandatory in the existing form and new fields added for weight and height, batch number for vaccines and biological products, de challenge and rechallenge results to the suspected medicine and concomitantly used medicines. To improve the quality of information in the consumer reporting form an awareness campaign is also suggested.

PMID: 27188794 [PubMed - indexed for MEDLINE]

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 2018/05/22

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.

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 2018/05/22

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.

Cefepime vs. cefoperazone/sulbactam in combination with amikacin as empirical antibiotic therapy in febrile neutropenia.

Support Care Cancer. 2018 May 17;:

Authors: Ponraj M, Dubashi B, Harish BH, Kayal S, Cyriac SL, Pattnaik J, Ranjith K, Pillai US, Jadhav N, Matta KK, Singh J, Jaffa E, Prakash B

Abstract
PURPOSE: Beta lactams are standard empirical therapy for febrile neutropenia (FN). The aim of this study was to evaluate the efficacy and safety of cefepime monotherapy compared with cefoperazone/sulbactam plus amikacin (CS + A) for empirical treatment of high risk FN.
METHODS: One hundred seventy-five patients with 336 FN episodes were randomized to receive either cefepime (2 g q8h for adults and 50 mg/kg q8h for children) or CS (2 g q8h for adults and 50 mg/kg q8h for children) plus amikacin (15 mg/kg once a day). Positive response was defined as afebrile within 72 h of starting antibiotics, persistent afebrile status more than 48 h and no requirement of second-line antibiotics and antifungal agents.
RESULTS: Three hundred thirty-six episodes were assessable for efficacy (168 cefepime, 168 CS + A). The positive response to antibiotics was identical for cefepime (53%) and CS + A (53%). Positive response was similar in MDI (microbiologically documented infection), 50 vs. 35% (p = 0.248), CDI (clinically documented infection), 50 vs. 35% (p = 0.259), combination CDI + MDI, 25 vs. 15% (p = 0.400), FUO (fever of unknown origin), 68 vs. 72% (p = 0.577) respectively in the two groups. The successful discontinuation of antibiotics at 72 h in FUO was similar in both groups (60 vs. 59%, p = 0.544). Total drug-related adverse events were similar in both groups (8 vs. 6%) except renal dysfunction was high in CS + A (1 vs. 7 events). Mortality was the same between two groups (8 vs 7%).
CONCLUSIONS: Cefepime monotherapy and CS + A had similar efficacy as first-line therapy for FN. Discontinuation of empirical antibiotics is safe and feasible approach in selected group of FUO patients.

PMID: 29774477 [PubMed - as supplied by publisher]

Phase 2 study of everolimus for relapsed or refractory classical Hodgkin lymphoma.

Exp Hematol Oncol. 2018;7:12

Authors: Johnston PB, Pinter-Brown LC, Warsi G, White K, Ramchandren R

Abstract
Background: The current standard of care for classical Hodgkin lymphoma (HL) is multiagent chemotherapy with or without radiation. In patients who relapse or fail to respond, additional high-dose chemotherapy with autologous hematopoietic stem cell transplantation (AHSCT) can improve progression-free survival (PFS). Novel therapies are required for patients refractory to chemotherapy and AHSCT. The mammalian target of rapamycin inhibitor everolimus has shown preliminary activity in preclinical models of HL and promising efficacy in patients with relapsed or refractory HL.
Methods: This was an open-label, two-stage, phase 2 study that enrolled 57 patients aged ≥ 18 years with classic HL that had progressed after standard therapy. Patients received everolimus 10 mg daily until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision. The primary endpoint was overall response rate; secondary endpoints included PFS, overall survival, time to response, duration of response, and safety.
Results: Overall response rate was 45.6% (95% confidence interval [CI] 32.4-59.3%); five patients (8.8%) experienced a complete response and 21 patients had a partial response (36.8%). Median PFS was 8.0 months (95% CI 5.1-11.0 months). Seven patients (12%) were long-term responders (≥ 12 months). The most common study drug-related adverse events were thrombocytopenia (45.6%), fatigue (31.6%), anemia (26.3%), rash (24.6%), and stomatitis (22.8%).
Conclusions: Everolimus 10 mg/day demonstrated favorable results in patients with heavily pretreated, relapsed, or refractory classical HL. These findings support the further evaluation of everolimus in this indication.Trial registration ClinicalTrials.gov NCT01022996. Registered November 25, 2009.

PMID: 29774169 [PubMed]

Constipation and other common symptoms reported by women and men in methadone and buprenorphine maintenance treatment.

Drug Alcohol Depend. 2017 Dec 01;181:132-139

Authors: Haber PS, Elsayed M, Espinoza D, Lintzeris N, Veillard AS, Hallinan R

Abstract
BACKGROUND: Opioid substitution treatment (OST) is often continued long-term and, therefore, opioid-associated symptoms are of interest. Symptoms associated with methadone maintenance treatment (MMT) in men are well described, but there are fewer reports concerning symptoms associated with buprenorphine maintenance treatment (BMT) and very few reports among women.
METHOD: Recipients of BMT (n=113) and MMT (n=184), non-opioid users (n=105) and opioid users not receiving OST (n=87) completed the Patient Assessment of Constipation (PAC-SYM) and a general symptom checklist. Multivariate analysis included other potential moderators of opioid-associated symptoms.
FINDINGS: Opioid users reported a higher frequency and severity of symptoms than non-opioid users. Constipation, dry mouth, decreased appetite, sweating and fatigue were highly prevalent in the previous 30days (51-80%). Nausea, itchy skin, trouble urinating, menstrual problems, lightheadedness, blurred vision, heart racing were also common (30-50%). Non-OST opioid users had significantly higher frequency and severity than OST recipients of nausea, vomiting, diarrhoea, decreased appetite, sweating and itchy skin. Sweating was significantly more common in MMT than BMT. Constipation scores were higher in women, otherwise most sex differences were small. Higher PAC-SYM scores were associated with vomiting (OR=1.04) and sweating (OR=1.06). Cannabis use was associated with vomiting (OR=2.19). Constipation (OR=1.07), insomnia (OR=2.5) and depression (OR=2.82) were associated with fatigue.
CONCLUSION: Men and women receiving OST report similarly high rates of somatic symptoms, though less than opioid users not receiving OST. There were few differences between BMT and MMT. Buprenorphine might be preferred where sweating is problematic. Several modifiable factors were identified.

PMID: 29054032 [PubMed - indexed for MEDLINE]