Drug-Induced Thrombophilic or Prothrombotic States: An Underestimated Clinical Problem That Involves Both Legal and Illegal Compounds.

Clin Appl Thromb Hemost. 2017 Oct;23(7):775-785

Authors: Girolami A, Cosi E, Tasinato V, Santarossa C, Ferrari S, Girolami B

Abstract
Vascular thrombosis, both arterial and venous, is a condition associated with significant morbidity and mortality. There are multiple risk factors for thrombosis, both congenital and acquired, and in the majority of cases, these risk factors are not modifiable. Over the past 2 decades, multiple drugs (both illegal and legal) have been associated with increased risk of thrombosis. However, due to limited scientific literature regarding the prothrombotic tendencies of these drugs, there is a concomitant limited understanding of the pathophysiology of drug-induced thrombosis. As drugs are one of the few modifiable risk factors for thrombosis, further study and dissemination of knowledge regarding drug-associated and drug-induced thrombosis are essential and have the potential to lead to decreased future incidence of thrombosis. The mechanisms at the basis of the thrombophilic activity of these drugs are variable and sometimes still ill recognized. Increased levels of clotting factors, reduction in coagulation natural inhibitors, decreased fibrinolysis, activated clotting factors, increased blood viscosity, endothelial damage, and increased platelet number and activation are the most frequent causes. Arterial steal or coronary arteries no flow has also been implicated. In some cases due to the intake of several drugs, more than one mechanism is present in a given patient. The purpose of the present review is to analyze all the drugs demonstrated to be potentially thrombotic. It is hoped that a prudent use or nonuse of these drugs might result in a reduction of thrombosis-associated diseases.

PMID: 27301402 [PubMed - indexed for MEDLINE]

Is the higher incidence of clozapine induced myocarditis in Australia due to awareness and monitoring?

Schizophr Res. 2018 Jun 13;:

Authors: Dawson JL, Clark SR, Sluggett JK, Procter NG, Simon Bell J

PMID: 29907491 [PubMed - as supplied by publisher]

Steroid-induced hyperglycemia: An underdiagnosed problem or clinical inertia? A narrative review.

Diabetes Res Clin Pract. 2018 May;139:203-220

Authors: Bonaventura A, Montecucco F

Abstract
Corticosteroids are widely diffused drugs. An important side effect is the impairment of glycemic control both in patients with known diabetes and in normoglycemic ones potentially leading to steroid-induced diabetes mellitus (SIDM). In this review based on papers released on PubMed, MEDLINE, and EMBASE from January 2015 to October 2017, we summarized and discussed main updates about the definition, the diagnosis, and the pathophysiology of steroid-induced hyperglycemia (SIH), with a look to new therapies. Main alterations responsible for the diabetogenic effect of corticosteroids are a negative impact on insulin sensitivity along with a derangement on insulin secretion, explaining the typical post-prandial hyperglycemia linked to the promotion of gluconeogenesis. An early and precise diagnosis of SIH and/or SIDM is necessary, but current criteria do not seem sensible enough. As an afterthought, the treatment should be reasoned and tailored according to proposed glycemic thresholds and patient comorbidities, choosing between antidiabetic oral drugs and insulin, the latter being preferable among hospitalized patients. SIDM and SIH are frequent problems, but often underdiagnosed due to old diagnostic criteria. Dedicated guidelines universally shared are mandatory in order to harmonize the treatment of these conditions, thus overtaking single therapeutic strategies mostly arising from literature.

PMID: 29530386 [PubMed - indexed for MEDLINE]

Pharmacokinetic drug-drug interactions in the intensive care unit - single-centre experience and literature review.

Anaesthesiol Intensive Ther. 2017;49(4):259-267

Authors: Łój P, Olender A, Ślęzak W, Krzych ŁJ

Abstract
BACKGROUND: Drug-drug interactions constitute a serious health hazard in everyday clinical practice in critically ill patients. Drug-drug interactions may be pharmacokinetic or pharmacodynamic in their nature. We aimed to investigate the quantity and quality of possible drug-drug interactions, and their possible side effects in intensive care unit patients in a 12-month period.
METHODS: This retrospective study covered data on pharmacological treatment of 43 consecutive patients (11 females, 32 males) aged 62 ± 15 years, hospitalized between January 2015 and February 2016. Pharmacokinetic DDIs were identified and graded. Only severe and clinically important drug-drug interactions were subjected for further analysis.
RESULTS: Median baseline SAPS III was 53 (IQR 38-67) points. Median intensive care unit stay was 12 (6-25) days. Subjects were treated with a median number of 22 (12-27) drugs. We identified 27 (16-41) possible drug-drug interactions per patient, including 3 (1-7) drug-drug interactions of a severe grade. The total number of severe and clinically important drug-drug interactions was 253 of which 227 were analyzed in detail. No possible side-effects of drug-drug interactions were identified.
CONCLUSIONS: DDIs as well as their side-effects are challenging regarding their precise evaluation, especially due to the need for multidrug treatment in critically ill patients. Concentration-controlled therapy should be recommended, especially for treatment with vancomycin, digoxin and valproate. Pantoprazole should be a proton pump-inhibitor of choice. Drug dose modification is necessary in combined treatment with fluconazole and amiodarone or rifampicin. From a clinical point of view, the most important impact of drug-drug interactions is on antibiotic treatment effectiveness, especially with meropenem when valproate is also prescribed.

PMID: 29027654 [PubMed - indexed for MEDLINE]

Electrophysiological Adverse Effects of Direct-Acting Antivirals in Patients With Chronic Hepatitis C.

J Clin Pharmacol. 2017 07;57(7):931-932

Authors: Rossotti R, Garcia-Fraile Fraile LJ, Baiguera C, Puoti M

PMID: 28467638 [PubMed - indexed for MEDLINE]

Hydroxyurea-Induced Pneumopathy in a Patient With Myeloproliferative Syndrome.

Clin Med Insights Case Rep. 2018;11:1179547618770688

Authors: Galván OP, Moltó HP, Fabià-Mayans A, Xicoy B, Mate JL, Martí PR

Abstract
Hydroxyurea (HU) is a drug frequently used in the treatment of chronic myeloproliferative neoplasms. The most common side effects of this drug are pancytopenia, digestive and skin disorders. Respiratory complications are rare and there are less than 20 cases described, only 5 of which underwent an anatomopathological study. We present the case of a patient with chronic myeloproliferative neoplasm who developed interstitial pneumonitis probably due to HU according to histological study.

PMID: 29899671 [PubMed]

Safety and Efficacy of Budesonide Oral Suspension Maintenance Therapy in Patients With Eosinophilic Esophagitis.

Clin Gastroenterol Hepatol. 2018 Jun 11;:

Authors: Dellon ES, Katzka DA, Collins MH, Gupta SK, Lan L, Williams J, Hirano I

Abstract
BACKGROUND & AIMS: We aimed to determine the safety and efficacy of budesonide oral suspension (BOS) maintenance therapy in patients with eosinophilic esophagitis (EoE).
METHODS: We performed an open-label extension study of a 12-week, multicenter, randomized, double-blind, placebo-controlled trial. Patients with EoE (11-40 years old) who completed double-blind BOS (n=45) or placebo therapy (n=37) received 24 weeks' open-label BOS (2.0 mg once daily for 12 weeks, with optional dose increase [1.5-2.0 mg twice daily] for 12 weeks thereafter). Predefined efficacy outcomes included: proportion of patients with a histologic response (≤6 eosinophils/high-power field [eos/hpf]) and change in mean peak eosinophil counts after 24 weeks. Analyses were stratified by patients who received placebo (placebo/BOS) or BOS (BOS/BOS) during the double-blind trial.
RESULTS: BOS was well tolerated and drug-related adverse events were uncommon (placebo/BOS, 19% [7/37]; BOS/BOS, 4% [2/45]). Incidence of oral candidiasis (1 per group) and esophageal candidiasis (placebo/BOS group, n=4) remained low. Changes in morning serum cortisol levels were not clinically relevant. A histologic response was observed in 49% (16/33) of patients receiving placebo/BOS and 23% (9/39) receiving BOS/BOS. Mean peak eosinophil counts (baseline vs week 24 or early termination) were: placebo/BOS, 118.8 vs 29.1; P<.001 and BOS/BOS, 38.1 vs 72.4; P=.01. Of the patients who responded to double-blind therapy, 42% maintained a histologic response during the open-label extension; 4% of non-responders gained response.
CONCLUSIONS: In an open-label extension study of patients with EoE, BOS was well tolerated and drug-related adverse events were uncommon. BOS maintained a histologic response in some initial responders but few initial non-responders had a response. ClinicalTrials.gov no: NCT01642212.

PMID: 29902649 [PubMed - as supplied by publisher]

Assessing Drug Safety in Children - The Role of Real-World Data.

N Engl J Med. 2018 Jun 07;378(23):2155-2157

Authors: McMahon AW, Dal Pan G

PMID: 29874532 [PubMed - indexed for MEDLINE]

Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Crossover Study Evaluating the Abuse Potential of the Antiepileptic Drug Lacosamide in Healthy Recreational Drug Users.

J Clin Psychopharmacol. 2017 Dec;37(6):675-683

Authors: Schoedel KA, Andreas JO, Doty P, Eckhardt K, Sellers EM

Abstract
PURPOSE: This phase 1, randomized, double-blind, placebo- and active comparator-controlled crossover study assessed the abuse potential of the antiepileptic drug, lacosamide.
METHODS: After a qualification phase, 38 healthy, recreational central nervous system-depressant users were randomized to treatment sequences comprising single oral therapeutic (200 mg) and supratherapeutic (800 mg) doses of lacosamide, alprazolam (1.5 and 3 mg), and placebo. Subjective effects were assessed for 24 hours following each dose using a range of scales, with a 5- to 9-day washout between treatments.
FINDINGS: Mean subjective effects for 200 mg lacosamide were statistically similar to placebo and significantly lower than with alprazolam for most end points. Lacosamide 800 mg elicited transient, statistically significant positive effects compared with placebo, but also persistent Bad Drug Effects including statistically greater maximum effect (Emax) scores for Nausea and Dysphoria compared with other treatments (P < 0.0002). Consistent with this, the 800 mg lacosamide dose showed a significantly lower "at this moment" Drug Liking visual analog scale (VAS) Emax compared with 3 mg alprazolam, but was not different from 1.5 mg alprazolam (73.1/100, 85.4/100, and 78.9/100, respectively, where 50 is neutral). Overall Drug Liking VAS and Take Drug Again VAS Emax for 800 mg lacosamide were not significantly different from placebo and were lower than those for both alprazolam doses (P < 0.0001).
IMPLICATIONS: These results suggest that in recreational central nervous system-depressant users, lacosamide has detectable abuse-related subjective effects, but a relatively low potential for abuse compared with alprazolam. These findings contributed toward placement of lacosamide into Schedule V of the US Controlled Substances Act.

PMID: 28926353 [PubMed - indexed for MEDLINE]

Ustekinumab use in Crohn's disease: a Canadian tertiary care centre experience.

Scand J Gastroenterol. 2017 Dec;52(12):1354-1359

Authors: Greenup AJ, Rosenfeld G, Bressler B

Abstract
OBJECTIVES: Real world data regarding clinical response to ustekinumab in Crohn's disease is lacking. We report our experience of ustekinumab use using a novel subcutaneous (SC) induction strategy and aim to identify predictors of response.
MATERIALS AND METHODS: A retrospective, observational study of compassionate ustekinumab use in Crohn's disease was conducted with the use of a standard or high dose SC induction protocol. Symptomatic response was assessed after 3 months (short-term), and if remaining on therapy, within 3-12 months (medium-term) and at least 12 months (long-term). Endoscopic or radiologic response was assessed when available. Survival analysis of time to failure (cessation of ustekinumab) and multivariate logistic regression to identify predictors of response were performed.
RESULTS: Seventy-nine patients commenced ustekinumab, with six patients lost to follow-up and five asymptomatic at baseline. Symptomatic response was assessed in 68 patients; 56% (38) of patients had a short-term symptomatic response. Type of preceding anti-TNF response was the only significant predictor of short-term response, with primary non-response being a strong predictor. In the medium-term, symptomatic response occurred in 72% (30/42) of patients and endoscopic or radiologic response was achieved in 72% (26/36) of patients assessed. The median time to failure was 22 months. Maintenance dose escalation to 90 mg every 4 weeks was successful in three of 16 patients.
CONCLUSIONS: Fifty-six percent of patients had short-term symptomatic response, with a history of primary non-response to prior anti-TNF therapy being a predictor of response. Dose escalation had only modest benefit.

PMID: 28885058 [PubMed - indexed for MEDLINE]

Optimizing Thiopurine Therapy in Inflammatory Bowel Disease Among 2 Real-life Intercept Cohorts: Effect of Allopurinol Comedication?

Inflamm Bowel Dis. 2017 Nov;23(11):2011-2017

Authors: Meijer B, Seinen ML, van Egmond R, Bouma G, Mulder CJJ, van Bodegraven AA, de Boer NKH

Abstract
BACKGROUND: Thiopurines (azathioprine and mercaptopurine) are frequently used immunosuppressive drugs to maintain remission in patients with inflammatory bowel disease. Half of the conventional thiopurine-derivative users have to discontinue treatment within 5 years, mainly because of intolerable adverse events. Over recent years, different strategies to optimize thiopurine treatment were suggested, yet, studies describing the clinical effectiveness of these strategies remain scarce. The aims of this study were to compare tolerability and sustained clinical benefit of conventional thiopurine derivatives therapy among two 5-year real-life intercept cohorts and to assess the clinical value of specifically allopurinol cotherapy.
METHODS: In this retrospective single-center cohort study, we analyzed data from patients in whom weight-based thiopurine monotherapy was initiated between 2005 and 2009 (cohort 1) or between 2010 and 2014 (cohort 2). The initiation of the second cohort was synchronic to the start of allopurinol-based optimization in our center. Optimization strategies were extracted from patient charts.
RESULTS: In total, 105 patients were included (60 in cohort 1, and 45 in cohort 2). Metabolite measurement was performed in 37% versus 84% of the patients (P < 0.001). Subsequent optimization strategies were applied in 33% versus 58% of the patients because of inadequate metabolite concentrations, intolerance, or ineffectiveness (P = 0.01). Allopurinol was coadministered to therapy in 18 patients (40%) in the second cohort. Therapy was switched to thioguanine in 11 versus 6 patients (P > 0.05). Overall, total duration was longer in the second cohort (10.8 versus 34.1 months, P < 0.001). The number of ongoing thiopurine users (20% versus 49%) and sustained clinical benefit (13% versus 38%) were higher in the second cohort (both P < 0.05). This was mainly because of a decrease in hepatotoxicity after optimization (P < 0.01).
CONCLUSIONS: Optimization of thiopurine therapy by the use of therapeutic drug monitoring with subsequent administration of allopurinol cotherapy successfully enhanced sustained clinical benefit and tolerability in patients with inflammatory bowel disease.

PMID: 28617756 [PubMed - indexed for MEDLINE]

Too much of a good thing: a retrospective study of β-lactam concentration-toxicity relationships.

J Antimicrob Chemother. 2017 Oct 01;72(10):2891-2897

Authors: Imani S, Buscher H, Marriott D, Gentili S, Sandaradura I

Abstract
Objectives: To determine the existence of concentration-toxicity relationships for common β-lactam antibiotic adverse effects and define thresholds above which toxicity is more likely.
Patients and methods: Retrospective review of consecutive patients treated with piperacillin, meropenem or flucloxacillin who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015. Adverse events investigated included neurotoxicity, nephrotoxicity, hepatotoxicity and opportunistic Clostridium difficile infection. Toxicity was measured using observational grading criteria, clinical assessment and relevant serum biomarkers. These findings were correlated with trough TDM measurements at the time of toxicity presentation.
Results: TDM results from 378 patients (piperacillin = 223, meropenem = 94 and flucloxacillin = 61) were investigated. There was no difference in baseline patient characteristics across antibiotic groups. A statistically significant elevation in mean serum trough concentrations (Cmin) was found in patients diagnosed with neurotoxicity (piperacillin, P < 0.01; meropenem, P = 0.04; flucloxacillin, P = 0.01) and those who developed nephrotoxicity whilst being treated with piperacillin (P < 0.01) or meropenem (P < 0.01). Incidence of hepatotoxicity and C. difficile was not related to Cmin. Threshold concentrations for which there is 50% risk of developing a neurotoxicity event (piperacillin, Cmin >361.4 mg/L; meropenem, Cmin >64.2 mg/L; flucloxacillin, Cmin >125.1 mg/L) or nephrotoxicity (piperacillin, Cmin >452.65 mg/L; meropenem, Cmin >44.45 mg/L) varied across antibiotics.
Conclusions: Our data reveal an association between toxic concentrations for a number of β-lactam agents and neurotoxic/nephrotoxic effects. We have defined threshold concentrations above which these toxicities become more likely. Clinicians should balance concerns for therapeutic efficacy with potential toxicity when considering aggressive therapy.

PMID: 29091190 [PubMed - indexed for MEDLINE]

Successful outpatient parenteral antibiotic therapy delivery via telemedicine.

J Antimicrob Chemother. 2017 Oct 01;72(10):2898-2901

Authors: Tan SJ, Ingram PR, Rothnie AJ, Whitmore TJ, Robinson JO, Hatch JB, Italiano CM, Heath CH

Abstract
Objectives: Most outpatient parenteral antimicrobial therapy (OPAT) services use a hospital-based model of care in which patients remain in proximity to large hospitals facilitating clinical review. We aimed to evaluate clinical outcomes and complication rates for patients living in geographically isolated locations managed by telemedicine-supported OPAT. Methods: This was a retrospective cohort study.
Results: Between 2011 and 2015, we delivered 88 episodes of care involving 83 adult patients resulting in 2261 days of OPAT. The median age was 56 years, 8 of 83 (10%) were indigenous Australian and the median Charlson comorbidity index score was 2 (IQR 1-4). The median distance of patients' residence from our hospital was 288 km (IQR 201-715) and the median duration on the programme was 26 days (IQR 14-34). Bone and joint infections accounted for 75% of infections treated. Favourable clinical outcomes (improvement or cure) were achieved in 87% of patients and the unplanned, OPAT-related readmission rate was 8%. Nineteen percent and 10% of patients had drug-related and line-related adverse effects, respectively.
Conclusions: Despite a complex case mix, our adverse event and readmission rates are similar to the published literature describing a non-telemedicine model to deliver OPAT. High rates of favourable clinical outcomes and likely cost benefits suggest that telemedicine-supported OPAT is an efficacious and safe substitute for inpatient care in our setting.

PMID: 29091189 [PubMed - indexed for MEDLINE]

Radiological manifestations of immune-related adverse effects observed in patients with melanoma undergoing immunotherapy.

J Med Imaging Radiat Oncol. 2017 Dec;61(6):759-766

Authors: Sidhu P, Menzies AM, Long G, Carlino M, Lorens S, Kapoor R

Abstract
Immunotherapy drugs work by stimulating the patient's own immune system to recognize and destroy cancer cells. This subclass of drugs is increasingly administered to patients with advanced melanoma. They are also commonly incorporated into other cancer therapies such as non-small cell lung cancer, renal cancer, head and neck cancers and Hodgkin lymphoma. The most commonly administered immunotherapeutic agents in the treatment of melanoma include programmed cell death protein 1 (PD-1) inhibitors, cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors and a subclass of cytokines. During treatment with these antibodies, a unique set of adverse effects may occur which are often called immune-related adverse events (irAEs). It is vital for radiologists to be aware of and document these side effects during routine staging or body imaging during therapy. Some of these include pneumonitis, colitis, hypophysitis, lymphadenopathy or sarcoid-like syndrome and myositis. IrAEs such as sarcoid-like lymphadenopathy can mimic progression of disease. Serious side effects are seen in less than 10% of patients, and typically emerge between 6 and 12 weeks after commencing treatment. The clinical manifestations of these side effects typically vary from mild to severe and so do the radiological findings. Patients with mild side effects are often treated successfully with systemic corticosteroids, while severe cases require cessation of immunotherapy. We provide a pictorial article on the common irAEs and the associated radiological manifestations.

PMID: 29024572 [PubMed - indexed for MEDLINE]

Poisoning deaths in Poland: Types and frequencies reported in Łódź, Kraków, Sosnowiec, Gdańsk, Wrocław and Poznań during 2009-2013.

Int J Occup Med Environ Health. 2017 Oct 06;30(6):897-908

Authors: Krakowiak A, Piekarska-Wijatkowska A, Kobza-Sindlewska K, Rogaczewska A, Politański P, Hydzik P, Szkolnicka B, Kłopotowski T, Picheta S, Porębska B, Antończyk A, Waldman W, Sein Anand J, Matuszkiewicz E, Łukasik-Głębocka M

Abstract
OBJECTIVES: The aim of this study has been to assess the characteristics of acute poisoning deaths in Poland over a period of time 2009-2013.
MATERIAL AND METHODS: The analysis was based on the data obtained from the patient records stored in toxicology departments in 6 cities - Łódź, Kraków, Sosnowiec, Gdańsk, Wrocław and Poznań. Toxicological analyses were routinely performed in blood and/or urine. Major toxic substances were classified to one of the following categories: pharmaceuticals, alcohol group poisonings (ethanol and other alcohols), gases, solvents, drugs of abuse, pesticides, metals, mushrooms, others. Cases were analyzed according to the following criteria: year, age and gender of analyzed patients, toxic substance category and type of poisoning. The recorded fatal poisonings were classified according to the International Classification of Diseases.
RESULTS: The record of 261 deaths were retrospectively reviewed. There were 187 males (71.64%) and 74 females (28.36%) and the male to female ratio was 2.52. Alcohol group poisonings were more frequently responsible for deaths in men compared to all poisonings, 91.1% vs. 71.6%, respectively (p < 0.05), and pharmaceutical agents were more frequently responsible for deaths in women, 47.4% vs. 28.4%, (p < 0.05). Methanol was the most common agent in the alcohol group poisonings, accounting for 43.75% (N = 49), followed by ethylene glycol, 39.29% (N = 44), and ethanol, 16.96% (N = 19).
CONCLUSIONS: Epidemiological profile data from investigation of poisoning deaths in Poland may be very useful for the development of preventive programs. Int J Occup Med Environ Health 2017;30(6):897-908.

PMID: 28832029 [PubMed - indexed for MEDLINE]

Medication safety knowledge, attitudes and practices among community pharmacists in Lebanon.

Curr Med Res Opin. 2018 Jan;34(1):149-156

Authors: Hajj A, Hallit S, Ramia E, Salameh P, Order of Pharmacists Scientific Committee – Medication Safety Subcommittee

Abstract
BACKGROUND: The effectiveness of a national post-marketing surveillance program depends directly on the active participation of all health professionals. There is no current comprehensive and active pharmacovigilance program available in Lebanon.
OBJECTIVES: To assess the knowledge, attitudes, and practices (KAP) among community pharmacists in Lebanon with respect to potential pharmacovigilance and adverse-drug-reaction reporting in Lebanon.
METHODS: A cross-sectional descriptive study, using a self-administered KAP questionnaire and conducted between March and July 2016, included 1857 pharmacists practicing in community settings. Statistical analysis included χ2 test for dichotomous or multinomial qualitative variables, and Wilcoxon test for quantitative variables with non-homogeneous variances or non-normal distribution.
RESULTS: The majority of responders had good knowledge concerning the concept and purpose of pharmacovigilance as well as adverse drug reactions (how to report these/the importance of reporting adverse events/the definition of an adverse event and pharmacovigilance). Concerning community pharmacists' attitudes and practice towards pharmacovigilance, the majority described having a positive attitude towards their role in adverse drug reaction reporting and this activity was even seen as one of their core duties. The questionnaire revealed a lack of practice and training regarding pharmacovigilance. Nonetheless, the pharmacists agreed on the Order of Pharmacists in Lebanon and the Ministry of Health's role in promoting this practice and helping them be more involved in reporting adverse drug reactions (ADRs). The pharmacists thought that they are well positioned regarding patient-safety practice in their pharmacies and the results were not statistically different between pharmacy employers and employees.
CONCLUSION: Lebanese pharmacists have the required knowledge and positive attitude to start reporting ADRs, were aware of ADRs occurring with various medicines post-marketing, yet were currently not able to disseminate this information widely or to record it centrally, emphasizing the importance of establishing a national ADR reporting system.

PMID: 28758813 [PubMed - indexed for MEDLINE]

Predictors of Mortality, Rehospitalization for Syncope and Cardiovascular Events in Patients With Cardiovascular Syncope.

Circ J. 2017 Sep 25;81(10):1395-1402

Authors: Onuki T, Shoji M, Nakamura Y, Ogawa K, Ochi A, Inokuchi K, Kawasaki S, Onishi Y, Onuma Y, Munetsugu Y, Kikuchi M, Ito H, Minoura Y, Watanabe N, Adachi T, Kawamura M, Asano T, Tanno K, Kobayashi Y

Abstract
BACKGROUND: Predictors of poor outcomes remain unknown for cardiovascular syncope patients after discharge.Methods and Results:We reviewed the medical records of consecutive patients admitted to hospital with cardiovascular syncope. We then performed Cox stepwise logistic regression analysis to identify significant independent factors for death, rehospitalization for syncope, and cardiovascular events. The study group was 206 patients with cardiovascular syncope. Of them, bradycardia was diagnosed in 50%, tachycardia in 27%, and structural disease in 23%. During a 1-year follow-up period, 18 (8%) and 45 (23%) patients, respectively, were rehospitalized for syncope or a cardiovascular event, and 10 (4%) died. Independent predictors of cardiovascular events were systolic blood pressure <100 mmHg (odds ratio [OR] 3.25; 95%confidence interval [CI] 1.41-7.51, P=0.006) and implantation of a pacemaker (OR 0.19; 95% CI 0.05-0.51, P=0.0005) (inverse association). Drug-induced syncope (OR 4.57; 95% CI 1.54-12.8, P=0.007) was an independent risk factor for rehospitalization. Finally, a history of congestive heart failure (OR 11.0; 95% CI 2.78-54.7, P=0.0006) and systolic blood pressure <100 mmHg (OR 5.40; 95% CI 1.30-22.7, P=0.02) were identified as significant independent prognostic factors for death.
CONCLUSIONS: Drug-induced syncope, hypotension, no indication for a pacemaker, and a history of congestive heart failure are risk factors post-discharge for patients with cardiovascular syncope and careful follow-up of these patients for at least 1 year is recommended.

PMID: 28539561 [PubMed - indexed for MEDLINE]

Imaging after treatment in uterine malignancies: Spectrum of normal findings and most common complications.

J Med Imaging Radiat Oncol. 2017 Dec;61(6):777-790

Authors: Miccò M, Telesca AM, Gui B, Grimaldi PP, Cambi F, Marini MG, Valentini AL, Bonomo L

Abstract
Uterine malignancies account for the majority of gynaecologic cancers. Different treatment options are available depending on histology, disease grade and stage. Hysterectomy is the most frequent surgical procedure. Chemotherapy and radiation therapy (CRT) represents the preferred therapeutic choice for locally advanced uterine and cervical malignancies. Imaging of the female pelvis following these treatments is particularly challenging due to alteration of the normal anatomy. Radiologists should be familiar with both the expected post-treatment imaging findings and the imaging features of possible complications to make the correct interpretation and avoid possible pitfalls. The purpose of this review is to show the expected computed tomography (CT) and Magnetic Resonance Imaging (MRI) appearances of the female pelvis following surgery and CRT for uterine and cervical cancer, to illustrate the imaging findings of early and delayed most common complications after surgery and CRT, describing the suitable imaging modalities and protocols for evaluation of patients treated for gynaecologic malignancies.

PMID: 28517240 [PubMed - indexed for MEDLINE]

A Randomized, Placebo-Controlled Trial of Fidaxomicin for Prophylaxis of Clostridium difficile Associated Diarrhea in Adults undergoing Hematopoietic Stem Cell Transplantation.

Clin Infect Dis. 2018 Jun 09;:

Authors: Mullane KM, Winston DJ, Nooka A, Morris MI, Stiff P, Dugan MJ, Holland H, Gregg K, Adachi JA, Pergam SA, Alexander BD, Dubberke ER, Broyde N, Gorbach SL, Sears PS

Abstract
Background: Clostridium difficile-associated diarrhea (CDAD) is common during hematopoietic stem-cell transplantation (HSCT) and is associated with increased morbidity and mortality. We evaluated fidaxomicin for prevention of CDAD in HSCT patients.
Methods: In this double-blind study, subjects undergoing HSCT with fluoroquinolone prophylaxis stratified by transplant type (autologous/allogeneic) were randomized to once-daily oral fidaxomicin 200mg or matching placebo. Dosing began within 2 days of starting conditioning or fluoroquinolone prophylaxis and continued until 7 days after neutrophil engraftment or completion of fluoroquinolone prophylaxis/clinically indicated antimicrobials for up to 40 days. The primary endpoint was CDAD incidence through 30 days after study medication. The primary endpoint analysis counted confirmed CDAD, receipt of CDAD-effective medications (for any indication), and missing CDAD assessment (for any reason, including death) as failures; this composite analysis is referred to as "prophylaxis failure" to distinguish from the pre-specified sensitivity analysis, which counted only confirmed CDAD (by toxin immunoassay or nucleic acid amplification test) as failure.
Results: Of 611 subjects enrolled, 600 were treated and analyzed. Prophylaxis failure was similar in fidaxomicin and placebo recipients (28.6% vs 30.8%; difference 2.2% [-5.1, 9.5], p=0.278). However, most failures were due to non-CDAD events. Confirmed CDAD was lower in fidaxomicin vs placebo recipients (4.3% vs 10.7%; difference 6.4% [2.2, 10.6], p=0.0014). Drug-related adverse events occurred in 15.0% of fidaxomicin recipients and 20.0% of placebo recipients.
Conclusion: While no difference was demonstrated between arms in the primary analysis, results of the sensitivity analysis demonstrated that fidaxomicin significantly reduced the incidence of CDAD in HSCT recipients.
ClinicalTrials.gov: NCT01691248.

PMID: 29893798 [PubMed - as supplied by publisher]

The influence of genetic variation on late toxicities in childhood cancer survivors: A review.

Crit Rev Oncol Hematol. 2018 Jun;126:154-167

Authors: Clemens E, van der Kooi ALF, Broer L, van Dulmen-den Broeder E, Visscher H, Kremer L, Tissing W, Loonen J, Ronckers CM, Pluijm SMF, Neggers SJCMM, Zolk O, Langer T, Zehnhoff-Dinnesen AA, Wilson CL, Hudson MM, Carleton B, Laven JSE, Uitterlinden AG, van den Heuvel-Eibrink MM

Abstract
INTRODUCTION: The variability in late toxicities among childhood cancer survivors (CCS) is only partially explained by treatment and baseline patient characteristics. Inter-individual variability in the association between treatment exposure and risk of late toxicity suggests that genetic variation possibly modifies this association. We reviewed the available literature on genetic susceptibility of late toxicity after childhood cancer treatment related to components of metabolic syndrome, bone mineral density, gonadal impairment and hearing impairment.
METHODS: A systematic literature search was performed, using Embase, Cochrane Library, Google Scholar, MEDLINE, and Web of Science databases. Eligible publications included all English language reports of candidate gene studies and genome wide association studies (GWAS) that aimed to identify genetic risk factors associated with the four late toxicities, defined as toxicity present after end of treatment.
RESULTS: Twenty-seven articles were identified, including 26 candidate gene studies: metabolic syndrome (n = 6); BMD (n = 6); gonadal impairment (n = 2); hearing impairment (n = 12) and one GWAS (metabolic syndrome). Eighty percent of the genetic studies on late toxicity after childhood cancer had relatively small sample sizes (n < 200), leading to insufficient power, and lacked adjustment for multiple comparisons. Only four (4/26 = 15%) candidate gene studies had their findings validated in independent replication cohorts as part of their own report.
CONCLUSION: Genetic susceptibility associations are not consistent or not replicated and therefore, currently no evidence-based recommendations can be made for hearing impairment, gonadal impairment, bone mineral density impairment and metabolic syndrome in CCS. To advance knowledge related to genetic variation influencing late toxicities among CCS, future studies need adequate power, independent cohorts for replication, harmonization of disease outcomes and sample collections, and (international) collaboration.

PMID: 29759558 [PubMed - indexed for MEDLINE]