24 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 2017/04/30

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.

Safety, Pharmacokinetics and Pharmacologic Effects of the Selective Androgen Receptor Modulator, GSK2881078, in Healthy Men and Postmenopausal Women.

Br J Clin Pharmacol. 2017 Apr 27;:

Authors: Clark RV, Walker AC, Andrews S, Turnbull P, Wald JA, Magee MH

Abstract
AIM: Selective androgen receptor modulators (SARMs) induce anabolic effects on muscle without the adverse effects of androgenic steroids. In this first-in-human study, we report safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of the SARM GSK2881078.
METHODS: In Part A, healthy young men (n = 10) received a single dose of study drug (0 mg, 0.05 mg, 0.1 mg, 0.2 mg GSK2881078 or matching-placebo). In Part B, repeat-dose cohorts in men (n = 65) were 0.05 mg, 0.2 mg then 0.08 mg, 0.24 mg, 0.48 mg, 0.75 mg, or placebo; in women (n = 24), 0.24 mg, 0.35 mg, or placebo (7 days for 0.5 mg, 14 days for other doses).
RESULTS: PK analysis showed dose-proportional increases in exposure and a long >100-h half-life. No significant effects on vital signs, electrocardiograms, cardiac telemetry, or standard clinical lab studies were observed. A dose-response effect was observed on lowering both high-density lipoprotein and sex-hormone-binding globulin. In females at 0.35 mg, differences from placebo were -0.518 mmol/L (95% CI: -0.703, -0.334) and -39.1 nmol/L (-48.5, -29.7), respectively. Women showed greater sensitivity to these parameters at lower doses than men. Drug-related adverse events (AEs) were mild. One woman developed a drug rash and was withdrawn. Two men had elevated creatine phosphokinase after physical exertion during follow-up. A serious AE occurred in a subject on placebo.
CONCLUSIONS: These data demonstrate pharmacodynamic effects with acceptable tolerability and support further clinical evaluation of this SARM.

PMID: 28449232 [PubMed - as supplied by publisher]

Swallowing Disorders in Schizophrenia.

Dysphagia. 2017 Apr 26;:

Authors: Kulkarni DP, Kamath VD, Stewart JT

Abstract
Disorders of swallowing are poorly characterized but quite common in schizophrenia. They are a source of considerable morbidity and mortality in this population, generally as a result of either acute asphyxia from airway obstruction or more insidious aspiration and pneumonia. The death rate from acute asphyxia may be as high as one hundred times that of the general population. Most swallowing disorders in schizophrenia seem to fall into one of two categories, changes in eating and swallowing due to the illness itself and changes related to psychotropic medications. Behavioral changes related to the illness are poorly understood and often involve eating too quickly or taking inappropriately large boluses of food. Iatrogenic problems are mostly related to drug-induced extrapyramidal side effects, including drug-induced parkinsonism, dystonia, and tardive dyskinesia, but may also include xerostomia, sialorrhea, and changes related to sedation. This paper will provide an overview of common swallowing problems encountered in patients with schizophrenia, their pathophysiology, and management. While there is a scarcity of quality evidence in the literature, a thorough history and examination will generally elucidate the predominant problem or problems, often leading to effective management strategies.

PMID: 28447217 [PubMed - as supplied by publisher]

Serious Adverse Effects of Testosterone Abuse.

Am J Nurs. 2017 Feb;117(2):20-21

Authors: Aschenbrenner DS

PMID: 28125486 [PubMed - indexed for MEDLINE]

Nephrotoxic Medication Exposure in U.S. Adults with Predialysis Chronic Kidney Disease: Health Services Utilization and Cost Outcomes.

J Manag Care Spec Pharm. 2016 Aug;22(8):959-68

Authors: Davis-Ajami ML, Fink JC, Wu J

Abstract
BACKGROUND: Nephrotoxic medication exposure increases risks for acute kidney injury, permanent renal function loss, and costly preventable adverse drug events. Exposure to medications associated with inducing acute tubular nephritis or tubular toxicity versus nonexposure among those with predialysis renal disease-a population vulnerable to increased risk of kidney injury-may affect health services utilization and cost outcomes. Few studies quantify nephrotoxic medication exposure in chronic kidney disease (CKD) and associated costs.
OBJECTIVE: To examine exposure to medications associated with inducing acute tubular nephritis or tubular toxicity versus nonexposure and the effect on health services utilization and cost outcomes in a nationally representative sample of adults with predialysis CKD.
METHODS: This retrospective study used Medical Expenditure Panel Survey (MEPS) household component longitudinal files (years 2006-2012; panels 11-16). Participants included 809 MEPS respondents aged > 18 years with predialysis CKD, after excluding those participants with cancer, kidney stone, renal dialysis, or transplant procedures (approximately 14.7 million U.S. noninstitutionalized individuals). Two groups were created to evaluate the main measures: (1) participants prescribed 1 or more medications associated with risk of acute tubular nephritis and/or tubular toxicity (termed "nephrotoxic exposure") and (2) participants with nonexposure. Medications cited in published literature as associated with tubular kidney damage were used. Multivariable regression models assessed the pattern of nephrotoxic medication exposure and its effect on health services utilization and expenses.
RESULTS: Nephrotoxic medication exposure occurred in 72% of adult MEPS respondents. Of those, 47.2% and 52.8% were prescribed 1 and at least 2 nephrotoxic medications, respectively. Coexistent chronic conditions included hypertension (72.3%), diabetes (49.5%), coronary heart disease (33%), arthritis (23.6%), and chronic obstructive pulmonary disease (17.6%). Eligible MEPS respondents aged ≥ 65 years, from the U.S. South region, and with Charlson Comorbidity Index (CCI) score > 0 were 75% (vs. aged 18-45 years), 83% (vs. Northeast), and 72%-96% (vs. CCI = 0) more likely to be exposed to nephrotoxic medications. Uninsured participants showed 55% less likelihood of nephrotoxic exposure, compared with privately insured participants. Higher utilization was shown in the nephrotoxic medication exposure group (vs. nonexposure): prescription fills (52.8 vs. 26.8, P < 0.001), emergency department visits (56.2 vs. 29.3 per 1,000 patient months, P < 0.001), and hospitalization (51.8 vs. 23.4 per 1,000 patient months, P < 0.001). Unadjusted all-cause expenses were greater for the following categories: medical ($119,935 vs. $11,462, P < 0.001), prescription drug ($4,828 vs. $2,816, P < 0.001), and total health expenses ($24,663 vs. $14,277, P < 0.001). Adjusted all-cause expenses were greater for total (29.7% greater, P = 0.003), prescription medications (56.6% greater, P < 0.001), and medical (23.4% greater, P = 0.036), but there were no differences in predialysis CKD-related utilization and expenses.
CONCLUSIONS: Increased vigilance is needed when prescribing nephrotoxic medications in predialysis CKD, particularly in patients with comorbid conditions and the elderly. Nephrotoxic medication exposure in predialysis CKD has the potential for increased health services utilization and cost outcomes.
DISCLOSURES: There was no grant or intramural funding for this research. The authors have no conflicts of interest, financial or otherwise, to disclose. Study concept and design were primarily contributed by Davis-Ajami, along with Fink and Wu. Davis-Ajami took the lead in data collection, along with Wu, and data interpretation was performed by David-Ajami, Wu, and Fink. All authors participated in manuscript preparation and revision.

PMID: 27459659 [PubMed - indexed for MEDLINE]

Scrotal Cooling to Protect Against Cisplatin-induced Spermatogenesis Toxicity: Preliminary Outcome of an Experimental Controlled Trial.

Urology. 2016 05;91:90-8

Authors: Aminsharifi A, Hekmati P, Noorafshan A, Karbalay-Doost S, Nadimi E, Aryafar A, Hosseinabadi OK, Naseri MM, ZarePoor M

Abstract
OBJECTIVE: To investigate the protective effects of scrotal cooling on cisplatin-induced gonadal toxicity in an animal model.
METHODS: Twenty-one male BALB/c mice were divided into 3 groups. The cisplatin group received 2 cycles of cisplatin (2.5 mg/kg/day for 5 days with 16 days of recovery) intraperitoneally, and the cisplatin + cooling group received the same regimen of cisplatin with a cooling protocol: cooling induction for 30 minutes before injection and cooling for 60 minutes after injection. Mice in control group were given an injection of 2 mL normal saline intraperitoneally. After 35 days of recovery (1 cycle of spermatogenesis), the volume of the testes (Cavalieri method), volume density of the tubules and epithelium (point-counting method), and number of cells (optical dissector method) were estimated.
RESULTS: The volume of the testes, tubules, and epithelium was reduced between 61% and 66%, and the number of the spermatogonia, spermatocytes, round spermatids, and long spermatids was reduced between 70% and 93% in cisplatin group compared with that of control mice. Cisplatin affected spermatids to a greater extent, and Sertoli cells to a lesser extent than the other cells. The volume and number of the cells were reduced in the cisplatin + cooling group but to a lesser extent compared with those of mice in the cisplatin group. Sertoli cells were more intact in the cisplatin + cooling group compared with those of the control group.
CONCLUSION: Scrotal cooling during cisplatin administration seems to have beneficial effects on spermatogenesis. Scrotal cooling may hold promise as a way to protect fertility.

PMID: 26845053 [PubMed - indexed for MEDLINE]

The pharmacotherapy of cirrhosis: concerns and proposed investigations and solutions.

J Clin Pharm Ther. 2016 Dec;41(6):587-591

Authors: Hilscher MB, Odell LJ, Myhre LJ, Prokop L, Talwalkar J

Abstract
WHAT IS KNOWN AND OBJECTIVE: The presence of cirrhosis has a multifaceted impact on hepatic drug metabolism. An area of concern and uncertainty in the care of patients with cirrhosis is the safe use of both prescription and over-the-counter medications.
COMMENT: Retrospective studies indicate a high incidence of adverse drug reactions (ADRs) among patients with cirrhosis related to use of certain medication classes including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and non-steroidal anti-inflammatory drugs. Conversely, use of appropriate medications, such as statins, may be decreased in this population due to fear of precipitating hepatotoxicity.
WHAT IS NEW AND CONCLUSION: Pharmacotherapy in cirrhosis is an area of uncertainty and heterogeneity in clinical practice. Prescribing and dosing guidelines are needed to decrease the risk of serious ADRs in this high-risk patient population.

PMID: 27576303 [PubMed - indexed for MEDLINE]

Letter in response to "Efficacy and effectiveness of anti-digoxin antibodies in chronic digoxin poisonings from the DORA study (ATOM-1)".

Clin Toxicol (Phila). 2017 01;55(1):63

Authors: Wang JJ, Regina A, Hoffman RS

PMID: 27491930 [PubMed - indexed for MEDLINE]

Further evidence that a variant of the gene NUDT15 may be an important predictor of azathioprine-induced toxicity in Chinese subjects: a case report.

J Clin Pharm Ther. 2016 Oct;41(5):572-4

Authors: Ailing Z, Jing Y, Jingli L, Yun X, Xiaojian Z

Abstract
WHAT IS KNOWN AND OBJECTIVE: Thiopurine methyltransferase (TPMT) enzyme is an important component in the metabolism of azathioprine (AZA). Its mutation may lead to AZA-induced toxicity. The dysfunctional genetic variant TPMT *3C is of low frequency among Asians. Moreover, AZA-induced toxicity still occurs in some patients with normal TPMT activity. This suggests that additional factors, including other genetic variants, may contribute to such toxicity. Recent studies described a strong association between a variant of the NUDT15, a gene that mediates the hydrolysis of some nucleoside diphosphate derivatives, and thiopurine-related myelosuppression in Asians. We report the first case of a Chinese patient with AZA-induced severe toxicity with no clinically significant TPMT variant but with the NUDT15 c.415C>T allele.
CASE SUMMARY: A 40-year-old Chinese patient with PBC-AIH overlap syndrome had been receiving for one month, azathioprine (50 mg/day) and methylprednisolone (24 mg/day) based on his TPMT*3C wild-type genotype. The patient developed serious myelosuppression and hair loss. AZA was stopped, and the patient was given liver-protective drugs and supportive treatment. TPMT and NUDT15 gene sequencing suggests that NUDT15 c.415C>T mutation was the likely cause of the adverse reaction.
WHAT IS NEW AND CONCLUSION: NUDT15 c.415C>T may be another predictor of AZA-induced leukocytopenia. If further well-controlled studies validate this association with sufficient predictive power, NUDT15 and TPMT genotyping before starting AZA treatment may become appropriate.

PMID: 27381176 [PubMed - indexed for MEDLINE]

Anticholinergic medicines in an older primary care population: a cross-sectional analysis of medicines' levels of anticholinergic activity and clinical indications.

J Clin Pharm Ther. 2016 Oct;41(5):486-92

Authors: Magin PJ, Morgan S, Tapley A, McCowan C, Parkinson L, Henderson KM, Muth C, Hammer MS, Pond D, Mate KE, Spike NA, McArthur LA, van Driel ML

Abstract
WHAT IS KNOWN AND OBJECTIVES: Adverse clinical outcomes have been associated with cumulative anticholinergic burden (to which low-potency as well as high-potency anticholinergic medicines contribute). The clinical indications for which anticholinergic medicines are prescribed (and thus the 'phenotype' of patients with anticholinergic burden) have not been established. We sought to establish the overall prevalence of prescribing of anticholinergic medicines, the prevalence of prescribing of low-, medium- and high-potency anticholinergic medicines, and the clinical indications for which the medicines were prescribed in an older primary care population.
METHODS: This was a cross-sectional analysis of a cohort study of Australian early-career general practitioners' (GPs') clinical consultations - the Registrar Clinical Encounters in Training (ReCEnT) study. In ReCEnT, GPs collect detailed data (including medicines prescribed and their clinical indication) for 60 consecutive patients, on up to three occasions 6 months apart. Anticholinergic medicines were categorized as levels 1 (low-potency) to 3 (high-potency) using the Anticholinergic Drug Scale (ADS).
RESULTS: During 2010-2014, 879 early-career GPs (across five of Australia's six states) conducted 20 555 consultations with patients aged 65 years or older, representing 35 506 problems/diagnoses. Anticholinergic medicines were prescribed in 10·4% [95% CIs 9·5-10·5] of consultations. Of the total anticholinergic load of prescribed medicines ('community anticholinergic load') 72·7% [95% CIs 71·0-74·3] was contributed by Level 1 medicines, 0·8% [95% CIs 0·5-1·3] by Level 2 medicines and 26·5% [95% CIs 24·8-28·1] by Level 3 medicines. Cardiac (40·0%), Musculoskeletal (16·9%) and Respiratory (10·6%) were the most common indications associated with Level 1 anticholinergic prescription. For Level 2 and 3 medicines (combined data), Psychological (16·1%), Neurological (16·1%), Musculoskeletal (15·7%) and Urological (11·1%) indications were most common.
WHAT IS NEW AND CONCLUSION: Anticholinergic medicines are frequently prescribed in Australian general practice, and the majority of the 'community' anticholinergic burden is contributed by 'low'-anticholinergic potency medicines whose anticholinergic effects may be largely 'invisible' to prescribing GPs. Furthermore, the clinical 'phenotype' of the patient with high anticholinergic burden may be very different to common stereotypes (patients with urological, psychological or neurological problems), potentially making recognition of risk of anticholinergic adverse effects additionally problematic for GPs.

PMID: 27349795 [PubMed - indexed for MEDLINE]

Comparison of high-dose intravenous immunoglobulin (IVIG) in a 5% and a 10% solution does not reveal a significantly different spectrum of side-effects.

J Eur Acad Dermatol Venereol. 2016 Dec;30(12):e186-e188

Authors: Rappold LC, Denk K, Enk AH, Hadaschik EN

PMID: 26551028 [PubMed - indexed for MEDLINE]

The immunogenicity and safety of a Hib-MenAC vaccine: a non-inferiority randomized, observer-blind trial in infants aged 3-5 months.

Expert Rev Vaccines. 2017 May;16(5):515-524

Authors: Wang YX, Tao H, Hu JL, Li JX, Dai WM, Sun JF, Liu P, Tang J, Liu WY, Zhu FC

Abstract
BACKGROUND: The objective of this study was to evaluate the immunogenicity and safety of the novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroup A and C-tetanus toxoid conjugate vaccine (Hib-MenAC).
METHODS: We conducted a non-inferiority, randomized, observer-blind, positive control clinical trial in 900 healthy infants aged between 3-5 months in Funing County, Jiangsu Province, China. Participants were randomly allocated, in a ratio of 2:1 (block = 6), to receive experimental combined Hib-MenAC vaccines co-administrated with placebo or the co-administration of licensed Hib vaccine and MenAC vaccine, according to a three-dose immunization schedule. The seroconversion of antibody titer against meningococcal serogroups A, C and Hib was the primary endpoint.
RESULTS: The experimental vaccines was non-inferior to the licensed two control vaccines. Participants receiving experimental Hib-MenAC vaccines showed a seroconversion rate of 99.0%, 96.1% and 97.7% for rSBA-MenA, rSBA-MenC and anti-PRP antibodies, respectively. The Hib-MenAC vaccine did not result in an increase in adverse reaction, and no serious adverse event was judged to be related to the vaccination.
CONCLUSIONS: The novel combined Hib-MenAC conjugate vaccine was safe and highly immunogenic in infants aged between 3 to 5 months.

PMID: 28277801 [PubMed - indexed for MEDLINE]

Deprescribing in older people.

Maturitas. 2016 Sep;91:115-34

Authors: Page AT, Potter K, Clifford R, Etherton-Beer C

Abstract
Older people with chronic disease have great potential to benefit from their medications but are also at high risk of harm from their medications. The use of medications is particularly important for symptom control and disease progression in older people. Under-treatment means older people can miss out on the potential benefits of useful medications, while over-treatment (polypharmacy) puts them at increased risk of harm. Deprescribing attempts to balance the potential for benefit and harm by systematically withdrawing inappropriate medications with the goal of managing polypharmacy and improving outcomes. The evidence base for deprescribing in older people is growing. Studies to reduce polypharmacy have used a range of methods. Most evidence for deprescribing relates to the withdrawal of specific medications, and evidence supports attempts to deprescribe potentially inappropriate medicines (such as long-term benzodiazepines). There is also evidence that polypharmacy can be reduced by withdrawing specific medications using individualised interventions. More work is needed to identify the sub-groups of older people who may most benefit from deprescribing and the best approaches to undertaking the deprescribing interventions.

PMID: 27451330 [PubMed - indexed for MEDLINE]

Frailty, polypharmacy and deprescribing.

Drug Ther Bull. 2016 Jun;54(6):69-72

Authors:

Abstract
Multimorbidity and associated polypharmacy present a significant and increasing challenge to patients, carers and healthcare professionals.(1,2) While it is recognised that polypharmacy can be beneficial, there is considerable potential for harm, particularly through drug interactions, adverse drug events and non-adherence.(1) Such harms are amplified in people who are frail and who may require interventions to be tailored to their individual needs rather than strictly following guidance designed to manage single diseases. It is important to develop an approach that allows patients to make informed decisions and prioritise medicines for continuation or discontinuation, in order to maximise benefit and minimise harm.(1)The term 'deprescribing' has been suggested in recognition that the skills utilised in stopping medicines need to be as sophisticated as those used when initiating drug treatment.(3) Key to deprescribing, as with all medical interventions, is the active participation of the patient to ensure that their preferences and choices are taken into account. Particular care is needed when end-of-life considerations apply, so that treatment is optimised and the burden of taking medicines is minimised.(4) Although evidence is sparse, this article provides some practical observations on deprescribing.

PMID: 27284125 [PubMed - indexed for MEDLINE]

Efficacy, safety, tolerability and price of newly approved drugs in solid tumors.

Cancer Treat Rev. 2017 Apr 09;56:1-7

Authors: Barnes TA, Amir E, Templeton AJ, Gomez-Garcia S, Navarro B, Seruga B, Ocana A

Abstract
BACKGROUND: New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price.
METHODS: Drugs approved for solid tumor treatment between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes (group 1), anti-angiogenics (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the registration trials and pooled in a meta-analysis. Odds ratios for toxic death, treatment discontinuation and grade 3-4 toxicity were compared to control groups. The Micromedex Red Book was used to calculate the monthly price.
RESULTS: Analysis included 74 studies comprising 48,527 patients. Progression-free survival (PFS) was improved to a greater degree with groups 1 and 2 than with groups 3 and 4, (pooled HR: 0.54, 0.56, 0.63, and 0.76 for groups 1-4 respectively, p for difference <0.001). Compared to PFS, there was a lower magnitude of improvement overall survival in all groups and the degree of benefit was less for group 4 than for other groups (pooled HR: 0.77, 0.78, 0.68, and 0.83 for groups 1-4 respectively, p for difference=0.007). Compared to control groups in individual trials, immunotherapy was associated with better safety and tolerability than other groups. Drug prices have increased over time with no significant difference between groups. There was no meaningful correlation between pricing and efficacy.
CONCLUSIONS: Compared to control groups, immunotherapeutics and drugs targeting oncogenes or angiogenesis improve efficacy to a greater degree than chemotherapy. Immunotherapy appears to have better safety and tolerability profile compared to other cancer therapies. Market price of drugs is not related to efficacy.

PMID: 28437678 [PubMed - as supplied by publisher]

Pharmacokinetics and Safety of Travoprost 0.004% Ophthalmic Solution Preserved with Polyquad in Pediatric Patients with Glaucoma.

J Ocul Pharmacol Ther. 2017 Feb 24;:

Authors: Stahl E, Bremond-Gignac D, Landry T, Curtis M, Gedif K, Al Shahwan S, Dixon ER

Abstract
PURPOSE: To evaluate the systemic pharmacokinetics (PKs) of travoprost 0.004% preserved with Polyquad(®) (TRAVATAN(®)) in pediatric patients with glaucoma or ocular hypertension.
METHODS: This was a phase 1, open-label, multicenter clinical study of patients aged ≥2 months to <18 years. Patients received daily administration of travoprost 0.004% preserved with Polyquad in both eyes for 7 days. Plasma samples were collected 30 min before the final dose and at 10, 20, 40, and 80 min postdose. The main outcome measure was maximum concentration of travoprost free acid in plasma (Cmax).
RESULTS: Included in the PK analysis were 24 patients (average age 9.6 ± 4.9 years). At least 1 sample with quantifiable levels of travoprost free acid was collected for 11 patients. The mean Cmax was 0.0471 ± 0.0105 ng/mL for patients aged 2 months to <3 years; 0.0258 ± 0.0128 ng/mL for ages 3 to <12 years; and 0.0109 ± 0.0005 ng/mL for ages 12 to <18 years. Travoprost was undetectable in samples collected predose from pediatric patients. Treatment-related adverse events (AEs) included hyperemia, eye pain, and eye pruritus (n = 1 each). There were no discontinuations or drug-related serious AEs.
CONCLUSIONS: Travoprost free acid concentration in plasma was low in pediatric patients, detectable in only 11 of 24 patients. There was no accumulation of travoprost over the course of treatment. No clear relationship was observed between age/body surface area and Cmax. No increased risk was identified for the use of travoprost 0.004% preserved with Polyquad in patients <18 years of age.

PMID: 28437175 [PubMed - as supplied by publisher]

Management of skin adverse events associated with immune checkpoint inhibitors in patients with melanoma: A nursing perspective.

J Am Assoc Nurse Pract. 2017 Apr 24;:

Authors: Thebeau M, Rubin K, Hofmann M, Grimm J, Weinstein A, Choi JN

Abstract
PURPOSE: Immune checkpoint inhibitors are associated with a unique immune-related side effect profile that requires prompt recognition and management. Skin toxicities are the most common, and often earliest occurring, drug-related adverse events (AEs) of any grade observed upon treatment with these agents. The purpose of this review is to provide practical guidance on the identification and treatment of skin AEs associated with the immune checkpoint inhibitors (ipilimumab, nivolumab, and pembrolizumab) from a nursing perspective, and demonstrate hands-on application of the guidance using relevant patient case studies.
DATA SOURCES: Data for drug-related skin AEs were summarized from phase 3 nivolumab and nivolumab + ipilimumab trials and phase 2 and 3 pembrolizumab trials. Patient case studies were provided by the lead (M.T.) and senior (J.N.C.) authors.
CONCLUSIONS: The recommendations presented here, based on accumulated clinical trial and clinical practice experience are consistent with established treatment guidelines and reach beyond established guidelines and recommendations for the management of AEs associated with immune checkpoint inhibitors.
IMPLICATIONS FOR PRACTICE: The practical treatment guidance presented here may help familiarize medical teams with the recognition and management of skin AEs associated with these recently approved agents. The enclosed recommendations may contribute to optimized treatment through awareness of typical time to onset and clinical presentation, knowledge of management options, and appropriate application of treatment.

PMID: 28436601 [PubMed - as supplied by publisher]

Posttreatment Reactions After Single-Dose Diethylcarbamazine or Ivermectin in Subjects With Loa loa Infection.

Clin Infect Dis. 2017 Apr 15;64(8):1017-1025

Authors: Herrick JA, Legrand F, Gounoue R, Nchinda G, Montavon C, Bopda J, Tchana SM, Ondigui BE, Nguluwe K, Fay MP, Makiya M, Metenou S, Nutman TB, Kamgno J, Klion AD

Abstract
Background.: Severe adverse reactions have been observed in individuals with Loa loa infection treated with either diethylcarbamazine (DEC), the drug of choice for loiasis, or ivermectin (IVM), which is used in mass drug administration programs for control of onchocerciasis and lymphatic filariasis in Africa. In this study, posttreatment clinical and immunologic reactions were compared following single-dose therapy with DEC or IVM to assess whether these reactions have the same underlying pathophysiology.
Methods.: Twelve patients with loiasis and microfilarial counts <2000 mf/mL were randomized to receive single-dose DEC (8 mg/kg) or IVM (200 µg/kg). Clinical and laboratory assessments were performed at 4, 8, 24, 48, and 72 hours and 5, 7, 9, and 14 days posttreatment.
Results.: Posttreatment adverse events were similar following DEC or IVM, but peaked earlier in subjects who received DEC, consistent with a trend toward more rapid and complete microfilarial clearance in the DEC group. After a transient rise (post-IVM) or fall (post-DEC) in the first 24 hours posttreatment, the eosinophil count rose significantly in both groups, peaking at day 5 in the DEC group and day 9 in the IVM group. Serum interleukin 5 levels and eosinophil activation, as assessed by surface expression of CD69 and serum levels of eosinophil granule proteins, were increased posttreatment in both groups.
Conclusions.: Despite differences in eosinophil and lymphocyte counts during the first 24 hours posttreatment, the overall pattern of hematologic and immunologic changes suggest that posttreatment reactions following DEC and IVM share a common pathophysiology.
Clinical Trials Registration.: NCT01593722.

PMID: 28329346 [PubMed - indexed for MEDLINE]

Applying mixture toxicity modelling to predict bacterial bioluminescence inhibition by non-specifically acting pharmaceuticals and specifically acting antibiotics.

Chemosphere. 2017 Apr;173:387-394

Authors: Neale PA, Leusch FD, Escher BI

Abstract
Pharmaceuticals and antibiotics co-occur in the aquatic environment but mixture studies to date have mainly focused on pharmaceuticals alone or antibiotics alone, although differences in mode of action may lead to different effects in mixtures. In this study we used the Bacterial Luminescence Toxicity Screen (BLT-Screen) after acute (0.5 h) and chronic (16 h) exposure to evaluate how non-specifically acting pharmaceuticals and specifically acting antibiotics act together in mixtures. Three models were applied to predict mixture toxicity including concentration addition, independent action and the two-step prediction (TSP) model, which groups similarly acting chemicals together using concentration addition, followed by independent action to combine the two groups. All non-antibiotic pharmaceuticals had similar EC50 values at both 0.5 and 16 h, indicating together with a QSAR (Quantitative Structure-Activity Relationship) analysis that they act as baseline toxicants. In contrast, the antibiotics' EC50 values decreased by up to three orders of magnitude after 16 h, which can be explained by their specific effect on bacteria. Equipotent mixtures of non-antibiotic pharmaceuticals only, antibiotics only and both non-antibiotic pharmaceuticals and antibiotics were prepared based on the single chemical results. The mixture toxicity models were all in close agreement with the experimental results, with predicted EC50 values within a factor of two of the experimental results. This suggests that concentration addition can be applied to bacterial assays to model the mixture effects of environmental samples containing both specifically and non-specifically acting chemicals.

PMID: 28129616 [PubMed - indexed for MEDLINE]

Safety and immunogenicity of a recombinant Staphylococcus aureus α-toxoid and a recombinant Panton-Valentine leukocidin subunit, in healthy adults.

Hum Vaccin Immunother. 2017 Apr 03;13(4):791-801

Authors: Landrum ML, Lalani T, Niknian M, Maguire JD, Hospenthal DR, Fattom A, Taylor K, Fraser J, Wilkins K, Ellis MW, Kessler PD, Fahim RE, Tribble DR

Abstract
We conducted a randomized, double-blind, placebo-controlled dose-escalation study in healthy adults to evaluate the safety and immunogenicity of recombinant Staphylococcus aureus candidate vaccine antigens, recombinant α-toxoid (rAT) and a sub-unit of Panton-Valentine leukocidin (rLukS-PV). 176 subjects were enrolled and randomized within 1 of 11 treatment cohorts: monovalent rAT or rLukS-PV dosages of 10, 25, 50, and 100 μg; bivalent rAT:rLukS dosages of 10:10, 25:25, and 50:50 μg; and alum or saline placebo. All subjects were assessed at Days 0, 7, 14, 28, and 84. Subjects in the 50:50 μg bivalent cohort received a second injection on Day 84 and were assessed on Days 98 and 112. Incidence and severity of reactogenicity and adverse events (AEs) were compared. Geometric mean serum concentrations (GMC) and neutralizing activity of anti-rAT and anti-rLukS-PV IgG were assessed. Reactogenicity incidence was significantly higher in vaccine than placebo recipients (77% versus 55%, respectively; p = 0.006). However, 77% of reactogenicity events were mild and 19% were moderate in severity. The AE incidence and severity were similar between the cohorts. All monovalent and bivalent rAT dosages resulted in a significant increase in the anti-rAT IgG and anti- rLukS-PV GMCs between day 0 and 28 compared with placebo, and persisted through Day 84. Exploratory subgroup analyses suggested a higher GMC and neutralizing antibody titers for the 50 μg monovalent or bivalent rAT and rLukS-PV dose as compared to the other doses. No booster effect was observed after administration of the second dose. We conclude that the rAT and rLukS-PV vaccine formulations were well-tolerated and had a favorable immunogenicity profile, producing antibody with neutralizing activity through day 84. There was no benefit observed with a booster dose of the vaccine.

PMID: 28010246 [PubMed - indexed for MEDLINE]