Leflunomide: an unlikely trigger and mechanistically a beneficial drug for alopecia areata.

Clin Rheumatol. 2019 10;38(10):2957-2958

Authors: Sardana K, Gupta A, Gupta PK

PMID: 31332691 [PubMed - indexed for MEDLINE]

Detecting adverse drug reactions in discharge summaries of electronic medical records using Readpeer.

Int J Med Inform. 2019 08;128:62-70

Authors: Tang Y, Yang J, Ang PS, Dorajoo SR, Foo B, Soh S, Tan SH, Tham MY, Ye Q, Shek L, Sung C, Tung A

Abstract
BACKGROUND: Hospital discharge summaries offer a potentially rich resource to enhance pharmacovigilance efforts to evaluate drug safety in real-world clinical practice. However, it is infeasible for experts to read through all discharge summaries to find cases of drug-adverse event (AE) relations.
PURPOSE: The objective of this paper is to develop a natural language processing (NLP) framework to detect drug-AE relations from unstructured hospital discharge summaries.
BASIC PROCEDURES: An NLP algorithm was designed using customized dictionaries of drugs, adverse event (AE) terms, and rules based on trigger phrases, negations, fuzzy logic and word distances to recognize drug, AE terms and to detect drug-AE relations. Furthermore, a customized annotation tool was developed to facilitate expert review of discharge summaries from a tertiary hospital in Singapore in 2011.
MAIN FINDINGS: A total of 33 trial sets with 50 to 100 records per set were evaluated (1620 discharge summaries) by our algorithm and reviewed by pharmacovigilance experts. After every 6 trial sets, drug and AE dictionaries were updated, and rules were modified to improve the system. Excellent performance was achieved for drug and AE entity recognition with over 92% precision and recall. On the final 6 sets of discharge summaries (600 records), our algorithm achieved 75% precision and 59% recall for identification of valid drug-AE relations.
PRINCIPAL CONCLUSIONS: Adverse drug reactions are a significant contributor to health care costs and utilization. Our algorithm is not restricted to particular drugs, drug classes or specific medical specialties, which is an important attribute for a national regulatory authority to carry out comprehensive safety monitoring of drug products. Drug and AE dictionaries may be updated periodically to ensure that the tool remains relevant for performing surveillance activities. The development of the algorithm, and the ease of reviewing and correcting the results of the algorithm as part of an iterative machine learning process, is an important step towards use of hospital discharge summaries for an active pharmacovigilance program.

PMID: 31160013 [PubMed - indexed for MEDLINE]

Effects of Bifidobacterium breve A1 on the cognitive function of older adults with memory complaints: a randomised, double-blind, placebo-controlled trial.

Benef Microbes. 2019 May 28;10(5):511-520

Authors: Kobayashi Y, Kuhara T, Oki M, Xiao JZ

Abstract
In our previous study, we reported the therapeutic potential of Bifidobacterium breve A1 in preventing cognitive impairment in a mouse model of Alzheimer's disease and participants with mild cognitive impairment; we suggested that probiotic supplementation is an effective therapeutic strategy for managing cognitive function. Accordingly, we conducted a randomised, double-blind, placebo-controlled trial to assess whether 12-week B. breve A1 supplementation could affect the cognitive function of elderly subjects with memory complaints. We assessed cognitive function using the Japanese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Mini-Mental State Examination (MMSE) at baseline and after 12 weeks of probiotic supplementation. A total of 121 participants were randomised and received B. breve A1 capsules or placebo daily for 12 weeks; of these, 117 participants completed the study. At 12 weeks, neuropsychological test scores significantly increased in both groups; no significant intergroup difference was observed in terms of changes in scores from the baseline scores. However, a stratified analysis revealed a significant difference between B. breve A1 and placebo groups in terms of the subscale 'immediate memory' of RBANS and MMSE total score in the subjects with low RBANS total score at baseline. No significant differences in terms of blood parameters between the groups or adverse effects caused by B. breve A1 intervention were observed. The results of the present study suggest the safety of B. breve A1 supplementation and its potential in maintaining cognitive function in elderly subjects with memory complaints. However, future large-scale studies on individuals with impaired cognitive function are required to validate the present findings.

PMID: 31090457 [PubMed - indexed for MEDLINE]

Office-based assessment of cognitive impairment.

Aust J Gen Pract. 2018 09;47(9):602-605

Authors: Pond D

Abstract
BACKGROUND: Dementia is an increasingly prevalent condition, currently affecting over 400,000 Australians, and this is expected to rise to over one million by 2056. Diagnosis of dementia is a clinical one, as there is no single well-defined blood test, imaging or cognitive function test that validly diagnoses dementia. There are also many causes of cognitive impairment other than dementia, which need to be identified or excluded. General practitioners (GPs) are on the frontline of presentation and will therefore play an increasingly important role in identification and management.
OBJECTIVE: This article reviews what the GP can do in relation to office-based assessment for cognitive impairment.
DISCUSSION: Dementia is an increasingly common condition, and it is important that GPs become familiar with its assessment and management in order to optimise access to care services, advance care planning and management of other conditions for their patients.

PMID: 30244559 [PubMed - indexed for MEDLINE]

Radium-223 Dichloride in Combination with Vascular Endothelial Growth Factor-Targeting Therapy in Advanced Renal Cell Carcinoma with Bone Metastases.

Clin Cancer Res. 2018 09 01;24(17):4081-4088

Authors: McKay RR, Bossé D, Gray KP, Michaelson MD, Krajewski K, Jacene HA, Walsh M, Bellmunt J, Pomerantz M, Harshman LC, Choueiri TK

Abstract
Purpose: This study investigates the biologic activity of radium-223 with VEGF-targeted therapy in patients with advanced renal cell carcinoma (aRCC) and bone metastases.Patients and Methods: Fifteen treatment-naïve patients (n = 15) received pazopanib 800 mg orally once daily, and 15 previously treated patients received sorafenib 400 mg orally twice daily. Radium-223 55 kilobecquerel/kg was administered concurrently every 4 weeks for up to six infusions in both cohorts. The primary endpoint was decline in bone turnover markers (Procollagen I Intact N-Terminal, N-telopeptide, C-telopeptide, osteocalcin, and bone-specific alkaline phosphatase) compared with baseline. Secondary endpoints included safety, rate of symptomatic skeletal event (SSE) and time to first SSE, objective response rate, change in analgesic use, and quality of life. Exploratory analysis of tumor genomic alterations was performed.Results: Of the 30 patients enrolled, 83% had IMDC intermediate- or poor-risk disease, 33% had liver metastases, and 83% had a history of SSE prior to enrollment. No dose-limiting toxicity was observed. All bone turnover markers significantly declined from baseline at week 8 and 16. Forty percent of patients experienced treatment-related grade ≥3 adverse events. Response rates were 15% and 18% per RECIST v1.1 and bone response was 50% and 30% per MD Anderson criteria, in the pazopanib and sorafenib cohort, respectively. Median SSE-free interval was 5.8 months and not reached, respectively. Analgesic use remained stable over the study time.Conclusions: Radium-223 combined with VEGF-targeted therapy is biologically active and safe. Randomized-controlled trials are needed to define the role of radium-223 in aRCC with skeletal metastases. Clin Cancer Res; 24(17); 4081-8. ©2018 AACR.

PMID: 29848570 [PubMed - indexed for MEDLINE]

FDA Approval Summary: Niraparib for the Maintenance Treatment of Patients with Recurrent Ovarian Cancer in Response to Platinum-Based Chemotherapy.

Clin Cancer Res. 2018 09 01;24(17):4066-4071

Authors: Ison G, Howie LJ, Amiri-Kordestani L, Zhang L, Tang S, Sridhara R, Pierre V, Charlab R, Ramamoorthy A, Song P, Li F, Yu J, Manheng W, Palmby TR, Ghosh S, Horne HN, Lee EY, Philip R, Dave K, Chen XH, Kelly SL, Janoria KG, Banerjee A, Eradiri O, Dinin J, Goldberg KB, Pierce WF, Ibrahim A, Kluetz PG, Blumenthal GM, Beaver JA, Pazdur R

Abstract
The FDA approved niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, on March 27, 2017, for maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response to platinum-based chemotherapy. Approval was based on data from the NOVA trial comparing niraparib with placebo in two independent cohorts, based on germline BRCA mutation status (gBRCAm vs. non-gBRCAm). Progression-free survival (PFS) in each cohort was the primary endpoint. In the gBRCAm cohort, estimated median PFS on niraparib was 21 months versus 5.5 months on placebo [HR, 0.26; 95% confidence interval (CI), 0.17-0.41; P < 0.0001]. In the non-gBRCAm cohort, estimated median PFS for niraparib and placebo was 9.3 and 3.9 months, respectively (HR, 0.45; 95% CI, 0.34-0.61; P < 0.0001). Common adverse reactions (>20% and higher incidence in the niraparib arm) with niraparib included thrombocytopenia, anemia, neutropenia, nausea, constipation, vomiting, mucositis, fatigue, decreased appetite, headache, insomnia, nasopharyngitis, dyspnea, rash, and hypertension. There were five cases of myelodysplastic syndrome and acute myeloid leukemia (1.4%) in patients treated with niraparib compared with two cases (1.1%) on placebo. Niraparib is the first PARP inhibitor approved as maintenance therapy for patients with ovarian, fallopian tube, or primary peritoneal cancer, with improvement in PFS, regardless of gBRCAm status. Clin Cancer Res; 24(17); 4066-71. ©2018 AACRSee related commentary by Konstantinopoulos and Matulonis, p. 4062.

PMID: 29650751 [PubMed - indexed for MEDLINE]

Replik till Läkemedelsverket: - Risken för tandbiverkningar av doxycyklin är negligerbar.

Lakartidningen. 2017 11 01;114:

Authors: Bremell D, Trollfors B

PMID: 29292912 [PubMed - indexed for MEDLINE]

Nebenwirkungslisten sind kontraproduktiv!

MMW Fortschr Med. 2017 11;159(20):38

Authors: Holzgreve H

PMID: 29159625 [PubMed - indexed for MEDLINE]

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 2019/11/08

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 2019/11/08

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 2019/11/07

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 2019/11/05

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.

Drug-Drug Interactions in Prostate Cancer Treatment.

Clin Genitourin Cancer. 2019 May 27;:

Authors: Hebenstreit D, Pichler R, Heidegger I

Abstract
Polypharmacy is associated with an increased risk of drug-drug interactions (DDIs), which can cause serious and debilitating drug-induced adverse events. With a steadily aging population and associated increasing multimorbidity and polypharmacy, the potential for DDIs becomes considerably important. Prostate cancer (PCa) is the most common cancer in men and occurs mostly in elderly men in the Western world. Therefore, the aim of this review is to give an overview of DDIs in PCa therapy to better understand pharmacodynamic and pharm kinetic side effects as well as their interactions with other medications. Last, we explore potential future strategies, which might help to optimize treatment and reduce adverse events patients with polypharmacy and PCa.

PMID: 31677899 [PubMed - as supplied by publisher]

Effectiveness and Safety of Bupropion in Children and Adolescents with Depressive Disorders: A Retrospective Chart Review.

Clin Psychopharmacol Neurosci. 2019 Nov 20;17(4):537-541

Authors: Kweon K, Kim HW

Abstract
Objective: This study aimed to investigate the effectiveness and safety of bupropion extended-release for the treatment of depressive disorder in children and adolescents.
Methods: This was a 12-week, retrospective chart review of bupropion, which included 127 youth (age, 15.3 ± 2.3 years; 66 boys) with depressive disorders (105 with major depressive disorder, 14 with dysthymia, 11 with adjustment disorder with depressed mood, and seven with depressive disorder not otherwise specified). Illness severity at baseline and at the 4th, 8th, and 12th weeks was retrospectively scored using the Clinical Global Impressions-Depression-Severity (CGI-Depression-S) and/or Clinical Global Impressions-Depression-Improvement (CGI-Depression-I).
Results: The mean dose of bupropion was 180.0 ± 52.6 (range, 75-300) mg/day and the mean duration 33.9 ± 53.1 (range, 7-295) weeks. The CGI-Depression-S scores were significantly decreased over 12 weeks (F = 132.125, p < 0.001, partial η2 = 0.508). Fifty-eight subjects (45.7%) were determined to be responders at 12 weeks (defined by a CGI-Depression-I score ≤ 2). Forty-six patients (36.2%) discontinued bupropion before the 12 weeks (19 due to adverse events, 15 due to poor effectiveness, three due to referral to other clinics, and nine due to follow-up loss for unknown reasons). Overall, bupropion was well tolerated. The most common adverse event was irritability (n = 12, 9.4%), which resolved spontaneously in eight subjects or after drug discontinuation in four subjects.
Conclusion: Our results provide preliminary evidence of the effectiveness and safety of bupropion in children and adolescents with depressive episodes. Large, prospective, placebo-controlled studies are needed to confirm these findings.

PMID: 31671492 [PubMed]

Alemtuzumab-induced lung injury in multiple sclerosis: Learning from adversity in three patients.

Mult Scler Relat Disord. 2019 Oct 15;37:101450

Authors: Bianco A, Mari PV, Larici AR, Lucchini M, Nociti V, Losavio FA, De Fino C, Cicchetti G, Coraci D, Richeldi L, Mirabella M

Abstract
BACKGROUND: Respiratory alemtuzumab-related adverse events are clinically heterogeneous and include respiratory infections, infusion-related dyspnea, hypoxia and secondary autoimmune disorders.
CASE REPORT: Here we report three cases of drug-induced lung disease following treatment with alemtuzumab in multiple sclerosis patients. First case was diagnosed as a non-specified intestitial pneumonitis associated with organizing pneumonia with subacute onset, second case was an acute respiratory distress syndrome with onset during second cycle, third case was a diffuse acute alveolar hemorrhage during first cycle infusion. All patients developed acute respiratory failure, reversible after steroid therapy.
CONCLUSIONS: Clinicians should be aware to early recognize acute and subacute respiratory adverse events for a promptly management. In these patients re-treatment is challenging.

PMID: 31675637 [PubMed - as supplied by publisher]

Analysis of clinical pharmacist interventions in the neurology unit of a Brazilian tertiary teaching hospital.

PLoS One. 2019;14(1):e0210779

Authors: Rodrigues JPV, Marques FA, Gonçalves AMRF, Campos MSA, Reis TMD, Morelo MRS, Fontoura A, Girolineto BMP, Souza HPMC, Cazarim MS, Maduro LCDS, Pereira LRL

Abstract
It is estimated that around five to 10.0% of hospital admissions occur due to clinical conditions resulting from pharmacotherapy. Clinical pharmacist's activity can enhance drug therapy's effectiveness and safety through pharmacotherapy interventions (PIs), thus minimizing drug-related problems (DRPs) and optimizing the allocation of financial resources associated with health care. This study aimed to estimate the DRPs prevalence, evaluate PI which were performed by clinical pharmacists in the Neurology Unit of a Brazilian tertiary teaching hospital and to identify factors associated with the occurrence of PI-related DRP. A single-arm trial included adults admitted in the referred Unit from 2012 July to 2015 June. Patients were evaluated during their hospitalization period and PIs were performed based on trigger DRPs that were detected in medication reconciliation (admission or discharge) or during inpatient follow-up. Student's t-test, Chi-square test, Pearson and Multiple logistic regression models to analise the association among age, number of drugs, hospitalization period, and number of diagnoses with occurrence of DRPs. Analyses level of significance was 5%. In total 409 inpatients were followed up [51.1% male, mean age of 49.1 (SD 16.5)]. Patients received, on average, 11.9 (SD 5.8) drugs, ranging from two to 38 drugs per patient, and 54.3% of the sample presented at least one DRP whose most frequent description was "untreated condition". From all 516 performed PIs that resulted from DRPs, 82.8% were accepted and the majority referred to "drug introduction" (27.5%). Multiple logistic regression showed that age, length of hospital stay, number of drugs used, diagnosis of epilepsy, multiple sclerosis and myasthenia gravis would be clinical variables associated with DRP (p < 0,05). Monitoring the use of drugs allowed the clinical pharmacist to detect DRPs and to suggest interventions that promote rational pharmacotherapy.

PMID: 30657771 [PubMed - indexed for MEDLINE]

[Needs of Patients with Mild Cognitive Disorders in a Specialist Practice].

Psychiatr Prax. 2019 Oct 31;:

Authors: Bohlken J, Rädke A, Kohlmann T, Heller SR, Rapp M

Abstract
OBJECTIVE: To describe the needs of care for patients with mild cognitive impairment (PmMCI).
METHODS: Survey of 51 PmMCI in a specialist care practice. Questionnaire based on the CANE assessment scale. Control variables among others are MMST and GDS.
RESULTS: 35 % or 8 % experienced memory disorder as moderate or severe and 27 % or 8 % felt impaired frequently or continuous in everyday life. Over 70 % were in a balanced mood despite the memory problems. Physician-related expectations: follow-up (96 %), dementia risk assessment (73 %), memory training (55 %), drug treatment (33 %). Drug-related expectations: appreciable effect (41 %), willingness to endure side effects (29 %), preference for herbal medication (59 %). Non-drug therapy expectations: athletic activation (63 %), memory training (51 %) and nutritional counselling (37 %). The desire for psychotherapeutic discussions (27 %) was associated with higher depression levels of GDS.
CONCLUSION: PmMCI experienced memory disorder as a burden and impairment. They expected diagnostic and therapeutic support. PmMCI with depressive symptoms expected psychotherapeutic treatment.

PMID: 31671468 [PubMed - as supplied by publisher]

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report.

Surg Case Rep. 2019 Oct 30;5(1):166

Authors: Sato S, Senmaru N, Ishido K, Saito T, Poudel S, Muto J, Syouji Y, Hase R, Hirano S

Abstract
BACKGROUND: Pembrolizumab is an immune checkpoint inhibitor and is an anti-human programmed cell death-1 (PD-1) monoclonal antibody. Pembrolizumab is used for non-small cell lung carcinoma with high programmed cell death ligand-1 (PD-L1) expression. It has been found that better overall survival can be obtained using pembrolizumab compared to the existing chemotherapy. We report a case of perforation of small intestinal metastasis after pembrolizumab treatment.
CASE PRESENTATION: A 62-year-old man was treated by pembrolizumab for PD-L1 highly expressed lung adenocarcinoma, with multiple metastasis (small intestinal, lymph nodes, and bone). The treatment was stopped owing to drug-induced pneumonitis. One month after drug withdrawal, the patient visited the emergency department of our hospital with the complaint of severe stomachache. He had a rigid abdomen and generalized tenderness, and computed tomography scans showed free air within the abdomen. We diagnosed bowel perforation and performed emergency surgery. Surgical findings revealed multiple small intestine metastasis and mesenteric lymph node metastasis. Perforation was found in the metastatic site in the jejunum located around 40 cm anal to Treitz's ligament. This perforated part was resected, and functional end-to-end anastomosis was performed using linear staplers. The post-operative course was uneventful. Pathological examination revealed lung adenocarcinoma metastasis at the perforation site, and the effectiveness of pembrolizumab was grade 1b (Japanese Classification of the Colorectal Carcinoma, seventh edition).
CONCLUSIONS: This is the first report of perforation of small intestinal metastasis of lung adenocarcinoma after pembrolizumab treatment. Because pembrolizumab causes some side effects, particularly autoimmune side effects, careful attention during treatment is warranted.

PMID: 31667679 [PubMed]

Ceritinib-associated Hyperglycemia in the Japanese Adverse Drug Event Report Database.

J Diabetes Investig. 2019 Oct 29;:

Authors: Fujita H, Murakami T, Tomoike F, Yabe D, Inagaki N

Abstract
Genetic rearrangements of anaplastic lymphoma kinase (ALK) contribute to the pathogenesis of non-small-cell lung cancer (NSCLC); the ALK inhibitor ceritinib is widely used, as it is effective even in patients with NSCLC resistant to other ALK inhibitors. Although a case of possible ceritinib-induced hyperglycemia was reported, the association of ceritinib with hyperglycemia remains to be investigated. Disproportionality analysis was conducted using the Japanese Adverse Drug Event Report database, which contains all pharmacovigilance data based on spontaneous reports of adverse events between April 2004 and November 2018 to the Pharmaceuticals and Medical Devices Agency. The reporting odds ratio (ROR) of ceritinib for hyperglycemia was 2.25 [95% confidence interval (CI), 1.24-4.08], while those of crizotinib and alectinib were 0.07 (0.01-0.40) and 0.94 (0.30-2.94), respectively. Among reported events without anti-diabetes agent use, the ROR of ceritinib was still 2.54 (1.27-5.12). Thus, the possibility of hyperglycemia should be carefully monitored in patients receiving ceritinib.

PMID: 31663274 [PubMed - as supplied by publisher]

[Avoid polypharmacy: Less is more!]

MMW Fortschr Med. 2019 Oct;161(18):48-50

Authors: Maercks M, Weckbecker K

PMID: 31631301 [PubMed - indexed for MEDLINE]