Don't Make Things Harder Than They Need to Be.

Consult Pharm. 2017 May 01;32(5):246

Authors: Davidson HE

PMID: 28483004 [PubMed - indexed for MEDLINE]

Impact of early in-hospital medication review by clinical pharmacists on health services utilization.

PLoS One. 2017;12(2):e0170495

Authors: Hohl CM, Partovi N, Ghement I, Wickham ME, McGrail K, Reddekopp LN, Sobolev B

Abstract
BACKGROUND: Adverse drug events are a leading cause of emergency department visits and unplanned admissions, and prolong hospital stays. Medication review interventions aim to identify adverse drug events and optimize medication use. Previous evaluations of in-hospital medication reviews have focused on interventions at discharge, with an unclear effect on health outcomes. We assessed the effect of early in-hospital pharmacist-led medication review on the health outcomes of high-risk patients.
METHODS: We used a quasi-randomized design to evaluate a quality improvement project in three hospitals in British Columbia, Canada. We incorporated a clinical decision rule into emergency department triage pathways, allowing nurses to identify patients at high-risk for adverse drug events. After randomly selecting the first eligible patient for participation, clinical pharmacists systematically allocated subsequent high-risk patients to medication review or usual care. Medication review included obtaining a best possible medication history and reviewing the patient's medications for appropriateness and adverse drug events. The primary outcome was the number of days spent in-hospital over 30 days, and was ascertained using administrative data. We used median and inverse propensity score weighted logistic regression modeling to determine the effect of pharmacist-led medication review on downstream health services use.
RESULTS: Of 10,807 high-risk patients, 6,416 received early pharmacist-led medication review and 4,391 usual care. Their baseline characteristics were balanced. The median number of hospital days was reduced by 0.48 days (95% confidence intervals [CI] = 0.00 to 0.96; p = 0.058) in the medication review group compared to usual care, representing an 8% reduction in the median length of stay. Among patients under 80 years of age, the median number of hospital days was reduced by 0.60 days (95% CI = 0.06 to 1.17; p = 0.03), representing 11% reduction in the median length of stay. There was no significant effect on emergency department revisits, admissions, readmissions, or mortality.
LIMITATIONS: We were limited by our inability to conduct a randomized controlled trial, but used quasi-random patient allocation methods and propensity score modeling to ensure balance between treatment groups, and administrative data to ensure blinded outcomes ascertainment. We were unable to account for alternate level of care days, and therefore, may have underestimated the treatment effect in frail elderly patients who are likely to remain in hospital while awaiting long-term care.
CONCLUSIONS: Early pharmacist-led medication review was associated with reduced hospital-bed utilization compared to usual care among high-risk patients under 80 years of age, but not among those who were older. The results of our evaluation suggest that medication review by pharmacists in the emergency department may impact the length of hospital stay in select patient populations.

PMID: 28192477 [PubMed - indexed for MEDLINE]

Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis.

Crit Rev Toxicol. 2016 Jul;46(6):477-89

Authors: Onakpoya IJ, Heneghan CJ, Aronson JK

Abstract
We have systematically identified medicinal products withdrawn worldwide because of adverse drug reactions, assessed the level of evidence used for making the withdrawal decisions, and explored the patterns of withdrawals over time. We searched PubMed, the WHO database of withdrawn products, and selected texts. We included products that were withdrawn after launch from 1950 onwards, excluding non-human and over-the-counter medicines. We assessed the levels of evidence on which withdrawals were based using the Oxford Center for Evidence Based Medicine Levels of Evidence. Of 353 medicinal products withdrawn from any country, only 40 were withdrawn worldwide. Anecdotal reports were cited as evidence for withdrawal in 30 (75%) and deaths occurred in 27 (68%). Hepatic, cardiac, and nervous system toxicity accounted for over 60% of withdrawals. In 28 cases, the first withdrawal was initiated by the manufacturer. The median interval between the first report of an adverse drug reaction that led to withdrawal and the first withdrawal was 1 year (range 0-43 years). Worldwide withdrawals occurred within 1 year after the first withdrawal in any country. In conclusion, the time it takes for drugs to be withdrawn worldwide after reports of adverse drug reactions has shortened over time. However, there are inconsistencies in current withdrawal procedures when adverse drug reactions are suspected. A uniform method for establishing worldwide withdrawal of approved medicinal products when adverse drug reactions are suspected should be developed, to facilitate global withdrawals. Rapid synthesis of the evidence on harms should be a priority when serious adverse reactions are suspected.

PMID: 26941185 [PubMed - indexed for MEDLINE]

Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study.

J Clin Oncol. 2017 Aug 23;:JCO2017723064

Authors: Shore ND, Boorjian SA, Canter DJ, Ogan K, Karsh LI, Downs TM, Gomella LG, Kamat AM, Lotan Y, Svatek RS, Bivalacqua TJ, Grubb RL, Krupski TL, Lerner SP, Woods ME, Inman BA, Milowsky MI, Boyd A, Treasure FP, Gregory G, Sawutz DG, Yla-Herttuala S, Parker NR, Dinney CPN

Abstract
Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 10(11) vp/mL, n = 21; 3 × 10(11) vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd--IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy.

PMID: 28834453 [PubMed - as supplied by publisher]

Outcome of cancer-related seizures in patients treated with lacosamide.

Acta Neurol Scand. 2017 Aug 22;:

Authors: Toledo M, Molins A, Quintana M, Santamarina E, Martinez-Ricarte F, Martínez-Saez E, Salas-Puig J

Abstract
OBJECTIVES: Lacosamide is an antiepileptic drug (AED), which has proven to be effective to control seizures, including acute conditions such as status epilepticus. The aim of this study is to describe the clinical experience with lacosamide in neuro-oncological patients.
MATERIALS AND METHODS: Multicenter retrospective study in patients with cancer-related seizures, who received lacosamide as an add-on therapy.
RESULTS: Forty-eight patients with benign and malignant tumors, including primary brain tumors, lymphomas, systemic cancer with central nervous system involvement, or paraneoplastic encephalitis, were included. Lacosamide was effective in the control of chronic seizures in patients with either benign or malignant tumors. The success rate was greater in malignant tumors, and drug-resistant epilepsies were more likely associated with benign tumors. Adverse events occurred in nearly 70% of patients, particularly in acute conditions and associated with the concomitant use of radio-/chemotherapy. Lacosamide-related adverse events were more likely somnolence and dizziness, which usually resolved after dose adjustment. After starting lacosamide, nearly half of the patients discontinued one of the baseline AEDs and decreased or discontinued dexamethasone. Fifteen patients with status epilepticus were treated with intravenous lacosamide, and 73% of them had their condition resolved without serious drug-related adverse events.
CONCLUSION: Lacosamide is an AED to consider in cases of cancer-related seizures. Lacosamide pharmacodynamics and pharmacokinetics allow the achievement of responder rates over 50% with no serious adverse effects, amelioration of side effects from other AEDs or radio-/chemotherapy, and no significant drug interactions. Furthermore, the intravenous formulation shows clear benefits in acute conditions such as status epilepticus.

PMID: 28832891 [PubMed - as supplied by publisher]

The Marginal Costs of Adverse Drug Events Associated With Exposures to Anticoagulants and Hypoglycemic Agents During Hospitalization.

Med Care. 2017 Sep;55(9):856-863

Authors: Spector WD, Limcangco R, Furukawa MF, Encinosa WE

Abstract
BACKGROUND: Anticoagulants and hypoglycemic agents are 2 of the most challenging drug classes for medical management in the hospital resulting in many adverse drug events (ADEs).
OBJECTIVE: Estimating the marginal cost (MC) of ADEs associated with anticoagulants and hypoglycemic agents for adults in 5 patient groups during their hospital stay and the total annual ADE costs for all patients exposed to these drugs during their stay.
RESEARCH DESIGN AND SUBJECT: Data are from 2010 to 2013 Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases and Medicare Patient Safety Monitoring System (MPSMS). Deidentified patients were linked using probabilistic matching in the same hospital and year for 5 patient groups. ADE information was obtained from the MPSMS using retrospective structured record review. Costs were derived using HCUP cost-to-charge ratios. MC estimates were made using Extended Estimating Equations controlling for patient characteristics, comorbidities, hospital procedures, and hospital characteristics. MC estimates were applied to the 2013 HCUP National Inpatient Sample to estimate annual ADE costs.
RESULTS: Adjusted MC estimates were smaller than unadjusted measures with most groups showing estimates that were at least 50% less. Adjusted anticoagulant ADE costs added >45% and Hypoglycemic ADE costs added >20% to inpatient costs. The 2013 hospital cost estimates for ADEs associated with anticoagulants and hypoglycemic agents were >$2.5 billion for each drug class.
CONCLUSIONS: This study demonstrates the importance of accounting for confounders in the estimation of ADEs, and the importance of separate estimates of ADE costs by drug class.

PMID: 28742544 [PubMed - indexed for MEDLINE]

An assessor-blinded, randomized comparison of efficacy and tolerability of switching from olanzapine to ziprasidone and the combination of both in schizophrenia spectrum disorders.

J Psychiatr Res. 2017 Feb;85:59-65

Authors: Wang HH, Cai M, Wang HN, Chen YC, Zhang RG, Wang Y, McAlonan GM, Bai YH, Wu WJ, Guo L, Zhang YH, Tan QR, Zhang ZJ

Abstract
BACKGROUND: Ziprasidone (ZIP) is often used with olanzapine (OLZ) in 'switch' and combination therapy but empirical evidence to support these strategies is limited.
OBJECTIVE: This study was therefore designed to compare the efficacy and tolerability of switching from OLZ to ZIP, the combination of both medications, and OLZ and ZIP monotherapy, in patients with schizophrenia spectrum disorders (SSD).
METHODS: In this 12 week open-label, assessor-blinded randomized trial, 148 patients with SSD who had not used antipsychotics for at least 3 months were assigned to ZIP (n = 49) or OLZ monotherapy (n = 31); OLZ for 4 weeks then a switch to ZIP (OLZ/ZIP, n = 35); or combination therapy (OLZ + ZIP, n = 33). The severity of psychosis and abnormal involuntary movements was evaluated at baseline, 1, 2, 4, 8, and 12 weeks using standard instruments. Baseline-to-endpoint changes in weight gain and metabolic measures were compared.
RESULTS: The efficacy of both OLZ/ZIP and OLZ + ZIP was comparable OLZ monotherapy and better than ZIP monotherapy in reducing overall psychotic and negative symptoms at most 8 and 12 week measurement points. Changes in weight gain, glucose, and lipid measures did not differ between OLZ/ZIP and OLZ + ZIP, but were markedly higher following OLZ monotherapy. The OLZ + ZIP group had the lowest overall incidence of adverse events and extrapyramidal symptoms of all the treatment regimens.
CONCLUSIONS: We conclude that combining ZIP and OLZ at the outset of treatment is superior to switching from OLZ to ZIP in terms of improving psychotic symptoms and limiting movement side effects without increasing the risk of metabolic syndrome.

PMID: 27837658 [PubMed - indexed for MEDLINE]

[Pharmacovigilance in Germany : It is about time].

Internist (Berl). 2016 Jun;57(6):616-23

Authors: Douros A, Schaefer C, Kreutz R, Garbe E

Abstract
BACKGROUND: Pharmacovigilance is defined as the activities relating to the detection, assessment, and prevention of adverse drug reactions (ADRs). Although its beginnings in Germany date back more than 50 years, a stagnation in this field has been observed lately.
OBJECTIVES: Different tools of pharmacovigilance will be illustrated and the reasons for its stagnation in Germany will be elucidated.
CURRENT DATA: Spontaneous reporting systems are an important tool in pharmacovigilance and are based on reports of ADRs from treating physicians, other healthcare professionals, or patients. Due to several weaknesses of spontaneous reporting systems such as underreporting, media bias, confounding by comorbidity or comedication, and due to the limited quality of the reports, the development of electronic healthcare databases was publicly funded in recent years so that they can be used for pharmacovigilance research. In the US different electronic healthcare databases were merged in a project sponsored by public means resulting in more than 193 million individuals. In Germany the establishment of large longitudinal databases was never conceived as a public duty and has not been implemented so far. Further attempts to use administrative healthcare data for pharmacovigilance purposes are severely restricted by the Code of Social Law (Section 75, Book 10). This situation has led to a stagnation in pharmacovigilance research in Germany.
CONCLUSIONS: Without publicly funded large longitudinal healthcare databases and an amendment of Section 75, Book 10, of the Code of Social Law, the use of healthcare data in pharmacovigilance research in Germany will remain a rarity. This could have negative effects on the medical care of the general population.

PMID: 27224991 [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 2017/08/23

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.

A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout.

Ann Rheum Dis. 2017 Sep;76(9):1522-1528

Authors: Stamp LK, Chapman PT, Barclay ML, Horne A, Frampton C, Tan P, Drake J, Dalbeth N

Abstract
OBJECTIVES: To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach.
METHODS: A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for ≥1 month and SU ≥6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months. In the dose escalation group, allopurinol was increased monthly until SU was <6 mg/dL. The primary endpoints were reduction in SU and adverse events (AEs).
RESULTS: 183 participants (93 control, 90 dose escalation) were recruited. At baseline, mean (SD) urate was 7.15 (1.6) mg/dL and allopurinol dose 269 mg/day. 52% had CrCL<60 mL/min. Mean changes in SU at the final visit were -0.34 mg/dL in the control group and -1.5 mg/dL in the dose escalation group (p<0.001) with a mean difference of 1.2 mg/dL (95% CI 0.67 to 1.5, p<0.001). At month 12, 32% of controls and 69% in the dose escalation had SU <6 mg/dL. There were 43 serious AEs in 25 controls and 35 events in 22 dose escalation participants. Only one was considered probably related to allopurinol. Five control and five dose escalation participants died; none was considered allopurinol related. Mild elevations in LFTs were common in both groups, a few moderate increases in gamma glutamyl transferase (GGT) were noted. There was no difference in renal function changes between randomised groups.
CONCLUSIONS: Higher than CrCL-based doses of allopurinol can effectively lower SU to treatment target in most people with gout. Allopurinol dose escalation is well tolerated.
TRIAL REGISTRATION NUMBER: ANZCTR12611000845932; Results.

PMID: 28314755 [PubMed - indexed for MEDLINE]

Multicenter study of skin rashes and hepatotoxicity in antiretroviral-naïve HIV-positive patients receiving non-nucleoside reverse-transcriptase inhibitor plus nucleoside reverse-transcriptase inhibitors in Taiwan.

PLoS One. 2017;12(2):e0171596

Authors: Wu PY, Cheng CY, Liu CE, Lee YC, Yang CJ, Tsai MS, Cheng SH, Lin SP, Lin DY, Wang NC, Lee YC, Sun HY, Tang HJ, Hung CC

Abstract
OBJECTIVES: Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs.
METHODS: Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study. According to the national HIV treatment guidelines, patients were assessed at baseline, 2 and 4 weeks of cART initiation, and subsequently every 8 to 12 weeks. Plasma HIV RNA load, CD4 cell count and aminotransferases were determined. The toxicity grading scale of the Division of AIDS (DAIDS) 2014 was used for reporting clinical and laboratory adverse events.
RESULTS: During the 3.5-year study period, 2,341 patients initiated nNRTI-containing cART: NVP in 629 patients, EFV 1,363 patients, and RPV 349 patients. Rash of any grade occurred in 14.1% (n = 331) of the patients. In multiple logistic regression analysis, baseline CD4 cell counts (per 100-cell/μl increase, adjusted odds ratio [AOR], 1.125; 95% confidence interval [95% CI], 1.031-1.228) and use of NVP (AOR, 2.443; 95% CI, 1.816-3.286) (compared with efavirenz) were independently associated with the development of skin rashes. Among the 1,455 patients (62.2%) with aminotransferase data both at baseline and week 4, 72 (4.9%) developed grade 2 or greater hepatotoxicity. In multiple logistic regression analysis, presence of antibody for hepatitis C virus (HCV) (AOR, 2.865; 95% CI, 1.439-5.704) or hepatitis B surface antigen (AOR, 2.397; 95% CI, 1.150-4.997), and development of skin rashes (AOR, 2.811; 95% CI, 1.051-7.521) were independently associated with the development of hepatotoxicity.
CONCLUSIONS: The baseline CD4 cell counts and use of NVP were associated with increased risk of skin rashes, while hepatotoxicity was independently associated with HCV or hepatitis B virus coinfection, and development of skin rashes in antiretroviral-naïve HIV-positive Taiwanese patients within 4 weeks of initiation of nNRTI-containing regimens.

PMID: 28222098 [PubMed - indexed for MEDLINE]

Development of the Liverpool Adverse Drug Reaction Avoidability Assessment Tool.

PLoS One. 2017;12(1):e0169393

Authors: Bracken LE, Nunn AJ, Kirkham JJ, Peak M, Arnott J, Smyth RL, Pirmohamed M, Turner MA

Abstract
AIM: To develop and test a new tool to assess the avoidability of adverse drug reactions that is suitable for use in paediatrics but which is also applicable to a variety of other settings.
METHODS: The study involved multiple phases. Preliminary work involved using the Hallas scale and a modification of the existing Hallas scale, to assess two different sets of adverse drug reaction (ADR) case reports. Phase 1 defined, modified and refined a new tool using multidisciplinary teams. Phase 2 involved the assessment of 50 ADR case reports from a prospective study of paediatric inpatients by individual assessors. Phase 3 compared assessments with the new tool for individuals and groups in comparison to the 'gold standard' (the avoidability outcome set by a panel of senior investigators: an experienced clinical pharmacologist, paediatrician and pharmacist).
MAIN OUTCOME MEASURES: Inter-rater reliability (IRR), measure of disagreement and utilization of avoidability categories.
RESULTS: Preliminary work-Pilot phase: results for the original Hallas cases were fair and pairwise kappa scores ranged from 0.21 to 0.36. Results for the modified Hallas cases were poor, pairwise kappa scores ranged from 0.06 to 0.16. Phase 1: on initial use of the new tool, agreement between the two multidisciplinary groups was found on 13/20 cases with a kappa score of 0.29 (95% CI -0.04 to 0.62). Phase 2: the assessment of 50 ADR case reports by six individual reviewers yielded pairwise kappa scores ranging from poor to good 0.12 to 0.75 and percentage exact agreement (%EA) ranged from 52-90%. Phase 3: Percentage exact agreement ranged from 35-70%. Overall, individuals had better agreement with the 'gold standard'.
CONCLUSION: Avoidability assessment is feasible but needs careful attention to methods. The Liverpool ADR avoidability assessment tool showed mixed IRR. We have developed and validated a method for assessing the avoidability of ADRs that is transparent, more objective than previous methods and that can be used by individuals or groups.

PMID: 28046035 [PubMed - indexed for MEDLINE]

Risk Factors for Initiation of Potentially Inappropriate Medications in Community-Dwelling Older Adults with and without Alzheimer's Disease.

Drugs Aging. 2017 Jan;34(1):67-77

Authors: Hyttinen V, Taipale H, Tanskanen A, Tiihonen J, Tolppanen AM, Hartikainen S, Valtonen H

Abstract
BACKGROUND: Various criteria have been created to define potentially inappropriate medications (PIMs) to help improve the quality and safety of medicine use in older patients. Individuals with Alzheimer's disease (AD) may be at higher risk of adverse drug events associated with PIMs (such as falls).
OBJECTIVE: Our objective was to determine the risk factors for PIM initiation in a nationwide cohort of community dwellers aged ≥65 years with and without AD.
METHODS: The Finnish nationwide MEDALZ cohort includes all patients diagnosed with AD in 2005-2011 (n = 70,718) and two comparison individuals without AD (non-AD) matched for age, sex and region of residence for each person with AD. After a 1-year washout period for PIM use and exclusion of those aged <65 years, we included 50,494 patients with AD and 106,306 comparison subjects. PIM use was defined according to Finnish criteria.
RESULTS: Subjects without AD initiated PIMs more frequently than those with AD (16.4 vs. 12.2%, respectively; p < 0.001). The most common PIMs were muscle relaxants and urinary antispasmodics. Older individuals (aged ≥75 years) were less likely to initiate PIMs. In the AD group, women were less likely to initiate PIMs than men. More comorbidities were associated with PIM initiation, especially in the non-AD group. The use of opioids or psychotropic medicines was associated with PIM initiation in both cohorts. Regional differences between university hospital districts were observed.
CONCLUSION: PIM initiation was dependent on patient characteristics and possibly also some healthcare system-related factors such as differing regional treatment practices. It is important that medicines prescribed to the older vulnerable population are assessed regularly to avoid adverse effects and ensure safe pharmacotherapy, especially in those with multiple comorbidities.

PMID: 27838819 [PubMed - indexed for MEDLINE]

Long-term Outcomes of Thalidomide Therapy for Adults With Refractory Crohn's Disease.

Clin Gastroenterol Hepatol. 2016 Jul;14(7):966-972.e2

Authors: Simon M, Pariente B, Lambert J, Cosnes J, Bouhnik Y, Marteau P, Allez M, Colombel JF, Gornet JM

Abstract
BACKGROUND & AIMS: Little is known about the efficacy and safety of thalidomide therapy for patients with refractory Crohn's disease (CD), particularly in respect to long-term outcomes of patients.
METHODS: We conducted a retrospective multicenter observational study to evaluate thalidomide efficacy and the probability of its withdrawal because of either toxicity or lack/loss of efficacy. We analyzed data from 77 patients with active intestinal and/or perineal CD, refractory to conventional immunosuppressive therapies, treated with thalidomide at 5 tertiary referral inflammatory bowel disease centers in France. We also analyzed the long-term efficacy of thalidomide.
RESULTS: Fifty-four percent of the patients were in clinical remission after thalidomide treatment within the first year. The proportions of patients from whom thalidomide was withdrawn because of lack/loss of efficacy and/or toxicity were 35% at 3 months of treatment, 69% at 12 months, and 88% at 24 months. The proportions of patients from whom thalidomide was withdrawn because of toxicity alone were 22% at 3 months, 34% at 12 months, and 46% at 24 months. Overall, neuropathy occurred in 30 patients and was the main reason for thalidomide withdrawal.
CONCLUSIONS: On the basis of a retrospective multicenter observational study, thalidomide therapy is effective in most patients with refractory active intestinal and/or perineal CD. However, its toxicity limits its use as a maintenance therapy.

PMID: 26598226 [PubMed - indexed for MEDLINE]

12 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 2017/08/19

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.

13 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 2017/08/19

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.

12 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 2017/08/18

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.

A Case of IVIG-Induced Aseptic Chemical Meningitis.

S D Med. 2017 Mar;70(3):119-121

Authors: Patel A, Potu KC, Sturm T

Abstract
Intravenous immunoglobulin (IVIG) is a commonly used and generally well-tolerated medication. Common side effects include flu-like symptoms such as fevers, headaches, myalgia, fatigue, and nausea. One of the more rare side effects is aseptic meningitis, with a reported incidence rate of around 0.067 percent of all IVIG infusions. In this paper, we describe a 47-year-old female patient with a history of myasthenia gravis who presented with a headache, neck pain, and neck stiffness while undergoing IVIG infusions for a myasthenia crisis. On admission day, the patient was afebrile with stable vital signs. A physical examination revealed nuchal rigidity and tenderness with no focal neurological deficits. Cerebrospinal fluid (CSF) cytology noted an elevated white blood cell (WBC) count of 1,138 cells/μL with a neutrophil predominance (96 percent). CSF red blood cell count was unremarkable at 1 cell/μL. The patient's IVIG infusions were stopped, suspecting chemical meningitis. Given the markedly elevated CSF WBC count with neutrophil predominance, she was started on vancomycin and ceftriaxone to also cover for bacterial meningitis. The patient's meningeal signs and symptoms significantly improved 24 hours after admission. Given the clear temporal relationship to IVIG administration and the rapid improvement of symptoms, IVIG-induced aseptic meningitis is strongly suspected. The patient's antibiotics were discontinued. Forty-eight hours after stopping IVIG and 24 hours after discontinuing antibiotics, her meningitis symptoms completely resolved with the use of analgesics alone. The patient was then discharged uneventfully. CSF viral and bacterial studies, including a gram stain and cultures, did not result in anything noteworthy. Our case presents an interesting diagnostic dilemma where drug-induced (IVIG) aseptic meningitis mimics bacterial meningitis clinically and on CSF analysis. The clear temporal relationship to IVIG administration and the rapid resolution of symptoms upon stopping the drug can aid in the diagnosis of this rare event and help doctors avoid the use of unnecessary antibiotic therapy.

PMID: 28813773 [PubMed - in process]

Deprescribing: A simple method for reducing polypharmacy.

J Fam Pract. 2017 Jul;66(7):436-445

Authors: McGrath K, Hajjar ER, Kumar C, Hwang C, Salzman B

Abstract
Polypharmacy brings with it increased risks for adverse drug events and reduced functional capacity. This 4-step plan will help you safely deprescribe in older adults.

PMID: 28700758 [PubMed - indexed for MEDLINE]

Pretreatment serum uracil concentration as a predictor of severe and fatal fluoropyrimidine-associated toxicity.

Br J Cancer. 2017 May 23;116(11):1415-1424

Authors: Meulendijks D, Henricks LM, Jacobs BAW, Aliev A, Deenen MJ, de Vries N, Rosing H, van Werkhoven E, de Boer A, Beijnen JH, Mandigers CMPW, Soesan M, Cats A, Schellens JHM

Abstract
BACKGROUND: We investigated the predictive value of dihydropyrimidine dehydrogenase (DPD) phenotype, measured as pretreatment serum uracil and dihydrouracil concentrations, for severe as well as fatal fluoropyrimidine-associated toxicity in 550 patients treated previously with fluoropyrimidines during a prospective multicenter study.
METHODS: Pretreatment serum concentrations of uracil and dihydrouracil were measured using a validated LC-MS/MS method. The primary endpoint of this analysis was global (any) severe fluoropyrimidine-associated toxicity, that is, grade ⩾3 toxicity according to the NCI CTC-AE v3.0, occurring during the first cycle of treatment. The predictive value of uracil and the uracil/dihydrouracil ratio for early severe fluoropyrimidine-associated toxicity were compared. Pharmacogenetic variants in DPYD (c.2846A>T, c.1679T>G, c.1129-5923C>G, and c.1601G>A) and TYMS (TYMS 5'-UTR VNTR and TYMS 3'-UTR 6-bp ins/del) were measured and tested for associations with severe fluoropyrimidine-associated toxicity to compare predictive value with DPD phenotype. The Benjamini-Hochberg false discovery rate method was used to control for type I errors at level q<0.050 (corresponding to P<0.010).
RESULTS: Uracil was superior to the dihydrouracil/uracil ratio as a predictor of severe toxicity. High pretreatment uracil concentrations (>16 ng ml(-1)) were strongly associated with global severe toxicity (OR 5.3, P=0.009), severe gastrointestinal toxicity (OR 33.7, P<0.0001), toxicity-related hospitalisation (OR 16.9, P<0.0001), as well as fatal treatment-related toxicity (OR 44.8, P=0.001). None of the DPYD variants alone, or TYMS variants alone, were associated with severe toxicity.
CONCLUSIONS: High pretreatment uracil concentration was strongly predictive of severe, including fatal, fluoropyrimidine-associated toxicity, and is a highly promising phenotypic marker to identify patients at risk of severe fluoropyrimidine-associated toxicity.

PMID: 28427087 [PubMed - indexed for MEDLINE]