Acute aseptic arthritis: Case definition & guidelines for data collection, analysis, and presentation of immunisation safety data.

Vaccine. 2018 Oct 17;:

Authors: Woerner A, Pourmalek F, Panozzo C, Pileggi G, Hudson M, Caric A, Abraham S, Varricchio F, Velasco C, Oleske J, Bauwens J, Bonhoeffer J, Brighton Collaboration Acute Aseptic Arthritis Working Group

PMID: 30342899 [PubMed - as supplied by publisher]

Dexamethasone therapy versus surgery for chronic subdural haematoma (DECSA trial): study protocol for a randomised controlled trial.

Trials. 2018 Oct 20;19(1):575

Authors: Miah IP, Holl DC, Peul WC, Walchenbach R, Kruyt N, de Laat K, Koot RW, Volovici V, Dirven CMF, van Kooten F, Kho KH, den Hertog HM, van der Naalt J, Jacobs B, Groen RJM, Lingsma HF, Dammers R, Jellema K, van der Gaag NA, Dutch Subdural Hematoma Research Group (DSHR)

Abstract
BACKGROUND: Chronic subdural haematoma (CSDH) is a common neurological disease with a rapidly rising incidence due to increasing age and widespread use of anticoagulants. Surgical intervention by burr-hole craniotomy (BHC) is the current standard practice for symptomatic patients, but associated with complications, a recurrence rate of up to 30% and increased mortality. Dexamethasone (DXM) therapy is, therefore, used as a non-surgical alternative but considered to achieve a lower success rate. Furthermore, the benefit of DXM therapy appears much more deliberate than the immediate relief from BHC. Lack of evidence and clinical equipoise among caregivers prompts the need for a head-to-head randomised controlled trial. The objective of this study is to compare the effect of primary DXM therapy versus primary BHC on functional outcome and cost-effectiveness in symptomatic patients with CSDH.
METHODS/DESIGN: This study is a prospective, multicentre, randomised controlled trial (RCT). Consecutive patients with a CSDH with a Markwalder Grading Scale (MGS) grade 1 to 3 will be randomised to treatment with DXM or BHC. The DXM treatment scheme will be 16 mg DXM per day (8 mg twice daily, days 1 to 4) which is then halved every 3 days until a dosage of 0.5 mg a day on day 19 and stopped on day 20. If the treatment response is insufficient (i.e. persistent or progressive symptomatology due to insufficient haematoma resolution), additional surgery can be performed. The primary outcomes are the functional outcome by means of the modified Rankin Scale (mRS) score at 3 months and cost-effectiveness at 12 months. Secondary outcomes are quality of life at 3 and 12 months using the Short Form Health Survey (SF-36) and Quality of Life after Brain Injury Overall Scale (QOLIBRI), haematoma thickness after 2 weeks on follow-up computed tomography (CT), haematoma recurrence during the first 12 months, complications and drug-related adverse events, failure of therapy within 12 months after randomisation and requiring intervention, mortality during the first 3 and 12 months, duration of hospital stay and overall healthcare and productivity costs. To test non-inferiority of DXM therapy compared to BHC, 210 patients in each treatment arm are required (assumed adjusted common odds ratio DXM compared to BHC 1.15, limit for inferiority < 0.9). The aim is to include a total of 420 patients in 3 years with an enrolment rate of 60%.
DISCUSSION: The present study should demonstrate whether treatment with DXM is as effective as BHC on functional outcome, at lower costs.
TRIAL REGISTRATION: EUCTR 2015-001563-39 . Date of registration: 29 March 2015.

PMID: 30342554 [PubMed - in process]

The 'Developing Regorafenib Eye drops for neovascular Age-related Macular degeneration' (DREAM) study: an open-label phase II trial.

Br J Clin Pharmacol. 2018 Oct 20;:

Authors: Joussen AM, Wolf S, Kaiser PK, Boyer D, Schmelter T, Sandbrink R, Zeitz O, Deeg G, Richter A, Zimmermann T, Hoechel J, Buetehorn U, Schmitt W, Stemper B, Boettger MK

Abstract
AIMS: This program investigated topical regorafenib, a multikinase inhibitor, in patients with neovascular age-related macular degeneration (nAMD).
METHODS: Topical regorafenib was investigated in an open-label, phase IIa/b study in which patients with choroidal neovascularization (CNV) secondary to nAMD received regorafenib (25 μL, 30 mg/mL TID) for 12 weeks. The primary endpoint of the phase II/a/b study was mean change in best-corrected visual acuity (BCVA) from baseline to weeks 4 and 12.
RESULTS: In nAMD patients (N = 51), mean changes in BCVA were +1.2 (90% CI -0.61 to 2.97) and -2.4 (90% CI, -4.18 to -0.54) letters at weeks 4 and 12, respectively. Ocular treatment-emergent adverse events (TEAEs) (study eye) were reported in 21 patients by week 12. There was 1 serious ocular TEAE (visual acuity reduced) that was not drug related. Twenty patients required rescue (intravitreal ranibizumab).
CONCLUSIONS: The program was terminated after phase IIa ended because efficacy was less than with current nAMD treatments. According to elaborate post hoc analyses, the most likely reason was insufficient exposure in the target compartment (back of the eye).

PMID: 30341774 [PubMed - as supplied by publisher]

Tapering and Discontinuation of Biologics in Patients with Psoriatic Arthritis with Low Disease Activity.

Drugs. 2018 Oct 20;:

Authors: Ye W, Tucker LJ, Coates LC

Abstract
The introduction of biologic disease modifying anti-rheumatic drugs (bMDARDs) have revolutionised the treatment of psoriatic arthritis (PsA). This combined with a 'treat-to-target' approach, means that achieving remission is increasingly possible. In patients with well-controlled PsA, there is little consensus on whether bDMARDs should be continued, tapered or discontinued altogether. Tapering or discontinuation of bDMARDs could offer significant financial savings and minimise patient burden and unwanted drug-related side effects. However, there is a risk of loss of remission. The primary focus of this paper is to review the current evidence on bDMARD tapering and discontinuation in PsA. We explore the criteria employed by studies to define patients eligible for bDMARD tapering or discontinuation and the process by which this occurs. We also review the outcomes of bDMARD tapering and discontinuation, the predictors, and the likelihood of restoring remission following relapse. To date, bDMARD tapering seems to be feasible and safe in patients with PsA who are in remission or with low disease activity. Lower disease activity prior to tapering seems to increase the likelihood of successful bDMARD tapering. In contrast, discontinuing bDMARDs appears to carry a substantial risk of loss of remission. Those with higher disease activity at time of tumour necrosis factor inhibitors discontinuation, current smokers, male sex, increased skin involvement, and synovial hypertrophy seen on ultrasound prior to discontinuation are at greater risk of losing remission post-bDMARD discontinuation. In those who lose remission, reinstating the standard dose of bDMARD appears to be effective in restoring remission.

PMID: 30341684 [PubMed - as supplied by publisher]

Possible involvement of interleukin-18 in the pathology of hepatobiliary adverse effects related to treatment with ceritinib.

BMC Cancer. 2018 Oct 19;18(1):995

Authors: Hirano T, Koarai A, Ichikawa T, Sato T, Ohe T, Ichinose M

Abstract
BACKGROUND: Ceritinib demonstrated a statistically significant effect on the progression-free survival versus chemotherapy in patients with advanced anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) as the first therapy or after previous treatment with crizotinib and one or two prior chemotherapy regimens in global phase 3 studies. However, some serious adverse effects related to ceritinib therapy were reported across these clinical studies. Among them, a grade 3 and 4 increase in hepatobiliary enzymes was one of the common adverse events related to treatment with ceritinib. However, the pathology remains unclear. Previously, increased Interleukin (IL)-18 was observed in both biliary duct disease and liver disease. Therefore, we hypothesized that IL-18 is involved in the pathology of hepatobiliary adverse effects related to treatment with ceritinib and evaluated the serum IL-18.
CASE PRESENTATION: The patient was a 53-year-old Japanese woman that we previously reported as having severe hepatobiliary adverse effects related to ceritinib therapy. Laboratory data, CT and MRI were obtained at each time point. IL-18 was evaluated by ELISA method at each time point. Immunochemical staining of liver tissue was performed as a standard protocol using antibodies against IL-18. Our records showed that the levels of serum IL-18 increased from the early stage of hepatobiliary adverse effects related to the treatment with ceritinib and were became worse with an increase in hepatobiliary enzymes and the progression of imaging abnormalities in the bile duct. Furthermore, IL-18 positive cells were detected in the inflammatory sites around the interlobular bile duct of the liver tissue.
CONCLUSION: Our case report shows that the increase of serum IL-18 had a positive correlation with the progression of severe hepatobiliary adverse effects related to treatment with ceritinib and the involvement of IL-18 in the hepatobiliary inflammation by pathological evaluation. These results suggest that IL-18 could be a useful surrogate marker for the hepatobiliary toxicity of ceritinib. However, this is only one case report and further prospective observations will complement our data in the future.

PMID: 30340555 [PubMed - in process]

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

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

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

These pubmed results were generated on 2018/10/20

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

Myoclonus induced by salbutamol: A case report

Biomedica. 2018 09 01;38(3):303-307

Authors: Montoya-Giraldo MA, Montoya DV, Atehortúa DA, Buendía JA, Zuluaga AF

Abstract
Salbutamol is a β2 adrenergic agonist widely prescribed in patients with obstructive and restrictive lung diseases. The main side effects associated with its use are tachycardia and tremor. Myoclonus is an involuntary, irregular, abrupt, brief and sudden muscular contraction, which can be generalized, focal or multifocal. We report the case of a 61-year-old patient presenting with myoclonus difficult to treat who showed improvement only after the definitive discontinuation of the β2 adrenergic agonist. We describe the clinical findings, the interventions, and the outcomes related to the onset of myoclonus secondary to the use of salbutamol, as well as the possible genesis and importance of this adverse effect. We used the CARE guidelines to delineate the clinical case. Although myoclonus secondary to the use of different drugs has been described in the literature, as far as we know this is the fourth report of salbutamol-induced myoclonus to date.

PMID: 30335235 [PubMed - in process]

Potential Drug-Drug Interactions with Antimicrobials in Hospitalized Patients: A Multicenter Point-Prevalence Study.

Med Sci Monit. 2018 Jun 20;24:4240-4247

Authors: Kuscu F, Ulu A, Inal AS, Suntur BM, Aydemir H, Gul S, Ecemis K, Komur S, Kurtaran B, Ozkan Kuscu O, Tasova Y

Abstract
BACKGROUND Improper use of antimicrobials can cause adverse drug events and high costs. The purpose of this study was to investigate the frequency and potential drug-drug interactions associated with antimicrobials among hospitalized patients. MATERIAL AND METHODS This study was conducted on the same day in 5 different hospitals in Turkey. We included patients aged ³18 years who received at least 1 antimicrobial drug and at least 1 of any other drug. The Micromedex® online drug reference system was used to control and describe the interactions. Drug interactions were classified as contraindicated, major, moderate, and minor. RESULTS Potential drug-drug interactions with antimicrobials were 26.4% of all interactions. Five (42%) of 12 contraindicated interactions and 61 (38%) of 159 major interactions were with antimicrobials. Quinolones, triazoles, metronidazole, linezolid, and clarithromycin accounted for 173 (25.7%) of 673 prescribed antimicrobials, but were responsible for 141 (92.1%) of 153 interactions. In multivariate analysis, number of prescribed antimicrobials (odds ratio: 2.3001, 95% CI: 1.6237-3.2582), number of prescribed drugs (odds ratio: 1.2008, 95% CI: 1.0943-1.3177), and hospitalization in the university hospital (odds ratio: 1.7798, 95% CI: 1.0035-3.1564) were independent risk factors for developing drug interactions. CONCLUSIONS Due to risk of drug interactions, physicians should be more cautious when prescribing antimicrobials, particularly when prescribing quinolones, linezolid, azoles, metronidazole, and macrolides.

PMID: 29924770 [PubMed - indexed for MEDLINE]

Efficacy and safety of voriconazole in immunocompromised patients: systematic review and meta-analysis.

Infect Dis (Lond). 2018 07;50(7):489-494

Authors: Rosanova MT, Bes D, Serrano Aguilar P, Sberna N, Lede R

Abstract
BACKGROUND: Voriconazole is a second-generation triazole. It has excellent bioavailability and broad antifungal spectrum; thus, it is an attractive option for patients at high risk of invasive fungal infections (IFIs). Comparing efficacy and safety of voriconazole with other antifungals in prophylaxis or treatment of IFIs would be useful to draw conclusions regarding prevention and therapeutics of these infections.
AIM: To assess efficacy and safety of voriconazole compared with other options as prophylaxis or treatment of IFIs in haematology-oncology patients.
MATERIALS AND METHODS: A literature search was performed in MEDLINE database using the search term 'voriconazole' and completed with manual search.
STUDY SELECTION: Randomized controlled trials (RCTs) comparing voriconazole with other antifungal agents or placebo.
DATA EXTRACTION: Seven studies fulfilled the eligibility criteria.
RESULTS: Five studies compared voriconazole to another comparator as prophylaxis of IFIs and two as treatment. Pooled results showed that voriconazole was more effective than the comparator (RR = 1.17; 95%CI = 1.01-1.34), but heterogeneity was significant (Q test 32.7; p = .00001). Sub-analysis according to prophylaxis showed RR = 1.17; 95%CI = 1.00-1.37; while as treatment, RR = 1.23; 95%CI = 0.68-2.22. Risk of adverse events was not different from that observed for the comparator (RR = 1.06, 95%CI = 0.66-1.72) though significant heterogeneity was detected (p < .01).
CONCLUSIONS: Voriconazole was as effective and safe as comparators, probably better as prophylaxis than as treatment, but limitations due to variability in the sample size of studies, differences in the age of patients, and heterogeneity between studies' outcome measures indicate the need for further research.

PMID: 29262742 [PubMed - indexed for MEDLINE]

Liver disease and heart failure: Back and forth.

Eur J Intern Med. 2018 02;48:25-34

Authors: Correale M, Tarantino N, Petrucci R, Tricarico L, Laonigro I, Di Biase M, Brunetti ND

Abstract
In their clinical practice, physicians can face heart diseases (chronic or acute heart failure) affecting the liver and liver diseases affecting the heart. Systemic diseases can also affect both heart and liver. Therefore, it is crucial in clinical practice to identify complex interactions between heart and liver, in order to provide the best treatment for both. In this review, we sought to summarize principal evidence explaining the mechanisms and supporting the existence of this complicate cross-talk between heart and liver. Hepatic involvement after heart failure, its pathophysiology, clinical presentation (congestive and ischemic hepatopathy), laboratory and echocardiographic prognostic markers are discussed; likewise, hepatic diseases influencing cardiac function (cirrhotic cardiomyopathy). Several clinical conditions (congenital, metabolic and infectious causes) possibly affecting simultaneously liver and heart have been also discussed. Cardiovascular drug therapy may present important side effects on the liver and hepato-biliary drug therapy on heart and vessels; post-transplantation immunosuppressive drugs may show reciprocal cardio-hepatotoxicity. A heart-liver axis is drafted by inflammatory reactants from the heart and the liver, and liver acts a source of energy substrates for the heart.

PMID: 29100896 [PubMed - indexed for MEDLINE]

The cancer threshold of toxicological concern (TTC) in relation to foodstuffs and pharmaceuticals: A potentially useful concept compromised by a dubious derivation.

Hum Exp Toxicol. 2018 Aug;37(8):789-802

Authors: Snodin DJ

Abstract
The cancer threshold of toxicological concern (TTC) as determined by Kroes et al. in 2004 (0.15 µg/day and 1.5 µg/day at risk levels of 1 in 106 or 105, respectively) has been uncritically employed as a key metric in multiple regulatory guidance documents. There are numerous concerns regarding transparency and the highly conservative methodology in relation to its derivation; moreover, no formal confirmation has been undertaken by any regulatory body prior to its adoption. A recent joint report from the European Food Safety Authority and World Health Organization follows this trend, largely replicating previous conclusions and downplaying the need for a re-assessment. This view is challenged by Boobis et al. who confirm concerns regarding lack of transparency and stress that several of the assumptions and approaches used previously have been superseded by advances in knowledge; they recommend as a first step construction of a new dataset derived from the Carcinogenic Potency Database focusing on mutagenic DNA-reactive rodent carcinogens and a critical assessment of the relevance and reliability of carcinogenicity data. This type of approach is supported with two key exceptions: inclusion of data from the ToxTracker assay which provides a direct readout of DNA reactivity, and use of appropriate epidemiological data on acrylamide (AA) to determine a benchmark for human exposure to a typical DNA-reactive rodent carcinogen. It is concluded that a robust re-evaluation using an appropriate dataset and methodology is urgently needed to ensure the integrity of the cancer TTC before it is employed in its present form even more widely.

PMID: 29027486 [PubMed - indexed for MEDLINE]

Phase IB trial of ixabepilone and vorinostat in metastatic breast cancer.

Breast Cancer Res Treat. 2018 01;167(2):469-478

Authors: Luu T, Kim KP, Blanchard S, Anyang B, Hurria A, Yang L, Beumer JH, Somlo G, Yen Y

Abstract
PURPOSE: To translate promising preclinical data on the combination of vorinostat and ixabepilone for metastatic breast cancer (MBC) into clinical trials.
METHODS: We conducted a randomized two-arm Phase IB clinical trial of ascending doses of vorinostat and ixabepilone in prior -treated MBC patients. To determine the maximum tolerated dose (MTD), 37 patients were randomized to schedule A: every-3-week ixabepilone + vorinostat (days 1-14), or schedule B: weekly ixabepilone + vorinostat (days 1-7; 15-21) Pharmacokinetics were assessed. Nineteen additional patients were randomized to schedule A or B and objective response rate (ORR), clinical benefit rate (CBR), toxicity, progression-free survival (PFS), and overall survival (OS) were assessed.
RESULTS: The schedule A MTD was vorinostat 300 mg daily (days 1-14), ixabepilone 32 mg/m2 (day 2); 21-day cycle 27% dose-limiting toxicities (DLTs). The schedule B MTD was vorinostat 300 mg daily (days 1-7; 15-21), ixabepilone 16 mg/m2 (days 2, 9, 16); 28-day cycle; no DLTs. Vorinostat and ixabepilone clearances were 194 L/h and 21.3 L/h/m2, respectively. Grade 3 peripheral sensory neuropathy was reported in 8% (A) and 21% (B) of patients. The ORR and CBR were 22 and 22% (A); 30 and 35% (B). Median PFS was 3.9 (A) and 3.7 (B) months. OS was 14.8 (A) and 17.1 (B) months.
CONCLUSIONS: We established the MTD of vorinostat and ixabepilone. This drug combination offers a novel therapy for previously treated MBC patients. The potential for lower toxicity and comparable efficacy compared to current therapies warrants further study.

PMID: 28956187 [PubMed - indexed for MEDLINE]

Potentially high-risk medication categories and unplanned hospitalizations: a case-time-control study.

Sci Rep. 2017 01 23;7:41035

Authors: Lin CW, Wen YW, Chen LK, Hsiao FY

Abstract
Empirical data of medication-related hospitalization are very limited. We aimed to investigate the associations between 12 high risk medication categories (diabetic agents, diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulants, antiplatelets, antihypertensives, antiarrhythmics, anticonvulsants, antipsychotics, antidepressants, benzodiazepine (BZD)/Z-hypnotics, and narcotics) and unplanned hospitalizations. A population-based case-time-control study was performed using Taiwan's National Health Insurance Research Database. Patients who experienced an unplanned hospitalization (index visit) were identified as index subjects and matched to a randomly selected reference visit within users of a specific category of high-risk medication. An unplanned hospitalization was defined as a hospital admission immediately after an emergency department visit. Discordant exposures to the high-risk medication during the case period (1-14 days before the visit) and the control period (366-379 days before the visit) were examined in both index and reference visits. Antipsychotics was associated with the highest risk of unplanned hospitalizations (adjusted OR: 1.54, 95% CI [1.37-1.73]), followed by NSAIDs (1.50, [1.44-1.56]), anticonvulsants (1.34, [1.10-1.64]), diuretics (1.24, [1.15-1.33]), BZD/Z-hypnotics (1.23, [1.16-1.31]), antidepressants (1.17, [1.05-1.31]) and antiplatelets (1.16, [1.07-1.26]). NSAIDs and narcotics were associated with the highest risks of unplanned hospitalizations with a length of stay ≥10 days. These medication categories should be targeted for clinical and policy interventions.

PMID: 28112193 [PubMed - indexed for MEDLINE]

Implementation of Medication Safety Practice in Childhood Acute Lymphoblastic Leukemia Treatment

Asian Pac J Cancer Prev. 2018 May 26;19(5):1251-1257

Authors: Mulatsih S, Dwiprahasto I, Sutaryo

Abstract
Objective: Medical Safety Practice (MSP) is a safe procedure in medication process. It is important to investigate the use of MSP among childhood cancer patients because pediatric oncology is a high-risk area for potentially harmful adverse events. The purpose of this study is to determine the effects of the implementation of MSP in chemotherapy on the incidence of medication errors in childhood ALL patient at Dr. Sardjito Hospital, including in 1) transcribing, 2) administering, 3) monitoring, 4) the incidence of adverse drugs events. (ADEs). Methods: The study design is a quasi-experimental study with pre- and post-intervention without control. The sample consists of ALL patients who are taken care of at an academic hospital in Indonesia from 2012 to 2013. The sample was consecutively collected during the period of study. The data were collected through medical records, research form, observation, and discussion with the nurse. The intervention given is training and implementation of medical safety practice in chemotherapy. Result: Based on the analysis of the effect of the implementation of MSP (75 and 106 medical records of pre- and post-intervention), it is obtained: 1) the adherence of chemotherapy transcribing post-intervention increases significantly compared to pre-intervention (p<0.05), 2) the adherence of chemotherapy administering increases significantly in almost every aspect (p<0.05), except in preparing drugs by two different health worker, patient’s confirmation of ADEs management, and verification of drug’s expired date, 3) The adherence of chemotherapy monitoring improved significantly post-intervention (p<0.05), 4) Adverse Drug Events (ADE) decreased significantly post-intervention (p<0.05), from 52.1% to 30.5%. Conclusion: The implementation of MSP decreased the incidence of medication errors in ALL patients at Dr. Sardjito Hospital in ordering, dispensing, transcribing, administering, and monitoring chemotherapy. It also reduced the incidence of ADEs related to chemotherapy. Specific training for nurses are needed in order to improve the knowledge and skills, especially for medication error and skill in patients’ care.

PMID: 29801409 [PubMed - in process]

Comorbidities, potentially dangerous and low therapeutic index medications: factors linked to emergency visits.

Cien Saude Colet. 2018 May;23(5):1471-1482

Authors: Tramontina MY, Ferreira MB, Castro MS, Heineck I

Abstract
This article aims to investigate the morbidities related to medications, their risk factors and causes detected in patients who seek the Hospital Emergency Service of a University in the South of Brazil. Data collection was based on application of a questionnaire to patients of a minimum age of 18 years, that signing the Term of Free and Informed Consent (TFIC), during the period from October 2013 to March 2014, and analysis of electronic record charts. Cases were evaluated by pharmacists and a doctor to define whether it was a case of medication related morbidity (MRM) and to establish its possible causes. Avoidability of MRM was verified based on criteria previously established in the literature. In total 535 patients were interviewed, and the frequency of MRM was 14.6%, Approximately 45% of MRMs were related to safety in the use of medications, and approximately 50% presented user-related questions as the possible cause. Hospitalization was required in 44.8% of MRM cases; 62.7% of cases were considered avoidable. Presence of chronic disease and use of potentially dangerous medication and low therapeutic index were considered independent factors associated with development of MRM, according to statistical analysis.

PMID: 29768602 [PubMed - in process]

High OX40 expression in recurrent ovarian carcinoma is indicative for response to repeated chemotherapy.

BMC Cancer. 2018 04 16;18(1):425

Authors: Ramser M, Eichelberger S, Däster S, Weixler B, Kraljević M, Mechera R, Tampakis A, Delko T, Güth U, Stadlmann S, Terracciano L, Droeser RA, Singer G

Abstract
BACKGROUND: Ovarian carcinoma (OC) is the fifth most common female cancer and mostly diagnosed at an advanced stage. Surgical debulking is usually followed by adjuvant platinum-based chemotherapy. Only few biomarkers are known to be related to chemosensitivity. OX40 is a TNF receptor member and expressed on activated CD4+ and CD8+ T cells. It is known that OX40 signaling promotes survival and responds to various immune cells of the innate and adaptive immune system. Therefore we investigated the indicative value of OX40 expression for recurrence and survival in OC.
METHODS: A tissue microarray of biopsies of mostly high-grade primary serous OC and matched recurrences of 47 patients was stained with OX40. Recurrence within 6 months of the completion of platinum-based chemotherapy was defined as chemoresistance.
RESULTS: Chemosensitivity correlated significantly with high OX40 positive immune cell density in primary cancer biopsies (p = 0.027). Furthermore patients with a higher OX40 expression in recurrent cancer biopsies showed a better outcome in recurrence free survival (RFS) (p = 0.017) and high OX40 expression was associated with chemosensitivity (p = 0.008). OX40 positive TICI in recurrent carcinomas significantly correlated with IL-17 positive tumor infiltrating immune cells in primary carcinomas (r s  = 0.34; p = 0.023). Univariate cox regression analysis revealed a significant longer RFS and higher numbers of chemotherapy cycles for high OX40 tumor cell expression in recurrent cancer biopsies (HR 0.39, 95%CI 0.16-0.94, p = 0.036 and 1.28, 95%CI 1.05-1.55; p = 0.013).
CONCLUSION: High OX40 expression in OC is correlated with chemosensitivity and improved RFS in OC. Patients might therefore benefit from a second line therapy.

PMID: 29661166 [PubMed - in process]

Detection of the Incidence of Infections and Acute Biochemical Changes in Diffused Large B-Cell Lymphoma Patients Treated with Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP) with and without Rituximab.

Curr Drug Saf. 2018;13(2):102-106

Authors: Ali K, Sial AA, Baig MT, Ansari SH, Adil SO, Shamsi TS

Abstract
BACKGROUND: Acute biochemical changes, hepatotoxicity, nephrotoxicity and frequency of infections are common in diffuse large B-cell Lymphoma patients undergoing Cyclophosphamide, Doxorubicin, Oncovin (Vincristine) Prednisone (CHOP) and Rituximab plus CHOP chemo cycles. Eventually, it leads to prolonging hospital stay and suspending the next chemotherapy cycles.
AIMS AND OBJECTIVES: The objectives of our study were to determine the changes in biochemical disturbances induced by CHOP or RCHOP and second objective was to compare the effect of CHOP with or without rituximab on the incidence of the infections such as (Cytomegalovirus, Herpes Simplex Virus and Varicella-Zoster virus), bacterial infections and tuberculosis.
MATERIALS AND METHODS: Files were prospectively reviewed during the tenure of 2014-2016. Participants aged greater than or equal to 18 years old with a known case of DLBCL undergoing CHOP or RCHOP chemotherapy were allowed to be included in the study. Baseline and posttreatment patients profile of blood chemistry, liver functions test was collected and compared with the Common Terminology Criteria for adverse events v3.0 2009 CTCAE 2009 and the data regarding infection of Cytomegalovirus, Herpes Simplex Virus and Vericella-Zoster virus, bacterial infections and tuberculosis were drawn from the participant's profile.
RESULTS: Patients treated with CHOP therapy showed a significant difference of Alkaline Phosphatase (ALP) (p-value 0.009), direct bilirubin (p-value 0.034) and serum glutamic-pyruvic transaminase (SGPT) (p-value 0.004). Bacterial Pneumonia was only 1 (5%) and 1 (5%) CMV reported positive after the R-CHOP.
CONCLUSION: We propose that liver profile including (bilirubin, SGOT and SGPT) Urea, Creatinine and electrolytes should strictly be considered if found deranged before every treatment cycle and suspend chemotherapy in case of moderate or severe toxicity.

PMID: 29564988 [PubMed - in process]

Preventable adverse drug events in critically ill HIV patients: Is the detection of potential drug-drug interactions a useful tool?

Clinics (Sao Paulo). 2018 02 19;73:e148

Authors: Ramos GV, Japiassú AM, Bozza FA, Guaraldo L

Abstract
OBJECTIVES: The aim of this study was to develop a strategy to identify adverse drug events associated with drug-drug interactions by analyzing the prescriptions of critically ill patients.
METHODS: This retrospective study included HIV/AIDS patients who were admitted to an intensive care unit between November 2006 and September 2008. Data were collected in two stages. In the first stage, three prescriptions administered throughout the entire duration of these patients' hospitalization were reviewed, with the Micromedex database used to search for potential drug-drug interactions. In the second stage, a search for adverse drug events in all available medical, nursing and laboratory records was performed. The probability that a drug-drug interaction caused each adverse drug events was assessed using the Naranjo algorithm.
RESULTS: A total of 186 drug prescriptions of 62 HIV/AIDS patients were analyzed. There were 331 potential drug-drug interactions, and 9% of these potential interactions resulted in adverse drug events in 16 patients; these adverse drug events included treatment failure (16.7%) and adverse reactions (83.3%). Most of the adverse drug reactions were classified as possible based on the Naranjo algorithm.
CONCLUSIONS: The approach used in this study allowed for the detection of adverse drug events related to 9% of the potential drug-drug interactions that were identified; these adverse drug events affected 26% of the study population. With the monitoring of adverse drug events based on prescriptions, a combination of the evaluation of potential drug-drug interactions by clinical pharmacy services and the monitoring of critically ill patients is an effective strategy that can be used as a complementary tool for safety assessments and the prevention of adverse drug events.

PMID: 29466493 [PubMed - in process]

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

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

Authors: Meirinho S, Relvas R, Alves G

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

PMID: 29437014 [PubMed - in process]