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

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

These pubmed results were generated on 2020/09/22

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Efficacy and Safety of Capecitabine Alone or in Combination in Advanced Metastatic Breast Cancer Patients Previously Treated with Anthracycline and Taxane: A Systematic Review and Meta-Analysis.

Oncol Res Treat. 2020 Sep 18;:1-9

Authors: Alsaloumi L, Shawagfeh S, Abdi A, Basgut B

Abstract
BACKGROUND: Capecitabine is frequently used alone or combined with other chemotherapy agents for the treatment of metastatic breast cancer in relapsed patients.
OBJECTIVE: The objective of this meta-analysis is to evaluate the effectiveness and safety of capecitabine monotherapy versus combination in the treatment of metastatic breast cancer patients pretreated with anthracycline and taxane.
METHODS: Eligible randomized controlled trials examining the efficacy and safety of capecitabine alone compared to capecitabine combination were systematically searched. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grades 3-4 drug-related adverse events were the outcomes assessed.
RESULTS: A total of 6,714 patients of 9 trials were involved in the pooled analysis. Our findings demonstrated that capecitabine combination is significantly superior to capecitabine monotherapy in improving PFS (hazard ratio [HR] 1.32, 95% CI 1.13-1.54, p < 0.0001) and ORR (risk ratio [RR] 0.67, 95% CI 0.54-0.83, p < 0.001), but it was insignificant in OS (HR 1.09, 95% CI 0.98-1.22, p = 0.12). On the other hand, the incidence of non-hematological adverse events such as hand-foot syndrome and diarrhea was lower in capecitabine combination compared to capecitabine monotherapy.
CONCLUSION: Capecitabine-based combination chemotherapy showed superiority over capecitabine monotherapy in terms of PFS and ORR, with no significant difference in OS. Non-hematological adverse effects such as hand-foot syndrome were fewer with a combination regimen. However, hematological adverse events were fewer with capecitabine monotherapy regimen.

PMID: 32950984 [PubMed - as supplied by publisher]

Efficacy and Safety of Glecaprevir/Pibrentasvir in Treatment-Naïve Adults with Chronic Hepatitis C Virus Genotypes 1-6 in Brazil.

Ann Hepatol. 2020 Sep 16;:

Authors: Peribañez-Gonzalez M, Cheinquer H, Rodrigues L, Lima MP, Álvares-da-Silva MR, Madruga J, Parise ER, Pessoa MG, Furtado J, Villanova M, Ferreira A, Mazzoleni F, Nascimento E, Silva GF, Fredrick L, Krishnan P, Burroughs M, Reuter T

Abstract
INTRODUCTION AND OBJECTIVES: Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve Brazilian adults without cirrhosis or with compensated cirrhosis.
PATIENTS AND METHODS: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve Brazilian adults with hepatitis C infection genotype 1-6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored.
RESULTS: 100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0-99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported ≥1 adverse event, the most common being headache (18.0%). Four patients reported serious adverse events; none were considered drug related or led to study drug discontinuation. No hepatic decompensations were observed.
CONCLUSIONS: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03219216.

PMID: 32949786 [PubMed - as supplied by publisher]

Hydroxychloroquine and chloroquine retinal safety concerns during COVID-19 outbreak.

Int Ophthalmol. 2020 Sep 18;:

Authors: Nicolò M, Ferro Desideri L, Bassetti M, Traverso CE

Abstract
PURPOSE: The current coronavirus disease 2019 (COVID-19) has been declared by the World Health Organization a global pandemic. Chloroquine (CQ) and hydroxychloroquine (HCQ) have been largely adopted in the clinical setting for the management of SARS-CoV-2 infection; however, their known retinal toxicity has raised some safety concerns, especially considering the higher-dosage employed for COVID-19 patients as compared with their suggested posology for their usual indications, including systemic lupus erythematosus and other rheumatic diseases. In this review, we will discuss the optimal dosages recommended for COVID-19 patients when treated with HCQ and CQ.
METHODS: A comprehensive literature search was performed in PubMed, Cochrane library, Embase and Scopus, by using the following search terms: "chloroquine retinal toxicity" and "hydroxychloroquine retinal toxicity" alone or in combination with "coronavirus", "COVID-19", " SARS-CoV-2 infection " from inception to August 2020.
RESULTS: Although there is still no consistent evidence about HCQ/CQ retinal toxicity in patients with COVID-19, these possible drug-related retinal adverse events may represent a major safety concern. For this reason, appropriate screening strategies, including telemedicine, should be developed in the near future.
CONCLUSION: A possible future clinical perspective for patients with COVID-19 treated with HCQ/CQ could reside in the multidisciplinary collaboration between ophthalmologists monitoring the risk of HCQ/CQ-related retinal toxicity and those physicians treating COVID-19 infection.

PMID: 32946004 [PubMed - as supplied by publisher]

Drug reaction with eosinophilia and systemic symptoms (DRESS) with severe and atypical lung involvement.

Radiol Case Rep. 2020 Nov;15(11):2178-2182

Authors: Guerrero Gómez DA, París Zorro S, Aponte Barrios W, Carrillo Bayona JA

Abstract
Drug reaction with eosinophilia and systemic symptoms is a rare and potentially fatal drug hypersensitivity reaction. Reactions include skin eruption, fever, hematologic abnormalities (eosinophilia or atypical lymphocytosis), enlarged lymph nodes, and/or organic involvement. The liver is the most commonly compromised organ. We present a case of drug reaction with eosinophilia and systemic symptoms associated with Naproxen intake in a young female patient with severe lung involvement. The patient's chest tomography highlights the presence of adenomegalies, pericardial and pleural effusion, peribroncovascular consolidations, and centrilobular nodules. After reviewing the literature few similar cases were found. The main radiological alterations in those cases included interstitial opacities attributed to pneumonitis. Therefore, this case study is considered an unusual case with atypical presentation of drug-induced eosinophilic lung disease.

PMID: 32944113 [PubMed]

Comparative effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for resected low-grade appendiceal mucinous neoplasm (LAMN): A protocol for systematic review and network meta-analysis.

Medicine (Baltimore). 2020 Sep 04;99(36):e22071

Authors: Yang W, Nie P, Liu X, Peng J

Abstract
BACKGROUND: Whether prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) offers long-term survival benefit to patients with low-grade appendiceal mucinous neoplasms (LAMNs) after resection surgery is still under heated debate. The aim of the present meta-analysis is to investigate the comparative effectiveness and safety of prophylactic HIPEC regimens in LAMNs METHODS:: A systematic search of MEDLINE, EMBASE, PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform (ICTRP), clinicaltrials.gov and controlledtrials.com will be performed. All published RCTs and quasi-RCTs through July 20, 2020 with language restricted in English will be included in this review study. Two reviewers will independently conduct the procedures of study identification, data collection, and methodological quality assessment. The primary outcomes are overall survival (OS) and disease-free survival (DFS). The secondary outcomes consist of peritonitis and sepsis, colonic fistula, chemotherapy-associated adverse events, and adhesive intestinal obstruction. The pooled odds ratios (ORs) or hazard ratios (HRs) and relative 95% confident intervals (CIs) of each outcome measurement will be calculated. EndNote X9 software will be applied to manage all citations. The Stata software version 14.0 and R x64 software version 3.5.1 will be employed for main statistical analyses.
DISCUSSION: This study will employ a network meta-analysis to summarize direct and indirect evidence in the specific area to provide detailed individualized guidance on surgical management for LAMNs.
REGISTRATION: This protocol was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) on 25 July 2020 (registration number INPLASY202070112).

PMID: 32899075 [PubMed - indexed for MEDLINE]

Allergies, asthma or hypersensitivity to NSAIDs - are they an equally important risk factor for the development of a specific CRS phenotype?

Otolaryngol Pol. 2019 Oct 11;74(2):8-16

Authors: Stryjewska-Makuch G, Janik M, Kolebacz B, Ścierski W, Lisowska G

Abstract
INTRODUCTION: CRS is a complex systemic disease affecting more than 10% of the population. There are two main types of CRS phenotypes: CRSwNP and CRSsNP. In the Caucasian population, the prevalence of inflammation markers typical of the Th1 profile is observed in CRSsNP, whereas Th2 and Th17 in CRSwNP. Th2 inflammation is observed in the CRSwNP phenotype with concomitant allergies, asthma or hypersensitivity to NSAIDs.
OBJECTIVES: The aim of the study was to evaluate, based on the authors' own material, whether allergies, asthma or hypersensitivity to NSAIDs were a risk factor for the development of a specific CRS phenotype. An attempt was also made to investigate the influence of comorbidities on the extent of sinus endoscopic procedures, which depended on the severity of inflammation.
METHODS: In the years 2006-2015, ESS was performed on 2217 patients with different CRS phenotypes. Patients with an allergy, bronchial asthma and hypersensitivity to NSAIDs were subjected to analysis.
RESULTS: Based on logistic regression, it was found that among the mentioned comorbidities, only asthma (P &lt; 0.0001) and hypersensitivity to NSAIDs (P = 0.0007) significantly affect the occurrence of the phenotype with polyps, whereas the impact of allergies is statistically insignificant (P = 0.1909). The relationship between the type of ESS and CRS phenotypes is statistically significant (P &lt; 0.0001).
CONCLUSIONS: Bronchial asthma and hypersensitivity to NSAIDs have a statistically significant effect on the occurrence of the CRSwNP phenotype. This effect was not observed in allergies. The impact of allergies, asthma and hypersensitivity on the phenotype was observed in the group of patients subjected to the most extensive surgery (ESS 4).

PMID: 32022698 [PubMed - indexed for MEDLINE]

Pharmacy Students' Ability to Identify Fall Risk-Increasing Drugs Using an Innovative Assessment Tool.

Am J Pharm Educ. 2019 12;83(10):7461

Authors: Wahler RG, Piccione C, Maerten-Rivera J

Abstract
Objective. To evaluate change in the ability of third-year pharmacy students to identify drugs that increase fall risk after training in and experience using the Medication Falls Risk Assessment Tool (MFRAT). Methods. An assessment was administered to students prior to MFRAT use and after MFRAT use. The assessment consisted of 10 medication regimens for various chronic conditions (50 distinct drug choices with 30 correct answers and 20 distractors), and students were to identify fall risk increasing drugs (FRIDs). Using a flipped-classroom approach, students viewed an online presentation on FRIDs and then participated in instructor guided, in-class application of the MFRAT using student-collected data from an actual patient case. Students completed medication therapy management (MTM) documentation. The assessment data for students who had previously used the MFRAT (experienced) were analyzed separately from first time users (inexperienced). Results. Three assessment scores were evaluated: number correct (maximum 30; higher score is better), number of distractors (maximum 20; lower score better), and a combined total score (maximum 50; higher score better). In inexperienced users (n=104), pre- and post-assessment means improved significantly for correct score (24.9 vs 29.5) and total score (39.4 vs 44.3). Among experienced users (n=10), pre- and post-assessment means improved significantly for correct responses (27.3 vs 29.7), distractors (7.0 vs 3.5), and total score (40.3 vs 46.2). Conclusion. The ability of both pharmacy students who had used the MFRAT previously and those who had not to correctly identify FRIDs increased on the post-assessment.

PMID: 32001880 [PubMed - indexed for MEDLINE]

Analysis and management of drug related problems on a nephrology ward from a pharmacist's point of view.

Pharmazie. 2019 10 01;74(10):625-629

Authors: Dvořáčková E, Rychlíčková J, Pávek P, Hojný M, Vlček J

Abstract
The main goal of the study was to determine the incidence and the character of drug related problems (DRPs) identified in chronic kidney disease patients by the clinical pharmacist at the nephrology department. As secondary objective, the aim was to identify the frequency and character of DRPs of selected high risk drugs in medication reviews. The clinical pharmacist reviewed patients' medication records and made drug therapy-related recommendations to physicians. The clinical pharmacists' interventions were categorized using an adaptation of the Pharmaceutical Care Network Europe. During the study period (January 2016 - June 2018) the clinical pharmacist performed 1192 interventions in 1870 adult patients admitted to the Nephrology Department. The most frequent DRP was untreated indication 324 (27.18%) of all interventions, and incorrect dose 248 (20.81%). Anti-infectives were identified as the drug category with the highest frequency of interventions. Almost 93% of all interventions were accepted by the attending physicians. Still within the second objectives, underdosing was observed as the most frequent problem for renally excreted drugs. It was found that an incorrect dose is a very frequent issue at the nephrology department. Surprisingly, the main problem was underdosing. In the category of renally excreted drugs, underdosing was observed in antithrombotics and antivirals. The above- mentioned results prove the need of a clinical pharmacist, preferably in sense of maximizing of the treatment effect and improving the care of patients.

PMID: 31685090 [PubMed - indexed for MEDLINE]

Evaluation of irrational dose assignment definitions using the continual reassessment method.

Clin Trials. 2019 12;16(6):665-672

Authors: Wages NA, Bagley E

Abstract
BACKGROUND: This article studies the notion of irrational dose assignment in Phase I clinical trials. This property was recently defined by Zhou and colleagues as a dose assignment that fails to de-escalate the dose when two out of three, three out of six, or four out of six patients have experienced a dose-limiting toxicity event at the current dose level. The authors claimed that a drawback of the well-known continual reassessment method is that it can result in irrational dose assignments. The aim of this article is to examine this definition of irrationality more closely within the conduct of the continual reassessment method.
METHODS: Over a broad range of assumed dose-limiting toxicity probability scenarios for six study dose levels and a variety of target dose-limiting toxicity rates, we simulated 2000 trials of n = 36 patients. For each scenario, we counted the number of irrational dose assignments that were made by the continual reassessment method, according to the definitions of Zhou and colleagues. For each of the irrational decisions made, we classified the dose assignment as an underdose assignment, a target dose assignment, or an overdose assignment based on the true dose-limiting toxicity probability at that dose.
RESULTS: Across eight dose-toxicity scenarios, there were a total of 181,581 dose assignments made in the simulation study. Of these assignments, 8165 (4.5%) decisions were made when two out of three, three out of six, or four out of six patients had experienced a dose-limiting toxicity at the current dose. Of these 8165 decisions, 1505 (18.4%) recommended staying at the current dose level and would therefore be classified as irrational by Zhou and colleagues. Among the irrational decisions, 41.2% were misclassified, meaning they were made either at the true target dose (17.9%) or at a true underdose (23.3%). The remaining 58.8% were made at a true overdose and therefore truly irrational. Overall, irrational dose assignments comprised <1% of the total dose assignments made during the simulation study. Similar findings are reported in simulations across 100 randomly generated dose-toxicity scenarios from a recently proposed family of curves.
CONCLUSION: Zhou and colleagues argue that the behavior of the continual reassessment method is disturbing due to its ability to make irrational dose assignments. These definitions are based on rules that mimic the popular 3 + 3 design, which should not be the benchmark used to construct guidelines for trial conduct of modern Phase I methods. Our study illustrates that these dose assignments occur very seldom in the continual reassessment method and that even when they do occur, they can often be considered sensible when accounting for all accumulated data in the study.

PMID: 31547691 [PubMed - indexed for MEDLINE]

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

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

These pubmed results were generated on 2020/09/18

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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

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

These pubmed results were generated on 2020/09/18

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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

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

These pubmed results were generated on 2020/09/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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

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

These pubmed results were generated on 2020/09/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Lung adenocarcinoma with tumor resolution and dystrophic calcification after salvage surgery following immune checkpoint inhibitor therapy: A case report.

Thorac Cancer. 2020 Sep 15;:

Authors: Sumi T, Uehara H, Masaoka T, Tada M, Keira Y, Kamada K, Shijubou N, Yamada Y, Nakata H, Mori Y, Chiba H

Abstract
A clinical trial of immune checkpoint inhibitors for advanced non-small cell lung cancer reported an overall survival plateau with a long tail to the survival curve, suggesting that immune checkpoint inhibitors prolong survival. However, little evidence supports the efficacy of immune checkpoint inhibitors as neoadjuvant chemotherapy. We performed salvage surgery on a patient who was treated with an anti-programmed cell death protein-1 (PD-1) antibody and whose tumor size had not changed over time. A 69-year-old Japanese female with advanced lung adenocarcinoma was initially administered pembrolizumab therapy; however, owing to the development of various immune-related adverse events (irAEs), the patient was switched to chemotherapy following steroid therapy. The tumor continued to shrink and calcification within the tumor increased. We performed salvage surgery following which the tumor cells disappeared and necrosis and calcification were detected in the tumor. We concluded that if calcification develops within the tumor and tumor shrinkage is maintained after treatment with anti-PD-1 drugs, the calcification may be dystrophic owing to drug-induced tumor necrosis, and salvage surgery might be beneficial in removing the tumor. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: If calcification develops within the tumor and tumor shrinkage is maintained after treatment with anti-PD-1 drugs, the calcification may be dystrophic owing to tumor necrosis caused by drug effects, and salvage surgery might be beneficial in removing the tumor. WHAT THIS STUDY ADDS: This study showed the efficacy of immune checkpoint inhibitors as neoadjuvant chemotherapy to be followed by salvage surgery for unresectable advanced lung adenocarcinoma.

PMID: 32930490 [PubMed - as supplied by publisher]

Aspiration in lethal drug abuse-a consequence of opioid intoxication.

Int J Legal Med. 2020 Sep 14;:

Authors: Nicolakis J, Gmeiner G, Reiter C, Seltenhammer MH

Abstract
AIMS: The primary objective of this study was to investigate whether the fatalities of opioid abuse are not only related to respiratory depression but also as a result of other side effects such as emesis, delayed gastric emptying, a reduction of the cough reflex, and impaired consciousness leading to the aspiration of gastric contents, a finding regularly observed in drug-related deaths.
DESIGN: A retrospective exploratory study analyzing heroin/morphine/methadone-related deaths submitted to court-ordered autopsy.
SETTING: Center for Forensic Medicine, Medical University of Vienna, Austria (2010-2015).
PARTICIPANTS: Two hundred thirty-four autopsy cases were included in the study: morphine (n = 200), heroin (n = 11), and methadone (n = 23) intoxication.
FINDINGS: Analyses revealed that 41.88% of all deceased showed aspiration of gastric contents with equal gender distribution (p = 0.59). Aspiration was more frequent in younger deceased (χ2 = 8.7936; p = 0.012) and in deceased with higher body mass index (BMI) (χ2 = 6.2441; p = 0.044). Blood opioid concentration was lower in deceased with signs of aspiration than in non-aspirators (p = 0.013). Toxicological evaluation revealed a high degree of concomitant substance abuse (91%)-benzodiazepines (61.6%) and/or alcohol (21.8%).
CONCLUSIONS: There are lower opioid concentrations in deceased with signs of aspiration, a fact which strongly points to aspiration as alternative cause of death in opioid-related fatalities. Furthermore, this study highlights the common abuse of slow-release oral morphine in Vienna and discusses alternative medications in substitution programs (buprenorphine/naloxone or tamper-resistant slow-release oral morphine preparations), as they might reduce intravenous abuse and opioid-related deaths.

PMID: 32929594 [PubMed - as supplied by publisher]

Role of peripheral sensory neuron mu-opioid receptors in nociceptive, inflammatory, and neuropathic pain.

Reg Anesth Pain Med. 2020 Sep 14;:

Authors: Barpujari A, Ford N, He SQ, Huang Q, Gaveriaux-Ruff C, Dong X, Guan Y, Raja S

Abstract
BACKGROUND AND OBJECTIVE: The role of peripheral mu-opioid receptors (MOPs) in chronic pain conditions is not well understood. Here, we used a combination of mouse genetics, behavioral assays, and pharmacologic interventions to investigate the contribution of primary afferent MOPs to nociceptive, inflammatory, and neuropathic pain, as well as to opioid analgesia.
METHODS: We generated conditional knockout mice in which MOPs were selectively deleted in primary sensory neurons. Inflammatory and neuropathic pain states were induced in mutant and control wild-type mice and their behavioral responses to noxious stimuli were compared. Gross motor function was also evaluated. Immunohistochemistry was used to assess MOP expression in the dorsal root ganglia, periaqueductal gray, and small intestine. The effects of MOP agonists DALDA (dermorphin [D-Arg2, Lys4] (1-4) amide) and morphine were evaluated in pain behavior assays, and their effects on neuronal physiology in the dorsal root ganglia were evaluated in whole-cell patch-clamp recordings.
RESULTS: Conditional MOP knockouts and control mice exhibited similar behavioral responses to acute nociceptive stimuli and developed similar inflammation-induced hypersensitivity. Unilateral nerve injury in animals lacking peripheral MOPs induced enhanced, bilateral mechanical allodynia. Subcutaneously administered DALDA was unable to decrease the hypersensitivity induced by inflammation and nerve injury in MOP knockout animals, and morphine's antinociceptive effects were significantly attenuated in the absence of peripheral MOPs.
CONCLUSION: MOPs in primary sensory neurons contribute to the modulation of neuropathic pain behavior and opioid analgesia. Our observations highlight the clinical potential of peripherally acting opioid agonists in the management of inflammatory and neuropathic pain.

PMID: 32928995 [PubMed - as supplied by publisher]

Sleep-disordered breathing in patients on opioids for chronic pain.

Reg Anesth Pain Med. 2020 Sep 14;:

Authors: Selvanathan J, Peng PWH, Wong J, Ryan CM, Chung F

Abstract
The past two decades has seen a substantial rise in the use of opioids for chronic pain, along with opioid-related mortality and adverse effects. A contributor to opioid-associated mortality is the high prevalence of moderate/severe sleep-disordered breathing, including central sleep apnea and obstructive sleep apnea, in patients with chronic pain. Although evidence-based treatments are available for sleep-disordered breathing, patients are not frequently assessed for sleep-disordered breathing in pain clinics. To aid healthcare providers in this area of clinical uncertainty, we present evidence on the interaction between opioids and sleep-disordered breathing, and the prevalence and predictive factors for sleep-disordered breathing in patients on opioids for chronic pain. We provide recommendations on how to evaluate patients on opioids for risk of moderate/severe sleep-disordered breathing in clinical care, which could lead to earlier use of therapeutic interventions for opioid-associated sleep-disordered breathing, such as opioid cessation or positive airway pressure therapy. This would improve quality of life and well-being of patients with chronic pain.

PMID: 32928994 [PubMed - as supplied by publisher]

Aripiprazole vs. brexpiprazole for acute schizophrenia: a systematic review and network meta-analysis.

Psychopharmacology (Berl). 2020 May;237(5):1459-1470

Authors: Kishi T, Ikuta T, Matsuda Y, Sakuma K, Iwata N

Abstract
RATIONALE: What is the difference between aripiprazole and brexpiprazole?
OBJECTIVES: This systematic review, network meta-analysis of randomized trials evaluated the efficacy and safety/tolerability of aripiprazole and brexpiprazole for treating acute schizophrenia.
METHODS: We searched Scopus, MEDLINE, and Cochrane Library from inception until May 22, 2019. The response rate was set as the primary outcome. Other outcomes were discontinuation rate and incidence of individual adverse events. The risk ratio (RR) and 95% credible interval (95%CrI) were calculated.
RESULTS: Fourteen studies were identified (n = 3925). Response rates of both aripiprazole and brexpiprazole were superior to that of the placebo (RR [95%CrI]: aripiprazole = 0.84 [0.78, 0.92], brexpiprazole = 0.84 [0.77, 0.92]). Aripiprazole and brexpiprazole were associated with a lower incidence of all-cause discontinuation (0.80 [0.71, 0.89], 0.83 [0.72, 0.95]), adverse events (0.67 [0.47, 0.97], 0.64 [0.46, 0.94]), and inefficacy (0.56 [0.40, 0.77], 0.68 [0.48, 0.99]) compared with the placebo. Although brexpiprazole was associated with a lower incidence of schizophrenia as an adverse event compared with the placebo (0.57 [0.37, 0.85]), aripiprazole and brexpiprazole were associated with a higher incidence of weight gain compared with the placebo (2.12 [1.28, 3.68], 2.14 [1.35, 3.42]). No significant differences were found in other individual adverse events, such as somnolence, akathisia, extrapyramidal symptoms, and dizziness between aripiprazole or brexpiprazole and placebo. Any outcome between aripiprazole and brexpiprazole were not different.
CONCLUSIONS: Differences in short-term efficacy and safety for acute schizophrenia were not apparent between aripiprazole and brexpiprazole. Future studies are warranted to evaluate whether there are differences in the long-term outcome between treatments.

PMID: 32002559 [PubMed - indexed for MEDLINE]

Intrahepatic Administration of Human Liver Stem Cells in Infants with Inherited Neonatal-Onset Hyperammonemia: A Phase I Study.

Stem Cell Rev Rep. 2020 02;16(1):186-197

Authors: Spada M, Porta F, Righi D, Gazzera C, Tandoi F, Ferrero I, Fagioli F, Sanchez MBH, Calvo PL, Biamino E, Bruno S, Gunetti M, Contursi C, Lauritano C, Conio A, Amoroso A, Salizzoni M, Silengo L, Camussi G, Romagnoli R

Abstract
Previous studies have shown that human liver stem-like cells (HLSCs) may undergo differentiation in vitro into urea producing hepatocytes and in vivo may sustain liver function in models of experimentally induced acute liver injury. The aim of this study was to assess the safety of HLSCs intrahepatic administration in inherited neonatal-onset hyperammonemia. The study was approved by the Agenzia Italiana del Farmaco on favorable opinion of the Italian Institute of Health as an open-label, prospective, uncontrolled, monocentric Phase I study (HLSC 01-11, EudraCT-No. 2012-002120-33). Three patients affected by argininosuccinic aciduria (patient 1) and methylmalonic acidemia (patients 2 and 3) and included in the liver transplantation list were enrolled. In all patients, HLSCs were administered by percutaneous intrahepatic injections (once a week for two consecutive weeks) within the first months of life. The first patient received 125,000 HLSCs x gram of liver/dose while the other two patients received twice this dose. No immunosuppression was administered since HLSCs possess immunomodulatory activities. None of the patients experienced infections, hyperammonemia decompensation, or other adverse events during the whole observation period. No donor specific antibodies (DSA) against HLSCs were detected. Patients were metabolic stable despite an increase (~30%) in protein intake. Two patients underwent liver transplantation after 19 and 11 months respectively, and after explantation, the native livers showed no histological alterations. In conclusion, percutaneous intrahepatic administration of HLSCs was safe in newborn with inherited neonatal-onset hyperammonemia. These data pave the way for Phase II studies in selected inherited and acquired liver disorders.

PMID: 31792768 [PubMed - indexed for MEDLINE]