Bevacizumab Does Not Influence the Efficacy of Partial Splenic Embolization in the Management of Chemotherapy-Induced Hypersplenism.

Clin Colorectal Cancer. 2020 Jun 12;:

Authors: Jácome AA, Ohinata A, Mahvash A, Overman MJ, Kee B, Fogelman D, Morris VK, Johnson B, Rothschild ND, Wolff RA, Eng C

Abstract
BACKGROUND: Antiangiogenics attenuate chemotherapy-related hepatotoxicity and portal hypertension. The potential impact of bevacizumab on the efficacy and safety of partial splenic embolization (PSE) in the management of chemotherapy-induced hypersplenism (CIH) has never been investigated.
PATIENTS AND METHODS: We conducted a retrospective study with gastrointestinal cancer patients who have undergone PSE for the treatment of thrombocytopenia resulting from hypersplenism. Pre- and post-PSE platelet count (PC), the percentage of patients who resumed systemic therapy, and complication rates were compared between patients exposed and not exposed to bevacizumab.
RESULTS: A total of 110 patients were eligible. Colorectal cancer was the predominant neoplasm (60%), and 5-fluorouracil, oxaliplatin, and bevacizumab were the most commonly provided drugs (70%, 65%, and 65% of patients, respectively). After PSE, 80% of patients recovered PC ≥ 100 × 109/L (100K). Systemic therapy was resumed in 81% of patients. Seventy-one patients exposed to bevacizumab had a median PC before PSE of 77.5K and after PSE of 167.0K, with a mean difference of 108K (P < .0001). Thirty-nine patients not exposed to bevacizumab had a median PC of pre-PSE of 73.0K and post-PSE of 187.0K, with a mean difference of 117.7K (P < .0001). Both groups had similar values of percentages of patients with PC post-PSE ≥ 100K (83% vs. 74%; P = .463), resumption of systemic therapy (85% vs. 74%; P = .213), and complication rates. A linear association between splenic infarction rate and increment in PC was found (P < .0001).
CONCLUSION: PSE is a safe and effective procedure in the management of CIH, regardless of the provision of bevacizumab. Splenic infarction rate should be optimized to enhance patient outcomes.

PMID: 32680816 [PubMed - as supplied by publisher]

Nivolumab plus Ipilimumab versus Existing Immunotherapies in Patients with PD-L1-Positive Advanced Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.

Cancers (Basel). 2020 Jul 15;12(7):

Authors: Ando K, Kishino Y, Homma T, Kusumoto S, Yamaoka T, Tanaka A, Ohmori T, Ohnishi T, Sagara H

Abstract
No head-to-head trials have compared the efficacy and safety of nivolumab (Niv) plus ipilimumab (Ipi) combination therapy (Niv+Ipi) and existing regimens with immunotherapies approved as first-line treatment in patients with programmed cell death ligand 1 (PD-L1)-positive previously untreated advanced non-small cell lung cancer (NSCLC). We conducted a network meta-analysis of four relevant Phase Ⅲ trials to compare the efficacy and safety of Niv+Ipi, pembrolizumab (Pem) plus platinum-based chemotherapy (PBC) (Pem+PBC), Pem, Niv, or PBC using Bayesian analysis. The primary efficacy endpoint was progression-free survival (PFS) in patients with advanced NSCLC with PD-L1 expression ≥1%. The primary safety endpoint was the incidence of Grade 3-5 drug-related adverse events (G3-5AEs). Efficacy and safety were ranked using surface under the cumulative ranking curve (SUCRA). With regard to PFS, Niv+Ipi was inferior to Pem+PBC, and superior to Pem, Niv, or PBC alone. SUCRA ranking showed Pem+PBC had the highest efficacy for PFS, followed by Niv+Ipi, Niv, PBC, and Pem. The safety outcome analysis revealed Niv+Ipi was generally well tolerated compared to existing immunotherapy regimens. These results provide clinical information regarding the efficacy and safety of Niv+Ipi and indicate the possibility of the Niv+Ipi combination as a new therapeutic option in PD-L1-positive advanced NSCLC.

PMID: 32679702 [PubMed - as supplied by publisher]

Durable Suppression and Low Rate of Virologic Failure 3 Years After Switch to Dolutegravir + Rilpivirine 2-Drug Regimen: 148-Week Results From the SWORD-1 and -2 Randomized Clinical Trials.

J Acquir Immune Defic Syndr. 2020 Jul 13;:

Authors: van Wyk J, Orkin C, Rubio R, Bogner J, Baker D, Khuong-Josses MA, Parks D, Angelis K, Kahl LP, Matthews J, Wang R, Underwood M, Wynne B, Nascimento MC, Vandermeulen K, Gartland M, Smith KY

Abstract
BACKGROUND: The SWORD trials showed that in participants who achieved virologic suppression taking 3- or 4-drug regimens, switching to the 2-drug regimen dolutegravir plus rilpivirine was non-inferior in maintaining HIV-1 RNA <50 copies/mL at the Week 48 primary endpoint. We present pooled Week 148 analysis results from both studies.
SETTING: SWORD-1: 65 centers, 13 countries; SWORD-2: 60 centers, 11 countries.
METHODS: SWORD-1 and SWORD-2 are identical, open-label, phase III studies. Participants with screening HIV-1 RNA <50 copies/mL for ≥6 months; no prior virologic failure; and no documented resistance-associated major PI, INI, NRTI, or NNRTI mutations or integrase resistance-associated substitution R263K were randomly assigned 1:1 to switch to once-daily dolutegravir 50 mg plus rilpivirine 25 mg on Day 1 (Early-Switch group) or to continue their current antiretroviral regimen and, if virologically suppressed at Week 48, switch to dolutegravir plus rilpivirine at Week 52 (Late-Switch group) until Week 148.
RESULTS: Using Snapshot algorithm at Week 148, 432/513 (84%) Early-Switch participants (148 weeks of exposure) and 428/477 (90%) Late-Switch participants (96 weeks of exposure) maintained HIV-1 RNA <50 copies/mL. Eleven participants (1%) on dolutegravir plus rilpivirine met the confirmed virologic withdrawal criterion through Week 148 (Early-Switch group, n=8; Late-Switch group, n=3) with no integrase resistance identified. NNRTI resistance-associated mutations were identified in 6 participants (<1%). Drug-related adverse events (grades 2-4) were observed in 31 (6%) Early-Switch and 16 (3%) Late-Switch participants. Significant improvements in bone biomarkers were observed. Significant improvements were observed in renal biomarkers in participants taking tenofovir disoproxil fumarate pre-switch.
CONCLUSION: Switching to the 2-drug regimen dolutegravir plus rilpivirine maintained virologic suppression for a high proportion of participants through 3 years, with low rates of virologic failure and a well-tolerated safety profile.

PMID: 32675772 [PubMed - as supplied by publisher]

Predictors of Time to Discontinuation of Levodopa-Carbidopa Intestinal Gel Infusion: A Retrospective Cohort Study.

J Parkinsons Dis. 2020 Jul 15;:

Authors: Moes H, Groenendal-Laurensse J, Drent M, Tissingh G, van Laar T

Abstract
BACKGROUND: Continuous intra-duodenal infusion of levodopa-carbidopa intestinal gel (LCIG) is a well-established therapy for patients with advanced Parkinson's disease (PD) suffering from motor complications despite optimized treatment with oral dopaminomimetics. However, time to discontinuation of treatment with LCIG varies considerably between patients, ranging from a few months to more than ten years. To improve the selection of candidates for LCIG, knowledge of prognostic factors is of paramount importance.
OBJECTIVE: To explore baseline predictors of time to discontinuation of LCIG.
METHODS: In this two-center retrospective cohort study, we reviewed the medical files of 98 PD patients treated with LCIG between April 2006 and December 2015 (53% male; mean age: 66.2 years; mean disease duration: 12.3 years). Baseline patient characteristics were used as covariates in Cox regression models.
RESULTS: During follow-up (mean observation time: 2.6 years; range: 0.1-9.3) eighteen patients discontinued treatment (18.4%), while seven patients died (7.1%). Median duration of treatment with LCIG, estimated with Kaplan-Meier analysis, was 7.8 years (95% CI: 6.7-9.0). Disease duration (in years) at baseline was a statistically significant predictor of time to discontinuation of LCIG (HR: 0.85; 95% CI: 0.75-0.96, p = 0.006). All other characteristics studied, e.g. age >70 years, did not show statistically significant associations with the total duration of treatment with LCIG.
CONCLUSION: Our findings show a low overall rate of discontinuation of LCIG infusion, with a median duration of treatment of 7.8 years. Shorter disease duration at baseline appeared to be a predictor of earlier discontinuation of LCIG.

PMID: 32675420 [PubMed - as supplied by publisher]

Characteristics and circumstances of death related to new psychoactive stimulants and hallucinogens in Australia.

Drug Alcohol Depend. 2019 11 01;204:107556

Authors: Darke S, Duflou J, Peacock A, Farrell M, Lappin J

Abstract
BACKGROUND: New psychoactive stimulants and hallucinogens comprise a range of "designer drugs" that have risen to prominence in the 21st century. The study aimed to: 1. Determine the characteristics, and circumstances of death, of all recorded cases of new psychoactive stimulant and hallucinogen-related death in Australia; 2. Determine the toxicology of such deaths; and 3. Determine the major organ pathology of cases.
METHODS: All cases in which new psychoactive stimulants were a mechanism contributory to death were retrieved from the National Coronial Information System (2000-2017). Information was collected on cause of death, demographics, drug use history, circumstances of death, toxicology and major organ pathology.
RESULTS: 82 cases were identified. The mean age was 30.7yrs and 86.6% were male. Circumstances of death were: accidental drug toxicity (59.8%), traumatic accident (15.9%), suicide (12.2%) and natural disease (2.4%). The most common clinical presentation observed proximal to death was delirium (26.8%). Delirium was mostly frequently observed after phenethylamine consumption (72.2%). The most common cardiovascular diagnosis at autopsy was replacement fibrosis, indicative of previous ischemia (10.5%). New psychoactive stimulants and hallucinogens detected in toxicology were: cathinones (75.7%), phenethylamines (22.0%) and piperazines (6.1%). Other substances were present in 83.5% of cases, most commonly established controlled psychostimulants (58.2%).
CONCLUSIONS: Acute toxicity was the most common cause of death, but more than a third of deaths were due to trauma. Cathinones were the most commonly detected of the new psychoactive stimulants and hallucinogens. Delirium was the most frequently reported clinical sign proximal to death and was strongly associated with the phenethylamines.

PMID: 31546120 [PubMed - indexed for MEDLINE]

Effectiveness and Safety of Anti-Tumor Necrosis Factor-Alpha Agents Treatment in Behcets' Disease-Associated Uveitis: A Systematic Review and Meta-Analysis.

Front Pharmacol. 2020;11:941

Authors: Hu Y, Huang Z, Yang S, Chen X, Su W, Liang D

Abstract
Purpose: We conducted a systematic review and meta-analysis to determine the effectiveness and safety of anti-tumor necrosis factor-alpha (TNF-α) agents in the treatment of Behcets' disease (BD)-associated uveitis.
Method: Three electronic databases, Embase, MEDLINE, and the Cochrane Library, were searched for eligible papers focusing on the anti-TNF-α agents treatment in BD-associated uveitis with at least 6 months follow-up time. A systematic review and meta-analysis was conducted on selected papers with appropriate clinical and methodological homogeneity. The effectiveness outcomes included inflammation remission, visual acuity (VA) improvement, central macular thickness (CMT) decrease, corticosteroid (CS)-sparing effects, and the safety outcomes included minor and severe drug-related adverse events (AEs).
Result: From Jan 2010 to Dec 2019, there were 504 records produced in total, in which 18 clinical trials were selected for meta-analysis (15 trials were retrospective studies, and 3 were prospective studies). The number of patients in each study ranged from 11 to 163 and the mean follow-up time from 0.9 to 6.44 years. During the follow-up, the pooled inflammation remission rate was 68% with a 95% confidence interval (CI) of 0.59-0.79, VA improvement rate was 60% (95% CI 0.47-0.77), CMT decrease was 112.70 μm (95% CI 72.8-153.0 μm). The proportions of patients who had CS-suspended and CS-tapered reached 38% (95% CI 0.23-0.65) and 34% (95% CI 0.16-0.70), respectively. The severe AEs were reported but not common, which included severe infusion reactions, pneumonia, bacteremia, tuberculosis, melanoma, and lymphoma.
Conclusion: Anti-TNF-α agents treatment has high effectiveness including efficient inflammation remission, satisfactory VA improvement, obvious CMT reduction, and significant CS-sparing effects. Although some drug-related AEs were reported, the incidence of severe AEs was acceptable. Anti-TNF-α agents treatment is a promising option for controlling BD-associated uveitis.

PMID: 32670062 [PubMed]

An Ex Vivo Study to Evaluate the Effect of Tegaserod on Platelet Activation and Aggregation.

J Cardiovasc Pharmacol Ther. 2020 Jul 16;:1074248420942004

Authors: Gurbel PA, Bliden K, Barnett SD, Witt C, Zou H, Tantry U

Abstract
INTRODUCTION: Tegaserod, an orally active, potent 5-hydroxytryptamine-4 serotonin receptor agonist, was previously indicated for irritable bowel syndrome but was voluntarily withdrawn due to potential cardiovascular side effects. In vitro studies suggested that tegaserod increased platelet aggregation, but these results were not reproduced or were inconclusive. We sought to assess ex vivo effects of tegaserod on platelet aggregation.
METHODS: In this double-blind, placebo-controlled, crossover study, we randomized a majority of healthy patients with no history of cardiovascular risk factors (n = 21) to receive tegaserod or matching placebo for 7 + 2 days followed by a 7- to 10-day washout period, and then patients were crossed over to the other study drug for the next 7 + 2 days. Unstimulated and agonist-stimulated platelet aggregation; P-selectin expression; serum thromboxane (Tx)B2 and urinary 11-dehydro (11-dh) TxB2; and tegaserod and M29.0 concentrations were serially assessed.
RESULTS: There was no significant difference in percentage change in unstimulated or adenosine diphosphate (ADP)- and ADP + serotonin-, collagen- and thrombin receptor activating peptide-induced maximum platelet aggregation and in platelet P-selectin expression in the presence of tegaserod at any time point when compared to placebo. Similarly, there was no significant difference in percentage change in serum TxB2 or urinary 11-dhTxB2 levels between placebo and tegaserod. No new or unexpected findings were observed in evaluations of safety or pharmacokinetic parameters.
CONCLUSION: This comprehensive pharmacodynamic study, by employing established markers used in prior investigations, which have been considered by the Food and Drug Administration to indicate drug-related platelet effects, does not demonstrate any influence of tegaserod treatment on platelet function.

PMID: 32672062 [PubMed - as supplied by publisher]

Hepatotoxicty of Agents Used in the Management of Inflammatory Bowel Disease: a 2020 Update.

Curr Gastroenterol Rep. 2020 Jul 15;22(9):47

Authors: Barnhill MS, Steinberg JM, Jennings JJ, Lewis JH

Abstract
PURPOSE OF REVIEW: As treatment options for inflammatory bowel disease (IBD) continue to expand, the opportunity for hepatotoxicity remains a clinical concern. This review looks to update the current literature on drug-induced liver injury (DILI) and liver-related complications from current and emerging treatments for Crohn's disease (CD) and ulcerative colitis (UC).
RECENT FINDINGS: An extensive literature review on currently used medications to treat IBD and their liver-related side effects that includes mesalamine, thiopurines, certain antibiotics, methotrexate, anti-TNF agents including recently introduced biosimilars, anti-integrin therapy, anti-IL 12/IL 23 therapy, and small molecule JAK inhibitors. Hepatotoxicity remains an important clinical issue when managing patients with IBD. Clinicians need to remain aware of the potential for liver-related adverse events with various medication classes and adjust their clinical monitoring as appropriate based on the agents being used.

PMID: 32671616 [PubMed - in process]

Imaging of Novel Oncologic Treatments in Lung Cancer Part 1: Systemic Therapies.

J Thorac Imaging. 2020 Jan;35(1):26-36

Authors: Halpenny D, O'Dwyer E, Girshman J, Ginsberg MS

Abstract
Thoracic tumors are a leading cause of cancer-related morbidity and mortality. In recent years, developments in oncologic treatments for these tumors have ushered in an era of targeted therapy, and, in many cases, these novel treatments have replaced conventional strategies to become standard therapeutic options, particularly in those with lung cancer. Targeted medical therapies for lung cancer now include angiogenesis inhibitors, tyrosine kinase inhibitors, and immunotherapeutic agents. Several novel ablative therapies have also gained widespread acceptance as alternatives to conventional surgical options in appropriately selected patients. Tumors treated with targeted medical therapies can respond to treatment differently when compared with conventional therapies. For example, pseudoprogression is a well-described phenomenon in patients receiving checkpoint inhibitor immunotherapy in which an initial increase in tumor burden is followed by a decrease in tumor burden and sometimes partial or complete response, while the frequent cavitating responses seen when antiangiogenic agents are used can be difficult to quantify using existing response assessment criteria. In some cases, novel response assessment criteria are needed to adequately capture response. In addition, numerous treatment-related side effects have been described, which are important to recognize, both to ensure appropriate treatment and to avoid misclassification as worsening tumor. Imaging plays a vital role in the assessment of patients receiving targeted medical therapy, and it is essential that thoracic radiologists are familiar with the rationale underpinning these treatments and the expected posttherapy findings.

PMID: 31855947 [PubMed - indexed for MEDLINE]

Deferred treatment with a fixed-dose combination of sofosbuvir-velpatasvir for chronic hepatitis C virus genotype 1, 2, 4 and 6 infection.

J Viral Hepat. 2019 10;26(10):1229-1232

Authors: Asselah T, Shafran SD, Bourgeois S, Lai CL, Mathurin P, Willems B, Nguyen MH, Davis MN, Huang KC, Svarovskaia E, Osinusi A, McNally J, Brainard DM, Shaikh OS, Tran TT

Abstract
Sofosbuvir-velpatasvir is approved for the treatment of chronic hepatitis C virus (HCV) infection. In this single-arm, open-label, phase 3, deferred treatment study, we investigated the efficacy and safety of sofosbuvir-velpatasvir among patients randomized to the placebo group in the ASTRAL-1 study. Patients received sofosbuvir-velpatasvir (400/100 mg) once daily for 12 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response 12 weeks after the end of therapy (SVR12). The primary safety endpoint was any adverse events (AEs) leading to the permanent discontinuation of study drug. Overall, 108/111 (97%, 95% confidence interval [CI], 92%-99%) achieved SVR12, and only one patient had virological failure. SVR12 was achieved by 61/63 (97%, 95%CI, 89%-100%) genotype 1 patients, 20/20 (100%; 95%CI, 83%-100%) with genotype 2, 19/19 (100%; 95%CI, 82%-100%) with genotype 4 and 8/9 (89%; 95% CI, 52%-100%) with genotype 6. All (19/19; 95%CI, 82-100) patients with cirrhosis and all (31/31, 95%CI, 89-100) with prior treatment experience achieved SVR12. The safety profile during treatment was similar to that observed in patients receiving placebo treatment. The most common AEs were headache, fatigue and nausea. One patient (1%) discontinued treatment due to an AE of gallbladder carcinoma, which was not considered related to treatment. Of five reported serious AEs, none were considered related to study drug. Sofosbuvir-velpatasvir for 12 weeks was effective and well tolerated among untreated and previously treated patients with HCV genotype 1, 2, 4 or 6 infection, including those with compensated cirrhosis (ClinicalTrials.gov NCT02346721).

PMID: 31216086 [PubMed - indexed for MEDLINE]

A Review of Factors Influencing the Three Phases of Medication Adherence in People with Attention-Deficit/Hyperactivity Disorder.

J Child Adolesc Psychopharmacol. 2019 08;29(6):398-418

Authors: Khan MU, Aslani P

Abstract
Objectives: Factors affecting adherence to medications in people with attention-deficit/hyperactivity disorder (ADHD) are not well understood in the context of their influence on the different phases of adherence, that is, initiation, implementation, and discontinuation. This review aimed to identify the factors affecting the three phases of medication adherence in people with ADHD. Methods: Six electronic databases, including Medline, PubMed, IPA, CINAHL, Embase, and PsycINFO, were systematically searched from inception through October 2018 with the limitations of English language and human studies. The search strategy was based on three concepts (adherence, ADHD, and factors) and their relevant terminologies. Results: Considerable variability was observed with regards to the criteria used to define adherence in identified studies (n = 48). Most studies focused on the implementation phase of adherence (n = 27), while only a handful focused on the initiation (n = 6) and discontinuation (n = 5) phase of adherence. The remaining studies (n = 10) examined multiple phases of adherence. Conflicting information received about medication, medication frequency, and fears of medication's effect on growth were the unique factors impacting initiation, implementation, and discontinuation, respectively. Moreover, factors within each phase of adherence also differed with different populations such as parents, children, adolescents, and adults. Fear of addiction, medication effectiveness, psychiatric comorbidity, and medication side effects were the most common factors identified in all three phases of adherence. Conclusions: This review found some unique factors in each phase of adherence while some overlap was also noted. Future interventions to improve adherence should be phase- and group specific rather than consider adherence as a single variable.

PMID: 31120328 [PubMed - indexed for MEDLINE]

Management of Immunotherapy-Related Toxicities, Version 1.2019.

J Natl Compr Canc Netw. 2019 03 01;17(3):255-289

Authors: Thompson JA, Schneider BJ, Brahmer J, Andrews S, Armand P, Bhatia S, Budde LE, Costa L, Davies M, Dunnington D, Ernstoff MS, Frigault M, Hoffner B, Hoimes CJ, Lacouture M, Locke F, Lunning M, Mohindra NA, Naidoo J, Olszanski AJ, Oluwole O, Patel SP, Reddy S, Ryder M, Santomasso B, Shofer S, Sosman JA, Wahidi M, Wang Y, Johnson-Chilla A, Scavone JL

Abstract
The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions and ASCO, consisting of medical and hematologic oncologists with expertise in a wide array of disease sites, and experts from the fields of dermatology, gastroenterology, neuro-oncology, nephrology, emergency medicine, cardiology, oncology nursing, and patient advocacy. Several panel representatives are members of the Society for Immunotherapy of Cancer (SITC). The initial version of the NCCN Guidelines was designed in general alignment with recommendations published by ASCO and SITC. The content featured in this issue is an excerpt of the recommendations for managing toxicity related to immune checkpoint blockade and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to chimeric antigen receptor T-cell therapy, visit NCCN.org.

PMID: 30865922 [PubMed - indexed for MEDLINE]

Adverse Event extraction from Structured Product Labels using the Event-based Text-mining of Health Electronic Records (ETHER) system.

Health Informatics J. 2019 12;25(4):1232-1243

Authors: Pandey A, Kreimeyer K, Foster M, Dang O, Ly T, Wang W, Forshee R, Botsis T

Abstract
Structured Product Labels follow an XML-based document markup standard approved by the Health Level Seven organization and adopted by the US Food and Drug Administration as a mechanism for exchanging medical products information. Their current organization makes their secondary use rather challenging. We used the Side Effect Resource database and DailyMed to generate a comparison dataset of 1159 Structured Product Labels. We processed the Adverse Reaction section of these Structured Product Labels with the Event-based Text-mining of Health Electronic Records system and evaluated its ability to extract and encode Adverse Event terms to Medical Dictionary for Regulatory Activities Preferred Terms. A small sample of 100 labels was then selected for further analysis. Of the 100 labels, Event-based Text-mining of Health Electronic Records achieved a precision and recall of 81 percent and 92 percent, respectively. This study demonstrated Event-based Text-mining of Health Electronic Record's ability to extract and encode Adverse Event terms from Structured Product Labels which may potentially support multiple pharmacoepidemiological tasks.

PMID: 29359620 [PubMed - indexed for MEDLINE]

Community-level electronic prescribing and adverse drug event hospitalizations among older adults.

Health Informatics J. 2019 09;25(3):661-675

Authors: Bhavsar GP, Probst JC, Bennett KJ, Hardin JW, Qureshi Z

Abstract
This study sought to determine how the proportion of physicians using electronic prescribing in nine US states was associated with the hospitalization rate for adverse drug events among older adult patients. A discharge-level analysis of the relationship between county electronic prescribing and adverse drug event hospitalization rates was conducted. Data from the 2011 State Inpatient Databases, the Office of the National Coordinator Health IT Dashboard, and the Area Health Resource File were obtained for nine US states. The analysis examined the odds that a discharge for older adults would have been adverse drug event associated, versus other causes, using multivariable logistic regression models. After adjusting for patient, provider, health infrastructure, and community factors, the lowest county electronic prescribing rate quartile was associated with significantly greater odds of an adverse drug event hospitalization (odds ratio: 1.10; 95% confidence interval: 1.02-1.19). Early results indicate greater odds of adverse drug event hospitalizations among older adults living in counties with low electronic prescribing rates when compared to those in high electronic prescribing counties.

PMID: 28737062 [PubMed - indexed for MEDLINE]

Clinical impact of vonoprazan-based dual therapy with amoxicillin for H. pylori infection in a treatment-naïve cohort of junior high school students in Japan.

J Gastroenterol. 2020 Jul 14;:

Authors: Gotoda T, Kusano C, Suzuki S, Horii T, Ichijima R, Ikehara H

Abstract
BACKGROUND: Although 7-day triple therapy, consisting of vonoprazan, amoxicillin (AMO), and clarithromycin (CLA), is recommended for Helicobacter pylori (H. pylori) eradication in adults. However, the importance of reducing antibiotic use in pediatric patients is well recognized. Therefore, our aim was to compare the effectiveness and safety of vonoprazan and AMO (VA) dual therapy to vonoprazan-based (VAC) triple therapy for H. pylori eradication in a cohort of treatment-naïve junior high school students in Japan.
METHODS: This was a prospective observational study of second-year junior high-school students in Yurihonjo and Nikaho Cities, Japan. Between 2015 and 2017, 161 students were treated with VAC-triple therapy (20 mg vonoprazan, 750 mg AMO, and 200 mg CLA, twice a day for 7 days), while 60 students were treated with VA-dual therapy (20 mg vonoprazan and 750 mg AMO, twice a day for 7 days) since 2018. The success rate of H. pylori eradication and drug-related adverse events were compared between the two therapy groups. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed.
RESULTS: Groups were comparable at baseline. The ITT and PP eradication rates were 85.0% (95% confidence interval [CI] 75.8-94.2%) and 86.4% (95% CI 77.4-95.5%), respectively, with VA-dual therapy and 82.0% (95% CI 76.0%-87.9%) and 84.1% (95% CI 78.3-89.8%), respectively, with VAC-triple therapy. VA-dual therapy was non-inferior to VAC-triple therapy (ITT, p = 0.018; PP, p = 0.020). The adverse event rate was 10.0% with VA-dual therapy and 19.8% with VAC-triple therapy (p = 0.108).
CONCLUSIONS: The effectiveness of VA-dual therapy was comparable to that of VAC-triple therapy in H. pylori treatment-naïve junior high school students, while reducing the use of antibiotics.

PMID: 32666199 [PubMed - as supplied by publisher]

Lisinopril-Induced Liver Injury: An Unusual Presentation and Literature Review.

Eur J Case Rep Intern Med. 2020;7(7):001600

Authors: Al-Rifaie A, Khan MA, Ali A, Dube AK, Gleeson D, Hoeroldt B

Abstract
Lisinopril is an angiotensin converting enzyme inhibitor (ACE-I) that has been on market for more than 25 years. ACE-I are usually well tolerated and rarely have serious or life-threatening side effects. We describe an unusual presentation of fulminant hepatic cholestasis probably secondary to lisinopril. To our knowledge, this is the second case report which shows lisinopril-induced liver injury though a cholestatic mechanism. The patient was a 59-year-old woman with type 2 diabetes, a high body mass index and hypertension, who presented with a 5-week history of jaundice and itching. She had been started on lisinopril for diabetic nephropathy 8 weeks before admission. Other causes for cholestasis had been excluded through non-invasive immunology and virology screening, an ultrasound of the liver, magnetic resonance cholangiopancreatography and a liver biopsy. The biopsy was consistent with drug-induced liver injury. Lisinopril was stopped 2 weeks before admission. The patient's hospital stay was complicated by contrast nephropathy and influenza A which were both treated appropriately. Unfortunately, the liver cholestasis did not completely resolve following withdrawal of lisinopril and the patient died after 4 months. A literature search yielded only six other reported cases of lisinopril-induced liver injury. Five cases described hepatocellular damage and one showed cholestatic injury.
LEARNING POINTS: Angiotensin converting enzyme inhibitors (ACE-I) rarely have serious or life-threatening side effects.Lisinopril-induced liver injury can present as hepatocellular or cholestatic injury.Severe hepatotoxicity secondary to lisinopril can be life threatening irrespective of the liver injury pattern.

PMID: 32665926 [PubMed]

Acute Renal Failure in a Patient with Rivaroxaban-Induced Hypersensitivity Syndrome: A Case Report with a Review of the Literature and of Pharmacovigilance Registries.

Case Rep Nephrol. 2020;2020:6940183

Authors: Marcelino G, Hemett OM, Descombes E

Abstract
Direct oral anticoagulants (DOACs) are among the most commonly prescribed medications, and DOAC-associated kidney dysfunction may be a problem that is underrecognized by clinicians. We report on the case of an 82-year-old patient who, two weeks after the prescription of rivaroxaban for atrial fibrillation, was hospitalized for a drug-induced hypersensitivity syndrome whose main clinical manifestations were low-grade fever with a petechial rash in the legs and acute renal failure (ARF). Within one week after rivaroxaban withdrawal, the patient's clinical condition improved and the renal function normalized. In a review of the literature, we only found five case reports of rivaroxaban-related ARF: two patients had tubulo-interstitial nephritis (TIN), two had anticoagulant-related nephropathy (ARN), and the last one had IgA nephropathy. As some recent publications suggest that kidney injury due to anticoagulation drugs may be largely underdiagnosed, we also analyzed the data from the VigiAccess database, the World Health Organization pharmacovigilance program that collects drug-related adverse events from 134 national registries worldwide. Among all the rivaroxaban-associated adverse events reported in VigiAccess since 2006, 4,323 (3.5%) were renal side effects, of which 2,351 (54.3%) were due to unspecified ARF, 363 (8.4%) were due to renal hemorrhage (characteristically associated with ARN), and 24 (0.6%) were due to TIN. We also compared these results with those reported in VigiAccess for other DOACs and vitamin K antagonists. This analysis suggests that the frequency of renal adverse events associated with rivaroxaban and other DOACs may be appreciably higher than what one might currently consider based only on the small number of fully published cases.

PMID: 32665869 [PubMed]

Oral immunotherapy for treatment of peanut allergy.

J Investig Med. 2020 Jul 14;:

Authors: Dunlop JH

Abstract
The US Food and Drug Administration's approval of a peanut oral immunotherapy product in January 2020 is a landmark development in the field of food allergy therapy. While food allergy prevalence has been increasing, this product is the first approved therapy for food allergy. Oral immunotherapy has many similarities to subcutaneous immunotherapy and drug desensitization protocols, but does not lead to sustained unresponsiveness. The studies leading to approval of the Palforzia product demonstrated increase in the amount of peanut protein able to be consumed, with 67% of subjects randomized to the treatment arm able to consume 600 mg of peanut protein in double-blind placebo-controlled food challenge at study exit. However, side effects are an important consideration, and dropout rates in studies of Palforzia ranged from 11% to 21%. Postmarketing surveillance of this product will be critical in assessing its long-term risks and benefits.

PMID: 32665367 [PubMed - as supplied by publisher]

FAS and FASL variations in outcomes of tobacco- and alcohol-related head and neck squamous cell carcinoma patients.

Tumour Biol. 2020 Jul;42(7):1010428320938494

Authors: Costa EFD, Lima TRP, Lopes-Aguiar L, Nogueira GAS, Visacri MB, Quintanilha JCF, Pincinato EC, Calonga L, Mariano FV, Altemani AMAM, Altemani JMC, Moriel P, Chone CT, Ramos CD, Lima CSP

Abstract
Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher's exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42-21.43), 4.03 (95% CI: 1.51-10.79), and 5.77 (95% CI: 1.23-27.04) more chances of presenting chemoradiation-related anemia of grades 2-4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.

PMID: 32628088 [PubMed - indexed for MEDLINE]

HERBALIFE® ASSOCIATED SEVERE HEPATOTOXICITY IN A PREVIOUSLY HEALTHY WOMAN.

Acta Clin Croat. 2019 Dec;58(4):771-776

Authors: Jurčić D, Gabrić M, Troskot Perić R, Liberati Pršo AM, Mirat J, Včev A, Alerić I, Ebling B

Abstract
Lately there has been an increased consumption of herbal preparations, distributed as nutritional supplements, often claimed to be 'natural' and harmless. However, as their use is not subjected to strict pre-marketing testing and regulations, their ingredients are not clearly defined and there is no quality control or proof of their effectiveness and safety. A growing body of references accentuate their harmful effects, in particular hepatotoxicity, which varies from minimal hepatogram changes to fulminant hepatitis requiring liver transplantation. This case report describes liver damage that was highly suspected to originate from Herbalife® products consumption. We excluded alcohol, viral, metabolic, autoimmune and neoplastic causes of liver lesions, as well as vascular liver disease, but we noticed a connection between the use of Herbalife® products and liver damage. The exact mechanism of liver damage in our patient was not determined. After removing the Herbalife® products, liver damage resolved and there was no need to perform liver biopsy. Taking into consideration the growing consumption of herbal products and their potential harmfulness, we consider that more strict regulations of their production process and sale are necessary, including exact identification of active substances with a list of ingredients, toxicologic testing and obligatory side effect report.

PMID: 32595263 [PubMed - indexed for MEDLINE]