Identifying Adverse Drug Events in Older Community-Dwelling Patients.

Ann Fam Med. 2019 03;17(2):133-140

Authors: Cahir C, Wallace E, Cummins A, Teljeur C, Byrne C, Bennett K, Fahey T

Abstract
PURPOSE: To evaluate a patient-report instrument for identifying adverse drug events (ADEs) in older populations with multimorbidity in the community setting.
METHODS: This was a retrospective cohort study of 859 community-dwelling patients aged ≥70 years treated at 15 primary care practices. Patients were asked if they had experienced any of a list of 74 symptoms classified by physiologic system in the previous 6 months and if (1) they believed the symptom to be related to their medication, (2) the symptom had bothered them, (3) they had discussed it with their family physician, and (4) they required hospital care due to the symptom. Self-reported symptoms were independently reviewed by 2 clinicians who determined the likelihood that the symptom was an ADE. Family physician medical records were also reviewed for any report of an ADE.
RESULTS: The ADE instrument had an accuracy of 75% (95% CI, 77%-79%), a sensitivity of 29% (95% CI, 27%-31%), and a specificity of 93% (95% CI, 92%-94%). Older people who reported a symptom had an increased likelihood of an ADE (positive likelihood ratio [LR+]: 4.22; 95% CI, 3.78-4.72). Antithrombotic agents were the drugs most commonly associated with ADEs. Patients were most bothered by muscle pain or weakness (75%), dizziness or lightheadedness (61%), cough (53%), and unsteadiness while standing (52%). On average, patients reported 39% of ADEs to their physician. Twenty-six (3%) patients attended a hospital outpatient clinic, and 32 (4%) attended an emergency department due to ADEs.
CONCLUSION: Older community-dwelling patients were often not correct in recognizing ADEs. The ADE instrument demonstrated good predictive value and could be used to differentiate between symptoms of ADEs and chronic disease in the community setting.

PMID: 30858256 [PubMed - indexed for MEDLINE]

Drug knowledge bases and their applications in biomedical informatics research.

Brief Bioinform. 2019 07 19;20(4):1308-1321

Authors: Zhu Y, Elemento O, Pathak J, Wang F

Abstract
Recent advances in biomedical research have generated a large volume of drug-related data. To effectively handle this flood of data, many initiatives have been taken to help researchers make good use of them. As the results of these initiatives, many drug knowledge bases have been constructed. They range from simple ones with specific focuses to comprehensive ones that contain information on almost every aspect of a drug. These curated drug knowledge bases have made significant contributions to the development of efficient and effective health information technologies for better health-care service delivery. Understanding and comparing existing drug knowledge bases and how they are applied in various biomedical studies will help us recognize the state of the art and design better knowledge bases in the future. In addition, researchers can get insights on novel applications of the drug knowledge bases through a review of successful use cases. In this study, we provide a review of existing popular drug knowledge bases and their applications in drug-related studies. We discuss challenges in constructing and using drug knowledge bases as well as future research directions toward a better ecosystem of drug knowledge bases.

PMID: 29304188 [PubMed - indexed for MEDLINE]

Assessment of the Feasibility and Safety of Durvalumab for Treatment of Solid Tumors in Patients With HIV-1 Infection: The Phase 2 DURVAST Study.

JAMA Oncol. 2020 Apr 09;:

Authors: Gonzalez-Cao M, Morán T, Dalmau J, Garcia-Corbacho J, Bracht JWP, Bernabe R, Juan O, de Castro J, Blanco R, Drozdowskyj A, Argilaguet J, Meyerhans A, Blanco J, Prado JG, Carrillo J, Clotet B, Massuti B, Provencio M, Molina-Vila MA, Mayo de Las Casa C, Garzon M, Cao P, Huang CY, Martinez-Picado J, Rosell R

Abstract
Importance: Therapies targeting the programmed cell death 1 (PD-1) receptor or its ligand (PD-L1), such as the humanized monoclonal antibody durvalumab, have shown durable clinical responses in several tumor types. However, concerns about the safety and feasibility of PD-1/PD-L1 blockade in HIV-1-infected individuals have led to the exclusion of these patients from clinical trials on cancer immunotherapies.
Objective: To evaluate the feasibility and safety of durvalumab treatment in patients with advanced cancer and virologically controlled HIV-1 infection.
Design, Setting, and Participants: The DURVAST study was a nonrandomized, open-label, phase 2 clinical trial in patients with any solid tumor type in which anti-PD-1 or anti-PD-L1 antibodies have approved indications or for which there are data of antitumoral activity with no other available curative therapy. All patients had basal undetectable plasma viremia while undergoing combination antiretroviral therapy.
Interventions: Treatment consisted of intravenous infusion of durvalumab (1500 mg every 4 weeks) until disease progression or unacceptable toxic effects.
Main Outcomes and Measures: Adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1.
Results: A total of 20 HIV-1-infected patients with advanced cancer were enrolled; 16 (80%) were male, the median (range) age was 54 (30-73) years, and 12 (60%) had progressed with previous cancer treatment lines. A median (range) of 4 (1-16) cycles of durvalumab were administered. Drug-related adverse events were observed in 50% of patients, and all were grade 1 and 2 (mainly diarrhea, asthenia, and arthromyalgia). Four of 16 response-evaluable patients (25%) had a partial response. Five patients (31%) had stable disease, including 4 with durable stable disease (disease control rate of 50%). CD4+ and CD8+ T-cell counts and plasma HIV-1 viremia remained stable throughout the study.
Conclusions and Relevance: Durvalumab treatment was feasible and safe in HIV-1-infected patients with cancer receiving combination antiretroviral therapy. HIV-1-infected patients on suppressive antiretroviral therapy with advanced cancer should have access to cancer immunotherapy treatments.
Trial Registration: ClinicalTrials.gov Identifier: NCT03094286.

PMID: 32271353 [PubMed - as supplied by publisher]

Re: Cognitive and Mood Side Effects of Lower Urinary Tract Medication.

J Urol. 2020 05;203(5):855-856

Authors: Kaplan SA

PMID: 32073981 [PubMed - indexed for MEDLINE]

The Quality of Spontaneous Adverse Drug Reaction Reports in China: A Descriptive Study.

Biol Pharm Bull. 2019;42(12):2083-2088

Authors: Chen Y, Niu R, Xiang Y, Wang N, Bai J, Feng B

Abstract
Pharmacovigilance is important to monitor the safety of drugs. There are, however, problems with the quality of adverse drug reaction reports in China. This study aimed to analyze the quality of adverse drug reaction reports in China, identify the factors affecting it, and propose measures to improve it. In our study, the western province of Shaanxi, the central province of Hubei and the eastern province of Jiangsu were chosen as typical, and adverse drug reaction reports from these three provinces from 2015 to 2017 were systematically sampled. The sampling reports were scored and graded to assess their quality. The results showed that only 10.18% were considered high quality in a total of 3429 reports. There were statistically significant differences in quality by year, province, report type, report source, and occupation of the reporter (p < 0.001). Reports from Shaanxi were slightly poorer quality, and "new" and "serious" reports and those from pharmacists were higher quality. Five indicators were particularly poor quality: patient information, adverse drug reaction, reporter information, drug information and vigilance. In conclusion, the quality of adverse drug reaction reports in China still needs improvement. Factors affecting quality included timing, location, report type, report source, and reporter's occupation. It may be helpful to publicize the importance of monitoring adverse drug reactions and improve the knowledge of reporters.

PMID: 31787723 [PubMed - indexed for MEDLINE]

Antibiotic stewardship initiative in a Medicine unit of a tertiary care teaching hospital in India: A pilot study.

Indian J Med Res. 2019 08;150(2):175-185

Authors: Swamy A, Sood R, Kapil A, Vikram NK, Ranjan P, Jadon RS, Soneja M, Sreenivas V

Abstract
Background & objectives: The models for implementation of antibiotic stewardship programme (ASP) in the acute care settings of developing countries are lacking. In most of the hospitals, patient turnover is high and a proper system for recording antibiotic-related information and tracking hospital-acquired infections is not in place. This pilot study was conducted in a tertiary care teaching hospital in north India to assess the feasibility of implementation of an ASP in a Medicine unit and to evaluate the effect of implementation as per the criteria applicable in this set up.
Methods: A pre-post-quasi-experimental non-randomized study was conducted in two phases. In the first phase, current practices in the Medicine wards were observed. In the second phase, the ASP was implemented in a single Medicine unit, along with prospective audit and feedback, tracking of the process, as well as outcome measures. Patient risk stratification, blood culture on day one, day 3 bundle, dose optimization, de-escalation and intravenous to oral conversion of antibiotics were the key elements focused upon.
Results: There was a significant improvement in the appropriateness of antibiotic prescription (66 vs. 86%, P<0.001) and reduction in the mean number of antibiotics used per person (4.41 vs. 3.86, P<0.05) along with decrease in the duration of hospital stay (17 vs. 14 days, P<0.05). There was a significant improvement in sending of blood cultures on day one during the stewardship phase (P<0.001).
Interpretation & conclusions: The ASP approach used in our pilot study may be feasible and beneficial. However, it needs further confirmation in other settings and on a large scale.

PMID: 31670273 [PubMed - indexed for MEDLINE]

A comprehensive safety profile of tafamidis in patients with transthyretin amyloid polyneuropathy.

Amyloid. 2019 Dec;26(4):203-209

Authors: Huber P, Flynn A, Sultan MB, Li H, Rill D, Ebede B, Gundapaneni B, Schwartz JH

Abstract
Background: Tafamidis is approved in over 40 countries to delay neurologic progression in patients with transthyretin amyloid polyneuropathy (ATTR-PN). A comprehensive, integrated analysis of safety data from interventional, observational and surveillance studies of tafamidis in ATTR-PN patients was conducted. Methods: Safety data from all sponsored, completed, or ongoing, Phase 2/3 studies of tafamidis in ATTR-PN patients as of 3 January 2017 were pooled. Also assessed were safety data from the ongoing Transthyretin Amyloidosis Outcomes Survey (THAOS) as of 3 January 2017 and post-marketing surveillance reports as of 31 March 2017. Results: There were 137 patients in Phase 2/3 studies (mean duration of tafamidis exposure, 44.2 months), with 134 (97.8%) experiencing ≥1 treatment-emergent adverse event (TEAE) and 46 (33.6%) ≥1 treatment-emergent serious adverse event (TESAE). The most common TEAEs were diarrhoea (26.3%), urinary tract infection (UTI; 25.5%) and influenza (21.2%). In THAOS, 661 subjects had tafamidis exposure (mean duration, 27.6 months), with 250 (37.8%) experiencing ≥1 TEAE and 96 (14.5%) ≥1 TESAE. The most common TEAE was UTI (6.1%). Post-marketing surveillance reports generally reflected the known safety profile of tafamidis. Conclusions: This analysis did not reveal any significant new safety findings; tafamidis was generally safe and well tolerated in ATTR-PN patients. ClinicalTrials.gov: NCT00409175, NCT00791492, NCT00630864, NCT01435655, NCT00925002, and NCT00628745.

PMID: 31353964 [PubMed - indexed for MEDLINE]

Mining in Twitter for adverse events from malaria drugs: the case of doxycycline.

Cad Saude Publica. 2019 05 23;35(5):e00033417

Authors: Duval FV, Silva FABD

Abstract
During the post-marketing period, when medicines are used by large population contingents and for longer periods, unexpected adverse events (AE) can occur, potentially altering the drug's risk-benefit ratio enough to demand regulatory action. AE are health problems that can occur during treatment with a pharmaceutical product, which in the drug's post-marketing period can require a significant increase in health care and result in unnecessary and often fatal harm to patients. Therefore, a key objective for the health system is to identify AE as soon as possible in the post-marketing period. Some countries have pharmacovigilance systems responsible for collecting voluntary reports of post-marketing AE, but studies have shown that social networks can be used to obtain more and faster reports. The current project's main objective is to build a totally automated system using Twitter as a source to detect both new and previously known AE and conduct the statistical analysis of the resulting data. A system was thus built to collect, process, analyze, and assess tweets in search of AE, comparing them to U.S. Food and Drug Administration (FDA) data and the reference standard. The results allowed detecting new and existing AE related to the drug doxycycline, showing that Twitter can be useful in pharmacovigilance when employed jointly with other data sources.

PMID: 31141025 [PubMed - indexed for MEDLINE]

Is Granulocyte colony-stimulating factor associated with development of aortitis?

Cytokine. 2019 08;120:191

Authors: Bidhendi Yarandi R, Panahi MH

Abstract
The aim of this study was to mention some methodological issues in a study which investigate the effect of Granulocyte colony-stimulating factor on developing of aortitis.

PMID: 31100683 [PubMed - indexed for MEDLINE]

Patterns of immunotherapy use and management of toxicities in regional and tertiary settings.

Intern Med J. 2019 08;49(8):1010-1015

Authors: Hamilton B, Xu K, Honeyball F, Balakrishnar B, Zielinski R

Abstract
BACKGROUND: The introduction of the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) immune checkpoint inhibitors and their subsequent listing on the Pharmaceutical Benefits Scheme for use in metastatic melanomas, renal cell carcinomas and non-small-cell lung cancers has resulted in routine use of these agents in oncology practices, including in regional areas. Although immunotherapeutic agents generally have a favourable toxicity profile compared to chemotherapy, they can provoke immune-related adverse effects (irAE) caused by an unregulated and hyperstimulated immune response. Some of these effects can be serious and life-threatening.
AIMS: To compare the utilisation of immunotherapy and the rates, management and outcomes of irAE between a regional oncology service and a tertiary service.
METHODS: We reviewed the medical records for all patients treated with immunotherapy in the participating services for the 5-year period from 31 July 2012 to 31 July 2017.
RESULTS: Data demonstrated that rates of immunotherapy use are both similar and increasing across the tertiary and regional services. The rates, types and severity of irAE are equivalent and in concordance with pre-existing literature. Immune-related adverse events appear to be identified and treated earlier in the regional service with the corresponding reduction in the duration of immunosuppression and requirement for inpatient management.
CONCLUSION: The use of immunotherapy in a regional setting is safe and equivalent to that of a tertiary centre.

PMID: 30693623 [PubMed - indexed for MEDLINE]

27 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 2020/04/09

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.

One-Month Outcomes of Cases Receiving Ticagrelor after Percutaneous Coronary Intervention; a Case Series.

Arch Acad Emerg Med. 2020;8(1):e42

Authors: Namazi MH, Saemifard F, Pishgahi M

Abstract
Introduction: Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist that can block ADP-induced platelet aggregation. This study aimed to describe one-month follow-up findings of cases undergoing ticagrelor therapy after percutaneous coronary intervention (PCI).
Methods: This case series was performed on acute coronary syndrome (ACS) patients who were candidates for PCI and received aspirin plus ticagrelor after PCI. Patients were followed for one month and their outcomes were described.
Results: 156 cases with the mean age of 59.74 ± 9.24 years were studied (63% male). 45 (28.8%) cases complained of dyspnea (39 cases with mild and 6 cases with severe dyspnea). Bleeding occurred in 4 (2.5%) cases (intra-cranial hemorrhage (ICH) in one, hematuria in two, and skin hemorrhage in one case). There were no cases with bradycardia or thrombosis. One (0.6%) patient developed drug hypersensitivity reaction, which manifested as skin rash. The use of drug was stopped in 10 (6.4%) cases due to severe dyspnea (n= 6), ICH (n=1), skin rash (n=1), and concomitant left ventricular (LV) clot (n=2).
Conclusion: The most important finding of one-month ticagrelor consumption were dyspnea, bleeding, and hypersensitivity reaction. No case of bradycardia and stent thrombosis was detected. In our study , iranian population has more susceptibility to dyspnea than PLATO result. The rate of drug discontinuation in this series of cases was 6.4 %.

PMID: 32259131 [PubMed - as supplied by publisher]

Safety of Naloxone in Opioid-Naïve Methadone Intoxicated Patients; a Case Series Study.

Arch Acad Emerg Med. 2020;8(1):e16

Authors: Shakeri SHR, Hassanian-Moghaddam H, Zamani N

Abstract
Introduction: Studies have shown that naloxone can cause behavioral changes in naïve normal volunteers. This study aimed to investigate the possible complications of naloxone in methadone-overdosed opioid-naïve patients.
Methods: In this pilot study, a total number of 20 opioid-naïve methadone-poisoned patients underwent naloxone challenge test to receive naltrexone. 0.2, 0.6, and 1.2 mg doses of naloxone were administered on minutes 0, 5, and 15-20. The patients were followed for 30 minutes after administration of naloxone and monitored for any upsetting signs and symptoms. Patients with clinical opiate withdrawal scale (COWS) lower than 5 were considered not addicted and the severity of patients' symptoms was calculated using subjective opiate withdrawal syndrome (SOWS).
Results: 20 patients with mean age of 25.5±8.09 years were evaluated (70% female). Median ingested dose of methadone was 25 mg [IQR; 10 to 50 mg] and mean time interval between ingestion of methadone and naloxone challenge test was 7.1±4.9 hours. Fourteen patients reported some discomfort after administration of a mean dose of 1.7±0.5 mg of naloxone lasting for a maximum of four hours. The most common patients' complaints were headache (45%) followed by nausea (20%), agitation (20%), abdominal pain (20%), and flushing (20%). Two (10%) mentioned severe panic attack and sensation of near-coming death. SOWS significantly correlated with female gender (p = 0.004) and time elapsed post methadone ingestion (p = 0.001).
Conclusion: It seems that naloxone is not a completely safe medication even in opioid-naïve patients, and administrating adjusted doses of naloxone even in opioid-naïve methadone intoxicated patients may be logical.

PMID: 32259115 [PubMed - as supplied by publisher]

A Meta-Analysis of Dropout and Metabolic Effects of Antipsychotics in Anorexia Nervosa.

Front Psychiatry. 2020;11:208

Authors: Kan C, Eid L, Treasure J, Himmerich H

Abstract
Background: Second-generation antipsychotics are often used off-label in the treatment of anorexia nervosa (AN) across the clinical spectrum. Patients with anorexia nervosa often cite concerns about metabolic effects, such as weight gain, as reasons for their reluctance to start or continue second-generation antipsychotics. Improving our understanding of the metabolic effect patients experience and reasons underlying their disinclination will enable us to build rapport and guide our clinical decisions. We therefore aimed to conduct a comprehensive review of dropouts, metabolic effects, and patient-reported outcomes associated with second-generation antipsychotic in people with AN.
Method: EMBASE, Medline, and PsycINFO were searched for all relevant studies published until 2019, and retrieved studies were assessed for eligibility as per predefined inclusion criteria. A random-effects meta-analysis was conducted to assess overall dropout rates.
Results: Of 983 citations retrieved, 21 studies met the inclusion criteria for the systematic review and 10 studies had appropriate data for meta-analysis. Using the random effects model, the pooled dropout rate in the intervention arm (95% confidence interval) from psychopharmacological trials was 28% (19 to 38%) in people with AN. Personal reasons or factors associated with study were commonest reason for dropout, not adverse events or metabolic effects as hypothesized.
Conclusion: Compared to personal reasons, drug-related factors such as side effects seem to play a lesser role for the discontinuation of antipsychotic treatment under trial conditions. This suggests an urgent need to consider and fully examine potential individual and patient-related factors that influence dropout rates in psychopharmacological trials and treatment compliance in clinical settings.

PMID: 32256415 [PubMed - as supplied by publisher]

The Efficacy and Safety of High-dose Daptomycin in the Treatment of Complicated Skin and Soft Tissue Infections in Asians.

Int J Infect Dis. 2020 Apr 03;:

Authors: Dong XM, Xu NN, Yao YY, Guan YY, Li QY, Zheng F, Chen FZ, Wang G

Abstract
OBJECTIVE: To compare the efficacy and safety of standard-dose (SD) daptomycin with those of high-dose (HD) daptomycin in complicated skin and soft tissue infections (cSSTIs) in an Asian population.
MATERIALS AND METHODS: Patients from three medical centers diagnosed with cSSTIs were screened in the clinical information system. Patients included in the analysis were divided into two groups: those who received daptomycin at doses ≥ 6 mg/kg (HD group) and those receiving 4 mg/kg (SD group). The demographics and clinical treatment information were analyzed.
RESULTS: Overall, 155 patients were recruited, including 108 patients in the SD group and 47 patients in the HD group. The rate of healthcare-associated infections was higher in the HD group (61.70% vs. 37.04%), demonstrating a statistically significant difference (P = 0.005). Compared with the SD group, the HD group had statistically significant early clinical stabilization (72.34% vs 52.78%, P = 0.023). The results of the multivariate analysis indicated that HD daptomycin was an independent effector for early clinical stabilization (HR=0.394, P < 0.001). The rate of drug-related adverse events was equally distributed in the HD and SD groups (36.17% vs. 26.85%, P = 0.243).
CONCLUSION: Compared with SD daptomycin, HD daptomycin increased the rate of early clinical stabilization in Asian patients with cSSTIs, whereas the incidence of adverse events did not increase.

PMID: 32251792 [PubMed - as supplied by publisher]

Cell-permeable succinate prodrugs rescue mitochondrial respiration in cellular models of acute acetaminophen overdose.

PLoS One. 2020;15(4):e0231173

Authors: Piel S, Chamkha I, Dehlin AK, Ehinger JK, Sjövall F, Elmér E, Hansson MJ

Abstract
Acetaminophen is one of the most common over-the-counter pain medications used worldwide and is considered safe at therapeutic dose. However, intentional and unintentional overdose accounts for up to 70% of acute liver failure cases in the western world. Extensive research has demonstrated that the induction of oxidative stress and mitochondrial dysfunction are central to the development of acetaminophen-induced liver injury. Despite the insight gained on the mechanism of acetaminophen toxicity, there still is only one clinically approved pharmacological treatment option, N-acetylcysteine. N-acetylcysteine increases the cell's antioxidant defense and protects liver cells from further acetaminophen-induced oxidative damage. Because it primarily protects healthy liver cells rather than rescuing the already injured cells alternative treatment strategies that target the latter cell population are warranted. In this study, we investigated mitochondria as therapeutic target for the development of novel treatment strategies for acetaminophen-induced liver injury. Characterization of the mitochondrial toxicity due to acute acetaminophen overdose in vitro in human cells using detailed respirometric analysis revealed that complex I-linked (NADH-dependent) but not complex II-linked (succinate-dependent) mitochondrial respiration is inhibited by acetaminophen. Treatment with a novel cell-permeable succinate prodrug rescues acetaminophen-induced impaired mitochondrial respiration. This suggests cell-permeable succinate prodrugs as a potential alternative treatment strategy to counteract acetaminophen-induced liver injury.

PMID: 32251487 [PubMed - as supplied by publisher]

A Phase 1 Study of SLC-0111, a Novel Inhibitor of Carbonic Anhydrase IX, in Patients With Advanced Solid Tumors.

Am J Clin Oncol. 2020 Apr 02;:

Authors: McDonald PC, Chia S, Bedard PL, Chu Q, Lyle M, Tang L, Singh M, Zhang Z, Supuran CT, Renouf DJ, Dedhar S

Abstract
OBJECTIVES: SLC-0111 is an ureido-substituted benzenesulfonamide small molecule inhibitor of carbonic anhydrase IX. The objectives of this first-in-human Phase 1 study were to determine the safety and tolerability of SLC-0111 in patients with advanced solid tumors and to establish the recommended Phase 2 dose for future clinical investigations.
MATERIALS AND METHODS: Using a 3+3 design, dose escalation started at 500 mg oral daily dosing of SLC-0111 in cohort 1 and increased to 1000 and 2000 mg in cohorts 2 and 3. Drug-related adverse events (AEs) were monitored to determine safety and tolerability. Pharmacokinetic analyses assessed plasma concentrations of single and repeated doses of SLC-0111. RECIST 1.1 criteria were used to assess disease progression.
RESULTS: No dose-limiting toxicities were reported and patients dosed at ≤1000 mg exhibited fewer drug-related AEs ≥ grade 3 and fewer AEs such as nausea and vomiting, compared with the 2000-mg cohort. Forty-one percent of patients experienced dose interruptions or discontinuation and the majority (71%) of these occurred in the 2000-mg cohort. Mean Cmax and AUC(0-24) values for single doses were similar at the 1000-mg and 2000-mg dose levels. Mean Tmax and T1/2 values of SLC-0111 were similar after single and repeated dosing. Power-law analysis of Cmax and AUC0-24 showed that exposure to SLC-0111 was generally dose proportional. No objective responses were observed, but stable disease >24 weeks was observed in 2 patients.
CONCLUSIONS: SLC-0111 was safe in patients with previously treated, advanced solid tumors. The safety and pharmacokinetic data support 1000 mg/d as the recommended phase 2 dose for SLC-0111.

PMID: 32251122 [PubMed - as supplied by publisher]

Simplified approach to incorporating glycemic response within a continuous insulin infusion algorithm to improve incidence of hypoglycemia in a single burn center.

J Burn Care Res. 2020 Apr 06;:

Authors: Hendrix HA, Velamuri SR, Sultan-Ali I, Arif F, Hickerson WL, Hill DM

Abstract
Attaining adequate glycemic control in burn patients has been shown to reduce infection-related mortality. Previous internal evaluation of continuous insulin infusion (CII) use revealed a hypoglycemia rate of 0.6% and an average time within goal glycemic range (70-149 mg/dL) of 13.8 hours / day. A new algorithm, designed to adjust dosage based on glycemic response, underwent six iterations over two years before the final version was implemented. The purpose of this retrospective study was to assess the post-implementation performance of the newly-developed CII algorithm. The current study was powered to detect a 50% reduction in hypoglycemic events, as compared to a pre-implementation historical control. The cohort was 62 percent male with mean age of 54.5± 17.4. Sixty five percent had thermal injuries with a median 23.5 (11, 45) percent TBSA. . There were no differences in demographics between groups. Among the 20 records reviewed, 5,239 point-of-care glucoses were assessed. Post implementation, hypoglycemia rates were significantly lower (0.6% vs 0.2%; p < 0.001). There was no difference in median blood glucose between groups (149.9 mg / dL vs. 146.5 mg / dL; p = 0.56). Time spent within goal glycemic range was not significantly different (13.8 vs. 14.7 hours / day; p = 0.23). There were no differences in infection, length of stay, or survival. The consolidation, education, and implementation of a single, dynamic CII algorithm reduced the incidence of hypoglycemia. The authors expect, education and diligence with follow up glucose monitoring will further improve time within goal glycemic range by preventing rebound hyperglycemia.

PMID: 32249298 [PubMed - as supplied by publisher]

Acute mitragynine administration suppresses cortical oscillatory power and systems theta coherence in rats.

J Psychopharmacol. 2020 Apr 04;:269881120914223

Authors: Thériault RK, Manduca JD, Blight CR, Khokhar JY, Akhtar TA, Perreault ML

Abstract
BACKGROUND: Mitragynine is the major alkaloid of Mitragyna speciosa (kratom) with potential as a therapeutic in pain management and in depression. There has been debate over the potential side effects of the drug including addiction risk and cognitive decline.
AIMS: To evaluate the effects of mitragynine on neurophysiological systems function in the prefrontal cortex (PFC), cingulate cortex (Cg), orbitofrontal cortex, nucleus accumbens (NAc), hippocampus (HIP), thalamus (THAL), basolateral amygdala (BLA) and ventral tegmental area of rats.
METHODS: Local field potential recordings were taken from animals at baseline and for 45 min following mitragynine administration (10 mg/kg, intraperitoneally). Drug-induced changes in spectral power and coherence between regions at specific frequencies were evaluated. Mitragynine-induced changes in c-fos expression were also analyzed.
RESULTS: Mitragynine increased delta power and reduced theta power in all three cortical regions that were accompanied by increased c-fos expression. A transient suppression of gamma power in PFC and Cg was also evident. There were no effects of mitragynine on spectral power in any of the other regions. Mitragynine induced a widespread reduction in theta coherence (7-9 Hz) that involved disruptions in cortical and NAc connectivity with the BLA, HIP and THAL.
CONCLUSIONS: These findings show that mitragynine induces frequency-specific changes in cortical neural oscillatory activity that could potentially impact cognitive functioning. However, the absence of drug effects within regions of the mesolimbic pathway may suggest either a lack of addiction potential, or an underlying mechanism of addiction that is distinct from other opioid analgesic agents.

PMID: 32248751 [PubMed - as supplied by publisher]

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 2020/04/04

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.