Patients suffering from migraine, tension-type headache (TTH), or combined headache (CH) are at risk of developing drug-induced headache (DIH) due to regular use of analgesics, ergot alkaloids, and triptans. The aim of our study was to determine (1) the clinical features of DIH, (2) the outcome of withdrawal therapy using high methodological standards, and (3) predictors which could explain the high relapse rate (more than 40%) after a previously successful withdrawal therapy. We retrospectively reviewed 103 patients with migraine or TTH who underwent withdrawal therapy between 1994 and 1998. The long-term follow-up (2–4 years after therapy) was conducted by phone and by specially trained psychologists using a structured interview which enclosed characteristics of headache and medication behavior as well as patients global assessment of success. Complete sets of data were available from 83 patients (38 migraine, 26 TTH, 19 CH). The most frequently abused drugs were caffeine-combined analgesics (24%), followed by caffeine-combined ergotamines (19%), pure ergot alkaloids (17%), and monoanalgesics (17%). 48.5% of the patients suffered an abuse relapse within 4 years and developed the complete features of DIH again. Analgesic and ergot alkaloid combinations with caffeine lead significantly more often to a relapse. A long-term successful therapy is connected with a significant reduction of the frequency of headache attacks. Under relapse conditions, the patients reached their former headache frequency level. The data show a higher relapse rate than previously assumed and that certain substance groups bear a higher relapse risk.

Background: A marked proportion of multiple sclerosis (MS) relapses is followed by incomplete recovery. Our aim was to considerably increase the evidence of the clinical use of immunoadsorption (IA) as escalation therapy for patients with MS relapse. Methods: A retrospective multicenter study was performed in MS patients with steroid refractory relapse who were treated with tryptophan IA. The main outcome parameter was change of acute relapse-related disability assessed by Expanded Disability Status Scale (EDSS) and visual acuity (VA) measurements for patients with optic neuritis (ON). IA treatments were performed using single-use tryptophan adsorbers. Results: Data of 147 MS patients and 786 single IA treatments were analyzed. Treatment with IA was commenced in mean 32 ± 35 days after the onset of relapse. One hundred and five out of 147 patients (71.4%) improved functionally after mean 5.4 IA treatments within 7-10 days. EDSS improved from median 5 (interquartile range, IQR 3.5) to 4 (IQR 2.5) (p < 0.001). In patients with ON (n = 32), VA improved after the IA series in 84% of cases from median 0.2 (IQR 0.6) to 0.6 (IQR 0.66) (p < 0.001). In 98.9% of IA treatments, no clinically relevant side effect was reported. Conclusion: Tryptophan IA was found to be effective and well tolerated as escalation therapy for MS relapse.

BackgroundOxaliplatin is an effective medicine for adjuvant or metastatic treatment of patients with colorectal cancer (CRC). Common side-effects include acute cold-induced as well as chronic neurotoxicity resulting in dose reduction or even complete oxaliplatin discontinuation and treatment modification. For patients receiving high cumulative doses of oxaliplatin (780 to 850 mg/m2), the incidence of grade 2 or 3 neurotoxicity has been shown to be 12% to 18%.1 PurposeThe aim of our study was to investigate both the incidence and significance of neurotoxicity in patients receiving cumulative oxaliplatin doses of 1000 mg/m2 or higher. We could then determine whether the pre-emptive intervention of a clinical pharmacist is justified.Material and methodsIn the period from January 2016 to July 2017, 484 patients diagnosed with CRC received oxaliplatin as part of their treatment regimen. Among them, 40 patients who had received cumulative doses of 1000 mg/m2 or more were selected for evaluation of neurotoxicity symptoms based on their clinical records. An oxaliplatin-specific scale (NCI-CTC 2.0) was used to assess the level of neurotoxicity.2 ResultsSymptoms presented as moderate paraesthaesia (grade 1) occurred in 11 patients (28%), while six patients (15%) reported mild or moderate objective sensory loss (grade 2). Dose-limiting neurotoxicity (grade 2 and 3) was observed in nine patients (22.5%) with a complete oxaliplatin discontinuation being required in three patients (7.5%) due to sensory loss, polyneuropathy and pain (grade 3). Eleven patients (27.5%) remained asymptomatic according to the NCI-CTC scale.ConclusionThe results of our study are in agreement with published data. Based on the findings that over one-fifth of patients receiving high cumulative doses of oxaliplatin experience significant neurotoxicity, a clinical pharmacist’s intervention in the form of a consultation with the physician is thereby warranted in order to re-evaluate the benefit of chemotherapy treatment versus the impact on a patient’s quality of life.References and/or Acknowledgements1. de Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol2000;18:2938–2947.2. Greothey A. Oxaxliplatin-safety profile: neurotoxicity. Seminars in OncologyAugust 2003;30(No. 4, Suppl. 15):5–13.No conflict of interest

Background The Oncology Institute of Ljubljana (OIL) is the main cancer care institution in Slovenia. Extravasation is a serious complication of intravenous chemotherapy. Clinical outcomes vary from minor symptoms to severe tissue damage. The aim of the guidelines is to provide appropriate, professional and clear instructions on how to treat the patients in whom extravasations occur. Purpose To develop guidelines for treating anticancer drug extravasation, which contain the management algorithm of antidotes and treatments that should be performed, as well as risk factors and strategies to prevent extravasation. Furthermore, to statistically review all documented cases of anticancer drug extravasations from January 2010 to September 2013. Materials and methods 47 different intravenous anticancer drugs are available in chemotherapy protocols in OIL. Our extravasation guidelines were based on a literature review, through research and analysis of guidelines and articles obtained. Results Anticancer drugs are classified according to their damage-causing potential as vesicant, non vesicant and irritant; this determines the treatment regimens recommended. From the literature reviewed it was obvious that some anticancer drugs differ in classification according to their injury-inflicting potential and treatment regimens. In our guidelines we did not consider that distinction between vesicant and non-vesicant drugs to be absolute. The measures to be taken when chemotherapy extravasation occurs are based on the classification of their potential, ATC classification and knowledge of the actions of the drug and its antidote. Our guidelines include three specific antidotes: dimethyl sulfoxide, hyaluronidase and dexrazoxane, found in the literature review. A total of 47 anticancer drugs available in our guidelines were divided into 10 vesicants, 10 irritants and 16 non-vesicant drugs. 8 drugs were classified as both vesicant and irritant and 3 drugs as both irritant and non vesicant. Topical application of cold packs is recommended for 20 anticancer drugs, warm packs for 4 drugs, for 5 drugs we can use either of them and 18 drugs require none of the above. Specific management of some anticancer drugs (packs, antidotes) is changed when a large volume and high concentration is extravasated. In the events reported, the extravasated drugs were classified as vesicant in 59% of cases, irritant in 17% and non-vesicant in 24% of cases. In 60 cases specific antidotes and in 77 cases cold packs were administered but in 32 cases further action was required. Antidotes were administered in 11% of cases studied: mainly dimethyl sulfoxide (48%) and hyaluronidase (41%) but also dexrazoxane. Conclusions The guidelines are a valuable tool for our institute as well as for other medical centres throughout Slovenia. In addition each case of extravasation is documented through an anticancer drug extravasation documentation form. No conflict of interest.

Materials and Methods Five databases were searched from their inception to 2011: MEDLINE, EMBASE, CINAHL, Web of Science (including a citation search of relevant papers) and the Cochrane Library. Relevant systematic reviews and personal archives were also hand-searched for studies for inclusion. Only original research papers published in English describing pharmacist-led medicines reviews in a hospital setting including a minimum of 100 patients were included in the final assessment. Results A total of 836 research papers were identified and 30 publications were included in the study. Twenty studies were descriptive studies while ten studies were controlled to some extent. Only six studies were randomised controlled trials. Generally, the interventions were well implemented with acceptance rates between 39-100%. The key findings indicated positive effects on quality of prescribing, quality of life, readmission rates and emergency department visits, time to readmission and costs. However, no effect on survival rates was found in addition to several other statistically insignificant results.Conclusions Only a few papers describing pharmacist-led medicines reviews in the hospital setting were designed as randomised controlled trials and were evaluated using hard endpoints. Future research within this area should be designed using rigorous methodology and include outcome measures for patient health outcomes.No conflict of interest. Medicines and Their cosTs in The LasT six days of Life