Trigger factors of cutaneous lupus erythematosus: a review of current literature.

Lupus. 2017 Jul;26(8):791-807

Authors: Szczęch J, Samotij D, Werth VP, Reich A

Abstract
It is currently believed that autoimmune conditions are triggered and aggravated by a variety of environmental factors such as cigarette smoking, infections, ultraviolet light or chemicals, as well as certain medications and vaccines in genetically susceptible individuals. Recent scientific data have suggested a relevant role of these factors not only in systemic lupus erythematosus, but also in cutaneous lupus erythematosus (CLE). A variety of environmental factors have been proposed as initiators and exacerbators of this disease. In this review we focused on those with the most convincing evidence, emphasizing the role of drugs in CLE. Using a combined search strategy of the MEDLINE and CINAHL databases the following trigger factors and/or exacerbators of CLE have been identified and described: drugs, smoking, neoplasms, ultraviolet radiation and radiotherapy. In order to give a practical insight we emphasized the role of drugs from various groups and classes in CLE. We also aimed to present a short clinical profile of patients with lesions induced by various drug classes.

PMID: 28173739 [PubMed - indexed for MEDLINE]

Efficacy of olanzapine for the prophylaxis of chemotherapy-induced nausea and vomiting: a meta-analysis.

Br J Clin Pharmacol. 2017 Jul;83(7):1369-1379

Authors: Yang T, Liu Q, Lu M, Ma L, Zhou Y, Cui Y

Abstract
AIM: The aim of the present study was to evaluate the efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV).
METHODS: The literature was searched for randomized controlled trials (RCTs) evaluating the efficacy of olanzapine for the prophylaxis of CINV using PubMed, Embase, Central, as well as clinicaltrials.gov for unpublished studies. The endpoints of the study were the number of patients who achieved a complete response (CR; no emesis and no rescue) and no nausea in the acute, delayed and overall phases. Two authors independently selected studies, assessed the risk of bias and extracted data. The included RCTs were analysed using RevMan 5.3 provided by the Cochrane Collaboration.
RESULTS: Ten RCTs were identified for the meta-analysis. Compared with other antiemetic agents, olanzapine significantly improved the CR in the delayed and overall phases, but did not enhance the CR in the acute phase. For the control of CINV, olanzapine was better than and comparable with aprepitant in the acute phase and delayed phase, respectively. Compared with placebo, treatment with 5 mg and 10 mg olanzapine exhibited similar efficacy in terms of the CR in the delayed and overall phases.
CONCLUSIONS: Olanzapine is an excellent alternative for the prophylaxis of CINV. Olanzapine 5 mg per day should be recommended as the initial dose because of equivalent efficacy to a 10 mg dose but a lower potential risk of side effects. Further studies are needed to explore the optimal combination of medicines.

PMID: 28112422 [PubMed - indexed for MEDLINE]

The northeast regional SPS meeting update: Safety pharmacology innovations and applications.

J Pharmacol Toxicol Methods. 2017 May - Jun;85:82-86

Authors: Pannirselvam M, Brabham T, Botchway AW, Hodges DB, Traebert M, Pugsley MK

Abstract
The Safety Pharmacology Society (SPS) held a Northeast (NE) regional meeting in Boston, MA on May 13, 2016 at the Vertex Pharmaceuticals Incorporated site. There were 103 attendees from the pharmaceutical industry, contract research organizations (CROs), academia, and global regulatory agencies. An assortment of scientific topics were presented by 7 speakers that included broad topics in the cardiovascular (organ on chip, statistical power and translation of rat cardiovascular telemetry data and dual inhibition of IKr and IKs on QT interval prolongation) and central nervous system (in vitro platform for neurotoxicity, an integrated risk assessment of suicidal ideation and behavior, and EEG advances in safety pharmacology) and a novel topic discussing preclinical challenges faced in the development of a novel gene therapy. A highlight of the meeting was an in-depth discussion on the fatty acid acyl hydrolase (FAAH) inhibitor BIA 10-2474 which involved a comprehensive overview of the biology and pharmacology of FAAH followed by a presentation from the Biotrial (Rennes, France) team that conducted the clinical trial. An additional poster session was held that included 13 fascinating posters on cutting edge safety pharmacology topics.

PMID: 27913272 [PubMed - indexed for MEDLINE]

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity.

J Vis Exp. 2018 Mar 16;(133):

Authors: Sheehan K, Sheth S, Mukherjea D, Rybak LP, Ramkumar V

Abstract
The systemic administration of protective agents to treat drug-induced ototoxicity is limited by the possibility that these protective agents could interfere with the chemotherapeutic efficacy of the primary drugs. This is especially true for the drug cisplatin, whose anticancer actions are attenuated by antioxidants which provide adequate protection against hearing loss. Other current or potential otoprotective agents could pose a similar problem, if administered systemically. The application of various biologicals or protective agents directly to the cochlea would allow for high levels of these agents locally with limited systemic side effects. In this report, we demonstrate a trans-tympanic method of delivery of various drugs or biological reagents to the cochlea, which should enhance basic science research on the cochlea and provide a simple way of directing the use of otoprotective agents in the clinics. This report details a method of trans-tympanic drug delivery and provides examples of how this technique has been used successfully in experimental animals to treat cisplatin ototoxicity.

PMID: 29608150 [PubMed - in process]

Comparison of Two Versions of the Beers Criteria and Adverse Outcomes in Older Hospitalized Patients.

Consult Pharm. 2017 Dec 01;32(12):752-763

Authors: Ozalas SM, Huang V, Brunetti L, Reilly T

Abstract
OBJECTIVE: To compare the performance of the 2003 and 2012 Beers criteria (BC) to predict negative clinical outcomes associated with potentially inappropriate medications in hospitalized older adults.
DESIGN: Retrospective cohort study.
SETTING: Acute Care of Elders (ACE) unit in a community-based teaching hospital.
PARTICIPANTS: All patients admitted to an ACE unit who were older than 65 years of age and prescribed at least one medication upon hospital admission.
MAIN OUTCOME MEASURE(S): The primary outcome was hospital length of stay (LOS). Secondary outcomes included likelihood of experiencing adverse drug events (ADEs) and in-hospital mortality.
RESULTS: A total of 340 patients were included in this study. Inpatients prescribed a BC drug at any time had a longer hospital LOS than those not prescribed a BC drug (2003 BC: adjusted geometric mean, 5.93 vs. 5.50 days, P = 0.003; 2012 BC: adjusted geometric mean, 5.87 vs. 4.21 days, P < 0.001). Patients prescribed a 2003 BC drug had an increased risk of experiencing an ADE compared with those not prescribed a BC drug (odds ratio [OR] = 1.86, 95% confidence interval [CI] 1.11-3.11); however, this outcome was not statistically significant after adjusting for confounders (OR = 1.51, 95% CI 0.870-2.63). There was no statistically significant difference in ADEs when using the 2012 BC (adjusted OR = 1.27, 95% CI 0.689-2.33). There was no difference in hospital mortality regardless of the BC version used.
CONCLUSION: Prescription of BC drugs in an acute care setting is associated with an increased hospital LOS; however, there is no difference in the risk of ADEs or in-hospital mortality.

PMID: 29467068 [PubMed - indexed for MEDLINE]

Clinical Alerts to Decrease High-Risk Medication Use in Older Adults.

J Gerontol Nurs. 2017 Jul 01;43(7):7-12

Authors: Lord-Adem W, Brandt NJ

Abstract
High-risk medications (HRMs) account for 14.6% to 54.6% of all medications used in older adults, and have been linked to >50% of adverse drug events (ADEs). HRM-related ADEs lead to increased morbidity and mortality, increased hospital length of stay, and financial costs for patients and health care systems. It has been well documented that incorporating information technology in patient care in the form of clinical alert systems can effectively decrease HRM use and improve patient safety. The current article seeks to identify and discuss clinical alert systems focusing on HRMs, their impact on prescribing for older adults, and challenges to the implementation of electronic decision systems. [Journal of Gerontological Nursing, 43(7), 7-12.].

PMID: 28651030 [PubMed - indexed for MEDLINE]

Personalized Medicine: New Perspectives for the Diagnosis and the Treatment of Renal Diseases.

Int J Mol Sci. 2017 Jun 10;18(6):

Authors: Gluba-Brzózka A, Franczyk B, Olszewski R, Banach M, Rysz J

Abstract
The prevalence of renal diseases is rising and reaching 5-15% of the adult population. Renal damage is associated with disturbances of body homeostasis and the loss of equilibrium between exogenous and endogenous elements including drugs and metabolites. Studies indicate that renal diseases are influenced not only by environmental but also by genetic factors. In some cases the disease is caused by mutation in a single gene and at that time severity depends on the presence of one or two mutated alleles. In other cases, renal disease is associated with the presence of alteration within a gene or genes, but environmental factors are also necessary for the development of disease. Therefore, it seems that the analysis of genetic aspects should be a natural component of clinical and experimental studies. The goal of personalized medicine is to determine the right drug, for the right patient, at the right time. Whole-genome examinations may help to change the approach to the disease and the patient resulting in the creation of "personalized medicine" with new diagnostic and treatment strategies designed on the basis of genetic background of each individual. The identification of high-risk patients in pharmacogenomics analyses will help to avoid many unwarranted side effects while optimizing treatment efficacy for individual patients. Personalized therapies for kidney diseases are still at the preliminary stage mainly due to high costs of such analyses and the complex nature of human genome. This review will focus on several areas of interest: renal disease pathogenesis, diagnosis, treatment, rate of progression and the prediction of prognosis.

PMID: 28604601 [PubMed - indexed for MEDLINE]

Optimistic bias, advertising skepticism, and consumer intentions for seeking information about the health risks of prescription medicine.

Health Mark Q. 2017 Apr-Jun;34(2):81-96

Authors: Park JS, Ahn HA, Haley EJ

Abstract
Based on a survey of prescription drug users (N = 408), this study revealed that: (a) the frequency of consumers' personal experience of prescription medicine adverse reactions negatively related to the extent of their optimistic bias about the chances of such events, (b) consumers' perceived personal control over adverse reactions positively related to optimistic bias, and (c) optimistic bias related more negatively to intentions to seek risk information when consumer skepticism toward direct-to-consumer advertising was high. When skepticism was low to average, optimistic bias did not inhibit such intentions. Implications and recommendations for the practice of direct-to-consumer advertising are provided.

PMID: 28590885 [PubMed - indexed for MEDLINE]

Potential drug-drug interactions in pediatric patients admitted to intensive care unit of Khyber Teaching Hospital, Peshawar, Pakistan: A cross-sectional study.

J Crit Care. 2017 Aug;40:243-250

Authors: Ismail M, Aziz S, Noor S, Haider I, Shams F, Haq I, Khadim F, Khan Q, Khan F, Asif M

Abstract
PURPOSE: To investigate frequencies, levels, clinical relevance and predictors of potential drug-drug interactions (pDDIs) in pediatric intensive care unit (PICU).
METHODS: Case notes of 411 patients were reviewed for pDDIs through Micromedex. Frequencies, levels and clinical relevance of pDDIs were reported. Logistic regression was applied to calculate the odds-ratios for predictors of pDDIs.
RESULTS: We recorded pDDIs in 59.4% patients. Major-pDDIs were found in 34.5% patients. Total 990 pDDIs were identified, of which, 37.8% were of moderate-severity and 30.6% of major-severity. Patient's case notes of top-ten pDDIs showed presence of signs/symptoms such as fever, jaundice, vomiting, anorexia, tachycardia, drowsiness, & lethargy; and abnormalities in labs such as total leukocytes count, blood urea nitrogen, alanine aminotransferase, & potassium-level. Odds of exposure to major-pDDIs were significantly higher in patients aged 6-12years (p=0.008); hospital stay of ≥7days (p=0.05); and ≥11 prescribed medicines (p<0.001).
CONCLUSION: Substantial numbers of patients in PICU are exposed to pDDIs. Major-pDDIs are of particular concern. Timely identification of pDDIs, preferably with computerized source, is crucial point for their management. Monitoring of clinically relevant parameters and identification of various predictors are needed to minimize or prevent the associated negative consequences of pDDIs.

PMID: 28458171 [PubMed - indexed for MEDLINE]

Pediatric Off-Label and Unlicensed Drug Use and Its Implications.

Curr Clin Pharmacol. 2017;12(1):18-25

Authors: Gore R, Chugh PK, Tripathi CD, Lhamo Y, Gautam S

Abstract
BACKGROUND: Worldwide, in the absence of standard pediatric prescribing information, clinicians often use medicines in children in a dosage form or for an indication that has not been approved for use. Inadequate clinical trials increase exposure to drugs that lack safety-efficacy data in pediatric population. Hence, off-label and unlicensed drug use must be regarded as a patient safety-issue that is known to be associated with increased risks of adverse drug reactions apart from under- or overdosing due to lack of pharmacokinetic data. This review aims to give an overview of the worldwide reported rates of off-label and unlicensed drug use in different patient populations in pediatric settings, with a brief summary of the related adverse drug reactions (ADRs) and a discussion of the existing regulatory provisions and possible solutions for ensuring safe use of medicines in children.
METHOD: Literature searches were conducted and we included studies that evaluated unlicensed or off-label drug use in various pediatric patient populations. The definition of off-label drug use and unlicensed drug varied between different studies.
RESULTS: Fourteen studies from different countries were included in the review and were grouped as: studies conducted in the patients admitted in neonatal intensive care units, in pediatric wards, in hospitalized children and in pediatric outpatient settings. The number of patients studied ranged from 34 in neonatal intensive care units to 355 409 hospitalized children. Many studies reported high rates of off-label (9% to 78.7%) and unlicensed (0.3% to 35%) drug use in different pediatric patient settings.
CONCLUSION: Given the prevalence of unlicensed and off-label drug use, the cooperation of various stakeholders including health professionals, pediatric population and their parents/caregivers, regulatory authorities, and the pharmaceutical industry is integral to instituting individual measures to avoid exposing children to unnecessary risks and avoid depriving them of potentially effective pharmacotherapy. Initiatives to encourage clinical trials for licensing drug use in children by providing market exclusivity and patent extension could aid in bridging the gap between approval and contemporary drug prescribing practices. Enforcement of legislations in the drug development process and subsequent pharmacovigilance could improve the quality of information and accountability of pharmaceutical industry to support and facilitate drug research in children.

PMID: 28322168 [PubMed - indexed for MEDLINE]

Cytochrome 2B6 polymorphism and efavirenz-induced central nervous system symptoms : a substudy of the ANRS ALIZE trial.

HIV Med. 2017 Sep;18(8):537-545

Authors: Gallien S, Journot V, Loriot MA, Sauvageon H, Morlat P, Reynes J, Reliquet V, Chêne G, Molina JM, ANRS 099 ALIZE trial study group

Abstract
OBJECTIVES: Single nucleotide polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been associated with high interindividual variation in efavirenz pharmacokinetics. However, clinical data on the relationship of CYP2B6 polymorphisms with the occurrence of efavirenz-induced central nervous system (CNS) symptoms are limited.
METHODS: We analysed four polymorphisms in the CYP2B6 (516 G>T), CYP3A5 (6986 A>G) and ATP-binding cassette, sub-family B, member 1 (ABCB1) (2677 G>T/A and 3435 C>T) genes in HIV-infected adults virologically suppressed on a protease inhibitor-based regimen who switched to a regimen containing emtricitabine, didanosine and efavirenz in the setting of the ANRS ALIZE trial. Kaplan-Meier methods and Cox regression analysis were used to investigate their association with efavirenz plasma levels and CNS events up to 48 months after switching.
RESULTS: In total, 191 patients with a median age of 41 years, who were 87% male and 85% Caucasian, were enrolled in the study. Variant allelic frequencies were 0.49, 0.93, 0.59 and 0.63 for CYP2B6 516, CYP3A5 392, ABCB1 2677 and ABCB1 3435, respectively. The median efavirenz plasma concentration (MEPC) was 2.2 mg/L [interquartile range (IQR) 1.7-2.8 mg/L] and was significantly higher in patients with the deficient CYP2B6 516T. Overall, 242 CNS events were reported in 104 individuals (54%). No correlation was found between MEPC and CNS events. The occurrence of a first CNS event was lower in patients with the CYP2B6 516 G/G genotype vs. CYP2B6 516 T genotypes [50% (IQR: 40-60%) vs. 66% (IQR: 56-75%), respectively; P = 0.02]. In an adjusted Cox regression model, there was a tendency towards a higher risk of a first CNS event among carriers of the variant CYP2B6 516 T allele (relative risk 1.4 [95% CI, 0.99-2.1]; P?=?.06), compared with noncarriers.
CONCLUSIONS: The deficient CYP2B6 516 T allele is associated with higher efavirenz plasma drug levels and more frequent CNS-related symptoms.

PMID: 28145050 [PubMed - indexed for MEDLINE]

Health care professionals knowledge and perception of pharmacovigilance in a tertiary care teaching hospital in Amman, Jordan.

J Eval Clin Pract. 2017 Jun;23(3):608-613

Authors: Abu Hammour K, El-Dahiyat F, Abu Farha R

Abstract
RATIONALE, AIMS, AND OBJECTIVES: Underreporting of adverse drug reactions (ADRs) by health care professionals is a common inherent health problem encountered in many countries. This could be explained by the lack of awareness and knowledge about the guidelines to follow to identify and report ADRs. Thus, this study aimed to evaluate the awareness, knowledge, and perceptions among medical doctors and nurses regarding their role as ADRs reporters in Jordan.
METHODS: A cross-sectional study was conducted between September 2015 to January 2016 at the Jordan University Hospital in Amman. During the study period, a total of 670 validated questionnaires were distributed to medical doctors and nurses in different departments.
RESULTS: Most of health care professionals were not aware of the concept of pharmacovigilance. Medical doctors showed a better overall knowledge compared with nurses (P < .05). Interestingly, despite the low level of awareness, the majority of respondents believed in the necessity of reporting ADRs.
CONCLUSION: Although there is a low level of awareness among health care professionals regarding pharmacovigilance, there is strong agreement among them about the necessity of reporting ADRs and attending educational sessions about pharmacovigilance which will help them to improve the quality of services they provide.

PMID: 28090715 [PubMed - indexed for MEDLINE]

Impact of a Pharmacy-Cardiology Collaborative Practice on Dofetilide Safety Monitoring.

Ann Pharmacother. 2017 Jan;51(1):39-43

Authors: Quffa LH, Panna M, Kaufmann MR, McKillop M, Dietrich NM, Franck AJ

Abstract
BACKGROUND: Limited studies have been published examining dofetilide's postmarketing use and its recommended monitoring.
OBJECTIVE: To evaluate the impact of a collaborative pharmacy-cardiology antiarrhythmic drug (AAD) monitoring program on dofetilide monitoring.
METHODS: This retrospective cohort study was performed to assess if a novel monitoring program improved compliance with dofetilide-specific monitoring parameters based on the Food and Drug Administration's Risk Evaluation and Mitigation Strategy.
RESULTS: A total of 30 patients were included in the analysis. The monitoring parameters evaluated included electrocardiogram, serum potassium, serum magnesium, and kidney function. The primary outcome evaluated was the composite of these dofetilide monitoring parameters obtained in each cohort. In the standard cohort, 245 of 352 (69.6%) monitoring parameters were completed versus 134 of 136 (98.5%) in the intervention group ( P < 0.05).
CONCLUSION: A collaborative pharmacy-cardiology AAD monitoring program was associated with a significant improvement in dofetilide monitoring. This improvement could potentially translate into enhanced patient safety outcomes, such as prevention of adverse drug reactions and decreased hospitalizations.

PMID: 27630191 [PubMed - indexed for MEDLINE]

Efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity-Prospective, randomized, double-blind, placebo-controlled study.

Neurourol Urodyn. 2018 Mar 31;:

Authors: Krhut J, Borovička V, Bílková K, Sýkora R, Míka D, Mokriš J, Zachoval R

Abstract
AIMS: To assess the efficacy and safety of mirabegron in the treatment of neurogenic detrusor overactivity.
METHODS: This prospective, multicenter, randomized, double-blind, placebo-controlled study was conducted in three tertiary centers, and included 78 patients suffering from spinal cord injury or multiple sclerosis. Patients were randomized for Mirabegron 50 mg (Group A) or placebo (Group B). Urodynamic parameters, the 24 h pad-weight test, and patient-reported outcomes were assessed. Safety assessments included monitoring the incidence and severity of adverse events. Changes in time and differences between groups were assessed with nonparametric Kruskal-Wallis one-way analysis of variance; P ≤ 0.05 was considered statistically significant.
RESULTS: In total, 66 patients were eligible for inclusion in the final analysis. There was a significant increase of volume at the first detrusor contraction (P = 0.00047) and an improvement in bladder compliance (P = 0.0041) in the mirabegron group compared with the placebo-treated group, whereas the increase in cystometric capacity did not reach statistical significance (P = 0.061). There was a clear tendency to reduced urine leakage (P = 0.056) in Group A. There were significant changes in all the patient-reported outcomes, favoring the mirabegron group. The incidence of drug-related adverse events was 3.13%.
CONCLUSIONS: Mirabegron (50 mg) improved both urodynamic variables and patient-reported outcomes in patients with NDO. The treatment was tolerated well.

PMID: 29603781 [PubMed - as supplied by publisher]

Treatment outcomes in older patients with advanced gastrointestinal stromal tumor (GIST).

J Geriatr Oncol. 2018 Mar 27;:

Authors: Rutkowski P, Bylina E, Lugowska I, Teterycz P, Klimczak A, Streb J, Czarnecka AM, Osuch C

Abstract
BACKGROUND: The aim of the study was to analyze the treatment results of advanced GIST in the largest, homogenous series of older patients.
METHODS: Between 2001 and 2016, 686 patients with metastatic/unresectable GIST were treated initially with imatinib and 656 were included in the analysis. Subsequently 232 patients were treated with sunitinib after imatinib failure. We have analyzed the outcomes of patients who have been treated with the tyrosine kinase inhibitor at the age ≥ 70 years and compared to control group of patients younger than 70 years old.
RESULTS: In the group of patients treated with imatinib, 139 (21%) started therapy at the age of at least 70 years (median age of the entire cohort: 60). Median progression-free survival (PFS) on 1st line imatinib did not differ between patients ≥70 yo (years old) and < 70yo (38.5 vs 44.9 months), but median overall survival (OS) was significantly better for younger patients (81 months vs. 50; p = 0.0001; although disease-specific survival - DSS was similar). Distribution of primary tumor mutational status was generally similar in older and younger patients. Permanent dose reduction (300-100 mg/day) was required for 23 patients (16.9%) in the older group and was significantly more frequent as compared to younger patients (5%). Drug-related adverse events were mainly of grades 1/2, but grade 3/4 toxicity occurred more frequently in older (14.7%) than in younger patients (3.8%). Similarly in group of patients treated with second-line sunitinib median PFS and DSS were comparable in groups of patients ≥70 yo (n = 55) and < 70yo (9.7 months vs 10.3 months; p = 0.7, and 21.5 vs 22.9 months). >40% of patients in both groups required dose adjustments to 37.5-25 mg daily.
CONCLUSIONS: Our study confirms that current therapy of advanced GIST with tyrosine kinase inhibitors (both in 1st and 2nd line) in older patients enable to achieve the similar disease control rate and final outcomes as in younger patients, but it demands close cooperation of experienced oncologist with patients for dose modifications and side effects management. Limitation of our study is that the patients did not undergo a comprehensive geriatric assessment, what might be helpful for personalized management of patients. Nevertheless, we confirm that older patients with GIST should not receive less treatment irrespective of comorbidities.

PMID: 29602734 [PubMed - as supplied by publisher]

Effects of exercise on cancer patients suffering chemotherapy-induced peripheral neuropathy undergoing treatment: A systematic review.

Crit Rev Oncol Hematol. 2018 Jan;121:90-100

Authors: Duregon F, Vendramin B, Bullo V, Gobbo S, Cugusi L, Di Blasio A, Neunhaeuserer D, Zaccaria M, Bergamin M, Ermolao A

Abstract
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is the most common neurological and clinically relevant side effect of many commonly used chemotherapeutic agents. Moreover, little effort has been done to investigate the potentially beneficial effects of specific exercises to counteract the CIPN symptoms.
OBJECTIVE: This document aims to summarize and analyze systematically the current body of evidence about the effects of specific exercise protocols on CIPN symptoms, balance control, physical function and quality of life in patients with CIPN.
LITERATURE SURVEY: Specific terms were identified for the literature research in MEDLINE, Scopus, Bandolier, PEDro, and Web of Science.
METHODOLOGY: Five manuscripts were considered eligible for this review. Quality appraisal distinguished two studies as high quality investigations while three with low quality. Results were summarized in the following domains: "CIPN symptoms", "Static balance control", "Dynamic balance control", "Quality of life and Physical function".
SYNTHESIS: Significant improvements were detected on postural control. Additionally, patients' quality of life and independence were found ameliorated after exercise sessions. Combined exercise protocols including endurance, strength and sensorimotor training showed larger improvements.
CONCLUSIONS: This systematic review comes from a highly selected but small source of data. Nevertheless, specific exercise for cancer patients undergoing chemotherapy with CIPN symptoms should be recommended since these interventions appeared as feasible and have been demonstrated as useful tools to counteract some of the limitations due to chemotherapy.

PMID: 29198853 [PubMed - indexed for MEDLINE]

Trial of dextromethorphan/quinidine to treat levodopa-induced dyskinesia in Parkinson's disease.

Mov Disord. 2017 Jun;32(6):893-903

Authors: Fox SH, Metman LV, Nutt JG, Brodsky M, Factor SA, Lang AE, Pope LE, Knowles N, Siffert J

Abstract
BACKGROUND: Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia.
METHODS: PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2-week double-blind, crossover treatment periods, with intervening 2-week washout. After 14 days, a 2-hour intravenous levodopa-infusion was administered. Patient examinations were videotaped before infusion ("off" state) and every 30 minutes during and afterwards until patients returned to "off." The primary endpoint was dyskinesia-severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area-under-curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical-change, and adverse-events.
RESULTS: A total of 13 patients were randomized and completed the study (efficacy-evaluable population). Dyskinesia-severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area-under-curve 966.5 vs 1048.8; P = .191 [efficacy-evaluable patients]), and significantly lower in a post-hoc sensitivity analysis of the per-protocol-population (efficacy-evaluable patients with ≥ 80% study-drug-compliance, n = 12) when measured from infusion start to 4-hours post-infusion completion (area-under-curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion-start to return to "off" (13.3 vs 14.9; P = .018 [efficacy-evaluable patients]). A total of 9 patients rated dyskinesia "much/very much improved" on dextromethorphan/quinidine versus 1-patient on placebo. Dextromethorphan/quinidine did not worsen PD-motor scores, was generally well tolerated, and was associated with more frequent adverse events.
CONCLUSION: This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa-induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society.

PMID: 28370447 [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 2018/03/30

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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 2018/03/30

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.

Primaquine Pharmacokinetics in Lactating Women and Breastfed Infant Exposures.

Clin Infect Dis. 2018 Mar 24;:

Authors: Ellen Gilder M, Hanpithakphong W, Hoglund RM, Tarning J, Htun Win H, Hilda N, Chu CS, Bancone G, Carrara VI, Singhasivanon P, White NJ, Nosten F, McGready R

Abstract
Background: Primaquine is the only drug providing radical cure of Plasmodium vivax malaria. It is not recommended for breastfeeding women as it causes hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals, and breast milk excretion and thus infant exposure are not known.
Methods: Healthy G6PD normal breastfeeding women with previous P.vivax infection and their healthy G6PD normal infants between 28 days and 2 years old were enrolled. Mothers took primaquine 0.5 mg/kg/day for 14 days. Primaquine and carboxyprimaquine concentrations were measured in maternal venous plasma, capillary plasma, and breast milk samples and infant capillary plasma samples taken on days 0, 3, 7, and 13.
Results: In 20 mother-baby pairs primaquine concentrations were below measurement thresholds in all but one infant capillary plasma sample (that contained primaquine 2.6 ng/mL) and carboxyprimaquine was likewise unmeasurable in the majority of infant samples (maximum value 25.8 ng/mL). The estimated primaquine dose received by infants, based on measured breast milk levels, was 2.98 µg/kg/day (i.e. ~0.6% of a hypothetical infant daily dose of 0.5 mg/kg). There was no evidence of drug-related hemolysis in the infants. Maternal levels were comparable to non-lactating patients, and adverse events in mothers were mild.
Conclusions: The concentrations of primaquine in breast milk are very low and therefore very unlikely to cause adverse effects in the breast-feeding infant. Primaquine should not be withheld from mothers breastfeeding infants or young children. More information is needed in neonates.

PMID: 29590311 [PubMed - as supplied by publisher]