Use of nonsteroidal anti-inflammatory drugs and renal failure in nursing home residents-results of the study "Inappropriate Medication in Patients with Renal Insufficiency in Nursing Homes".

Wien Klin Wochenschr. 2016 Apr;128(7-8):287-90

Authors: Dörks M, Herget-Rosenthal S, Schmiemann G, Hoffmann F

Abstract
BACKGROUND: Use of potentially inappropriate medications may result in increased morbidity, mortality and resource utilisation. Due to polypharmacy and age-related decline in renal function the elderly population is at particular risk. Therefore, the Beers Criteria include use of nonsteroidal anti-inflammatory drugs in chronic renal failure stage 4 and 5 as these drugs may worsen renal function. According to the summary of product characteristics, the nonsteroidal anti-inflammatory drugs ibuprofen and diclofenac are contraindicated in these patients. Objective was to assess the extent of nonsteroidal anti-inflammatory drug use in nursing homes with a focus on residents with severe renal failure.
METHODS: Multi-centre cross-sectional study in 21 German nursing homes. The study population comprised residents for whom at least one serum creatinine value and information about sex were available, so that creatinine clearance rate could be estimated.
RESULTS: In all, 685 of 852 residents were included as they fulfilled the abovementioned criteria. Renal failure was severe (estimated creatinine clearance rate < 30 ml/min) in 106 residents (15.5 %). Approximately one-fifth was treated with at least one nonsteroidal anti-inflammatory drug in both the total study population (20.3 %) and that with severe renal failure (20.8 %). With one exception, all residents prescribed nonsteroidal anti-inflammatory drugs with severe renal failure were treated with at least one nonsteroidal anti-inflammatory drug that was contraindicated due to the underlying renal function.
CONCLUSIONS: Notwithstanding their classification as potentially inappropriate medications and underlying contraindications, use of nonsteroidal anti-inflammatory drugs is common among nursing home residents with severe renal failure.

PMID: 26759317 [PubMed - indexed for MEDLINE]

Cinnarizine and dimenhydrinate in the treatment of vertigo in medical practice.

Wien Klin Wochenschr. 2016 May;128(9-10):341-7

Authors: Scholtz AW, Ilgner J, Loader B, Pritschow BW, Weisshaar G

Abstract
The efficacy and safety of the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg in the treatment of vertigo of various origins have been investigated in a prospective, noninterventional study involving private practices throughout Germany. A total of 1275 patients with an average age of 61.2 years participated in the study. The vertigo symptoms, measured by a validated mean vertigo score (primary efficacy endpoint) improved by 61 % in the course of the observational period (median: 6 weeks). Concomitant symptoms frequently associated with vertigo such as nausea, vomiting and tinnitus were also markedly reduced by 84, 85 and 51 %, respectively. Overall efficacy has been rated by the physicians as 'very much improved' or 'much improved' in 95 % of the patients. A total of 47 patients (3.7 %) reported 51 adverse drug reactions (all nonserious). The results indicate a good tolerability and efficacy of the fixed combination of cinnarizine and dimenhydrinate in the treatment of vertigo in daily medical practice, which is in line with previous findings of numerous interventional, randomised, double-blind, controlled clinical trials.

PMID: 26659910 [PubMed - indexed for MEDLINE]

Selective inhibition of nuclear export with selinexor in patients with non-Hodgkin's lymphoma.

Blood. 2017 May 03;:

Authors: Kuruvilla J, Savona M, Baz R, Mau-Sorensen M, Gabrail N, Garzon R, Stone R, Wang M, Savoie L, Martin P, Flinn I, Jacoby M, Unger TJ, Saint-Martin JR, Rashal T, Friedlander S, Carlson R, Kauffman M, Shacham S, Gutierrez M

Abstract
Patients with relapsed or refractory (R/R) non-Hodgkin's lymphoma (NHL) have a poor prognosis and limited treatment options. We evaluated selinexor, an orally bioavailable, first-in-class inhibitor of the nuclear export protein XPO1, in this phase 1 trial to assess safety and determine a recommended phase 2 dose (RP2D). Seventy-nine patients with various NHL histologies, including diffuse large B cell lymphoma (DLBCL), Richter's transformation, mantle cell lymphoma (MCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) were enrolled. In the dose escalation phase, patients received 3-80 mg/m(2) of selinexor in 3- or 4-week cycles and were assessed for toxicities, pharmacokinetics and anti-tumor activity. In the dose expansion phase, patients were treated with selinexor at 35 mg/m(2) or 60 mg/m(2) The most common grade 3-4 drug-related adverse events were thrombocytopenia (47%), neutropenia (32%), anemia (27%), leukopenia (16%), fatigue (11%) and hyponatremia (10%). Tumor biopsies showed decreases in cell signaling pathways (Bcl-2, Bcl-6, c-Myc), reduced proliferation (Ki67), nuclear localization of XPO1 cargos (p53, PTEN) and increased apoptosis after treatment. Twenty-two (31%) of the 70 evaluable patients had an objective response (OR), including 4 complete responses (CR) and 18 partial responses (PR), which were observed across a spectrum of NHL subtypes. A dose of 35 mg/m(2) (60mg) was identified as the RP2D. These findings suggest that inhibition of XPO1 with oral selinexor at 35 mg/m(2) is a safe therapy with encouraging and durable anti-cancer activity in patients with R/R NHL. The trial is registered to www.clinicaltrials.gov as NCT01607892.

PMID: 28468797 [PubMed - as supplied by publisher]

Reduction of Medical Cost through Pharmaceutical Inquiries by Community Pharmacists and Relation with Iyaku Bungyo Rates: A Nationwide Survey on Prescription Inquiries.

Yakugaku Zasshi. 2016;136(9):1263-73

Authors: Shikamura Y, Mano Y, Komoda M, Negishi K, Sato T, Miyazaki S

Abstract
This nationwide survey aimed to evaluate reduction of drug and medical costs due to prevention of serious adverse drug reactions through pharmaceutical inquires by community pharmacist, and investigate relation with iyaku bungyo (separation of dispensing from medical practice) rates. Using the national list of pharmacies, 10% of pharmacies were randomly selected by prefecture and asked to participate in an Internet-based survey. The survey period was 7 days, from July 21 to July 27, 2015. Of the 5575 pharmacies queried, 818 responded to the survey (response rate: 14.7%). The proportion of inquiries to total prescriptions was 2.6%. Among these, the proportion of prescriptions changed in response to inquiry was 74.9%. An estimated 103 million yen was saved by reducing drug costs, and 133 million yen was saved by reducing medical costs due to prevention of serious adverse drug reactions. Comparison of prescription change rates between pharmacies with high and low iyaku bungyo rates indicated that the proportion of prescriptions changed was significantly higher in pharmacies with high iyaku bungyo rates than in those with low iyaku bungyo rates (78.2% vs. 69.9%, p<0.01). The findings suggest that inquiries about prescriptions are useful in ensuring the safety of pharmacotherapy and reducing the cost of healthcare. They also suggest that iyaku bungyo promotes prescription changes through inquiries, leading to proper use of pharmaceutical products.

PMID: 27592829 [PubMed - indexed for MEDLINE]

Safety Assessment and Power Analyses in Published Anti-Vascular Endothelial Growth Factor Randomized Controlled Trials.

Am J Ophthalmol. 2016 Sep;169:68-72

Authors: Esen F, Alhan O, Kuru P, Sahin O

Abstract
PURPOSE: To investigate a certain set of methodological limitations in published anti-vascular endothelial growth factor (VEGF) randomized controlled trials (RCTs).
DESIGN: Descriptive methodological study.
METHODS: We did a PubMed search with the terms "bevacizumab OR ranibizumab OR pegaptanib OR aflibercept" and the limitations "humans" and "randomized controlled trials" in 15 of the highest-impact-factor general medicine and ophthalmology journals. We included only RCTs published as original articles, where an anti-VEGF agent was used to treat eye disease. Two independent observers (O.A., P.K.) read through each article and classified the articles according to a predefined set of criteria.
RESULTS: The PubMed search yielded 209 articles, and 93 were classified as eligible. In most of the studies, the study drug was bevacizumab (52.6%, n = 49), followed by ranibizumab (44.1%, n = 41), pegaptanib (7.5%, n = 7), and aflibercept (5.4%, n = 5). Basic epidemiologic data, including sex distribution (2.2%, n = 2) and mean age (3.2%, n = 3), were missing in 3.2% of the published RCTs. The power calculation for efficacy was mentioned in 48% (n = 45) of the published work, and a power calculation for safety was considered in only 1 study (1.1%). Only 6 RCTs (6.5%) reported negative results.
CONCLUSIONS: Power calculations for efficacy, an important component of an RCT, were missing in 51% of the RCTs we surveyed, while a power calculation for safety was only present in 1.1%. Around 60% of the published RCTs were labeled as an "efficacy and safety trial," and none of those studies had a power calculation for safety.

PMID: 27320058 [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 2017/05/04

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.

The end of a dogma: the safety of doxycycline use in young children for malaria treatment.

Malar J. 2017 Apr 13;16(1):148

Authors: Gaillard T, Briolant S, Madamet M, Pradines B

Abstract
Anti-malarial drug resistance to chloroquine and sulfadoxine-pyrimethamine has spread from Southeast Asia to Africa. Furthermore, the recent emergence of resistance to artemisinin-based combination therapy (ACT) in Southeast Asia highlights the need to identify new anti-malarial drugs. Doxycycline is recommended for malaria chemoprophylaxis for travel in endemic areas, or in combination with the use of quinine for malaria treatment when ACT is unavailable or when the treatment of severe malaria with artesunate fails. However, doxycycline is not used in young children under 8 years of age due to its contraindication due to the risk of yellow tooth discolouration and dental enamel hypoplasia. Doxycycline was developed after tetracycline and was labelled with the same side-effects as the earlier tetracyclines. However, recent studies report little or no effects of doxycycline on tooth staining or dental enamel hypoplasia in children under 8 years of age. In the United States, the Centers for Disease Control and Prevention have recommended the use of doxycycline for the treatment of acute and chronic Q fever and tick-borne rickettsial diseases in young children. It is time to rehabilitate doxycycline and to recommend it for malaria treatment in children under 8 years of age.

PMID: 28407772 [PubMed - indexed for MEDLINE]

Association Between Readmission After Liver Transplant and Adverse Immunosuppressant Reactions: A Prospective Cohort With a 1-Year Follow-up.

Transplant Proc. 2017 Mar;49(2):330-337

Authors: Haddad L, Andrade K, Mendes L, Ducatti L, D'Albuquerque LA, Andraus W

Abstract
OBJECTIVE: To measure the association between readmission after liver transplantation and corresponding adverse drug reactions.
METHODS: A total of 48 patients undergoing liver transplantation were prospectively followed for 1 year. Of these, 23 were readmitted and evaluated by a pharmacist for causes of adverse drug reaction. The detection of adverse drug reactions was based on a combination of clinical interviews and physical and laboratory exams. Adverse reactions were defined in accordance with the Naranjo algorithm.
RESULTS: A total of 67.6% of all readmissions were related to adverse drug reactions, with tacrolimus accounting for 80% of the drug reactions. The most common cause of readmission was infection (48.6%), followed by procedure-related reasons (29.7%). Of all patients requiring admission, 39.1% had Model for End-stage Liver Disease (MELD) scores below 21 at the time of transplantation, 17.4% had MELD scores between 21 and 29, and 43.5% had MELD scores above 29. Most (66.7%) of those readmitted more than twice had MELD scores above 29.
CONCLUSION: Adverse drug reactions related to immunosuppressants frequently lead to readmission among liver transplant patients, and in our series tacrolimus was the most frequently associated drug.

PMID: 28219594 [PubMed - indexed for MEDLINE]

Adverse drug reactions of botulinum neurotoxin type A in children with cerebral palsy: a pharmaco-epidemiological study in VigiBase.

Dev Med Child Neurol. 2017 Mar;59(3):329-334

Authors: Montastruc J, Marque P, Moulis F, Bourg V, Lambert V, Durrieu G, Montastruc JL, Montastruc F

Abstract
AIM: The aim of this study was to assess the risk of adverse drug reactions (ADRs) with botulinum neurotoxin type A (BoNT-A) in children with cerebral palsy (CP) using the World Health Organization global individual case safety report (ICSR) database, VigiBase.
METHOD: We extracted all children ICSRs for ADRs with BoNT-A used as anti-spastic drug in CP recorded between 1995 and 2015 in VigiBase. We also performed a case/non-case method (disproportionality analysis) to assess the link between exposure to BoNT-A and each ADR of interest in children and adults, calculating reporting odds ratios (RORs).
RESULTS: In VigiBase, 162 ICSRs were registered. They involved mainly males (n=95, 59%) and mean (SD) age was 7 years 11 months (4y 4mo). The most frequent ADR was dysphagia (27 ICSRs, 17%) followed by asthenia and muscular weakness (25 ICSRs each, 16%). Nineteen ICSRs (12%) were lethal. There was a significant association between BoNT-A and death in children (ROR=11.1 95%, confidence interval [CI] 7.0-17.7) but not in adults.
INTERPRETATION: In children with CP, most ADRs seem to be linked to a systemic spread of BoNT-A. Our study suggests a higher risk of ADRs with BoNT-A in children than in adults.

PMID: 27682175 [PubMed - indexed for MEDLINE]

mRECIST response combined with sorafenib-related adverse events is superior to either criterion alone in predicting survival in HCC patients treated with TACE plus sorafenib.

Int J Cancer. 2017 Jan 15;140(2):390-399

Authors: Wang W, Bai W, Wang E, Zhao Y, Liu L, Yang M, Cai H, Xia D, Zhang L, Niu J, Yin Z, Zhang Z, Fan D, Xia J, Han G

Abstract
The mRECIST and dermatologic adverse events (AEs) can be used to assess the patient response to transarterial chemoembolization (TACE) and/or sorafenib for hepatocellular carcinoma (HCC). Here, we aimed to combine the two criteria to stratify the prognosis in patients with unresectable HCC receiving TACE plus sorafenib (TACE-S). In total, 176 consecutive HCC patients treated with TACE-S were enrolled. CT scans and laboratory tests were conducted pretreatment (at baseline, 5-7 days before the TACE-S) and post-treatment (at 1, 2 and 3 months). The radiological response was assessed according to mRECIST. Sorafenib-related AEs were recorded every 2 weeks after oral administration, and patients with dermatologic AEs of Grade 2 or more were defined as dermatologic responders. The earliest time at which mRECIST and dermatologic responses correlated with survival was 2 months after therapy. The mRECIST-dermatologic AE combination assessment stratified patients into three different prognoses; responders on both assessments exhibited the longest median overall survival (OS), followed by responders on one assessment and non-responders on both assessments (30.5, 17.4 and 8.3 months, respectively; p < 0.001). Achieving the highest C-index, the mRECIST-dermatologic AE combination showed better performance in predicting survival than either mRECIST or dermatologic AEs alone. Furthermore, the mRECIST-dermatologic AE combination remained a significant predictor of OS, even when the patients were stratified according to the BCLC stage, ECOG score or alpha-fetoprotein (AFP) value. This study showed that the combination of mRECIST response and dermatologic AEs is superior to either criterion used alone for predicting the survival of HCC patients treated with TACE-S.

PMID: 27681592 [PubMed - indexed for MEDLINE]

Patterns of Prescription Drug Use Before and After Fragility Fracture.

JAMA Intern Med. 2016 Oct 01;176(10):1531-1538

Authors: Munson JC, Bynum JP, Bell JE, Cantu R, McDonough C, Wang Q, Tosteson TD, Tosteson AN

Abstract
Importance: Patients who have a fragility fracture are at high risk for subsequent fractures. Prescription drugs represent 1 factor that could be modified to reduce the risk of subsequent fracture.
Objective: To describe the use of prescription drugs associated with fracture risk before and after fragility fracture.
Design, Setting, and Participants: Retrospective cohort study conducted between February 2015 and March 2016 using a 40% random sample of Medicare beneficiaries from 2007 through 2011 in general communities throughout the United States. A total of 168 133 community-dwelling Medicare beneficiaries who survived a fracture of the hip, shoulder, or wrist were included. Cohort members were required to be enrolled in fee-for-service Medicare with drug coverage (Parts A, B, and D) and to be community dwelling for at least 30 days in the immediate 4-month postfracture period.
Exposures: Prescription drug use during the 4-month period before and after a fragility fracture.
Main Outcomes and Measures: Prescription fills for drug classes associated with increased fracture risk were measured using Part D retail pharmacy claims. These were divided into 3 categories: drugs that increase fall risk; drugs that decrease bone density; and drugs with unclear fracture risk mechanism. Drugs that increase bone density were also tracked.
Results: A total of 168 133 patients with a fragility fracture (141 569 women; 84.2%) met the inclusion criteria for this study; 91.8% were white. Across all fracture types, the mean (SD) age was 80.0 (7.7) years, and 53.2% of the fracture cohort was hospitalized at the time of the index fracture, although this varied significantly depending on fracture type (100% of hip fractures, 8.2% of wrist fractures, and 15.0% of shoulder fractures). The frequency of discharge to an institution for rehabilitation following hospitalization also varied by fracture type, but the mean (SD) duration of acute rehabilitation did not: 28.1 (19.8) days. Most patients were exposed to at least 1 nonopiate drug associated with increased fracture risk in the 4 months before fracture (77.1% of hip, 74.1% of wrist, and 75.9% of shoulder fractures). Approximately 7% of these patients discontinued this drug exposure after the fracture, but this was offset by new users after fracture. Consequently, the proportion of the cohort exposed following fracture was unchanged (80.5%, 74.3%, and 76.9% for hip, wrist, and shoulder, respectively). There was no change in the average number of fracture-associated drugs used. This same pattern of use before and after fracture was observed across all 3 drug mechanism categories. Use of drugs to strengthen bone density was uncommon (≤25%) both before and after fracture.
Conclusions and Relevance: Exposure to prescription drugs associated with fracture risk is infrequently reduced following fragility fracture occurrence. While some patients eliminate their exposure to drugs associated with fracture, an equal number initiate new high-risk drugs. This pattern suggests there is a missed opportunity to modify at least one factor contributing to secondary fractures.

PMID: 27548843 [PubMed - indexed for MEDLINE]

Primary Care Requirements for Pharmacists-Clinical Reasoning Education at Schools of Pharmaceutical Sciences.

Yakugaku Zasshi. 2016;136(7):939-44

Authors: Ashizawa T

Abstract
For appropriate primary care practice corresponding to the various symptoms of a patient, team medicine on that combines the expertise of physicians and other medical staff has been recommended in recent years. It results in (1) higher quality of medical care, (2) lower burden on the physician, (3) better medical safety, and (4) reduced medical expenses. In order to promote team medicine through inter-professional collaboration, the responsibilities of the medical staff need to be reviewed to expand their respective roles. The Ministry of Health, Labour and Welfare designated nine specific medical acts by pharmacists in 2010. Some acts require clinical reasoning (medical interview and physical assessment) in order to manage side effects in patients undergoing drug therapy. The new curriculum introduced in 2015 includes primary care education for pharmacists who see patients before they are seen by a physician. Because such patients are usually seen by the pharmacist on a walk-in basis, medical interview and inspection education is especially important in this situation. However, there is incongruity in the physical assessment education of prospective pharmacists among schools of pharmaceutical sciences in recent years, which tends to focus primarily on vital signs. Moreover, there is currently no consensus among physicians on the optimum range of procedures performed by a pharmacist before the patient is seen by a physician. In this presentation, the practice of primary care by pharmacists is discussed from the following perspectives: (1) target symptoms and patients, (2) clinical reasoning education at pharmaceutical schools, and (3) future issues.

PMID: 27374954 [PubMed - indexed for MEDLINE]

Influence of inhaled corticosteroids on pubertal growth and final height in asthmatic children.

Pediatr Allergy Immunol. 2016 08;27(5):499-506

Authors: De Leonibus C, Attanasi M, Roze Z, Martin B, Marcovecchio ML, Di Pillo S, Chiarelli F, Mohn A

Abstract
BACKGROUND: Controversial data exist on the possibility that inhaled corticosteroids (ICs) affect growth in children with mild-to-moderate asthma. We assessed whether ICs affect growth and final height (FH) in asthmatic children compared to controls.
METHODS: A retrospective study was conducted on 113 asthmatic children compared with 66 control children. Asthmatic children presented with mild-to-moderate asthma and had exclusive ICs. Anthropometric data of four specific time-points were collected for both groups (pre-puberty, onset and late puberty, and FH) and converted to standard deviation scores (SDS). Growth trajectories were assessed as follows: (i) in puberty, using peak height velocity (PHV) and pubertal height gain SDS (PHG-SDS); (ii) until FH achievement, using FH-SDS and FH gain SDS (FHG-SDS). Repeated measurement analysis was performed across longitudinal study visits. A general linear model (GLM) was performed in asthmatic group evaluating the effect of corticosteroid type, treatment duration, and cumulative dose on FH corrected for multiple variables.
RESULTS: At pre-puberty, height and weight SDS were similar between the groups (p > 0.05). Height SDS progressively declined over the study period in asthmatic patients from pre-puberty to FH (p-trend < 0.05), whereas it did not change over time in controls (p-trend > 0.05), in both boys and girls. Asthmatic children had exclusive ICs [budesonide (n = 36) vs. fluticasone (n = 43) vs. mometasone (n = 34)] for a mean period of 6.25 ± 1.20 years and a mean cumulative dose of 560.07 ± 76.02 mg. They showed decreased PHG-SDS and lower PHV compared to controls (all p < 0.05). FH-SDS and FHG-SDS were significantly reduced in asthmatic group compared to controls. FH in asthmatic patients was 2.5 ± 2.89 cm lower in boys and 2.0 ± 2.03 cm lower in girls than controls. The GLM showed that FH achievement was dependent on the type of ICs, duration of the treatment, and cumulative dose (p < 0.05).
CONCLUSIONS: ICs affect pubertal growth determining reduced final height in asthmatic children compared to controls, in a dose- and duration-dependent manner.

PMID: 26919136 [PubMed - indexed for MEDLINE]

The prospective IQ-CSRC trial: A prototype early clinical proarrhythmia assessment investigation for replacing the ICH E14 thorough QTc (TQT) study.

J Pharmacol Toxicol Methods. 2016 Jul-Aug;80:1-8

Authors: Cavero I, Holzgrefe H, Clements M

Abstract
INTRODUCTION: Early clinical Phase I ECG investigations designed to replace the currently applied thorough QT (TQT) study are reviewed to examine how they could complement and verify the conclusions of nonclinical investigations and, in particular, the Comprehensive in vitro Proarrhythmia Assay (CiPA).
TOPICS: The IQ-CSRC trial is a prospective ascending multiple-dose first in human (FIH) type investigation performed as a possible replacement for the thorough QT study (TQT). Designed in accordance with the results of a simulation study by the FDA QT Interdisciplinary Review Team (IRT), it succeeded in correctly categorizing 5/5 established QTc-prolonging agents free of notable heart rate effects (dofetilide, dolasetron, moxifloxacin, ondansetron, and quinine) and the QTc-negative drug, levocetirizine.
DISCUSSION: The positive results obtained with the IQ-CSRC study require additional confirmation with threshold QTc-positive and negative drugs and established QTc prolongers producing both increases and decreases in heart rate. In the future, similar studies should also adopt and validate innovative proarrhythmic metrics, in addition to, or instead of, the traditional proarrhythmic surrogate of QTc, to assess the proarrhythmic safety of candidate drugs.

PMID: 26903171 [PubMed - indexed for MEDLINE]

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]