[In process].

Pflege Z. 2017 Apr;70(4):36-8

Authors: Ebbers B

PMID: 29425435 [PubMed - indexed for MEDLINE]

Evaluation of accuracy of IHI Trigger Tool in identifying adverse drug events: a prospective observational study.

Br J Clin Pharmacol. 2018 Jun 06;:

Authors: das Dores Graciano Silva M, Martins MAP, de Gouvêa Viana L, Passaglia LG, de Menezes RR, de Queiroz Oliveira JA, da Silva JLP, Ribeiro ALP

Abstract
AIMS: Adverse drug events (ADEs) can seriously compromise the safety and quality of care provided to hospitalized patients, requiring the adoption of accurate methods to monitor them. We sought to prospectively evaluate the accuracy of the triggers proposed by the Institute for Healthcare Improvement (IHI) for identifying ADEs.
METHODS: A prospective study was conducted in a public university hospital, in 2015, with patients ≥18 years. Triggers proposed by IHI and clinical alterations suspected to be ADEs were searched daily. The number of days in which the patient was hospitalized was considered as unit of measure to evaluate the accuracy of each trigger.
RESULTS: Three hundred patients were included in this study. Mean age was 56.3 years (standard deviation (SD) 16.0), and 154 (51.3%) were female. The frequency of patients with ADEs was 24.7% and with at least one trigger was 53.3%. From those patients who had at least one trigger, the most frequent triggers were antiemetics (57.5%) and "abrupt medication stop" (31.8%). Triggers' sensitivity ranged from 0.3 to11.8 % and the positive predictive value ranged from 1.2 to 27.3%. Specificity and negative predictive value were greater than 86%. Most patients identified by the presence of triggers did not have ADEs (64.4%). No triggers were identified in 40 (38.5%) ADEs.
CONCLUSIONS: IHI Trigger Tool did not show good accuracy in detecting ADEs in this prospective study. The adoption of combined strategies could enhance effectiveness in identifying patient safety flaws. Further discussion might contribute to improve trigger usefulness in clinical practice.

PMID: 29874704 [PubMed - as supplied by publisher]

Effect of Low-Dose Vs Standard-Dose Valganciclovir in the Prevention of Cytomegalovirus Disease in Kidney Transplantation Recipients: A Systemic Review and Meta-Analysis.

Transplant Proc. 2018 Jun 02;:

Authors: Hwang SD, Lee JH, Lee SW, Kim JK, Kim MJ, Song JH

Abstract
BACKGROUND: Valganciclovir is widely used to prevent post-transplant cytomegalovirus (CMV) infection in kidney transplant patients. However, the currently used dose remains controversial because the continuous use of this drug decreases kidney function and can induce leukopenia.
OBJECTIVE: The purpose of this study was to measure the appropriate dose of valganciclovir required to prevent CMV infection.
METHODS: A systematic review and meta-analysis were performed by using a random effects model. The Cochrane Central Register, MEDLINE, EMBASE, and PubMed databases were searched up to April 15, 2017. We conducted analysis on low-dose (450 mg) and standard-dose (900 mg) valganciclovir groups.
RESULTS: After completion of the research, the analysis revealed that the glomerular filtration rate, graft loss, tacrolimus level, antibody-mediated rejection, and fungal and Candida infection rates did not differ between the 2 groups. However, the incidence of CMV tended to decrease in the low-dose group (0.584 [95% confidence interval [CI], 0.352-0.967]; P = .036). The biopsy-proven rejection rate decreased by 0.427 times in the low-dose group compared with the standard-dose group (95% CI, 0.274-0.667; P = .002). Furthermore, the incidence of leukopenia decreased by 0.371 times in the low-dose group compared with the standard-dose group (95% CI, 0.264-0.523; P = .001).
CONCLUSIONS: The 450-mg dose of valganciclovir effectively prevented post-transplantation CMV infection and decreased drug-induced side effects such as leukopenia. In the future, the lower dose of valganciclovir should be considered to prevent CMV infection and enhance cost-effectiveness.

PMID: 29871773 [PubMed - as supplied by publisher]

Cognitive Effects of Androgen Deprivation Therapy in Men With Advanced Prostate Cancer.

Urology. 2017 05;103:167-172

Authors: Gunlusoy B, Ceylan Y, Koskderelioglu A, Gedizlioglu M, Degirmenci T, Ortan P, Kozacioglu Z

Abstract
OBJECTIVE: To evaluate the prostate cancer effects of androgen deprivation therapy (ADT) by using a systematic set of methods to calculate specific cognitive functions in men with locally advanced or metastatic prostate cancer.
MATERIALS AND METHODS: From April 2014 to February 2016, a prospective, comparative study was done to evaluate the cognitive effects of hormone therapy. Group 1 consisted of 78 patients with locally advanced or metastatic prostate cancer who received complete ADT treatment continuously for 12 months and group 2 (control group) consisted of 78 patients who underwent radical prostatectomy without any additional treatment. The Montreal Cognitive Assessment (MoCA) test and the Frontal Assessment Battery (FAB) test with Turkish language version were used to evaluate multiple domains of cognitive function.
RESULTS: Post-treatment results of both tests revealed that patients in group 1 achieved lower mean total scores than group 2. In MoCA test, the deficits were especially prominent in the areas of language ability and short-term memory capacity (P < .05 and P < .05). No significant differences could be identified between groups in respect to attention, executive functions, visuospatial abilities, abstract thinking, calculating abilities, and orientation. In FAB test, the deficits were especially prominent in the areas of mental flexibility and inhibitory control (P < .05 and P < .05). No significant differences could be identified between groups in conceptualization, motor series, conflicting instructions, and environmental autonomy.
CONCLUSION: ADT affects cognitive functions such as language ability, short-term memory capacity, mental flexibility, and inhibitory control. Urologists should keep in mind these side effects and inform the patients and their families for the early symptoms of cognitive dysfunction.

PMID: 28188757 [PubMed - indexed for MEDLINE]

A Predictive Model for Toxicity Effects Assessment of Biotransformed Hepatic Drugs Using Iterative Sampling Method.

Sci Rep. 2016 12 09;6:38660

Authors: Tharwat A, Moemen YS, Hassanien AE

Abstract
Measuring toxicity is one of the main steps in drug development. Hence, there is a high demand for computational models to predict the toxicity effects of the potential drugs. In this study, we used a dataset, which consists of four toxicity effects:mutagenic, tumorigenic, irritant and reproductive effects. The proposed model consists of three phases. In the first phase, rough set-based methods are used to select the most discriminative features for reducing the classification time and improving the classification performance. Due to the imbalanced class distribution, in the second phase, different sampling methods such as Random Under-Sampling, Random Over-Sampling and Synthetic Minority Oversampling Technique are used to solve the problem of imbalanced datasets. ITerative Sampling (ITS) method is proposed to avoid the limitations of those methods. ITS method has two steps. The first step (sampling step) iteratively modifies the prior distribution of the minority and majority classes. In the second step, a data cleaning method is used to remove the overlapping that is produced from the first step. In the third phase, Bagging classifier is used to classify an unknown drug into toxic or non-toxic. The experimental results proved that the proposed model performed well in classifying the unknown samples according to all toxic effects in the imbalanced datasets.

PMID: 27934950 [PubMed - indexed for MEDLINE]

Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Evaluations Following Single Oral Doses of GSK2330672 in Healthy Japanese Volunteers.

Clin Pharmacol Drug Dev. 2018 Jun 05;:

Authors: Ino H, Endo A, Wakamatsu A, Ogura H, Numachi Y, Kendrick S

Abstract
GSK2330672 is an inhibitor of the ileal bile acid transporter, designed to have minimal systemic exposure, and is under development as a potential therapeutic for pruritus associated with primary biliary cholangitis and other cholestatic liver diseases. A phase 1, double-blind, placebo-controlled, 4-period crossover study was conducted to evaluate the safety, tolerability, and pharmacokinetic/pharmacodynamic characteristics of GSK2330672 in healthy Japanese participants. Sixteen healthy male participants received single oral doses of GSK2330672 (10-180 mg) or placebo in each period. No serious adverse events and no adverse events leading to study discontinuation or withdrawal were reported. Drug-related adverse events reported included gastrointestinal symptoms (mostly diarrhea) and positive fecal occult blood tests, and were all mild and resolved without any interventions. GSK2330672 was undetectable in the majority of participants' plasma. Pharmacodynamic observations included a tendency for total serum bile acids to reduce and for serum 7α-hydroxy-4-cholesten-3-one, a key intermediate of bile acid synthesis, to increase with increasing doses of GSK2330672. In the context of recently published indications of potential efficacy for cholestatic pruritus in non-Japanese populations, these data support further evaluations of GSK2330672 in Japanese patients.

PMID: 29870578 [PubMed - as supplied by publisher]

Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer.

Niger J Clin Pract. 2017 Nov;20(11):1422-1427

Authors: Yang J, Jia B, Yan J, He J

Abstract
PURPOSE: Pancreatic carcinoma is the most lethal cancer, with a 5-year survival rate of <5%. Hyperglycemia is one of the severe adverse drug reactions (ADRs) in cancer treatment. The aim was to analyze the blood glucose-related ADR of antineoplastics in treating pancreatic cancer.
MATERIALS AND METHODS: Antineoplastic drugs were selected from Martindale-The Complete Drug Reference (36th edition). ADR data were extracted from VigiBase, the WHO Uppsala Monitoring Centre, and the WHO's specialist center for drug safety.
RESULTS: Nineteen antineoplastic drugs were selected; VigiBase provided their ADR records including total 235,625 records and 27 heading ADR items, 1348 records of glucose metabolism disorders (GMDs), and 807 records of hyperglycemia. Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; fludarabine and flutamide with high ADR of GMD ratio. All the hyperglycemia ratios of the 9 antineoplastics were more than 50.0%, except pemetrexed and sorafenib. Thoroughly, doxorubicin carried high absolute records and ratios in hyperglycemic conditions.
CONCLUSIONS: Pancreatic carcinoma is an aggressive malignancy typically associated with severe hyperglycemia. Furthermore, hyperglycemia is one of the severe ADRs from antineoplastics, which must be paid special attention to when treating in pancreatic carcinoma, especially doxorubicin, fluorouracil, and gemcitabine. Such real-time monitoring or pretreatment gene test can be suggested.

PMID: 29303126 [PubMed - indexed for MEDLINE]

Mining Adverse Events of Dietary Supplements from Product Labels by Topic Modeling.

Stud Health Technol Inform. 2017;245:614-618

Authors: Wang Y, Gunashekar DR, Adam TJ, Zhang R

Abstract
The adverse events of the dietary supplements should be subject to scrutiny due to their growing clinical application and consumption among U.S. adults. An effective method for mining and grouping the adverse events of the dietary supplements is to evaluate product labeling for the rapidly increasing number of new products available in the market. In this study, the adverse events information was extracted from the product labels stored in the Dietary Supplement Label Data-base (DSLD) and analyzed by topic modeling techniques, specifically Latent Dirichlet Allocation (LDA). Among the 50 topics generated by LDA, eight topics were manually evaluated, with topic relatedness ranging from 58.8% to 100% on the product level, and 57.1% to 100% on the ingredient level. Five out of these eight topics were coherent groupings of the dietary supplements based on their adverse events. The results demonstrated that LDA is able to group supplements with similar adverse events based on the dietary supplement labels. Such information can be potentially used by consumers to more safely use dietary supplements.

PMID: 29295169 [PubMed - indexed for MEDLINE]

Automating the Identification of Patient Safety Incident Reports Using Multi-Label Classification.

Stud Health Technol Inform. 2017;245:609-613

Authors: Wang Y, Coiera E, Runciman W, Magrabi F

Abstract
Automated identification provides an efficient way to categorize patient safety incidents. Previous studies have focused on identifying single incident types relating to a specific patient safety problem, e.g., clinical handover. In reality, there are multiple types of incidents reflecting the breadth of patient safety problems and a single report may describe multiple problems, i.e., it can be assigned multiple type labels. This study evaluated the abilty of multi-label classification methods to identify multiple incident types in single reports. Three multi-label methods were evaluated: binary relevance, classifier chains and ensemble of classifier chains. We found that an ensemble of classifier chains was the most effective method using binary Support Vector Machines with radial basis function kernel and bag-of-words feature extraction, performing equally well on balanced and stratified datasets, (F-score: 73.7% vs. 74.7%). Classifiers were able to identify six common incident types: falls, medications, pressure injury, aggression, documentation problems and others.

PMID: 29295168 [PubMed - indexed for MEDLINE]

Phenotyping and Visualizing Infusion-Related Reactions for Breast Cancer Patients.

Stud Health Technol Inform. 2017;245:599-603

Authors: Sun D, Sarda G, Skube SJ, Blaes AH, Khairat S, Melton GB, Zhang R

Abstract
Infusion-related reactions (IRRs) are typical adverse events for breast cancer patients. Detecting IRRs and visualizing their occurance associated with the drug treatment would potentially assist clinicians to improve patient safety and help researchers model IRRs and analyze their risk factors. We developed and evaluated a phenotyping algorithm to detect IRRs for breast cancer patients. We also designed a visualization prototype to render IRR patients' medications, lab tests and vital signs over time. By comparing with the 42 randomly selected doses that are manually labeled by a domain expert, the sensitivity, positive predictive value, specificity, and negative predictive value of the algorithms are 69%, 60%, 79%, and 85%, respectively. Using the algorithm, an incidence of 6.4% of patients and 1.8% of doses for docetaxel, 8.7% and 3.2% for doxorubicin, 10.4% and 1.2% for paclitaxel, 16.1% and 1.1% for trastuzumab were identified retrospectively. The incidences estimated are consistent with related studies.

PMID: 29295166 [PubMed - indexed for MEDLINE]

Mining Adverse Drug Reactions in Social Media with Named Entity Recognition and Semantic Methods.

Stud Health Technol Inform. 2017;245:322-326

Authors: Chen X, Deldossi M, Aboukhamis R, Faviez C, Dahamna B, Karapetiantz P, Guenegou-Arnoux A, Girardeau Y, Guillemin-Lanne S, Lillo-Le-Louët A, Texier N, Burgun A, Katsahian S

Abstract
Suspected adverse drug reactions (ADR) reported by patients through social media can be a complementary source to current pharmacovigilance systems. However, the performance of text mining tools applied to social media text data to discover ADRs needs to be evaluated. In this paper, we introduce the approach developed to mine ADR from French social media. A protocol of evaluation is highlighted, which includes a detailed sample size determination and evaluation corpus constitution. Our text mining approach provided very encouraging preliminary results with F-measures of 0.94 and 0.81 for recognition of drugs and symptoms respectively, and with F-measure of 0.70 for ADR detection. Therefore, this approach is promising for downstream pharmacovigilance analysis.

PMID: 29295108 [PubMed - indexed for MEDLINE]

Unblinded ASCOT study results do not rule out that muscle symptoms are an adverse effect of statins.

Evid Based Med. 2017 12;22(6):210

Authors: Adhyaru BB, Jacobson TA

PMID: 29056606 [PubMed - indexed for MEDLINE]

Incidence of early anxiety aggravation in trials of selective serotonin reuptake inhibitors in depression.

Acta Psychiatr Scand. 2017 10;136(4):343-351

Authors: Näslund J, Hieronymus F, Emilsson JF, Lisinski A, Nilsson S, Eriksson E

Abstract
OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) may aggravate anxiety and agitation during the first days of treatment but the frequency of such reactions remains unknown.
METHOD: We analysed patient-level data from placebo-controlled trials of sertraline, paroxetine or citalopram in depressed adults. Somatic anxiety, psychic anxiety and psychomotor agitation as assessed using the Hamilton Depression Rating Scale (HDRS) were analysed in all trials (n = 8262); anxiety-related adverse events were analysed in trials investigating paroxetine and citalopram (n = 5712).
RESULTS: After one but not two weeks, patients on an SSRI were more likely than those on placebo to report enhanced somatic anxiety (adjusted risk 9.3% vs. 6.7%); likewise, mean rating of somatic anxiety was higher in the SSRI group. In contrast, patients receiving an SSRI were less likely to report aggravation of psychic anxiety (adjusted risk: 7.0% vs. 8.5%) with mean rating of psychic anxiety and agitation being lower in the SSRI group. The adverse event 'nervousness' was more common in patients given an SSRI (5.5% vs. 2.5%). Neither aggravation of HDRS-rated anxiety nor anxiety-related adverse events predicted poor antidepressant response.
CONCLUSION: Whereas an anxiety-reducing effect of SSRIs is notable already during the first week of treatment, these drugs may also elicit an early increase in anxiety in susceptible subjects that however does not predict a poor subsequent response to treatment.

PMID: 28859218 [PubMed - indexed for MEDLINE]

Safety of the 2D/3D direct-acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis - A pooled analysis.

J Hepatol. 2017 Oct;67(4):700-707

Authors: Poordad F, Nelson DR, Feld JJ, Fried MW, Wedemeyer H, Larsen L, Cohen DE, Cohen E, Mobashery N, Tatsch F, Foster GR

Abstract
BACKGROUND & AIMS: Chronic hepatitis C virus (HCV)-infected patients with cirrhosis are a high-priority population for treatment. To help inform the benefit-risk profile of the all-oral direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir (OBV/PTV/r±DSV) in patients with Child-Pugh A cirrhosis, we undertook a comprehensive review of AbbVie-sponsored clinical trials enrolling patients with Child-Pugh A cirrhosis.
METHODS: Twelve phase II or III clinical trials of the 2-DAA regimen of OBV/PTV/r±ribavirin (RBV) or the 3-DAA regimen of OBV/PTV/r+DSV±RBV that included patients with Child-Pugh A cirrhosis were reviewed; patients who completed treatment by November 16, 2015 were included in a pooled, post hoc safety assessment. The number and percentage of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs consistent with hepatic decompensation were reported.
RESULTS: In 1,066 patients with Child-Pugh A cirrhosis, rates of serious TEAEs and TEAEs leading to study drug discontinuation were 5.3% (95% confidence interval [CI]: 4.1-6.8) and 2.2% (95% CI: 1.4-3.2), respectively. Thirteen patients (1.2%; 95% CI: 0.7-2.1) had a TEAE that was consistent with hepatic decompensation. The most frequent TEAEs consistent with hepatic decompensation were ascites (n=8), esophageal variceal hemorrhage (n=4), and hepatic encephalopathy (n=2).
CONCLUSIONS: This pooled analysis in 1,066 HCV-infected patients with Child-Pugh A cirrhosis confirms the safety of OBV/PTV/r±DSV±RBV in this population. These results support the use of OBV/PTV/r±DSV±RBV in this high-priority population. Lay summary: This pooled safety analysis in 1,066 HCV-infected patients with compensated cirrhosis, receiving treatment with ombitasvir, paritaprevir, and ritonavir with or without dasabuvir, with or without ribavirin, shows that the rate of hepatic decompensation events was similar to previously reported rates in untreated patients.

PMID: 28645740 [PubMed - indexed for MEDLINE]

Impact of an Integrated Antibiotic Allergy Testing Program on Antimicrobial Stewardship: A Multicenter Evaluation.

Clin Infect Dis. 2017 Jul 01;65(1):166-174

Authors: Trubiano JA, Thursky KA, Stewardson AJ, Urbancic K, Worth LJ, Jackson C, Stevenson W, Sutherland M, Slavin MA, Grayson ML, Phillips EJ

Abstract
Background: Despite the high prevalence of patient-reported antibiotic allergy (so-called antibiotic allergy labels [AALs]) and their impact on antibiotic prescribing, incorporation of antibiotic allergy testing (AAT) into antimicrobial stewardship (AMS) programs (AAT-AMS) is not widespread. We aimed to evaluate the impact of an AAT-AMS program on AAL prevalence, antibiotic usage, and appropriateness of prescribing.
Methods: AAT-AMS was implemented at two large Australian hospitals during a 14-month period beginning May 2015. Baseline demographics, AAL history, age-adjusted Charlson comorbidity index, infection history, and antibiotic usage for 12 months prior to testing (pre-AAT-AMS) and 3 months following testing (post-AAT-AMS) were recorded for each participant. Study outcomes included the proportion of patients who were "de-labeled" of their AAL, spectrum of antibiotic courses pre- and post-AAT-AMS, and antibiotic appropriateness (using standard definitions).
Results: From the 118 antibiotic allergy-tested patients, 226 AALs were reported (mean, 1.91/patient), with 53.6% involving 1 or more penicillin class drug. AAT-AMS allowed AAL de-labeling in 98 (83%) patients-56% (55/98) with all AALs removed. Post-AAT, prescribing of narrow-spectrum penicillins was more likely (adjusted odds ratio [aOR], 2.81, 95% confidence interval [CI], 1.45-5.42), as was narrow-spectrum β-lactams (aOR, 3.54; 95% CI, 1.98-6.33), and appropriate antibiotics (aOR, 12.27; 95% CI, 5.00-30.09); and less likely for restricted antibiotics (aOR, 0.16; 95% CI, .09-.29), after adjusting for indication, Charlson comorbidity index, and care setting.
Conclusions: An integrated AAT-AMS program was effective in both de-labeling of AALs and promotion of improved antibiotic usage and appropriateness, supporting the routine incorporation of AAT into AMS programs.

PMID: 28520865 [PubMed - indexed for MEDLINE]

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Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma.

Int J Clin Pharm. 2018 Jun 02;:

Authors: Aguiar JP, Cardoso Borges F, Murteira R, Ramos C, Gouveia E, Passos MJ, Miranda A, da Costa FA

Abstract
Background Toxicity of oncology treatments in real-life patients is frequently disregarded and hence underreported. Objective To characterize adverse events (AEs) of immunotherapy and targeted therapy reported in patients with locally advanced or metastatic melanoma. Setting District Hospital for Cancer treatment (Instituto Português de Oncologia de Lisboa Francisco Gentil). Method A retrospective cohort of melanoma patients was established, comprising adult patients diagnosed with malignant melanoma treated with immunotherapy or targeted therapy. Exposure was characterized by nature, time and intensity of exposure. To account for different exposure periods, person-time was used as unit of analysis. Main outcomes measure Occurrence of AEs. Results Data from 111 patients included in the cohort indicates the majority received immunotherapy regimens (CTLA-4, anti-PD-1 and combination therapy; (n = 70; 63.1%), among which anti-PD-1 were the predominant treatment. Pembrolizumab was the most frequently prescribed drug (n = 30; 45.7%). Three hundred and seventy-one AEs were extracted. The incidence of AEs was lower in the anti-PD-1 mAc group (54 AEs per 1000 person.months) and the number of AEs/patient was also lower (3.1 ± 2.0). Grade 3 to 4 AEs occurred in 15.3% (n = 17) of the cohort, being more common in the targeted therapy group. Forty-two (11.6%) of the extracted AEs were not described in the Summary of Product Characteristics of the drugs under study. Conclusion This study suggests various known and unknown AEs of immunotherapy and targeted therapy may be identified using the Cancer Registry database. These events should be considered as signals worth further investigation for assessment of causality as the underreporting of AEs in cancer may have potential implications for the patient's quality of life.

PMID: 29860707 [PubMed - as supplied by publisher]

A randomized phase 2B trial of vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations - results of a prematurely terminated study.

Trials. 2018 Jun 01;19(1):305

Authors: Kalimuddin S, Chan YFZ, Phillips R, Ong SP, Archuleta S, Lye DC, Tan TT, Low JGH

Abstract
BACKGROUND: Studies have suggested the reduced effectiveness of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections with high vancomycin minimum inhibitory concentrations. Alternative agents such as daptomycin may be considered. We conducted a randomized controlled study comparing daptomycin against vancomycin in the treatment of MRSA bloodstream infections with high vancomycin minimum inhibitory concentrations.
METHODS: Patients were randomized to receive vancomycin or daptomycin for a minimum of 14 days. The primary end point was the rate of all-cause mortality at day 60.
RESULTS: A total of 14 patients were randomized in this study, with 7 patients in each treatment arm. The study was terminated early due to slow patient accrual. At day 60, there was one death in the vancomycin arm and none in the daptomycin arm. The median time to microbiological clearance was 4 days in both arms (IQR 3-5 days in the vancomycin arm and 3-7 days in daptomycin arm). Only one patient in the vancomycin arm had recurrence of bacteremia. Rates of adverse events were similar in both arms. There was one case of musculoskeletal toxicity and one case of drug-related nephrotoxicity - both events occurred in the daptomycin arm. None of the patients in either treatment arm required cessation of study treatment or addition of a second anti-MRSA agent because of worsening infection.
CONCLUSION: Based on the limited number of patients evaluated in this study, it remains unclear if alternative, more expensive agents such as daptomycin are superior to vancomycin in the treatment of high vancomycin minimum inhibitory concentration MRSA bloodstream infections. More studies are urgently needed but investigators may wish to consider employing novel, alternative trial methodologies to ensure a greater chance of success.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT01975662 . Registered on 5 November 2013.

PMID: 29859132 [PubMed - in process]

Lesson of the month 2: An unusual adverse reaction associated with pramipexole.

Clin Med (Lond). 2018 Jun;18(3):259-260

Authors: Tashkent Y, Aiyappan V

Abstract
Dopamine agonists such as pramipexole are commonly used in the treatment of restless legs syndrome (RLS) as well as Parkinson's disease. Pramipexole's common side effects are well documented; however, adverse skin reactions are less well known. In this case, a 45-year-old male farmer presented with excessive daytime tiredness and reported a history suggestive of RLS. He was initiated on pramipexole but developed a maculopapular erythematous rash in sun-exposed areas 8 days after its commencement. The skin rash resolved following pramipexole's cessation and it is thought the patient experienced a drug-induced photosensitivity reaction to pramipexole. This case highlights the potential for photosensitivity reactions to pramipexole, which is especially significant in countries like Australia where UV solar radiation is especially high.

PMID: 29858440 [PubMed - in process]

Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review.

Chonnam Med J. 2018 May;54(2):101-112

Authors: Wang SM, Han C, Bahk WM, Lee SJ, Patkar AA, Masand PS, Pae CU

Abstract
Randomized trials have shown that selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have better safety profiles than classical tricyclic antidepressants (TCAs). However, an increasing number of studies, including meta-analyses, naturalistic studies, and longer-term studies suggested that SSRIs and SNRIs are no less safe than TCAs. We focused on comparing the common side effects of TCAs with those of newer generation antidepressants including SSRIs, SNRIs, mirtazapine, and bupropion. The main purpose was to investigate safety profile differences among drug classes rather than the individual antidepressants, so studies containing comparison data on drug groups were prioritized. In terms of safety after overdose, the common belief on newer generation antidepressants having fewer side effects than TCAs appears to be true. TCAs were also associated with higher drop-out rates, lower tolerability, and higher cardiac side-effects. However, evidence regarding side effects including dry mouth, gastrointestinal side effects, hepatotoxicity, seizure, and weight has been inconsistent, some studies demonstrated the superiority of SSRIs and SNRIs over TCAs, while others found the opposite. Some other side effects such as sexual dysfunction, bleeding, and hyponatremia were more prominent with either SSRIs or SNRIs.

PMID: 29854675 [PubMed]