Anti-glioma effects of Caffeic acid phenethyl ester and Dasatinib combination therapy in an in vivo rat glioma model.

Anticancer Agents Med Chem. 2018 May 15;:

Authors: Balkhi H, Haq E, Guler T, Sana S

Abstract
BACKGROUND: Caffeic acid phenethyl ester and Dasatinib in combination, when used in congruous proportions and durations, present an antitumor potential for glioma in vitro, suggesting a high therapeutic potential for glioma treatment.
OBJECTIVE: In the present study, we addressed the question whether CAPE and Dasatinib target multiple pathways involved in tumor growth, proliferation and development on an in vivo rat model of glioma.
METHODS: Expression analysis of proteins thought to be mediating proliferation, cell motility, angiogenesis, and invasion was carried out to delineate the antineoplastic action of CAPE and Dasatinib.
RESULTS: CAPE and Dasatinib modulates the expression of proteins having potential interactive crosstalk with major oncogenic pathways involved in glioma progression. Our results showed that combination treatment modulates the expression of p53 in group co-administered with CAPE and Dasatinib after glioma induction in comparison to group induced with glioma only. EGFR and PCNA expression were significantly altered in the co-treated group in comparison to the glioma-induced group. The effects of CAPE and Dasatinib treatment were further evaluated on AKT pathway by Western blot analysis, the co-treated group showed a significant reduction in expression of AKT. The histopathological analysis further backed the antiproliferative and anti invasive effects of CAPE and Dasatinib.
CONCLUSION: This study in totality suggests that the combinational therapy remarkably reduces the proliferation of glioma cells in vivo, suggesting that CAPE and Dasatinib therapy could be exploited for the management of gliomas without showing drug-related resistances and side effects, suggesting a high therapeutic potential of the therapy in glioma.

PMID: 29766825 [PubMed - as supplied by publisher]

Successful administration of BI 695501, an adalimumab biosimilar, using an autoinjector (AI): results from a Phase II open-label clinical study (VOLTAIRE®-RL).

Expert Opin Drug Deliv. 2018 May 15;:1-4

Authors: Cohen S, Klimiuk PA, Krahnke T, Assudani D

Abstract
BACKGROUND: This study examined the patient handling experience and self-injection success of patients with rheumatoid arthritis (RA) administering BI 695501 using an AI.
METHODS: This Phase II, 7-week, open-label, interventional study (NCT02636907) included adult patients with moderately to severely active RA not adequately controlled by DMARDs, with no experience of self-injecting with AI/pen. Patients self-injected BI 695501 via AI every 2 weeks in the AI Assessment Period (AAP). Training was given on first injection; AI handling events were recorded. Percentage of self-injection success was the primary end point. Patients could enter a 42-week pre-filled syringe (PFS) safety extension.
RESULTS: The AAP was completed by 73/77 patients. In total, 216/218 (99.1%) self-injections on Days 15, 29, and 43, were successful. Nine (11.7%) patients had drug-related adverse events (AEs). Two patients reported four serious AEs (SAEs), none drug-related. Overall (in the AAP and PFS extension), 28 (36.4%) patients had drug-related AEs; nine patients had SAEs, one was considered drug-related. Five (6.5%) patients reported injection-site reactions in the AAP; 13 (18.1%) in the PFS extension.
CONCLUSIONS: After training, almost all patients were successfully able to self-administer BI 695501 using an AI. BI 695501 via AI (and via PFS in the extension) was well tolerated.
CLINICAL TRIAL REGISTRATION: NCT02636907.

PMID: 29764238 [PubMed - as supplied by publisher]

The safety and efficacy of transarterial chemoembolization combined with sorafenib and sorafenib mono-therapy in patients with BCLC stage B/C hepatocellular carcinoma.

BMC Cancer. 2017 Sep 12;17(1):645

Authors: Wu FX, Chen J, Bai T, Zhu SL, Yang TB, Qi LN, Zou L, Li ZH, Ye JZ, Li LQ

Abstract
BACKGROUND: Sorafenib and transarterial chemoembolization (TACE) are recommended therapies for advanced hepatocellular carcinoma (HCC), but their combined efficacy remains unclear.
METHODS: Between August 2004 and November 2014, 104 patients with BCLC stage B/C HCC were enrolled at the Affiliated Tumor Hospital of Guangxi Medical University, China. Forty-eight patients were treated with sorafenib alone (sorafenib group) and 56 with TACE plus sorafenib (TACE + sorafenib group). Baseline demographic/clinical data were collected. The primary outcomes were median overall survival (OS) and progression-free survival (PFS). Secondary outcomes were overall response rate (ORR) and sorafenib-related adverse events (AEs). Baseline characteristics associated with disease prognosis were identified using multivariate Cox hazards regression.
RESULTS: The mean age of the 104 patients (94 males; 90.38%) was 49.02 ± 12.29 years. Of the baseline data, only albumin level (P = 0.028) and Child-Pugh class (P = 0.017) differed significantly between groups. Median OS did not differ significantly between the sorafenib and TACE + sorafenib groups (18.0 vs. 22.0 months, P = 0.223). Median PFS was significantly shorter in the sorafenib group than that in the TACE + sorafenib group (6.0 vs. 8.0 months, P = 0.004). Six months after treatments, the ORRs were similar between the sorafenib and TACE + sorafenib groups (12.50% vs. 18.75%, P = 0.425). The rates of grade III-IV adverse events in sorafenib and TACE + sorafenib groups were 29.2% vs. 23.2%, respectively. TACE plus sorafenib treatment (HR = 0.498, 95% CI = 0.278-0.892), no vascular invasion (HR = 0.354, 95% CI = 0.183-0.685) and Child-Pugh class A (HR = 0.308, 95% CI = 0.141-0.674) were significantly associated with better OS, while a larger tumor number was predictive of poorer OS (HR = 1.286, 95% CI = 1.031-1.604). TACE plus sorafenib treatment (HR = 0.461, 95% CI = 0.273-0.780) and no vascular invasion (HR = 0.557, 95% CI = 0.314-0.988) were significantly associated with better PFS.
CONCLUSIONS: Compared with sorafenib alone, combining TACE with sorafenib might prolong survival and delay disease progression in patients with advanced HCC.

PMID: 28899349 [PubMed - indexed for MEDLINE]

Discovering associations between adverse drug events using pattern structures and ontologies.

J Biomed Semantics. 2017 Aug 22;8(1):29

Authors: Personeni G, Bresso E, Devignes MD, Dumontier M, Smaïl-Tabbone M, Coulet A

Abstract
BACKGROUND: Patient data, such as electronic health records or adverse event reporting systems, constitute an essential resource for studying Adverse Drug Events (ADEs). We explore an original approach to identify frequently associated ADEs in subgroups of patients.
RESULTS: Because ADEs have complex manifestations, we use formal concept analysis and its pattern structures, a mathematical framework that allows generalization using domain knowledge formalized in medical ontologies. Results obtained with three different settings and two different datasets show that this approach is flexible and allows extraction of association rules at various levels of generalization.
CONCLUSIONS: The chosen approach permits an expressive representation of a patient ADEs. Extracted association rules point to distinct ADEs that occur in a same group of patients, and could serve as a basis for a recommandation system. The proposed representation is flexible and can be extended to make use of additional ontologies and various patient records.

PMID: 28830518 [PubMed - indexed for MEDLINE]

The prescribing cascade revisited.

Lancet. 2017 05 06;389(10081):1778-1780

Authors: Rochon PA, Gurwitz JH

PMID: 28495154 [PubMed - indexed for MEDLINE]

Gastrointestinal tract as a side-effect target of medications.

Przegl Lek. 2016;73(9):652-8

Authors: Domagała-Rodacka R, Cibor D, Szczeklik K, Rodacki T, Mach T, Owczarek D

Abstract
World Health Organization (WHO) defines adverse drug reaction (ADR) as “a response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function”. ADRs are a serious problem of contemporary pharmacotherapy. Expenditures for treatment of ADRs in the United States may cost up to 30.1 billion dollars annually. Factors affecting the development of ADRs are: age, gender, body weight, polypharmacy. About 10% of ADRs is associated with gastrointestinal tract (GIT). ADR can affect every part of GIT. Xerostomia is the most common ADR occurring in oral cavity. ADRs affecting esophagus include irritation and inflammation of the mucosa. Approximately one-third of all cases of esophageal inflammation results from administration of non-steroid anti-inflammatory drugs (NSAIDs). The main cause of ulcerations involving stomach and small intestine are NSAIDs. Drug-induced diarrheas are the most common adverse effect accounting for approximately 7% of all observed cases of ADRs. They may be triggered by antibiotics, magnesium salts, laxatives and others. On the other hand, some groups of medications may induce constipation. These drugs comprise opioids, diuretics, calcium channel blockers, cholinolytics and others. Proton pump inhibitors, metformin, orlistat and colesevelam may lead to restricted absorption of certain vitamins and minerals. Physicians’ knowledge about most popular and well documented ADRs can improve patients’ safety and make pharmacotherapy more comfortable for them.

PMID: 29688675 [PubMed - indexed for MEDLINE]

NI-0801, an anti-chemokine (C-X-C motif) ligand 10 antibody, in patients with primary biliary cholangitis and an incomplete response to ursodeoxycholic acid.

Hepatol Commun. 2018 May;2(5):492-503

Authors: de Graaf KL, Lapeyre G, Guilhot F, Ferlin W, Curbishley SM, Carbone M, Richardson P, Moreea S, McCune CA, Ryder SD, Chapman RW, Floreani A, Jones DE, de Min C, Adams DH, Invernizzi P

Abstract
NI-0801 is a fully human monoclonal antibody against chemokine (C-X-C motif) ligand 10 (CXCL10), which is involved in the recruitment of inflammatory T cells into the liver. The safety and efficacy of NI-0801 was assessed in patients with primary biliary cholangitis. In this open-label phase 2a study, patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid received six consecutive intravenous administrations of NI-0801 (10 mg/kg) every 2 weeks. Patients were followed up for 3 months after the last infusion. Liver function tests, safety assessments, as well as pharmacokinetic and pharmacodynamic parameters were evaluated at different time points throughout the dosing period and the safety follow-up period. Twenty-nine patients were enrolled in the study and were treated with NI-0801. The most frequently reported adverse events included headaches (52%), pruritus (34%), fatigue (24%), and diarrhea (21%). No study drug-related serious adverse events were reported. NI-0801 administration did not lead to a significant reduction in any of the liver function tests assessed at the end of the treatment period (i.e., 2 weeks after final NI-0801 administration) compared to baseline. Conclusion: Despite clear pharmacologic responses in the blood, no therapeutic benefit of multiple administrations of NI-0801 could be demonstrated. The high production rate of CXCL10 makes it difficult to achieve drug levels that lead to sustained neutralization of the chemokine, thus limiting its targetability. (Hepatology Communications 2018;2:492-503).

PMID: 29761166 [PubMed]

Characterization of Thermally Activated Metalloenediyne Cytotoxicity in Human Melanoma Cells.

Radiat Res. 2018 May 15;:

Authors: Keller EJ, Porter M, Garrett JE, Varie M, Wang H, Pollok KE, Turchi JJ, Zaleski JM, Dynlacht JR

Abstract
Enediynes are a highly cytotoxic class of compounds. However, metallation of these compounds may modulate their activation, and thus their cytotoxicity. We previously demonstrated that cytotoxicity of two different metalloenediynes, including (Z)-N,N'-bis[1-pyridyl-2-yl-meth-(E)-ylidene]octa-4-ene-2,6-diyne-1,8-diamine] (PyED), is potentiated when the compounds are administered to HeLa cells during hyperthermia treatment at concentrations that are minimally or not cytotoxic at 37°C. In this study, we further characterized the concentration, time and temperature dependence of cytotoxicity of PyED on human U-1 melanoma cells. We also investigated the potential mechanisms by which PyED cytotoxicity is enhanced during hyperthermia treatment. Cell killing with PyED was dependent on concentration, temperature during treatment and time of exposure. Potentiation of cytotoxicity was observed when cells were treated with PyED at temperatures ≥39.5°C, and enhancement of cell killing increased with temperature and with increasing time at a given temperature. All cells treated with PyED were shown to have DNA damage, but substantially more damage was observed in cells treated with PyED during heating. DNA repair was also inhibited in cells treated with the drug during hyperthermia. Thus, potentiation of PyED cytotoxicity by hyperthermia may be due to enhancement of drug-induced DNA lesions, and/or the inhibition of repair of sublethal DNA damage. While the selective thermal activation of PyED supports the potential clinical utility of metalloenediynes as cancer thermochemotherapeutic agents, therapeutic gain could be optimized by identifying compounds that produce minimal toxicity at 37°C but which become activated and show enhancement of cytotoxicity within a tumor subjected to localized hyperthermic or thermal ablative treatment, or which might act as bifunctional agents. We thus also describe the development and initial characterization of a novel cofactor complex of PyED, platinated PyED (Pt-PyED). Pt-PyED binds to DNA-like cisplatin, and much like PyED, cytotoxicity is greatly enhanced after treatment with the drug at elevated temperatures. However, in contrast to PyED, Pt-PyED is only minimally cytotoxic at 37°C, at concentrations at which cytotoxicity is enhanced by hyperthermia. Further development of cisplatin-based enediynes may result in compounds which, when activated, will possess multiple DNA binding modalities similar to cisplatin, but produce less side effects in tissues at normothermic temperatures.

PMID: 29763378 [PubMed - as supplied by publisher]

Efficacy, safety and quality of life in patients receiving subcutaneous IgG treatment: experience in Bogotá, Colombia.

Immunotherapy. 2018 May 15;:

Authors: Ortega-López MC, Garay J, Pinilla ML

Abstract
AIM: Investigate efficacy, safety and quality of life of gammanorm® 16.5% (subcutaneous immunoglobulin [SCIG]) in patients with primary immunodeficiencies (PIDs) and safety and to lesser extent efficacy in autoimmune diseases.
PATIENTS & METHODS: Medical records were extracted from 31 pediatric and 12 adult patients who received SCIG as part of the Personalized Program at University Children's Hospital, Bogotá, Colombia.
RESULTS: Mean SCIG dose was 28.7 g/month. Serious bacterial infections were observed in 7/33 patients in the PID group, most often bacterial pneumonia (3/33). There were no serious adverse events related to SCIG treatment. Drug-related adverse reactions were reported in 2/43 patients.
CONCLUSION: Self-administration of SCIG provided effective protection, favorable tolerability and improved quality of life in patients with PIDs and autoimmune diseases from Colombia.

PMID: 29761739 [PubMed - as supplied by publisher]

[Pharmacological action and clinical outcome of newly developed NSAIDs patch, "LOQOA® tape"].

Nihon Yakurigaku Zasshi. 2018;151(5):221-227

Authors: Otsuka N, Yataba I

Abstract
Topical non-steroidal anti-inflammatory drugs (NSAIDs) patches are indispensable for the treatment of musculoskeletal diseases, while they are considered less effective than oral NSAIDs. LOQOA® tape is a tape-type patch containing esflurbiprofen (SFP) as a major active ingredient with potent cyclooxygenase inhibition and sufficient skin permeability. SFP patch (SFPP) showed higher percutaneous absorption rate, rapid pain relief, and potent anti-inflammatory efficacy comparing with existing NSAIDs patches in rat. SFPP showed dramatically higher synovial fluid and tissue concentration on SFP than that of flurbiprofen (FP) patch after single application to knee osteoarthritis (OA) patients. On the other hand, clinical dosage of SFPP was determined as not more than two patches a day from the estimation of systemic exposure to SFP of SFPP and oral FP. SFPP showed statistically significant differences in pain relief and all the other efficacy end points compared to inactive placebo or FP patch in knee OA patients. Efficacy on OA other than knee joint was also observed. In long-term study of SFPP, using up to two patches a day, a total of 201 patients was included and 161 patients achieved 52-week application. Among drug-related side effects, skin reaction at the application sites was observed in 46.8% and discontinued in 4.3%. Although gastro-intestinal reaction and abnormal changes in laboratory tests related to kidney function were observed as systemic drug-related side effects, most of them were mild in severity. SFPP, the new generation NSAIDs patch, would be one of effective options for the treatment of symptomatic OA patients.

PMID: 29760367 [PubMed - in process]

A content analysis of the representation of statins in the British newsprint media.

BMJ Open. 2017 Aug 21;7(8):e012613

Authors: Chisnell J, Marshall T, Hyde C, Zhelev Z, Fleming LE

Abstract
OBJECTIVE: This study reviewed the news media coverage of statins, seeking to identify specific trends or differences in viewpoint between media outlets and examine common themes.
DESIGN: The study is a content analysis of the frequency and content of the reporting of statins in a selection of the British newsprint media. It involved an assessment of the number, timing and thematic content of articles followed by a discourse analysis examining the underlying narratives. The sample was the output of four UK newspapers, covering a broad-spectrum readership, over a six month timeframe 1 October 2013 to 31 March 2014.
RESULTS: A total of 67 articles included reference to statins. The majority (39, 58%) were reporting or responding to publication of a clinical study. The ratio of negative to positive coverage was greater than 2:1 overall. In the more politically right-leaning newspapers, 67% of coverage was predominantly negative (30/45 articles); 32% in the more left-leaning papers (7/22 articles). Common themes were the perceived 'medicalisation' of the population; the balance between lifestyle modification and medical treatments in the primary prevention of heart disease; side effects and effectiveness of statins; pharmaceutical sponsorship and implications for the reliability of evidence; trust between the public and government, institutions, research organisations and the medical profession.
CONCLUSIONS: Newsprint media coverage of statins was substantially influenced by the publication of national guidance and by coverage in the medical journals of clinical studies and comment. Statins received a predominantly negative portrayal, notably in the more right-leaning press. There were shared themes: concern about the balance between medication and lifestyle change in the primary prevention of heart disease; the adverse effects of treatment; and a questioning of the reliability of evidence from research institutions, scientists and clinicians in the light of their potential allegiances and funding.

PMID: 28827228 [PubMed - indexed for MEDLINE]

Short-term treatment with taurolidine is associated with liver injury.

BMC Pharmacol Toxicol. 2017 Aug 11;18(1):61

Authors: Fahrner R, Möller A, Press AT, Kortgen A, Kiehntopf M, Rauchfuss F, Settmacher U, Mosig AS

Abstract
BACKGROUND: Taurolidine has been used for peritonitis, oncological and catheter-lock treatment because of its anti-inflammatory properties. It has been suggested that taurolidine has no severe side-effects, but after long-term use morphological and functional changes of the liver were reported. The aim of this study was to investigate the effect of short-term use of taurolidine on the liver.
METHODS: In HepaRG cell cultures and on a novel liver biochip dose-dependent effects of taurolidine treatment on hepatocyte adherence and cell viability was investigated. Furthermore, liver enzymes and interleukin- (IL-) 6 were measured in supernatants. Male rats were treated with low- or high-dose taurolidine, respectively, and compared to controls with physiological saline solution administration regarding blood serum parameters and histology.
RESULTS: In HepaRG cell cultures, hepatocyte adherence was significantly decreased, cell death and cleaved caspase-3 were significantly increased after administration of taurolidine in a dose-dependent manner. High-dose application of taurolidine led to elevated liver enzymes and IL-6 secretion in hepatic organoid. After 24 h a significant increase of serum GLDH and ASAT was observed in rats treated with high-dose taurolidine treatment.
CONCLUSIONS: Our results suggest that taurolidine caused liver injury after short-term use in in vitro and in vivo models probably due to direct toxic effects on hepatocytes. Therefore, the taurolidine dose should be titrated in further investigations regarding liver injury and inflammation.

PMID: 28800748 [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 2018/05/15

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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 2018/05/15

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

Long-term safety and efficacy of the novel β3 -adrenoreceptor agonist vibegron in Japanese patients with overactive bladder: A phase III prospective study.

Int J Urol. 2018 May 11;:

Authors: Yoshida M, Kakizaki H, Takahashi S, Nagai S, Kurose T

Abstract
OBJECTIVES: To evaluate the long-term safety and efficacy of vibegron 50 mg and 100 mg, a novel β3 -adrenoreceptor agonist, in Japanese patients with overactive bladder.
METHODS: This was a 1-year, multicenter, open-label, non-controlled study. After a 1-week observation phase, patients were treated with vibegron for 52 weeks. When the efficacy was insufficient after an 8-week treatment with 50 mg, the dose was increased to 100 mg and maintained for an additional 44 weeks.
RESULTS: Among a total of 169 patients receiving one or more doses of vibegron, 118 (69.8%) received vibegron 50 mg for 52 weeks, and the dose was increased to 100 mg in 51 (30.2%) patients. The incidence of drug-related adverse events was 18.1% (21/116) in the vibegron 50 mg group and 11.8% (6/51) in the vibegron 100 mg group. Most frequent drug-related adverse events were dry mouth (3.0%), residual urine volume increased (3.0%), constipation (2.4%) and cystitis (1.8%). Statistically significant changes in overactive bladder symptom variables (daily means of micturitions, urgency episodes, urgency incontinence episodes, incontinence episodes and night-time frequency) from baseline were observed at week 4 and maintained until week 52. The condition of patients who did not respond well to vibegron 50 mg was much improved by increasing the dose to 100 mg. Vibegron improved the quality of life, and the proportion of patients' satisfaction after the treatment with vibegron was high.
CONCLUSIONS: Long-term (52-week) treatment with vibegron is safe, well-tolerated and effective in patients with overactive bladder.

PMID: 29752752 [PubMed - as supplied by publisher]

Linezolid-Containing Treatment Regimens for Tuberculosis in Children.

Pediatr Infect Dis J. 2018 May 10;:

Authors: Prieto LM, Santiago B, Del Rosal T, Carazo B, Jiménez AB, Pérez-Gorricho B, Rubio F, Tagarro A, Blázquez D, Moreno-Pérez D, Mellado MJ, Baquero-Artigao F, Spanish Paediatric TB Research Network (pTBred)

Abstract
BACKGROUND: In recent years there is an increasing interest in the use of linezolid for the treatment of tuberculosis (TB).
METHODS: Patients under 18 years of age who received linezolid within the Spanish Pediatric TB Network (pTBred) from 2001 to 2016 were retrospectively included. Treatment characteristics, adverse events (AEs) and outcomes were analyzed.
RESULTS: Fifteen children were included (53% male) with a median age of 3.6 years (IQR: 1.6-6.2). Median follow up was 54 months (IQR: 38-76). The reasons for linezolid use were drug-resistant TB (DR-TB) in eight (53%) patients, drug-induced liver injury (DILI) in five (33%) patients and chronic liver disease (CLD) in two (13%) patients. Four children (26%) were on immunosuppressive therapy when TB was diagnosed. Five children (33%) were diagnosed with extrapulmonary TB. The median duration of linezolid treatment was 13 months (IQR: 7.5-17). Nine patients had 13 linezolid-related AEs. Hematologic toxicity was observed in eight patients (53%) and gastrointestinal intolerance in 3 patients (20%). In two patients linezolid dose was reduced and in two patients linezolid was discontinued because of AEs. A 2- year-old girl went back to her country of birth and was lost to follow-up. No relapses were observed among the other 14 patients (93%).
CONCLUSIONS: Linezolid may be considered when treating children with drug resistant TB but also in the cases of patients with chronic liver disease or drug induced liver injury. However, AEs should be closely monitored. Further studies are needed to determine the optimum dosage and the optimal duration of linezolid treatment in children.

PMID: 29750764 [PubMed - as supplied by publisher]

A phase I study of nintedanib combined with cisplatin/gemcitabine as first-line therapy for advanced squamous non-small cell lung cancer (LUME-Lung 3).

Lung Cancer. 2018 Jun;120:27-33

Authors: Forster M, Hackshaw A, De Pas T, Cobo M, Garrido P, Summers Y, Dingemans AC, Flynn M, Schnell D, von Wangenheim U, Loembé AB, Kaiser R, Lee SM

Abstract
BACKGROUND: There are limited treatment options for squamous non-small cell lung cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as first-line treatment for advanced sqNSCLC patients, were evaluated.
MATERIALS AND METHODS: A phase I, dose-escalation study administering drugs in a 21-day cycle: cisplatin (75 mg/m2, Day 1), gemcitabine (1250 mg/m2, Days 1 and 8) and nintedanib (Days 2-7, 9-21) were given for 4-6 cycles, followed by monotherapy until disease progression or adverse events (AEs). Two nintedanib doses were tested, 150 mg twice daily (bid) and 200 mg bid, to determine maximum tolerated dose (MTD) based on occurrence of dose-limiting toxicities (DLTs) during Cycle 1. DLTs were primarily defined as drug-related non-hematologic (Grade ≥3) or hematologic (Grade 4) AEs.
RESULTS: Sixteen patients were treated with nintedanib; n = 4 for 150 mg bid, n = 12 for 200 mg bid. No DLTs were observed in Cycle 1; therefore, the MTD was 200 mg bid. In subsequent cycles, two patients had DLTs: renal failure and reduced blood magnesium levels. The most common AEs were gastrointestinal. Three patients discontinued last study medication due to AEs and one had a nintedanib dose reduction. No relevant PK interactions were observed. Five patients had partial responses (31.3%) and eight had stable disease (50.0%); disease control rate was 81.3%. There were three long-term survivors (17-35 months).
CONCLUSIONS: The safety profile of nintedanib 200 mg bid plus cisplatin/gemcitabine was manageable, with AEs consistent with previous observations. PK data demonstrated no interaction, and preliminary antitumor activity was observed.

PMID: 29748012 [PubMed - in process]

Comparison of lacosamide versus sodium valproate in status epilepticus: A pilot study.

Epilepsy Behav. 2017 Nov;76:110-113

Authors: Misra UK, Dubey D, Kalita J

Abstract
PURPOSE: The purpose of this study was to compare the efficacy and safety of lacosamide (LCM) and sodium valproate (SVA) in lorazepam (LOR)-resistant SE.
METHODS: Patients with LOR-resistant SE were randomized to intravenous LCM 400mg at the rate of 60mg/kg/min or SVA 30mg/kg at the rate of 100mg/min. The SE severity score (STESS), duration of SE and its etiology, and MRI findings were noted. Primary outcome was seizure cessation for 1h, and secondary outcomes were 24h seizure remission, in-hospital death, and severe adverse events (SAE).
RESULTS: Sixty-six patients were included, and their median age was 40 (range 18-90) years. Thirty-three patients each received LCM and SVA. Their demographic, clinical, STESS, etiology, and MRI findings were not significantly different. One-hour seizure remission was not significantly different between LCM and SVA groups (66.7% vs 69.7%; P=0.79). Twenty-four-hour seizure freedom was insignificantly higher in SVA (20, 66.6%) compared with LCM group (15, 45.5%). Death (10 vs 12) and composite side effects (4 vs 6) were also not significantly different in LCM and SVA groups. LCM was associated with hypotension and bradycardia (1 patient), and SVA with liver dysfunction (6).
CONCLUSION: In patients with LOR-resistant SE, both LCM and SVA have comparable efficacy and safety.

PMID: 28919386 [PubMed - indexed for MEDLINE]

[Cross sectional study of comorbidities and concomitant medications in a cohort of human immunodeficiency virus-infected patients].

Aten Primaria. 2017 May;49(5):286-293

Authors: García Gonzalo MA, Santamaría Mas MI, Pascual Tomé L, Ibarguren Pinilla M, Rodríguez-Arrondo F

Abstract
AIM: To assess the prevalence of comorbidities, concomitant therapies and adverse effects associated with the medication in a cohort of patients with HIV infection.
DESIGN: Multicentre cross-sectional study.
SETTINGS: Infectious Diseases or Internal Medicine outpatient Clinics of 3 hospitals in the Basque Country.
PARTICIPANTS: During a 3 month period, patients with the following inclusion criteria were randomly selected: HIV infection, age>18years, antiretroviral treatment (ART) for at least 6months, and no changes in ART in the previous 4weeks. A total of 224 patients (of the 225 expected) were included.
MEASUREMENTS: Data were collected using a form, and include, epidemiological and anthropometric data, data related to HIV infection, comorbidities, current therapies, and adverse effects.
RESULTS: Of the 224 patients, 95.5% had at least one comorbidity, the most common being HCV infection (51.3%), dyslipidaemia (37.9%), diabetes mellitus or impaired fasting glucose (21.9%), and hypertension (21.9%). A total of 155 patients (69.2%) were taking concomitant medication: anxiolytics (21.4%), antihypertensives (19.6%), proton pump inhibitors (17.9%), statins (17%), and antidepressants (16.5%). Adverse effects (AE) were observed in 62.9% of subjects, the most common being, changes in body fat distribution (32.6%) and gastrointestinal (24.1%).
CONCLUSIONS: Patients with HIV infection are getting older, with more comorbidities, with very frequent use of concomitant treatments, and high number of adverse effects. This requires a multidisciplinary approach and a coordinated effort within the Primary Care setting.

PMID: 27720238 [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 2018/05/11

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.