Adverse events in hospitalised cancer patients: a comparison to a general hospital population.

Acta Oncol. 2017 Sep;56(9):1218-1223

Authors: Haukland EC, von Plessen C, Nieder C, Vonen B

Abstract
BACKGROUND: Patients with cancer are often treated by many healthcare providers, receive complex and potentially toxic treatments that can increase the risk for iatrogenic harm. The aim of this study is to investigate whether hospitalised cancer patients are at higher risk of adverse events (AEs) compared to a general hospital population.
MATERIAL AND METHODS: A total of 6720 patient records were retrospectively reviewed comparing AEs in hospitalised cancer patients to a general hospital population in Norway, using the IHI Global Trigger Tool method.
RESULTS: 24.2 percent of admissions for cancer patients had an AE compared to 17.4% of admissions of other patients (p < .001, rr 1.39, 95% CI 1.19-1.62). However, cancer patients did not have a higher rate of AEs per 1000 patient days compared to other patients, 37.1 vs. 36.0 (p = .65, rr 0.94, 95% CI 0.90-1.18). No particular cancer category is at higher risk. The rate of AEs increases by 1.05 times for each day spent in hospital. For every year increase in age, the risk for AEs increases by 1.3%. Cancer patients more often have hospital-acquired infections, other surgical complications and AEs related to medications.
CONCLUSIONS: Because of higher age, longer length of stay and surgical treatment, hospitalised cancer patients experience AEs more often than other patients.

PMID: 28379721 [PubMed - indexed for MEDLINE]

Immunogenicity and safety of an adjuvanted herpes zoster subunit candidate vaccine in adults ≥ 50 years of age with a prior history of herpes zoster: A phase III, non-randomized, open-label clinical trial.

Hum Vaccin Immunother. 2017 May 04;13(5):1051-1058

Authors: Godeaux O, Kovac M, Shu D, Grupping K, Campora L, Douha M, Heineman TC, Lal H

Abstract
This phase III, non-randomized, open-label, multi-center study (NCT01827839) evaluated the immunogenicity and safety of an adjuvanted recombinant subunit herpes zoster (HZ) vaccine (HZ/su) in adults aged ≥ 50 y with prior physician-documented history of HZ. Participants (stratified by age: 50-59, 60-69 and ≥ 70 y) received 2 doses of HZ/su 2 months apart and were followed-up for another 12 months. Anti-glycoprotein E (gE) antibodies were measured by enzyme-linked immunosorbent assay before vaccination and 1 month after the second dose (Month 3). Solicited local and general adverse events (AEs) were recorded for 7 d and unsolicited AEs for 30 d after each vaccination. Serious AEs were recorded until study end. The primary immunogenicity objective was met if the lower limit of the 95% confidence interval (CI) of the vaccine response rate (VRR), defined as a 4-fold increase in anti-gE over baseline, at Month 3 was ≥ 60%. 96 participants (32/age group) were enrolled. The primary immunogenicity objective was met, as the VRR at Month 3 was 90.2% (95% CI: 81.7-95.7). Geometric mean anti-gE antibody concentrations at Month 3 were similar across age groups. 77.9% and 71.6% of participants reported local and general solicited AEs, respectively. The most frequent solicited AEs were pain at injection site, fatigue, headache, myalgia and shivering. The HZ/su vaccine was immunogenic in adults aged ≥ 50 y with a physician-documented history of HZ, and no safety concerns were identified.

PMID: 28068212 [PubMed - indexed for MEDLINE]

Nivolumab in the Treatment of Hodgkin Lymphoma.

Clin Cancer Res. 2017 Apr 01;23(7):1623-1626

Authors: Ansell SM

Abstract
Despite an extensive immune infiltrate that is recruited to the tumor by malignant Reed-Sternberg cells in Hodgkin lymphoma, the antitumor immune response is ineffective and unable to eradicate the malignant cells. The ineffective immune response is in part due to PD-1 signaling that renders intratumoral immune cells anergic. Reed-Sternberg cells have been shown to upregulate expression of the PD-1 ligands, PD-L1 and PD-L2, due to either genetic alterations at chromosome 9p24.1 or Epstein-Barr virus infection, and these ligands suppress the function of PD-1+ intratumoral T cells. Blockade of PD-1 signaling has proven to be a highly successful therapeutic approach, and the use of the anti-PD-1 mAb nivolumab recently received accelerated approval by the FDA for patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous stem cell transplant and posttransplantation brentuximab vedotin. Initial clinical trials using nivolumab in this patient population resulted in high response rates that were durable. Adverse events associated with nivolumab included immune-mediated adverse reactions and infusion reactions, but these were well tolerated, allowing for continued nivolumab administration. Clinical trials are now in progress to test the use of nivolumab in combination with standard chemotherapy or with novel agents with a goal of improving the outcome of patients with Hodgkin lymphoma. Clin Cancer Res; 23(7); 1623-6. ©2016 AACR.

PMID: 27881581 [PubMed - indexed for MEDLINE]

Monitoring potential adverse event rate differences using data from blinded trials: the canary in the coal mine.

Stat Med. 2017 Jan 15;36(1):92-104

Authors: Gould AL, Wang WB

Abstract
The development of drugs and biologicals whose mechanisms of action may extend beyond their target indications has led to a need to identify unexpected potential toxicities promptly even while blinded clinical trials are under way. One component of recently issued FDA rules regarding safety reporting requirements raises the possibility of breaking the blind for pre-identified serious adverse events that are not the clinical endpoints of a blinded study. Concern has been expressed that unblinding individual cases of frequently occurring adverse events could compromise the overall validity of the study. However, if external information is available about adverse event rates among patients not receiving the test product in populations similar to the study population, then it may be possible to address the potential for elevated risk without unblinding the trial. This article describes a Bayesian approach for determining the likelihood of elevated risk suitable binomial or Poisson likelihoods that applies regardless of the metric used to express the difference. The method appears to be particularly appropriate for routine monitoring of safety information for project development programs that include large blinded trials. Copyright © 2016 John Wiley & Sons, Ltd.

PMID: 27666940 [PubMed - indexed for MEDLINE]

Randomized Multicenter Study Comparing Safety and Efficacy of Daptomycin Versus Standard of Care in Pediatric Patients with Staphylococcal Bacteremia.

Pediatr Infect Dis J. 2018 Feb 03;:

Authors: Arrieta AC, Bradley JS, Popejoy MW, Bensaci M, Grandhi A, Bokesch P, Glasser C, Du L, Kartsonis NA

Abstract
BACKGROUND: Staphylococcus aureus, including community-associated methicillin-resistant S. aureus, is an important cause of pediatric bacteremia. Daptomycin is a well-established treatment option for gram-positive bacteremia in adults, but its safety and efficacy in children require confirmation.
METHODS: This was a randomized (2:1), evaluator-blinded, multi-center, phase 4 clinical trial comparing intravenous daptomycin with standard-of-care (SOC) for treatment of S. aureus bacteremia in 1-17 year-old patients. Total treatment duration (intravenous followed by oral step-down therapy) was 5-42 days. Daptomycin was dosed once daily by patient age: 12-17 years, 7 mg/kg; 7-11 years, 9 mg/kg; 1-6 years, 12 mg/kg. The primary objective was to evaluate daptomycin safety in children who received ≥1 dose; secondary objectives included comparing daptomycin efficacy with SOC (the trial was not designed to confirm non-inferiority), and pharmacokinetic analysis.
RESULTS: 55 children were randomized to daptomycin and 27 to SOC (primarily vancomycin or cefazolin); 90% had S. aureus. In both groups, 15% of patients had drug-related adverse events, primarily diarrhea (4% daptomycin, 8% SOC) and increased creatine phosphokinase (4% daptomycin, 0% SOC). Clinical success (blinded evaluator-assessed complete/partial resolution of bacteremia signs and symptoms 7-14 days after end-of-treatment) rates were similar for daptomycin (88%) and SOC (77%; 95% CI for difference: -9% to 31%). Daptomycin plasma levels across age groups were comparable to those in adults receiving daptomycin at 6 mg/kg.
CONCLUSIONS: Once-daily, age-appropriate daptomycin was well tolerated in children with staphylococcal bacteremia; efficacy was comparable to SOC. Daptomycin in age-adjusted doses is a safe treatment alternative in this setting.(clinicaltrials.gov NCT01728376).

PMID: 29406465 [PubMed - as supplied by publisher]

Drug-Induced Ototoxicity: Diagnosis and Monitoring.

Drug Saf. 2018 Feb 06;:

Authors: Campbell KCM, Le Prell CG

Abstract
Ototoxicity diagnosis and management has historically been approached using a variety of methods. However, in recent years a consensus on useful and practical approaches has been developed through clinical guidelines of the American Speech Language Hearing Association, the American Academy of Audiology, and multiple clinical trials published in peer-reviewed literature. Some of the guidelines and approaches are used to detect and monitor ototoxicity, while others are used to grade adverse events. Some of the audiologic measures are primary, while others are adjunct measures and may be tailored to the specific needs of the patient or clinical trial. For some types of monitoring, such as drug-induced tinnitus or dizziness, validated paper survey instruments can be both sensitive and easy for fragile patients. This review addresses the characteristics of some of the most common clinical ototoxins and the most common methods for detecting and monitoring ototoxicity in clinical practice and clinical trials.

PMID: 29404977 [PubMed - as supplied by publisher]

Ketamine for Pain Management-Side Effects & Potential Adverse Events.

Pain Manag Nurs. 2017 Dec;18(6):372-377

Authors: Allen CA, Ivester JR

Abstract
An old anesthetic agent, ketamine is finding new use in lower doses for analgesic purposes. There are concerns stemming from its potential side effects-specifically psychomimetic effects. These side effects are directly related to dose amount. The doses used for analgesic purposes are much lower than those used for anesthesia purposes. A literature review was performed to ascertain potential side effects and/or adverse events when using ketamine for analgesia purposes. The search included CINAHL, PubMed, and Ovid using the search terms "ketamine," "ketamine infusion," "pain," "adverse events," "practice guideline," and "randomized controlled trial." Searches were limited to full-text, peer-reviewed articles and systematic reviews. Initially 1,068 articles were retrieved. The search was then narrowed by using the Boolean connector AND with various search term combinations. After adjusting for duplication, article titles and abstracts were reviewed, leaving 25 articles for an in-depth analysis. Specific exclusion criteria were then applied. The literature supports the use of ketamine for analgesic purposes, and ketamine offers a nonopioid option for the management of some pain conditions. Because ketamine is still classified as an anesthetic agent, health care institutions should develop their own set of policies and protocols for the administration of ketamine. By using forethought and understanding of the properties of ketamine, appropriate care may be planned to mitigate potential side effects and adverse events so that patients are appropriately cared for and their pain effectively managed.

PMID: 28743507 [PubMed - indexed for MEDLINE]

Psychiatric side effects and antiepileptic drugs: Observations from prospective audits.

Epilepsy Behav. 2017 Jun;71(Pt A):73-78

Authors: Stephen LJ, Wishart A, Brodie MJ

Abstract
Psychiatric comorbidities are common in people with epilepsy. A retrospective study of characteristics associated with withdrawal due to psychiatric side effects was undertaken in patients with treated epilepsy participating in prospective audits with new antiepileptic drugs (AEDs). A total of 1058 treated patients with uncontrolled seizures (942 focal-onset seizures, 116 generalized genetic epilepsies [GGEs]) participated in eight prospective, observational audits from 1996 to 2014. These patients were prescribed adjunctive topiramate (n=170), levetiracetam (n=220), pregabalin (n=135), zonisamide (n=203), lacosamide (n=160), eslicarbazepine acetate (n=52), retigabine (n=64), or perampanel (n=54). Doses were titrated according to efficacy and tolerability to optimize zeizure outcomes and reduce side effects. Psychiatric comorbidities were recorded prior to and after the addition of each AED. At baseline, patients with focal-onset seizures (189 of 942; 20.1%) were statistically more likely to have psychiatric diagnoses compared to patients with GGEs (14 of 116, 12.1%; p=0.039). Following adjunctive AED treatment, neuropsychiatric adverse effects led to AED withdrawal in 1.9-16.7% of patients. Patients with a pre-treatment psychiatric history (22 of 209; 10.5%) were statistically more likely to discontinue their new AED due to psychiatric issues compared to patients with no previous psychiatric diagnosis (50 of 849; 5.9%; p=0.017). Patients receiving sodium channel blocking AEDs (4 of 212, 1.9%) were statistically less likely to develop intolerable psychiatric problems, compared to those on AEDs possessing other mechanisms of action (68 of 846, 8.0%; p=0.012). Depression was the commonest problem, leading to discontinuation of AEDs in 2.8% (n=30) patients. Aggression was statistically more common in men (11 of 527, 2.1%) compared to women (1 of 531, 0.2%; p=0.004). Patients with learning disability (12 of 122, 9.8%; p=0.0015) were statistically less likely to have psychiatric issues prior to adjunctive AED treatment compared to other patients (208 of 936, 22.2%), but there were no statistically significant differences once the new AEDs were added (8 of 122 patients with learning disability, 6.6%; 64 of 936 other patients, 6.8%). Awareness of these issues may assist clinicians in avoiding, identifying and treating psychiatric comorbidities in people with epilepsy.

PMID: 28551500 [PubMed - indexed for MEDLINE]

Potential drug-drug interactions and adverse drug reactions in dermatological inpatients.

J Dtsch Dermatol Ges. 2016 Nov;14(11):1122-1129

Authors: Koch L, Kränke B, Aberer W

Abstract
OBJECTIVES: To present information on the frequency of drug-drug interactions and adverse drug reactions, and to provide assistance on how to minimize these major problems in the pharmacological treatment of dermatological inpatients.
PATIENTS AND METHODS: The medications given to 1,099 dermatological inpatients were retrospectively analyzed for drug-drug interactions and adverse drug reactions using web-based drug interaction software (Diagnosia® Check).
RESULTS: We report an overall frequency of relevant drug-drug interactions of 51.7 %, with an average of 3.2 interactions per affected inpatient. Drug combinations that should have been avoided were found in 5.7 % of the study population. Total drug count was the most important risk factor. Drug groups involved in the majority of interactions were analgesics, cardiovascular and antithrombotic agents, as well as antidepressants. The risk of developing adverse drug reactions was rated as "high" in 53.1 % of inpatients. The top five adverse reactions in this patient group were bleeding, constipation, anticholinergic effects, sedation, and orthostatic effects.
CONCLUSIONS: Potential drug-drug interactions as well as adverse drug reactions are alarmingly common in dermatological inpatients. Every other patient is at risk of experiencing such interactions or adverse reactions, and every twentieth patient receives a drug combination that should not be administered. Increased alertness is a must in order to identify patients at risk.

PMID: 27879085 [PubMed - indexed for MEDLINE]

Drug survival rates and reasons for drug discontinuation in psoriasis.

J Dtsch Dermatol Ges. 2016 Nov;14(11):1089-1099

Authors: Arnold T, Schaarschmidt ML, Herr R, Fischer JE, Goerdt S, Peitsch WK

Abstract
BACKGROUND AND OBJECTIVES: Moderate-to-severe psoriasis frequently requires long-term systemic therapy. Reflecting efficacy, safety, and treatment satisfaction, drug survival is an indicator of therapeutic success. The objective of the present study was to assess drug survival rates and reasons for discontinuation of fumaric acid esters (FAE), methotrexate (MTX), acitretin (ACI), cyclosporine A (CyA), adalimumab (ADA), etanercept (ETA), infliximab (INF), and ustekinumab (UST) in patients with moderate-to-severe psoriasis.
PATIENTS AND METHODS: We performed a retrospective analysis of 373 patients who had received a total of 696 treatment courses at a German university hospital in the period 1/2003-5/2014.
RESULTS: The crude probability of survival was highest for UST, followed by ADA, ETA, INF, FAE, MTX, ACI, and CyA. In multivariate regression analysis using FAE as reference, hazard ratios (HR) for discontinuation were 0.14 (95 % confidence interval: 0.06-0.35) for UST, 0.43 (0.26-0.73) for ADA, 2.11 (1.14-3.91) for ACI, and 3.26 (1.44-7.39) for CyA. INF showed longer survival when combined with MTX (HR 2.87, 1.21-6.81). Traditional systemic antipsoriatic agents as well as INF were most frequently discontinued due to adverse events; all other biologics, due to inefficacy with respect to cutaneous lesions.
CONCLUSIONS: Drug survival rates should be integrated into therapeutic decisions in order to provide patients with an optimal long-term strategy.

PMID: 27879076 [PubMed - indexed for MEDLINE]

U.S. Food and Drug Administration Approval: Cabozantinib for the Treatment of Advanced Renal Cell Carcinoma.

Clin Cancer Res. 2017 Jan 15;23(2):330-335

Authors: Singh H, Brave M, Beaver JA, Cheng J, Tang S, Zahalka E, Palmby TR, Venugopal R, Song P, Liu Q, Liu C, Yu J, Chen XH, Wang X, Wang Y, Kluetz PG, Daniels SR, Papadopoulos EJ, Sridhara R, McKee AE, Ibrahim A, Kim G, Pazdur R

Abstract
On April 25, 2016, the FDA approved cabozantinib (Cabometyx; Exelixis, Inc.) for the treatment of advanced renal cell carcinoma (RCC) in patients who have received prior antiangiogenic therapy. The approval was based on data from one randomized, open-label, multicenter study in which patients with RCC who had received prior antiangiogenic therapy were treated with either cabozantinib 60 mg orally once daily (n = 330) or everolimus 10 mg orally once daily (n = 328). The major efficacy outcome measure was progression-free survival (PFS) as assessed by a blinded independent radiology review committee in the first 375 randomized patients. A statistically significant improvement in PFS was seen, with a median PFS of 7.4 and 3.8 months in the cabozantinib and everolimus arms, respectively [hazard ratio (HR), 0.58; 95% confidence interval (CI), 0.45-0.74; P < 0.0001]. At a second interim analysis, a statistically significant improvement in overall survival (OS) in the intent-to-treat population was also demonstrated, with a median OS of 21.4 and 16.5 months in the cabozantinib and everolimus arms, respectively (HR, 0.66; 95% CI, 0.53-0.83; P = 0.0003). The most common (greater than or equal to 25%) adverse reactions included diarrhea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, hypertension, vomiting, weight loss, and constipation. Clin Cancer Res; 23(2); 330-5. ©2016 AACR.

PMID: 27793960 [PubMed - indexed for MEDLINE]

Temporal course of avascular femoral head necrosis in patients with pemphigus vulgaris.

J Dtsch Dermatol Ges. 2016 Oct;14(10):1016-1021

Authors: Balighi K, Daneshpazhooh M, Aghazadeh N, Saeidi V, Shahpouri F, Hejazi P, Chams-Davatchi C

Abstract
BACKGROUND AND OBJECTIVES: Pemphigus vulgaris (PV) is typically treated with systemic corticosteroids and immunosuppressive agents. Avascular necrosis (AVN) of the femoral head is a well-recognized major complication of corticosteroid therapy. The characteristics of this serious complication in PV remain unknown.
PATIENTS AND METHODS: Uncontrolled, retrospective study of all PV-related AVN cases diagnosed at an Iranian autoimmune bullous disease clinic between 1985 and 2013.
RESULTS: Of the 2,321 medical records of PV patients reviewed, 45 (1.93 %) cases showed femoral AVN, with 30 (66.7 %) individuals being male. The mean age at diagnosis of AVN was 47.4 ± 14.2 years. The mean interval between the diagnosis of PV and the onset of AVN was 25.3 ± 18.3 months. With the exception of eight cases (17.8 %), the majority of patients developed AVN within three years after the diagnosis of PV. The mean cumulative dose of prednisolone in patients with AVN was 13,115.8 ± 7041.1 mg. There was a strong correlation between the total prednisolone dose and the time of onset of AVN (p = 0.001). In patients with a history of alendronate intake, that interval was significantly shorter (p = 0.01).
CONCLUSIONS: Occurring in about 2 % of patients, AVN is a serious complication of corticosteroid treatment in patients with PV, predominantly in the first three years of treatment. In individuals receiving higher doses of prednisolone, AVN tends to occur earlier.

PMID: 27767268 [PubMed - indexed for MEDLINE]

The 12-year follow-up of survival, chronic adverse effects, and retention of arsenic in patients with acute promyelocytic leukemia.

Blood. 2016 09 15;128(11):1525-8

Authors: Zhu H, Hu J, Chen L, Zhou W, Li X, Wang L, Zhao X, Zhang Y, Zhao H, Wang A, Chen Y, Sun H, Chen Q, Chen Y, Zhao W, Mi J, Shen Z, Wang Z, Chen Z, Chen S, Li J

PMID: 27402972 [PubMed - indexed for MEDLINE]

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/02/06

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.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/02/05

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.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/02/03

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.

Benefits of and Barriers to Pharmacogenomics-Guided Treatment for Major Depressive Disorder.

Clin Pharmacol Ther. 2018 Feb 01;:

Authors: Ahmed AT, Weinshilboum R, Frye MA

Abstract
Antidepressants have reduced the symptom burden for many Major Depressive Disorder (MDD) patients, but drug-related side effects and treatment resistance continue to present major challenges. Pharmacogenomics represents one approach to enhance antidepressant efficacy and avoid adverse reactions, but concerns remain with regard to the overall "value equation," and several barriers must be overcome to achieve the full potential of MDD pharmacogenomics.

PMID: 29388201 [PubMed - as supplied by publisher]

[Development of "Patient Friendly Formulations" to Counter the Side Effects of Cancer Chemotherapy].

Yakugaku Zasshi. 2018;138(2):169-175

Authors: Hanawa T, Kawano Y, Satoh M

Abstract
　Anticancer drug-induced stomatitis develops in 30% to 40% of cancer patients undergoing chemotherapy. However, medications for this condition are not commercially available in Japan. The "hospital formulation" is a customized medicine which hospital pharmacists prepare when doctors cannot carry out the medical therapy most suitable for a patient using commercial medicines. However, as the duties of pharmacists increase, use of the "hospital fomulation" decreases. Therefore, development of "hospital fomulations" based on individual evidence has a limit. Irsogladine maleate (IM) is a drug with gastric mucosal protective properties. IM increases intracellular cAMP levels in the gastric mucosa and activates communication between cells. It has been reported that the oral administration of IM reduces the incidence of 5-FU-based chemotherapy-induced stomatitis. However, there have been no reports on the effect of the direct use of IM in treating stomatitis. Therefore, we studied the development of an IM oral spray for stomatitis treatment, and obtained evidence of a direct effect in an animal experiment using a stomatitis model. Next, rebamipide mouthwash was administered to patients who had stomatitis caused by cancer chemotherapy. The total scores were classified into Grades 0 to 4 and evaluated as a stomatitis evaluation score (SES). When comparing SES and changes in the stomatitis area in patients, gradual reductions in the extent of stomatitis were observed, even during the period when SES did not change. Having patients fill in an observation chart was effective for grasping changes in symptoms in outpatients.

PMID: 29386430 [PubMed - in process]

Analysis of Adverse Events Associated With Adult Moderate Procedural Sedation Outside the Operating Room.

J Patient Saf. 2017 Sep;13(3):111-121

Authors: Karamnov S, Sarkisian N, Grammer R, Gross WL, Urman RD

Abstract
INTRODUCTION: Moderate sedation outside the operating room is performed for a variety of medical and surgical procedures. It involves the administration of different drug combinations by nonanesthesia professionals. Few data exist on risk stratification and patient outcomes in the adult population. Current literature suggests that sedation can be associated with significant adverse outcomes.
OBJECTIVES: The aims of this study were to evaluate the nature of adverse events associated with moderate sedation and to examine their relation to patient characteristics and outcomes.
METHODS: In this retrospective review, 52 cases with moderate sedation safety incidents were identified out of approximately 143,000 cases during an 8-year period at a tertiary care medical center. We describe types of adverse events and the severity of associated harm. We used bivariate and multivariate analyses to examine the links between event types and both patient and procedure characteristics.
RESULTS: The most common adverse event and unplanned intervention were oversedation leading to apnea (57.7% of cases) and the use of reversal agents (55.8%), respectively. Oversedation, hypoxemia, reversal agent use, and prolonged bag-mask ventilation were most common in cardiology (84.6%, 53.9%, 84.6%, and 38.5% of cases, respectively) and gastroenterology (87.5%, 75%, 87.5%, and 50%) suites. Miscommunication was reported most frequently in the emergency department (83.3%) and on the inpatient floor (69.2%). Higher body mass index was associated with increased rates of hypoxemia and intubation but lower rates of hypotension. Advanced age boosted the rates of oversedation, hypoxemia, and reversal agent use. Women were more likely than men to experience oversedation, hypotension, prolonged bag-mask ventilation, and reversal agent use. Patient harm was associated with age, body mass index, comorbidities, female sex, and procedures in the gastroenterology suite.
CONCLUSIONS: Providers should take into account patient characteristics and procedure types when assessing the risks of harmful sedation-related complications.

PMID: 25203503 [PubMed - indexed for MEDLINE]

Outpatient treatment of acute bacterial skin and skin structure infections (ABSSSI) with tedizolid phosphate and linezolid in patients in the United States: Subgroup analysis of 2 randomized phase 3 trials.

Medicine (Baltimore). 2017 Dec;96(52):e9163

Authors: De Anda C, Anuskiewicz S, Prokocimer P, Vazquez J

Abstract
BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSI) are a frequent cause of hospital admissions in the United States. Safe and effective outpatient treatments may lower ABSSSI-associated health care costs by reducing unnecessary hospital admissions. Using data from 2 phase 3 trials (ESTABLISH-1, NCT01170221; ESTABLISH-2, NCT01421511), this post-hoc analysis explored the efficacy and safety of tedizolid in an outpatient setting.
METHODS: Subgroup analysis was performed on US outpatients (defined as patients who were not in hospital at the time of treatment initiation) with ABSSSI caused by presumed or proven gram-positive pathogens. Patients were randomly assigned to receive tedizolid phosphate 200 mg once daily for 6 days (n = 403) or linezolid 600 mg twice daily for 10 days (n = 410). The primary end point was early clinical response (48-72 hours after the start of treatment). Secondary end points included investigator-assessed clinical response at end of therapy (EOT) and post-therapy evaluation (PTE; 7-14 days after therapy). Additional assessments included the patient-reported level of pain using a visual analog scale (VAS) and the per-pathogen favorable microbiological response rate at the PTE visit. Compliance with treatment and safety outcomes was also recorded.
RESULTS: Early clinical response was similar between treatment groups (tedizolid, 82.4%; linezolid, 79.0%), as was investigator-assessed clinical response at EOT (tedizolid, 87.1%; linezolid, 86.1%) and PTE (tedizolid, 83.1%; linezolid, 83.7%). Mean changes from baseline to days 10 to 13 in VAS scores were identical between treatment groups (tedizolid, -51.9 mm; linezolid, -51.9 mm). Microbiological eradication rates were generally similar in both treatment groups for all key pathogens. Patients in both groups had favorable response at PTE. More tedizolid-treated patients (89.3%) than linezolid-treated patients (77.3%) were compliant with treatment. The most frequently reported drug-related treatment-emergent adverse events were nausea (tedizolid, 10.7%; linezolid, 13.8%), diarrhea (tedizolid, 4.5%; linezolid, 5.9%), and headache (tedizolid, 5.5%; linezolid, 4.4%). Treatment discontinuation rates were low for both treatment groups (tedizolid, 0.7%; linezolid, 1.0%).
CONCLUSION: Short-course therapy with tedizolid can successfully treat patients with ABSSSI caused by presumed or proven gram-positive pathogens in an outpatient setting.

PMID: 29384903 [PubMed - in process]