Improving Medicine Use for Children: A Global Imperative.

Clin Pharmacol Ther. 2017 Jun;101(6):715-717

Authors: MacLeod SM

Abstract
Professionals committed to optimal medical care of children recognize the need to increase future availability of thoroughly validated medicinal treatments. This will only be achieved through expanded efforts of pediatric clinical pharmacologists and clinical pharmacists equipped with the necessary skills in relevant research and educational methods. Recent research has demonstrated a shortfall in the human resource pool, particularly in low- and lower-middle-income countries where a majority of children under 14 years of age reside.

PMID: 28127760 [PubMed - indexed for MEDLINE]

Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis.

Toxicol Appl Pharmacol. 2016 Jul 01;302:1-9

Authors: Tolosa L, Gómez-Lechón MJ, Jiménez N, Hervás D, Jover R, Donato MT

Abstract
Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis.

PMID: 27089845 [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")

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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 2017/05/30

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.

Risk factors and mechanisms contributing to TKI-induced vascular events in patients with CML.

Leuk Res. 2017 May 12;59:47-54

Authors: Valent P, Hadzijusufovic E, Hoermann G, Füreder W, Schernthaner GH, Sperr WR, Kirchmair R, Wolf D

Abstract
Vascular adverse events (VAE) are an emerging problem in patients with chronic myeloid leukemia (CML) receiving second-generation BCR-ABL1 tyrosine kinase inhibitors (TKI). Relevant VAE comprise peripheral, cerebral, and coronary artery changes in patients receiving nilotinib, venous and arterial occlusive events during ponatinib therapy, and pulmonary hypertension in patients receiving dasatinib. Although each TKI binds to a unique profile of molecular targets in leukemic cells and vascular cells, the exact etiology of drug-induced vasculopathies remains uncertain. Recent data suggest that predisposing molecular factors, pre-existing cardiovascular risk factors as well as certain comorbidities contribute to the etiology of VAE in these patients. In addition, direct effects of these TKI on vascular endothelial cells have been demonstrated and are considered to contribute essentially to VAE evolution. In the current article, we discuss mechanisms underlying the occurrence of VAE in TKI-treated patients with CML, with special emphasis on vascular and perivascular target cells and involved molecular (vascular) targets of VAE-triggering TKI. In addition, we discuss optimal patient selection and drug selection through which the risk of occurrence of cardiovascular events can hopefully be minimized while maintaining optimal anti-leukemic effects in CML, thereby following the principles of personalized medicine.

PMID: 28549238 [PubMed - as supplied by publisher]

[Prevalence of potential drug-drug interactions involving antiretroviral drugs in Buenos Aires, Argentina].

Rev Chilena Infectol. 2016 Oct;33(Suppl 1):54-59

Authors: Córdova E, Porteiro N, Loiza E, Mingrone H

Abstract
INTRODUCTION: Antiretroviral agents (ARVs) have a high potential for drug interactions. However, the prevalence and risk factors for clinically significant drug-drug interactions (CSDDIs) with ARVs from Latin American countries is unknown.
AIM: To evaluate the prevalence and risk factors for CSDDIs in HIV outpatients attending at two centers in Buenos Aires, Argentina.
METHODS: Descriptive cross-sectional study (september to november 2012). HIV-1 infected patients under ARV treatment at the time of the study were randomly assessed for concomitant medication. CSDDIs were screened using the University of Liverpool Drug Interactions Program (www.hiv-druginteractions.org).
RESULTS: A total of 217 patients were included. Male sex: 64% (CI 95: 57-70). Median age (IQR): 41 (36-48). Presence of comorbidities: 19%. ARV regimen: NNRTI-based: 48%, PI-based: 50% and NNRTI plus PI: 2%. Median of CD4 T-cell count (IQR): 402 cells/mL (235-588). Viral load < 50 copies/mL: 78%. Overall, 64% (CI 95: 57-70) of patients had > 1 co-medication of whom a 49% had at least one CSDDI. Two patients had a CSDDI between ARVs. The most frequent co-medications observed were antimicrobial (40%), cardiovascular (25%) and gastrointestinal agents (22%). In the multivariate analysis the number of co-medications and use of CNS agents were associated with the presence of CSDDIs.
CONCLUSIONS: Co-medications and CSDDIs were common in our setting. In this context, training of HIV physicians in drug interactions is of major importance for adequate management of these patients.

PMID: 28453027 [PubMed - indexed for MEDLINE]

[The clinical relevance of drug interactions in patients with human immunodeficiency virus infection: update 2009-2014].

Rev Chilena Infectol. 2016 Oct;33(Suppl 1):36-53

Authors: Giraldo NA, Amariles P, Pino Marín DE, Faus MJ

Abstract
OBJECTIVE: To update information about drug interactions in patients with HIV/AIDS.
METHODS: Comprehensive literature review in MEDLINE/PubMed database from May of 2009 to December of 2014, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. Additionally, citation lists from identified articles were reviewed. The study inclusion was assessed by three independent researchers and by consensus among them when was necessary. Clinical relevance of drug interaction was grouped into four levels according to seriously and probability of occurrence.
RESULTS: Global, 546 different references were retrieved and 243 were selected. In addition 11 further manuscripts were identified in the references of the included articles. Overall, 935 pairs of drug interactions were identified, 95.7% pharmacokinetic (823 by enzyme induction or inhibition and 67 by changes in bioavailability). Of the 935 pairs of drug interactions, 402(43%) were classified as levels 1 or 2.
CONCLUSIONS: The most clinically relevant antiretroviral drug interactions are due to pharmacokinetic mechanism, mainly induction or enzyme inhibition, according to previous reviews, the protease inhibitors remain as the antiretrovirals with the highest number of clinical relevant interactions.

PMID: 28453026 [PubMed - indexed for MEDLINE]

Can Disproportionality Analysis of Post-marketing Case Reports be Used for Comparison of Drug Safety Profiles?

Clin Drug Investig. 2017 May;37(5):415-422

Authors: Michel C, Scosyrev E, Petrin M, Schmouder R

Abstract
Clinical trials usually do not have the power to detect rare adverse drug reactions. Spontaneous adverse reaction reports as for example available in post-marketing safety databases such as the FDA Adverse Event Reporting System (FAERS) are therefore a valuable source of information to detect new safety signals early. To screen such large data-volumes for safety signals, data-mining algorithms based on the concept of disproportionality have been developed. Because disproportionality analysis is based on spontaneous reports submitted for a large number of drugs and adverse event types, one might consider using these data to compare safety profiles across drugs. In fact, recent publications have promoted this practice, claiming to provide guidance on treatment decisions to healthcare decision makers. In this article we investigate the validity of this approach. We argue that disproportionality cannot be used for comparative drug safety analysis beyond basic hypothesis generation because measures of disproportionality are: (1) missing the incidence denominators, (2) subject to severe reporting bias, and (3) not adjusted for confounding. Hypotheses generated by disproportionality analyses must be investigated by more robust methods before they can be allowed to influence clinical decisions.

PMID: 28224371 [PubMed - indexed for MEDLINE]

Longitudinal assessment of nutritional risk in patients under chemo or radiotherapy.

Rev Assoc Med Bras (1992). 2016 Oct;62(7):659-663

Authors: Mastelaro I, Pupin MP, Ribeiro SM, Oliveira HF, Peria FM, Cunha SF

Abstract
Objective:: To compare nutritional risk in adult patients undergoing chemotherapy and radiotherapy in the beginning, middle, and end of oncologic treatment.
Method:: This prospective, comparative study included 83 adult patients, 44 undergoing chemotherapy (CT group) and 39 undergoing radiotherapy (RT group) at an oncology treatment center. Nutritional risk was determined by NRS-2002 in the beginning, middle, and end of therapy. Statistical analysis was performed using Statistica 8.0 software.
Results:: No differences in food intake or body mass index were observed between the CT (24.6±4.8 kg/m²) and RT groups (25.0±5.9 kg/m², p=0.75). Weight loss in the preceding 3 months was detected in 56.8% of CT group and 38.5% of RT group (p=0.09). The weight loss percentage compared with the usual weight within 3 months was greater (p<0.001) in the CT (11.4±6.5%) than in the RT group (3.9±6.8%). In the beginning of treatment, we observed high percentages of patients at moderate (18.2 vs. 15.4%, p=0.73) and high nutritional risk (61.4 vs. 48.7%, p=0.25), with no statistical difference between the CT and RT groups, respectively. During therapy, the nutritional risk remained unaltered in both groups. In the end of therapy, the majority of patients were at moderate (18.2 vs. 12.8%, p=0.50) or severe nutritional risk (50.0 vs. 51.3%, p=0.91), in the CT and RT groups, respectively, regardless of the type of oncologic treatment.
Conclusion:: The high prevalence of patients at moderate or high nutritional risk in the beginning of treatment indicates the need for an early and continuous follow-up of the nutritional status of patients undergoing oncologic treatment.

PMID: 27925046 [PubMed - indexed for MEDLINE]

Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study.

PLoS Med. 2016 Aug;13(8):e1002058

Authors: Hayes JF, Marston L, Walters K, Geddes JR, King M, Osborn DP

Abstract
BACKGROUND: There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine.
METHODS AND FINDINGS: We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64-3.43). Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45-0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45-0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47-0.80; p < 0.001). Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40-0.89; p = 0.012) and olanzapine (HR 0.48; 95% CI 0.29-0.77; p = 0.003), compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09-0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13-0.73; p = 0.007) and hypercalcemia (valproate HR 0.25; 95% CI 0.10-0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14-0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07-0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31-2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47-2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24-2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06-1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or hepatotoxicity. Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects.
CONCLUSIONS: Lithium use is associated with more renal and endocrine adverse events but less weight gain than commonly used alternative mood stabilizers. Risks need to be offset with the effectiveness and anti-suicidal benefits of lithium and the potential metabolic side effects of alternative treatment options.

PMID: 27483368 [PubMed - indexed for MEDLINE]

Hepatic complications induced by immunosuppressants and biologics in inflammatory bowel disease.

World J Hepatol. 2017 May 08;9(13):613-626

Authors: Tran-Minh ML, Sousa P, Maillet M, Allez M, Gornet JM

Abstract
The incidence of inflammatory bowel diseases (IBD) is rising worldwide. The therapeutic options for IBD are expanding, and the number of drugs with new targets will rapidly increase in coming years. A rapid step-up approach with close monitoring of intestinal inflammation is extensively used. The fear of side effects represents one the most limiting factor of their use. Despite a widespread use for years, drug induced liver injury (DILI) management remains a challenging situation with Azathioprine and Methotrexate. DILI seems less frequent with anti-tumor necrosis factor agents and new biologic therapies. The aim of this review is to report incidence, physiopathology and practical guidelines in case of DILI occurrence with the armamentarium of old and new drugs in the field of IBD.

PMID: 28539989 [PubMed - in process]

Chemoembolization Adopting Polyethylene Glycol Drug-Eluting Embolics Loaded With Doxorubicin for the Treatment of Hepatocellular Carcinoma.

AJR Am J Roentgenol. 2017 May 24;:1-5

Authors: Aliberti C, Carandina R, Sarti D, Mulazzani L, Pizzirani E, Guadagni S, Fiorentini G

Abstract
OBJECTIVE: The purpose of this study is to determine the efficacy and tolerability of transarterial chemoembolization (TACE) using polyethylene glycol (PEG) drug-elutable microspheres loaded with doxorubicin for treatment of hepatocellular carcinoma (HCC).
SUBJECTS AND METHODS: Forty-two patients with unresectable HCC, as determined by a tumor board, were assigned to undergo TACE and were treated with PEG drug-elutable embolics loaded with doxorubicin. Patients were prospectively enrolled and included 32 (76%) men and 10 (24%) women. Their median age was 65 years (range, 42-83 years). Patients were treated with 50 mg of doxorubicin loaded in 2 mL of PEG embolics (mean [± SD] diameter, 100 ± 25 µm) that were infused via a chemoembolization method. Data collected included previous cancer therapy, tumor size, number of lesions, history of TACE, tumor response (at 1, 3, and 6 months), type and intensity of adverse events, and quality of life (QOL) analysis.
RESULTS: One month after TACE, the overall tumor response rate was 79% (50% complete response, 29% partial response, 17% stable disease, and 5% progressive disease). At 3 months, the rates were 48% for complete response, 24% for partial response, 24% for stable disease, and 3% for progressive disease. At 6 months, the rates were 43% for complete response, 19% for partial response, 29% for stable disease, and 10% for progressive disease. TACE was well tolerated by all patients, with no evidence of procedure-related complications or systemic drug-related adverse events. Fever (33%), increase in transaminase level (17%), and pain (33%) were the most frequent adverse events, and their intensity was mostly mild (grades 1 and 2). The QOL scores were 80 at 1 month, 81 at 3 months, and 82 at 6 months after TACE.
CONCLUSION: These data suggest that PEG embolics are efficacious and safe for the treatment of HCC, as indicated by their good tolerability, QOL scores, and high tumor response.

PMID: 28537756 [PubMed - as supplied by publisher]

Low rates of pregnancy screening in adolescents before teratogenic exposures in a national sample of children's hospitals.

Cancer. 2016 Nov 15;122(21):3394-3400

Authors: Rao P, Li Y, Getz KD, Miller TP, Huang YS, Wilkes JJ, Seif AE, Bagatell R, Fisher BT, Gracia C, Aplenc R

Abstract
BACKGROUND: Adolescents with cancer engage in sexual behaviors and are exposed to teratogenic chemotherapy. There are no data regarding pregnancy screening patterns for adolescents before chemotherapy exposure.
METHODS: A cross-sectional study of leukemia and emergency room (ER) admissions in the Pediatric Health Information System from 1999 to 2011 was conducted. Females who were 10 to 18 years old and 1) had newly diagnosed acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) or 2) had ER visits with computed tomography (CT) of the abdomen/pelvis were included. The exposure was a hospital visit with either chemotherapy or an abdominal/pelvic CT scan. The main outcome was a pregnancy test billed on the same day or before the teratogenic exposure within the same index admission. Log-binomial regressions were used to compute prevalence ratios and 95% confidence intervals comparing pregnancy screening in the leukemia and ER cohorts.
RESULTS: A total of 35,650 admissions were identified. The proportion of visits with an appropriately timed pregnancy test was 35%, 64%, and 58% in the ALL (n = 889), AML (n = 127), and ER cohorts (n = 34,634), respectively. Patients with ALL were significantly less likely to have a pregnancy test than the ER cohort (adjusted prevalence ratio, 0.71; 95% confidence interval, 0.65-0.78), but there was no significant difference between the AML and ER cohorts (adjusted prevalence ratio, 1.12; 95% confidence interval, 0.99-1.27). There was substantial hospital-level variation in pregnancy screening patterns.
CONCLUSIONS: Adolescents with acute leukemia and ER visits have low rates of pregnancy screening before teratogenic exposures. Standardized practice guidelines for pregnancy screening among adolescents may improve screening rates. Cancer 2016;122:3394-3400. © 2016 American Cancer Society.

PMID: 27618636 [PubMed - indexed for MEDLINE]

Role of oral pentosan polysulphate in the reduction of local side effects of BCG therapy in patients with non-muscle-invasive bladder cancer: a pilot study.

BJU Int. 2016 Nov;118(5):758-762

Authors: Yadav S, Tomar V, Yadav SS, Priyadarshi S, Banerjee I

Abstract
OBJECTIVE: To assess the role of oral pentosan polysulphate (PPS) in the reduction of bacille Calmette-Guérin (BCG)-related local side effects in patients with high grade Ta/T1 non-muscle-invasive bladder cancer (NMIBC).
PATIENTS AND METHODS: A total of 32 symptomatic patients receiving BCG instillation were randomized into three groups: group A received placebo (vitamin B complex tablet) thrice daily; group B received PPS 100 mg thrice daily; and group C received PPS 100 mg once daily and placebo (vitamin B complex tablet) twice daily for 6 weeks. A visual analogue scale (VAS) score for bladder pain, Overactive Bladder-Validated 8 Question Screener (OAB-V8) scores and dysuria were evaluated in the three groups before and during each weekly visit for BCG instillation.
RESULTS: The mean ± sd post-treatment VAS scores were significantly lower in groups B (4.4 ± 1.2) and C (5.8 ± 0.8) than in group A (8 ± 0.4). In addition, the post-treatment VAS score was significantly lower in group B than in group C (P<0.01). The mean post-treatment OAB-V8 score was significantly lower only in group B (decreased from 15.5 to 9.7). Dysuria decreased in groups B and C but persisted in group A.
CONCLUSION: The present study shows that oral PPS (100 mg) thrice daily is effective in relieving BCG-related local side effects.

PMID: 27010115 [PubMed - indexed for MEDLINE]

Frequency of Adverse Events Before, During, and After Hospital Admission.

South Med J. 2016 Oct;109(10):631-635

Authors: Croft LD, Liquori ME, Ladd J, Day HR, Pineles L, Lamos EM, Mehrotra P, Perencevich EN, Harris AD, Morgan DJ

Abstract
OBJECTIVES: Adverse events (AEs) are unintended physical injuries resulting from or contributed to by medical or surgical care. We determined the frequency and type of AEs before, during, and after hospital admission.
METHODS: We conducted a cohort study of 296 adult hospital patients. We used the standardized Institute for Healthcare Improvement Global Trigger Tool for Measuring Adverse Events to review the medical records of the hospital patients for occurrence, timing relative to hospital admission, severity, and preventability of AEs. We also identified the primary physiologic system affected by the AE.
RESULTS: Among 296 patients, we identified 338 AEs. AEs occurred with similar frequency before (n = 148; 43.8%) and during hospital admission (n = 162; 47.9%). Fewer AEs occurred after discharge (n = 28; 8.3%). Half of all AEs (n = 169; 50.0%) were severe, whereas 47.9% (n = 162) were preventable.
CONCLUSIONS: AEs occur with similar frequency before and during hospitalization and may contribute more to hospital admissions than previously recognized. These findings suggest that efforts to improve patient safety should include outpatient settings in addition to the more commonly targeted acute care settings.

PMID: 27706501 [PubMed - indexed for MEDLINE]

[Drug therapy of otorhinolaryngological diseases in pregnancy : An update].

HNO. 2016 Nov;64(11):843-854

Authors: Riepl R, Friebe-Hoffmann U

Abstract
The majority of women take at least one form of medication during pregnancy. Due to often discrepant information about the risk assessment of pharmaceuticals during pregnancy, physicians are often beset by uncertainty with respect to prescription and the fear of medicolegal consequences is high. As prospective clinical trials on drug safety during pregnancy are prohibited due to ethical reasons and animal studies are of limited applicability to humans, drug recommendations often only rely on observational data. An objective examination of the topic not only contributes to effective treatment of illnesses in pregnancy but also prevents impairment of fetal outcome by omission of necessary maternal treatment. The aim of this article is to give a structured presentation of medications that can be used during pregnancy for treating medical conditions of the ear, nose and throat, in the sense of practical guidelines.

PMID: 27680545 [PubMed - indexed for MEDLINE]

Efficacy and Safety of Pulmonary Arterial Hypertension-specific Therapy in Pulmonary Arterial Hypertension: A Meta-analysis of Randomized Controlled Trials.

Chest. 2016 Aug;150(2):353-66

Authors: Liu HL, Chen XY, Li JR, Su SW, Ding T, Shi CX, Jiang YF, Zhu ZN

Abstract
BACKGROUND: Previous meta-analyses of pulmonary arterial hypertension (PAH)-specific therapy for PAH pooled PAH-specific combination therapy and monotherapy. This flaw may threaten the authenticity of their findings.
METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials that evaluated any PAH-specific medications in the treatment of PAH. We calculated ORs with 95% CIs for dichotomous data and standardized mean differences for continuous data.
RESULTS: In total, 35 randomized controlled trials involving 6,702 patients were included. In monotherapy vs placebo/conventional therapy, significance was obtained in mortality reduction (OR, 0.50 [95% CI, 0.33 to 0.76]; P = .001), 6-min walk test (mean difference, 31.10 m [95% CI, 25.40 to 36.80]; P < .00001), New York Heart Association/World Health Organization functional class (OR, 2.48 [95% CI, 1.51 to 4.07]; P = .0003), and hemodynamic status based on mean pulmonary artery pressure, pulmonary vascular resistance, cardiac index, and incidence of withdrawal due to adverse effects. In combination therapy vs monotherapy, significance was reached for the 6-min walk test (mean difference, 19.96 m [95% CI, 15.35 to 24.57]; P < .00001), functional class (OR, 1.65 [95% CI, 1.20 to 2.28]; P = .002), hemodynamic status, and incidence of withdrawal due to adverse effects (OR, 2.01 [95% CI, 1.54 to 2.61]; P < .00001) but not for mortality reduction (OR, 0.98 [95% CI, 0.57 to 1.68]; P = .94).
CONCLUSIONS: Our meta-analysis revealed that PAH-specific monotherapy could improve mortality, exercise capacity, functional class, and hemodynamic status compared with placebo or conventional therapy. However, combination therapy could further improve exercise capacity, functional class, and hemodynamic status compared with monotherapy, but it had no proven effect on mortality. Combination therapy had a much higher incidence of withdrawal due to adverse effects than monotherapy.

PMID: 27048870 [PubMed - indexed for MEDLINE]

The Impact of Aging and Medical Status on Dysgeusia.

Am J Med. 2016 Jul;129(7):753.e1-6

Authors: Syed Q, Hendler KT, Koncilja K

Abstract
Disorders of taste and smell can cause an aversion to food in a sick patient and therefore affect his/her ability to maintain optimal nutrition. This can lead to a reduced level of strength, muscle mass, function, and quality of life. Additionally, reduced ability to differentiate between various intensities or concentrations of a tastant can result in increased intake of salt and sugar and exacerbation of chronic diseases such as heart failure and diabetes. These implications can be heightened in the elderly, who are particularly frail and are challenged by polypharmacy and multiple comorbid conditions. In this article, we will review the prevalence, etiology, and management of taste disorders. Additionally, we will review the association between taste and smell disorders and how disorders of smell can affect perception of taste.

PMID: 26899755 [PubMed - indexed for MEDLINE]

The extent of medication errors and adverse drug reactions throughout the patient journey in acute care in Australia.

Int J Evid Based Healthc. 2016 Sep;14(3):113-22

Authors: Roughead EE, Semple SJ, Rosenfeld E

Abstract
AIM: To provide an estimate of the numbers of medication errors and adverse drug reactions that occur along a person's journey through their hospital stay in Australia.
METHODS: A search of databases and online resources was undertaken to identify published literature on medication safety in the acute care setting in Australia from 2008 to 2013. Data on the rates of adverse drug reactions and medication errors associated with hospitalization was extracted from the published studies. This evidence was synthesized with evidence from previous reviews of medication safety in the acute care setting in Australia conducted in 2002 and 2008.
RESULTS: Findings from the Australian literature across the two previous reviews of medication safety and the present review indicate the proportion of all hospital admissions that are medication-related is between 2 and 3%. Studies assessing medication errors on admission to hospital suggest there may be an overall rate of two errors for every three patients at the time of admission to hospital. Large studies examining the rates of prescribing errors in major Australian teaching hospitals give insight into the rates of prescription error and suggest that prescription error rates of up to one error per patient occur in the hospital system. The best available evidence from more recent research suggests that errors (excluding errors of timing) occur in around 9% of medication administrations in hospital. At hospital discharge, errors in medication documentation in discharge summaries may occur at a rate of up to two errors per patient.
CONCLUSIONS: Medication safety in the various stages of the patient journey through acute care in Australia continues to be a significant problem. However, the extent of medication-related problems in acute care needs to be interpreted within the context of increasingly complex health care. There are an estimated 230 000 medication-related hospital admissions occurring per year. This suggests an annual cost of medication-related admissions of AU$1.2 billion.

PMID: 26886682 [PubMed - indexed for MEDLINE]

Olanzapine-Induced Neuroleptic Malignant Syndrome.

Iran J Med Sci. 2017 May;42(3):306-309

Authors: Hosseini S, Elyasi F

Abstract
Neuroleptic malignant syndrome (NMS) is a rare but life-threatening idiosyncratic side effect resulting from neuroleptic drugs. NMS mainly occurs in patients treated with high-potency typical antipsychotics, but rarely caused by atypical antipsychotics. Although NMS is less common with atypical antipsychotic, but it seems that its incidence is rising due to increased administration of such drugs. We present the case of a 27-year-old man with a history of paranoid schizophrenia that showed signs consistent with NMS that occurred after treatment with olanzapine. The patient was adherent to treatment. He had decreased level of consciousness, muscle rigidity, diaphoresis, fever, drooling, urinary incontinence, and high blood pressure. This patient illustrates that NMS can occur due to treatment with atypical antipsychotic drugs like olanzapine, particularly in the presence of risk factors. This phenomenon is often unrecognized, underdiagnosed, or not treated properly. Physicians should be aware that NMS with extrapyramidal syndrome could occur with olanzapine at steady state doses without recent dosage adjustments or titration. It is essential that adequate and safe dose of medication is chosen and the patient is monitored by the signs and symptoms of this lethal syndrome.

PMID: 28533580 [PubMed - in process]