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Clinical practice guidelines support sustained use of renin-angiotensin-aldosterone-system (RAAS) inhibitors over time in heart failure with reduced ejection fraction, yet few data are available regarding the frequency, timing or predictors of early treatment discontinuation in clinical practice.Among prevalent or new users of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists (MRAs) in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, we estimated the frequency and independent predictors of treatment discontinuation during follow-up. Among sites with5 users of a given RAAS inhibitor, we evaluated practice variation in the proportion of patients with treatment discontinuation.Over median follow-up of 18 months, frequency of drug discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.7% (444 of 3509 users), 10.4% (140 of 1352 users), and 20.4% (435 of 2129 users), respectively. An additional, 149 (11.0%) of ARNI users were switched to ACEis/ARBs, and 447 (12.7%) of ACEi/ARB users were switched to ARNIs during follow-up. Across sites, the median proportion of discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.5% (25th-75th percentiles 6.9%-18.9%), 18.8% (25th-75th percentiles 12.5%-28.6%), and 19.6% (25th-75th percentiles 10.7%-27.0%), respectively. Chronic kidney disease was the only independent predictor of increased risk of discontinuation of each of the RAAS inhibitor classes (P0.02 for all). Higher Kansas City Cardiomyopathy Questionnaire overall summary scores independently predicted lower risk of discontinuation of ACEis/ARBs and ARNIs (both P0.001) but not of MRAs. Investigator clinical experience was predictive of lower risks of discontinuation of ACEis/ARBs and MRAs (P0.02) but not of ARNIs. All other independent predictors of discontinuation were unique to individual therapeutic classes.One in 10 patients discontinue ACEis/ARBs or ARNIs, and 1 in 5 discontinue MRAs in routine clinical practice of heart failure with reduced ejection fraction. Unique patient-level and clinician/practice-level factors are associated with premature discontinuation of individual RAAS inhibitors, which may help to guide structured efforts to promote treatment persistence in clinical care.

Objective Due to the increasing concerns about polypharmacy, there is a growing need for clinical recommendations for drug discontinuation. This requires studies investigating the process on several levels. This paper addresses the methodological problems of drug discontinuation trials (DDTs). To that end, we offer a new typology of research aims and corresponding methodological recommendations for trials evaluating drug discontinuation. Study Design and Setting Multi-stage development process, including literature search and expert panels. Results Clinical trials are only required in cases of scientific uncertainty. We identified three situations of uncertainty associated with drug discontinuation from which we derived three study types: 1) Uncertainty regarding the effectiveness and/or safety of a drug; 2) Uncertainty regarding the procedure of discontinuing a previously taken drug; 3) Uncertainty regarding the effectiveness of complex strategies used to discontinue one or more drugs. We developed specific methodological recommendations for each study type. Conclusion We offer a comprehensive definition of research aims, study designs, and methodological recommendations regarding DDTs. The typology we propose can help investigators clarify their research aims and study design. The type-specific methodological recommendation should improve the quality of future drug discontinuation trials.

Background Multidose drug dispensing (MDD) is used to help patients take their medicines appropriately. Little is known about drug regimen changes within these MDD systems and how they are effectuated by the community pharmacist. Manual immediate adjustments of the MDD system could introduce dispensing errors. MDD guidelines therefore recommend to effectuate drug regimen changes at the start of a new MDD system. Objective The aim of this study was to investigate the frequency, type, procedure followed, immediate necessity, and time taken to make MDD adjustments. Methods This was a cross-sectional study in eight community pharmacies in the Netherlands. All adjustments to MDD systems were systematically documented for 3 weeks by the community pharmacist. Results Overall, 261 MDD adjustments involving 364 drug changes were documented for 250 patients: 127 (35%) drug changes involved the addition of a new drug, 124 (34%) a change in dosage, and 95 (26%) drug discontinuation. Of the MDD adjustments, 135 (52%) were effectuated immediately: 81 (31%) by adjusting the MDD system manually, 49 (19%) by temporarily dispensing the drug separately from the MDD system, and 5 (2%) by ordering a new MDD system. Pharmacists considered that 36 (27%) of the immediate MDD adjustments could have been deferred until the next MDD system was produced. Immediate adjustment took significantly longer than deferred adjustment (p Conclusions This study shows that in patients using MDD systems, over half of the drug regimen changes are adjusted immediately. The necessity of these immediate changes should be critically evaluated.

Aims COVID-19 outbreak has created a public health catastrophe all over the world. Here, we have aimed to conduct a systematic review and meta-analysis on remdesivir use for COVID-19. Main methods We searched Pubmed, Scopus, Embase, and preprint sites and identified ten studies for qualitative and four studies for quantitative analysis using PRISMA guidelines. The quantitative synthesis was performed using fixed and random effect models in RevMan 5.4. Heterogeneity was assessed using the I-squared (I2) test. Key findings Comparing 10-day remdesivir group with placebo or standard of care (SOC) group, remdesivir reduced 14 days mortality (OR 0.61, CI 0.41–0.91), need for mechanical ventilation (OR 0.73, CI 0.54–0.97), and severe adverse effects (OR 0.69, 95% CI 0.54 to 0.88). Clinical improvement on day 28 (OR 1.59, CI 1.06–2.39), day 14 clinical recovery (OR 1.48, CI 1.19–1.84), and day 14 discharge rate (OR 1.41, CI 1.15–1.73) were better among remdesivir group. Earlier clinical improvement (MD −2.51, CI −4.16 to −0.85); and clinical recovery (MD −4.69, CI −5.11 to −4.28) were seen among the remdesivir group. Longer course (10 days) of remdesivir showed a higher discharge rate at day 14 (OR 2.11, CI 1.50–2.97), but there were significantly higher rates of serious adverse effects, and drug discontinuation than the 5-day course. Significance Remdesivir showed a better 14 days mortality profile, clinical recovery, and discharge rate. Overall clinical improvement and clinical recovery were earlier among the remdesivir group. 10-day remdesivir showed more adverse outcome than 5-day course with no significant benefits., Graphical abstract Unlabelled Image, Highlights • Remdesivir showed a better 14-day mortality, clinical recovery, and discharge rate comparing with placebo or standard of care in COVID-19. • Overall clinical improvement and clinical recovery were earlier among 10-day remdesivir group than placebo or standard of care. • No benefit on 28-day mortality, discharge rate, and overall adverse effect between 10-day remdesivir group and placebo or standard of care. • Longer course (10-day) of remdesivir is not favored over a shorter course (5-day).

Background We aimed to evaluate the impact of coronavirus disease 2019 (COVID-19)-related lockdown on adherence to lifestyle and drug regimens in stay-at-home chronic coronary syndromes patients living in urban and rural areas. Methods A cross-sectional population-based study was perfomed in patients with chronic coronary syndromes. A sample of 205 patients was randomly drawn from the RICO (Observatoire des infarctus de Côte d'Or) cohort. Eight trained interviewers collected data by phone interview during week 16 (April 13 to April 19), i.e. 4 weeks after implementation of the French lockdown (start March 17, 2020). Results Among the 195 patients interviewed (of the 205, 3 had died, 1 declined, 6 lost), mean age was 65.5 ± 11.1 years. Only six patients (3%) reported drug discontinuation, mainly driven by media influence or family members. All 166 (85%) patients taking aspirin continued their prescribed daily intake. Lifestyle rules were less respected since almost half (45%) declared >25% reduction in physical activity, 26% of smokers increased their tobacco consumption by >25%, and 24% of patients increased their body weight > 2 kg. The decrease in physical activity and the increase in smoking were significantly greater in urban patients (P, Highlights • Consequences of COVID-19 lockdown in stay-at-home chronic coronary syndromes patients is unknown. • Patients reported a very high cardiovascular drug adherence. • Lockdown negatively impacted lifestyle management.

Fingolimod is an oral medication for multiple sclerosis that sequesters certain subsets of lymphocytes in lymph nodes, reducing egress into blood and their subsequent CNS migration. The initial multi-site randomized Phase III controlled trials found rates of infection similar to those in control groups. However, post-marketing surveillance has revealed an association with several opportunistic infections, including cryptococcosis. We report a case of fingolimod-related cryptococcal meningoencephalitis and IRIS after drug discontinuation and suggest a surveillance and risk mitigation strategy.

Highlights • This is the first report regarding the perioperative management of patients with concurrent multiple myeloma and malignant solid tumor. • Our case highlights the need to devise a perioperative management strategy for multiple myeloma patients. • Surgeons should be familiar with the risks associated with discontinuation of multiple myeloma drugs. • Continuation of the multiple myeloma agent may be preferable in patients who do not have marked myelosuppression., Introduction The synchronous incidence of multiple myeloma (MM) and other primary malignant solid tumor is rare. No detailed studies have been published regarding the perioperative management of patients with concurrent MM and malignant solid tumor. We report a patient with concurrent MM and gastric cancer who experienced rapid progression of liver metastasis after lenalidomide was discontinued. Presentation of case An 82-year-old woman with MM was diagnosed with clinical T3N2M0 gastric cancer, and MM had been maintained in remission with lenalidomide. Preoperatively, pancytopenia was found, and lenalidomide was discontinued and lenograstim was administered. Blood transfusions were also administered preoperatively due to anemia caused by tumor bleeding. Surgery was performed after her pancytopenia improved. Intraoperatively, several nodules were found on the liver, which were diagnosed as adenocarcinoma metastases. On postoperative day 13, a low density mass in the liver that was not observed before surgery was shown. The patient received best supportive care because she did not desire adjuvant chemotherapy for gastric cancer or resumption of treatment for MM. She died of progressive gastric cancer on postoperative day 80. Discussion Discontinuation of lenalidomide in our case may have promoted tumor angiogenesis and lowered antitumor immunity, causing rapid tumor growth and liver metastasis. Continuation of the MM agent may be preferable in patients who do not have marked myelosuppression. Conclusion Surgeons should be familiar with the risks associated with discontinuation of MM drugs when operating on patients with MM and concurrent malignant solid tumor.

Crimean-Congo hemorrhagic fever (CCHF) is a tick borne viral disease which can also be transmitted by direct contact with blood or tissue specimens of infected animals or humans. We present a fatal case of CCHF, who was diagnosed after death, and describe the post-exposure management plan for the health care workers (HCWs) involved in her care. In total of 52 HCWs were involved in the patient’s care and they were stratified into risk groups. Overall, 20 HCWs were grouped in high and intermediate risk groups, including the HCW with needle stick injury. High and intermediate risk groups were offered post exposure prophlaxis (PEP) with ribavirin. Fourteen of 20 HCWs started PEP, however 10 ceased after negative CCHF-PCR results. Negative CCHF-PCR results were reported for all HCWs at the 5th day of exposure. Side effects with PEP developed in 5 of HCWs and were mainly gastrointestinal complaints which reversed after drug discontinuation. All HCWs were followed for 14 days both clinically and with laboratory tests. None of the HCWs developed CCHF. PEP with ribavirin can be considered as a safe option in protection.

Fibroblast growth factor receptor (FGFR) inhibitors have shown promising results in terms of objective response rates in phase I/II trials in various malignancies that harbor FGFR genetic aberrations. The class of medications brings in the concept of 'personalized' treatment by targeting susceptible FGFR genetic alterations in some rare but dismal cancers such as cholangiocarcinoma. Despite the fact that FGFR inhibitors are well-tolerated, these drugs are associated with toxicities that are distinct from that of other small-molecule tyrosine kinase inhibitors. These toxicities can result in dose reductions, interruptions, and even drug discontinuation as reported in the clinical trials. The prevention and effective management of the FGFR inhibitor-associated toxicities will allow patients to stay on these medications without the therapy interruptions. The current work is focused on summarizing the available literature on unique FGFR inhibitor-associated toxicities with a special emphasis in managing the unique adverse events.

We would like to thank Dr. Marques and colleagues for their interest in our paper. We merely wished to make the point that physicians should not be concerned about, or expect to see, the same impressive reductions in blood pressure observed with spironolactone in resistant hypertension in patients

Serenelli et al. ([1][1]) investigated the effects of mineralocorticoid receptor antagonists (MRAs) on systolic blood pressure (SBP) and outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Data from 2 randomized clinical trials using MRAs were compared with those with

Women are underrepresented across cardiovascular clinical trials. Whether women are more likely than men to prematurely discontinue study drug is unknown. Eleven phase 3 TIMI trials were included [135,879 men and 51,812 women (28%)]. The association between sex and odds of premature study drug

This research was designed to investigate patient-reported and doctor-reported reasons for the discontinuation of pharmacological treatment in Chinese patients with major depressive disorder (MDD), which was part of the National Survey on Symptomatology of Depression (NSSD) from 2014 to 2015.This cross-sectional study included 649 patients who had discontinued antidepressant medications and 711 patients who had remained on them, selected from a group of 3516 candidates who have had at least one depressive episode. Differences in the two groups' sociodemographic factors, clinical characteristics, medication use, and self-reported reasons for drug discontinuation were compared via Student's t-test or chi-square test. Logistic regression analysis was then used to determine the association of all non-subjective dichotomous and ordinal categorical variables, including the additional 63 items of our physician-evaluated symptomatic assessment, with drug compliance.Compared to the spontaneous drug discontinuation (SDD) group, the drug adherence (DA) group had significantly lower rates of the following: family history of mental disease (9.0% vs 13.6%), highest level of education achieved being post-graduate or above (1.6% vs 4.7%), smoking (5.8% vs 9.7%), and other health problems (33.9% vs 42.4%) (p's 0.05). On the other hand, first-episode depression (48.5% vs 21.9%) and taking of mood stabilizer(s) (8.3% vs 5.6%) were higher in the former group than in the latter (p's 0.05). Logistic Regression Analysis showed that five symptoms, such as depressed mood, were correlated positively with SDD, while another six symptoms, such as psychomotor retardation, were correlated negatively with it. The receiver operating characteristic (ROC) curve of this model yielded an area under the curve (AUC) of 0.701 (95% CI, 0.673-0.729). Notably, there were three main reasons given by patients in the DA group as to why they discontinued their medication(s): (1) concern about long-term side effects (36.1%), (2) no perceived need for taking said medication(s) long-term (34.2%), and (3) believing oneself to have been cured completely (30.0%).The aforementioned factors may affect patient compliance and elicit maladaptive thinking even from patients with good educational backgrounds, increasing the risk of drug discontinuation. Compliance of pharmacological treatment might be improved by increasing clarification and elucidation of different symptom clusters to the patient and combating the main reasons for drug discontinuation.

Background FPA150 is a fully human antibody against B7-H4 (a transmembrane protein of the B7 family) blocking negative regulatory function in T cells. FPA150 additionally exhibits enhanced antibody-dependent cell-mediated cytotoxicity and in vivo synergizes with anti-PD1 agents. We initiated a phase Ia/Ib evaluation of safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and activity in monotherapy (mono) and with anti-PD1 (combo). A current update of this ongoing trial is provided. Methods Trial design (see table).Table1198PTablePhasePatientsDesignDosesObjectiveStatus1aDose EscalationAdvanced solid tumorsAccelerated Titration; 3+3 escalation0.01-0.3mg/kg; 1-20mg/kgSafety, tolerability & PKComplete; recommended dose (RD) identifiedDose ExplorationB7-H4 + solid tumorsPre- and on-treatment biopsies (Bx)3mg/kg; 10mg/kgSafety, tolerability, PK & PDOngoing1a Combo Safety Lead-InB7-H4+ ovarian cancer3+3 De-escalationFPA150 at RD & 200mg pembrolizumab (pembro)Safety, tolerability, PK & RD FPA150Ongoing1b3 Mono cohortsB7-H4+ breast, ovarian & endometrialDose Expansion (Bx)20mg/kgSafety, tolerability, PD & efficacyOngoing1C1 ComboB7-H4+ ovarian cancerDose Expansion (Bx)200mg pembro & RD FPA150Safety, tolerability, PD & efficacyNot yet started Results At 3/15/2019 data snapshot, 29 pts with solid tumors (12 ovarian, 7 GI, 3 GYN, 3 head/neck, 2 GU, and 2 other) received FPA150 in dose escalation (n=21) and dose exploration (n=8). FPA150 demonstrated ∼ dose-proportional exposure at doses ≥0.3mg/kg and half-life of 1-2 weeks. To date, no dose-limiting toxicities, treatment-related serious adverse events or treatment-related adverse events (TRAEs) leading to drug discontinuation have been identified (1 Grade 3 TRAE of decreased lymphocyte count); others were Grade 1-2, with most common being diarrhea (16.7%), and fatigue (13.8%). Enrollment to phase Ib mono and phase Ia combo is ongoing. Expanded safety, PD and activity from phase Ib mono and phase Ia combo will be presented. Conclusions FPA150 RD for phase Ib mono identified as 20mg/kg (Sachdev, ASCO 2019). Mono appears well tolerated during dose escalation/exploration allowing evaluation in combination therapy. Sachdev, J et al. Phase Ia/1b study of first-in-class B7-H4 antibody, FPA150, as monotherapy in patients with advanced solid tumors. Proc Am. Soc. Clin. Oncol 2019. Clinical trial identification NCT03514121. Legal entity responsible for the study Five Prime Therapeutics, Inc. Funding Five Prime Therapeutics, Inc. Disclosure Z.A. Wainberg: Advisory / Consultancy: Bristol Meier Squibb; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Merck; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bayer. J.C. Sachdev: Honoraria (self): Celgene; Honoraria (self): Novartis; Honoraria (self): Puma Technology; Honoraria (self): Tempus; Honoraria (self): Ipsen; Advisory / Consultancy: Celgene; Research grant / Funding (institution): Celgene; Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy: Five Prime Therapeutics. T. Bauer: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, institution: Ignyta; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Guardant Health; Advisory / Consultancy, Research grant / Funding (institution): Loxo; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Self and institution: Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Moderna Therapeutics; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Medpacto; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): MabVax; Research grant / Funding (institution): Stemline Therapeutics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Glaxo Smith Kline; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Immunogen; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Merimack; Research grant / Funding (institution): Immunogen. S. Pant: Advisory / Consultancy: Mirati Therapeutics; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Red hill Biopharma Ltd; Advisory / Consultancy: Xencor; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Novartis; Advisory / Consultancy: Rgenix; Advisory / Consultancy: Sanofi-Aventis; Advisory / Consultancy: Arqule; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Onco Response; Advisory / Consultancy: Sanofi US Services Inc; Advisory / Consultancy: GlaxoSmith Kline; Speaker Bureau / Expert testimony: Tyme, Inc; Speaker Bureau / Expert testimony: 4-D Pharma. S. Chawla: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Threshold Pharmaceuticals; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: CytRx; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ignyta; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Immune Design; Honoraria (self), Speaker Bureau / Expert testimony: TRACON Pharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Karyopharm Therapeutics; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sarcoma Alliance for REsearch Through Collaboration; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen. N. Marina: Full / Part-time employment: Five Prime Therapeutics. H. Xiang: Full / Part-time employment: Five Prime Therapeutics. W. Deng: Full / Part-time employment: Five Prime Therapeutics. M. Schmidt: Full / Part-time employment: Five Prime Therapeutics. A. Patnaik: Advisory / Consultancy: Bayer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Bristo-Myers Squibb; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Plexxikon; Research grant / Funding (institution): Corvus Pharmaceuticals; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Forty-seven; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Infinity Pharmaceuticals; Research grant / Funding (institution): Proximagen; Research grant / Funding (institution): Pieris; Research grant / Funding (institution): Surface Oncology; Research grant / Funding (institution): Livson; Research grant / Funding (institution): Vigeo Therapeutics; Research grant / Funding (institution): Astella Pharma. P. LoRusso: Advisory / Consultancy: AbbVie; Advisory / Consultancy: Agios; Advisory / Consultancy: Alexion; Advisory / Consultancy: Ariad; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: GenMab; Advisory / Consultancy: Glenmark; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Menarini; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche-Genentech; Advisory / Consultancy: Genentech; Advisory / Consultancy: CytomX; Advisory / Consultancy: Omniox; Advisory / Consultancy: Ignyta; Advisory / Consultancy: Takeda; Advisory / Consultancy: SOTIO; Advisory / Consultancy: Cybrexa; Advisory / Consultancy: Agenus; Advisory / Consultancy: Tyme.

Appropriate periprocedural management of the hematologic parameters in a patient undergoing percutaneous image-guided intervention is highly complex, considering the wide range of procedures and patient demographics. This is further complicated by both the use of short-term and long-term anticoagulants and the increasing use of antiplatelet agents and other medications. Unfortunately, there is currently a general paucity of objective medical data regarding the periprocedural management of patients with abnormal coagulation parameters. In the absence of strong evidence regarding periprocedural management of this patient category, members of the Standards of Practice Committee of the Society of Interventional Radiology (SIR) have proposed general recommendations that may be useful to the practicing interventionalist. The various classes of medications that affect patient coagulation parameters were critically reviewed. When the evidence of literature was weak, conflicting, or contradictory, consensus for the parameter was reached by a minimum of 12 Standards of Practice Committee members by using a modified Delphi consensus method (1). For the purposes of these documents, consensus is defined as 80% Delphi participant agreement on a value or parameter. A time lapse of 5 half-lives of a particular agent (equivalent to about 3% of residual drug activity from the initial dose) is frequently used as a means of normalizing a patient’s bleeding risk (2,3). However, the use of laboratory coagulation thresholds is preferable, as half-lives may vary considerably in individual patients due to factors such as the potential presence of drug-drug interactions, idiosyncratic factors, differences in drug metabolism, or genetic influences. Additionally, the exact time point of drug discontinuation may be uncertain or unreliable. Nevertheless, when appropriate laboratory coagulation parameters are unavailable, disproportionally costly, or logistically cumbersome, the use of 5 halflives to normalize bleeding risk can be adequate. In this table formatted document, we summarize some of the current medications and available literature regarding periprocedural coagulation parameter surveillance and medical management of patients undergoing percutaneous image-guided procedures (Tables 1 and 2). Because of the lack of randomized controlled studies or other high-level evidence on this topic, a Delphi panel of experts constructed

Drug-induced liver injury (DILI) represents liver damage from various therapeutic drugs, herbal medicines, plants, or nutritional supplements. DILI is the most frequent reason for drug withdrawal and may lead to acute liver failure, liver transplant, or fatality. Its pathophysiology includes direct hepatotoxicity and idiosyncratic immune reactions. The diagnosis requires serum alanine aminotransferase or alkaline phosphatase elevation > 2-fold above the upper limit of normal, a causality assessment score ≥ 3, and exclusion of other possible causes of liver disease. While early diagnosis and drug discontinuation are imperative to recovery, continued drug exposure may lead to serious undesirable outcomes.

Psychotropic drugs are frequently used in both psychiatric and general medical practice. Familiarity with common side effects and their management may assist psychiatrists in the selection of agents to suit individual patient needs. The authors describe the morphologic features and pathologic basis of cutaneous reactions to drugs and discuss the common and reported cutaneous side effects of psychotropic drugs. Although most dermatologic reactions to drugs follow a benign course after drug discontinuation, more serious effects are known to occur with certain agents. An overview of the diagnosis and management of these adverse drug reactions is provided.

1. Benzodiazepines were discontinued in 16 patients who had recovered from panic disorder with agoraphobia after exposure treatment. 2. Drug discontinuation yielded a significant decrease in anxiety sensitivity and state anxiety in these long-term users. 3. Several likely explanations for the findings are discussed. 4. In the short term, treatment of panic disorder with benzodiazepines may lower anxiety symptoms. However, in the long run, it may decrease the individual tolerance to anxiety and discomfort.

Fibrosis stage was assessed by liver biopsy scores, FibroScan scores, or FibroTest scores. Post-treatment relapse shown through post-treatment week 12 for 3D+RBV arm and through post-treatment week 4 for TPV+pegIFN/RBV arm. Non-virologic treatment failure includes premature drug discontinuation and missing SVR data. *P-value ≤ 0.05 for the comparison with the TPV+pegIFN/RBV arm. For SVR4, P-value is based on logistic regression. Fisher's exact test was used for comparison of AE frequency.

Until 1994, rates of noncompliance for lipid-lowering therapies were largely drawn from clinical trials and showed favorable risks for drug discontinuation, ranging from 4–15% for 1-year risk to 11–30% for 5-year risk. Although cross-study comparisons are difficult to make because of variations in study design and measures collected, when evaluating compliance to antihyperlipidemic drugs in primary care settings, results in general show substantially higher rates of discontinuation than those reported from randomized clinical trials. Recent studies from the United States, Australia, and Canada support the conclusion that adherence to lipid-lowering drugs is very poor in primary care settings.

Reversible erectile dysfunction due to Topiramate has been linked to the effect of this antiepileptic drug on reproductive hormones levels. We described two epileptic male patients which experienced erectile dysfunction during Topiramate treatment. Serum sexual hormones were tested during treatment and at several time intervals following drug discontinuation. Topiramate did not seem to affect plasma levels of total, free and bioavailable testosterone and sex hormone-binding globulin. Since Topiramate erectile dysfunctions could not be related to changes in reproductive hormones levels, a vasogenic mechanism must be considered.

We present the case of a never medicated patient with a diagnosis of DSM-IV paranoid schizophrenia in which olanzapine therapy induced manic symptoms. The latter remitted after drug discontinuation.

Summary We assessed the length and the quality of remission of 13 unipolar endogenous depressed patients, DST non-suppressors before treatment, in a 2-year prospective study. During this period, we recorded stressful life events. Persistent dexamethasone non-suppression, after treatment and complete clinical recovery, correlated highly with early clinical relapse. All six non-normalizers but only one normalizer were rehospitalized within the following 2 years for a major depressive relapse. Persistent DST non-suppression was unrelated to any impact of drug discontinuation, the occurrence of stressful life events or the length of illness-free intervals in the patient’s prior course of illness. Persistent DST non-suppression appears to have significant prognostic value.

Guidelines for the discontinuation of antiepileptic drugs in neonatal seizures are not well defined. Some studies suggested possible criteria for antiepileptic drug discontinuation but no precise criteria have emerged. We performed a retrospective analysis of 58 infants with neonatal seizures during a 3 year period. Antiepileptic drugs were discontinued when patients were seizure-free for 3 months, had normal electroencephalography initially or at subsequent examination, and had a nonfocal examination. Normal initial electroencephalography was demonstrated to be a reliable predictor for discontinuing antiepileptic drugs successfully in 18 of 22 term infants; normal subsequent electroencephalography was a reliable predictor of successful discontinuation of antiepileptic drugs in 9 of 10 premature infants.

Four cases of amiodarone neuropathy are reported. Patients presented a sensorimotor neuropathy with distal predominance. Improvement occurred after drug discontinuation. Nerve conduction velocities were significantly decreased. Other secondary effects of amiodarone were noted in two cases. In one case serum levels of amiodarone and N-monodesethylamiodarone were evaluated during and after treatment. Pathological study of nerve with morphometric evaluation was performed. Axonal degeneration changes were predominant in 3 cases. Aspects of segmental demyelination and remyelination were noted in one case and related to secondary demyelination. Numerous lysosomal inclusions were present in Schwann cells, fibroblasts, capillary endothelial and perithelial cells and in perineural cells. Similar inclusions have been observed in other drug-induced lipidosis. The factors responsible for this neuropathy are unknown. In one case, amiodarone-induced hepatic failure might explain the persisting high serum levels of the drug.