Efficacy and Safety of Apatinib in Treatment of Unresectable Intrahepatic Cholangiocarcinoma: An Observational Study.

Cancer Manag Res. 2020;12:5345-5351

Authors: Hu Y, Lin H, Hao M, Zhou Y, Chen Q, Chen Z

Abstract
Purpose: Unresectable intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The aim of this study was to evaluate the efficacy and safety of apatinib for patients with unresectable ICC.
Patients and Methods: A total of 10 patients with unresectable ICC were enrolled for this single-center observational study between March 2, 2016, and August 27, 2019. Subjects received 500 mg apatinib on a daily basis. Tumor response was assessed by 1.1 response evaluation criteria in solid tumors. The progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The drug-related adverse effects were also monitored.
Results: Based on the follow-up computed tomography and magnetic resonance imaging after treatment, 4 (40.0%), 4 (40.0%), and 2 (20.0%) patients achieved a partial response, stable disease, and progression of the disease, respectively. The response rate and disease control rate were 40.0% and 80.0%, respectively. The median PFS was 4.5 months (95% confidence interval: 3.157~5.843 months); the median OS was 6.5 months (95% confidence interval: 4.744~8.256 months). Furthermore, 3-, 6-, and 9-month OS rates were 77.5%, 61.7%, and 15.0%, respectively. The most common hematologic grade 3 adverse event was neutropenia (10%); the most common nonhematologic grade 3 adverse events were hypertension (20.0%) and hand-foot syndromes (20.0%). No treatment-related grade 4 or 5 adverse events were recorded.
Conclusion: Apatinib revealed to have antitumour activity in unresectable ICC patients, with manageable toxicities, and thus might be used as a new treatment option for patients with unresectable ICC.

PMID: 32753952 [PubMed]

The safety profile of favipiravir should not be the first argument to suspend its evaluation in viral hemorrhagic fevers.

PLoS Negl Trop Dis. 2020 06;14(6):e0008259

Authors: Malvy D, Taburet AM, de Lamballerie X, Mentre F, Extramiana F

PMID: 32584817 [PubMed - indexed for MEDLINE]

Clinical and economic impact of medication reconciliation in cancer patients: a systematic review.

Support Care Cancer. 2020 Aug;28(8):3557-3569

Authors: Herledan C, Baudouin A, Larbre V, Gahbiche A, Dufay E, Alquier I, Ranchon F, Rioufol C

Abstract
PURPOSE: Medication reconciliation can reduce drug-related iatrogenesis by facilitating exhaustive information transmission at care transition points. Given the vulnerability of cancer patients to adverse drug events, medication reconciliation could provide a significant clinical benefit in cancer care. This review aims to synthesize existing evidence on medication reconciliation in cancer patients.
METHODS: A comprehensive search was performed in the PubMed/Medline, Scopus, and Web of Science databases, associating the keywords "medication reconciliation" and "cancer" or "oncology."
RESULTS: Fourteen studies met the selection criteria. Various medication reconciliation practices were reported: performed at admission or discharge, for hospitalized or ambulatory patients treated with oral or parenteral anticancer drugs. In one randomized controlled trial, medication reconciliation decreased clinically significant medication errors by 26%. Although most studies were non-comparative, they highlighted that medication reconciliation led to identification of discrepancies and other drug-related problems in up to 88% and 94.7% of patients, respectively. The impact on post-discharge healthcare utilization remains under-evaluated and mostly inconclusive, despite a trend toward reduction. No comparative economic evaluations were available but one study estimated the benefit:cost ratio of medication reconciliation to be 2.31:1, suggesting its benefits largely outweigh its costs. Several studies also underlined the extended pharmacist time required for the intervention, highlighting the need for further cost analysis.
CONCLUSION: Medication reconciliation can reduce adverse drug events in cancer patients. More robust and economic evaluations are still required to support its development in everyday practice.

PMID: 32189099 [PubMed - indexed for MEDLINE]

[A preliminary study on molecular target identification of drugs in individualized treatment of malignant solid tumors in children].

Zhonghua Yi Xue Za Zhi. 2020 Aug 04;100(29):2283-2287

Authors: Chen R, Zhang Y, Xu CH, Cheng XY, Wu Y, Song DY, Xu HC, Liu XY

Abstract
Objective: To explore the role of drug-related molecular target identification in the individualized treatment of malignant solid tumors in children. Methods: The clinical data of 40 patients diagnosed with malignant solid tumors from Beijing Tongren Hospital, Capital Medical University, between June 2017 and March 2019 were retrospectively analyzed. Immunohistochemistry, polymerase chain reaction and sequencing methods were used to determine the expression levels and mutations of tumor drug molecular targets, and to compare the efficiency as well as the incidence of toxic side effects of chemotherapy using anti-tumor drugs with various molecular targets. Results: A total of 4 tumor drug-related targets were identified in 40 tumor tissue samples, namely DNA topoisomerase-ⅡA (TOPOⅡA), β(3)-tubulin (Tubulinβ(3)), DNA topoisomerase-Ⅰ(TOPOⅠ) and dihydrofolate reductase gene polymorphisms [DHFR (C829T)]. The effective rates of platinum-based agents, methotrexate, irinotecan, vinblastine and anthracycline for malignant solid tumors in children were 90.0% (36/40), 85.0% (34/40), 70.0% (28/40), 67.5% (27/40), 62.5% (25/40), respectively. The effective rates of chemotherapy with irinotecan, methotrexate, and vinblastine in mesenchymal tumors were 68.9% (20/29), 62.1% (18/29), 68.9% (20/29), respectively, which were considerably higher than 18.2% (2/11), 36.4% (4/11) and 36.4% (4/11) in non-mesenchymal tumors, with significant differences (χ(2)=5.487, 15.345, 17.278, all P<0.05). The effective rate of chemotherapy of platinum-based drugs for non-mesenchymal tumors was 72.3% (8/11), which was significantly higher than 58.6% (17/29) in mesenchymal tumors, and the difference was statistically significant (χ(2)=11.231, P<0.05). The intensity of toxic side effects in order from high to low was anthracycline > platinum > methotrexate > vinblastine > irinotecan. Conclusion: Tumor drug-related molecular targets and the sensitivity of tumors of different origins to the same anti-tumor drug as well as side effects are predicted, which provides a theoretical and clinical basis for individualized treatment of malignant tumors in children.

PMID: 32746599 [PubMed - in process]

Safety and efficacy of tocilizumab in the treatment of severe acute respiratory syndrome coronavirus-2 pneumonia: A retrospective cohort study.

Indian J Med Microbiol. 2020 Jan-Mar;38(1):117-123

Authors: Patel A, Shah K, Dharsandiya M, Patel K, Patel T, Patel M, Reljic T, Kumar A

Abstract
Background: Cytokine release storm (CRS) in severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) is thought to be the cause for organ damage and death which is independent of the actual viral burden. Tocilizumab (TCZ), an interleukin-6 receptor antagonist, is approved for the treatment of CRS. We describe the efficacy and safety of TCZ in SARS CoV-2 pneumonia.
Methods: This retrospective study was conducted at a tertiary care hospital from April 20 2020 to May 21 2020. The primary endpoint was the cumulative incidence of a composite of either need for admission to the intensive care unit (ICU) with invasive mechanical ventilation or death. Safety outcomes included an increase in liver transaminases and/or evidence of infection.
Results: A total of 20 patients received TCZ during the study period. The median age was 54 years (95% confidence interval [CI] 47-63). About 85% of the patients were male. Nearly 70% of the patients had at least one comorbidity. About 55% required ICU admission. The median duration of ICU stay was 11 days (95% CI: 3-13 days). The cumulative incidence of the requirement for mechanical ventilation, clinical improvement and mortality was 11% (95% CI: 0.03%-1%), 74% (95% CI 37%-89%) and 25% (95% CI: 11%-63%), respectively. There was no difference in outcomes according to age, gender or computed tomography severity score. Asymptomatic transaminitis was the most common drug reaction (55%), and one patient developed bacteraemia.
Conclusions: TCZ is likely a safe and effective modality of treatment for improving clinical and laboratory parameters of SARS CoV-2 patients with a reduction in ICU stay and ventilatory care need.

PMID: 32719218 [PubMed - indexed for MEDLINE]

Adverse effects of antipsychotic medication in patients with 22q11.2 deletion syndrome: A systematic review.

Am J Med Genet A. 2019 11;179(11):2292-2306

Authors: de Boer J, Boot E, van Gils L, van Amelsvoort T, Zinkstok J

Abstract
The 22q11.2 deletion syndrome (22q11.2DS) is a multisystem condition and the most prevalent microdeletion syndrome in humans. Approximately 25% of individuals with 22q11.2DS receive antipsychotic treatment. To assess whether patients with 22q11.2DS are vulnerable to adverse effects of antipsychotic medication, we carried out a literature review. A systematic search strategy was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Publications describing adverse effects of antipsychotic medication in patients with 22q11.2DS were included in the review and assessed for their methodological quality. A total of 11 publications reporting on eight trials, cross-sectional or cohort studies, and 30 case reports were included. The most commonly reported adverse effects can be classified into the following categories: movement disorders, weight gain, seizures, cardiac side effects, and cytopenias. Many of these symptoms are manifestations of 22q11.2DS, also in the absence of antipsychotic medication. Based on the reviewed literature, a causal relation between antipsychotic medication and the reported adverse effects could not be established in the majority of cases. Randomized clinical trials are needed to make firm conclusions regarding risk of adverse effects of antipsychotics in patients with 22q11.2DS.

PMID: 31407842 [PubMed - indexed for MEDLINE]

Phase II study of nedaplatin and amrubicin as first-line treatment for advanced squamous cell lung cancer.

Thorac Cancer. 2019 09;10(9):1764-1769

Authors: Taniguchi H, Yamaguchi H, Dotsu Y, Shimada M, Gyotoku H, Senju H, Takemoto S, Kitazaki T, Fukuda M, Ogawara D, Soda H, Nakatomi K, Sugasaki N, Kinoshita A, Nagashima S, Ikeda T, Nakamura Y, Sakamoto N, Obase Y, Fukuda M, Mukae H

Abstract
BACKGROUND: The first-line treatment for squamous cell lung cancer (SCC) has not necessarily been established; however, our previous exploratory study suggested that the combination of nedaplatin and amrubicin would be a promising treatment approach for patients with SCC. Therefore, a phase II study of this chemotherapeutic combination was designed to evaluate its efficacy and safety for treatment-naïve patients with advanced SCC.
METHODS: A total of 21 treatment-naïve patients with stage IIIB/IV or postoperative recurrent SCC were enrolled from six institutions. Nedaplatin (100 mg/m2 ) on day 1 and amrubicin (25 mg/m2 ) on days 1-3 were administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR), while the secondary endpoints included overall survival (OS), progression-free survival (PFS), and drug toxicities.
RESULTS: Partial response was observed in seven of 21 cases (ORR, 33.3%; 95% confidence interval [CI], 14.5-52.2). Disease control rate, which includes stable disease, was 71.4%. Median OS and PFS was 14.6 and 4.1 months, respectively. This regimen did not cause any treatment-related deaths. Grade 3/4 neutropenia developed in 8 of 21 cases (38.1%); however, febrile neutropenia developed in only 9.5% of the cases. Grade 3/4 gastrointestinal or neuromuscular toxicities were not observed.
CONCLUSION: The efficacy of the combination of nedaplatin and amrubicin was comparable to that of other conventional chemotherapeutic regimens for treatment-naïve patients with advanced SCC, and no severe gastrointestinal or neuromuscular toxicities were observed. This combination therapy may be an alternative treatment approach, particularly in patients who cannot tolerate gastrointestinal or neuromuscular toxicities.

PMID: 31309738 [PubMed - indexed for MEDLINE]

Tetrahydrocannabinol - friend or foe? - Debate.

Clin Toxicol (Phila). 2020 02;58(2):75-81

Authors: Temple LM, Leikin JB

Abstract
Background: Tetrahydrocannabinol (THC) is a psychoactive cannabinoid that has been used to treat various conditions. However, due to various adverse effects, its widespread promotion and use has been controversial. It is this aspect (encouraged by various state legislatures) that forms the basis for an edited debate between an Integrative Family Medicine physician and a Medical Toxicologist.Methods: Pro/Con debate with literature review and commentary.Discussion: Medical THC is beneficial for various conditions (especially pain relief). However the dosing, titration and delivery system has of yet to be precisely defined. There is a paucity of studies focusing on cannabidiol (CBD) efficacy without THC, which further complicates medical cannabis clinical studies. Cannabis toxicity tends to be cumulative, which makes it more difficult to identify at the bedside.Conclusion: There is conflicting data regarding the efficacy and toxicity of medical use of THC.

PMID: 31062643 [PubMed - indexed for MEDLINE]

The Potential Role of the J-Tpeak Interval in Proarrhythmic Cardiac Safety: Current State of the Science From the American College of Clinical Pharmacology and the Cardiac Safety Research Consortium.

J Clin Pharmacol. 2019 07;59(7):909-914

Authors: Vicente J, Strauss DG, Upreti VV, Fossler MJ, Sager PT, Noveck R

PMID: 30907981 [PubMed - indexed for MEDLINE]

Fifteen-minute consultation: Polydipsia, polyuria or both.

Arch Dis Child Educ Pract Ed. 2019 06;104(3):141-145

Authors: Mahon M, Amaechi G, Slattery F, Sheridan AL, Roche EF

Abstract
Children can present with polydipsia and/or polyuria for a number of reasons. We will discuss polydipsia and polyuria, how a child may present and how to investigate further in order to establish the cause. We highlight the important areas to cover in the history and examination of a child presenting with polydipsia and/or polyuria.

PMID: 30131352 [PubMed - indexed for MEDLINE]

Development of a method to determine the cost of breast cancer treatment with chemotherapy at Groote Schuur Hospital, Cape Town, South Africa.

S Afr Med J. 2020 Mar 30;110(4):296-301

Authors: Guzha NT, Thebe T, Butler N, Valodia PN

Abstract
BACKGROUND: There has been no comprehensive study determining the financial burden of breast cancer in the South African (SA) public sector.
OBJECTIVES: To develop a method to determine the cost of breast cancer treatment with chemotherapy per episode of care and to quantify the associated costs relating to chemotherapy at Groote Schuur Hospital (GSH), a government hospital in SA. These costs included costs associated with the management of adverse events arising from chemotherapy.
METHODS: Retrospective patient-level data were collected for 200 patients from electronic databases and patient folders between 2013 and 2015. Direct medical costs were determined from the health funder's perspective. The information collected was categorised into the following cost components: chemotherapy medicines, support medicines, administration of chemotherapy, laboratory tests, radiology scans and imaging, doctor consultations and adverse events. Time-and-motion studies were conducted on a set of new patients and the data obtained were used for the study sample of 200 patients. All the above costs were used to determine the cost of chemotherapy per episode of care. The episode of care was defined as the care provided from 2 months prior to the date of commencing chemotherapy (pre-chemotherapy phase), during chemotherapy (treatment phase) and until 6 months after the date when the last cycle of chemotherapy was administered (follow-up phase).
RESULTS: A method was developed to determine the episode-of-care costs for breast cancer at GSH. The total direct medical cost for treatment of breast cancer at GSH for 200 patients was ZAR3 154 877, and the average episode-of-care cost per patient was ZAR15 774. The average cost of management of adverse events arising from the various treatment modalities was ZAR13 133 per patient. It was found that the cost of treating a patient with adverse events was 1.8 times higher than the cost of treating a patient without adverse events. Of the patients, 86.5% managed to complete their prescribed chemotherapy treatment cycles, and the average cost of treatment of these patients was 1.3 times more than the average cost for patients who could not complete their treatment, based on the number of treatment cycles received.
CONCLUSION: A comprehensive method to determine the costs associated with breast cancer management per episode of care was developed, and costs were quantified at GSH according to the treatment protocol used at the hospital.

PMID: 32657741 [PubMed - indexed for MEDLINE]

Identifying underlying medical causes of pediatric obesity: Results of a systematic diagnostic approach in a pediatric obesity center.

PLoS One. 2020;15(5):e0232990

Authors: Kleinendorst L, Abawi O, van der Voorn B, Jongejan MHTM, Brandsma AE, Visser JA, van Rossum EFC, van der Zwaag B, Alders M, Boon EMJ, van Haelst MM, van den Akker ELT

Abstract
BACKGROUND: Underlying medical causes of obesity (endocrine disorders, genetic obesity disorders, cerebral or medication-induced obesities) are thought to be rare. Even in specialized pediatric endocrinology clinics, low diagnostic yield is reported, but evidence is limited. Identifying these causes is vital for patient-tailored treatment.
OBJECTIVES: To present the results of a systematic diagnostic workup in children and adolescents referred to a specialized pediatric obesity center.
METHODS: This is a prospective observational study. Prevalence of underlying medical causes was determined after a multidisciplinary, systematic diagnostic workup including growth charts analysis, extensive biochemical and hormonal assessment and genetic testing in all patients.
RESULTS: The diagnostic workup was completed in n = 282 patients. Median age was 10.8 years (IQR 7.7-14.1); median BMI +3.7SDS (IQR +3.3-+4.3). In 54 (19%) patients, a singular underlying medical cause was identified: in 37 patients genetic obesity, in 8 patients cerebral and in 9 patients medication-induced obesities. In total, thirteen different genetic obesity disorders were diagnosed. Obesity onset <5 years (p = 0.04) and hyperphagia (p = 0.001) were indicators of underlying genetic causes, but only in patients without intellectual disability (ID). Patients with genetic obesity with ID more often had a history of neonatal feeding problems (p = 0.003) and short stature (p = 0.005). BMI-SDS was not higher in patients with genetic obesity disorders (p = 0.52). Patients with cerebral and medication-induced obesities had lower height-SDS than the rest of the cohort.
CONCLUSIONS: To our knowledge, this is the first study to report the results of a systematic diagnostic workup aimed at identifying endocrine, genetic, cerebral or medication-induced causes of pediatric obesity. We found that a variety of singular underlying causes were identified in 19% of the patients with severe childhood obesity. Because of this heterogeneity, an extensive diagnostic approach is needed to establish the underlying medical causes and to facilitate disease-specific, patient-tailored treatment.

PMID: 32384097 [PubMed - indexed for MEDLINE]

Antibiotics and adverse events: the role of antimicrobial stewardship programs in 'doing no harm'.

Curr Opin Infect Dis. 2019 12;32(6):553-558

Authors: Bauer KA, Kullar R, Gilchrist M, File TM

Abstract
PURPOSE OF REVIEW: Antimicrobial resistance (AMR) is a global threat worldwide, with deaths associated with AMR infections projected to exceed 10 million per year by the year 2050. The overuse and misuse of antibiotics is the primary driver of this resistance, with up to 50% of antibiotics prescribed in the hospital setting being either unnecessary or inappropriate. Antimicrobial stewardship (AMS) programs (ASPs) can mitigate some of this resistance, with the benefits well recognized; however, if we are to truly advance the state of AMS, the principles and practices should align with patient safety.
RECENT FINDINGS: In a recent evaluation, among 1488 adult patients receiving systemic antibiotic therapy, 298 (20%) experienced at least one antibiotic-associated adverse drug event (ADE). Fifty-six (20%) nonclinically indicated antibiotic regimens were associated with an ADE. It is also well recognized that besides ADEs, the inappropriate use of antibiotics is associated the development of multidrug-resistant infections and Clostridium difficile infection.
SUMMARY: Currently, there is a significant gap in ASPs correlating initiatives with patient safety goals, including reductions in antibiotic-associated ADEs and multidrug-resistant infections. Therefore, in this article, we provide the rationale for why ASPs are best suited to lead a collaborative effort to prevent antibiotic-associated ADEs and multidrug-resistant infections.

PMID: 31567566 [PubMed - indexed for MEDLINE]

Quality of life in pediatric acute myeloid leukemia: Report from the Children's Oncology Group.

Cancer Med. 2019 08;8(9):4454-4464

Authors: Nagarajan R, Gerbing R, Alonzo T, Johnston DL, Aplenc R, Kolb EA, Meshinchi S, Barakat LP, Sung L

Abstract
INTRODUCTION: Objectives were used to describe guardian proxy-report and child self-report quality of life (QoL) during chemotherapy for pediatric acute myeloid leukemia (AML) patients.
METHODS: Patients enrolled on the phase 3 AML trial AAML1031 who were 2-18 years of age with English-speaking guardians were eligible. Instruments used were the PedsQL Generic Core Scales, Acute Cancer Module, and Multidimensional Fatigue Scale. Assessments were obtained at the beginning of Induction 1 and following completion of cycles 2-4. Potential predictors of QoL included the total number of nonhematological grade 3-4 Common Terminology Criteria for Adverse Event (CTCAE) submissions.
RESULTS: There were 505 eligible guardians who consented to participate and 348 of their children provided at least one self-report assessment. The number of submitted CTCAE toxicities was significantly associated with worse physical health summary scores (β ± standard error (SE) -3.00 ± 0.69; P < 0.001) and general fatigue (β ± SE -2.50 ± 0.66; P < 0.001). Older age was significantly associated with more fatigue (β ± SE -0.58 ± 0.25; P = 0.022). Gender, white race, Hispanic ethnicity, private insurance status, risk status, bortezomib assignment, and duration of neutropenia were not significantly associated with QoL.
DISCUSSION: The number of CTCAE toxicities was the primary factor influencing QoL among children with AML. Reducing toxicities should improve QoL; identifying approaches to ameliorate them should be a priority.

PMID: 31190442 [PubMed - indexed for MEDLINE]

Side effects from opioids used for acute pain after emergency department discharge.

Am J Emerg Med. 2020 04;38(4):695-701

Authors: Daoust R, Paquet J, Cournoyer A, Piette É, Morris J, Lessard J, Castonguay V, Williamson D, Chauny JM

Abstract
OBJECTIVE: Opioid side effects are common when treating chronic pain. However, the frequency of opioid side effects has rarely been examined in acute pain conditions, particularly in a post emergency department (ED) setting. The objective of this study was to evaluate the short-term incidence of opioid-induced side effects (constipation, nausea/vomiting, dizziness, drowsiness, sweating, and weakness) in patients discharged from the ED with an opioid prescription.
METHODS: This is a prospective cohort study of patients aged ≥18 years who visited the ED for an acute pain condition (≤2 weeks) and were discharged with an opioid prescription. Patients completed a 14-day diary assessing daily pain medication use and side effects.
RESULTS: We recruited 386 patients with a median age of 54 years (IQR:43-66); 50% were women. During the 2-week follow-up, 80% of patients consumed opioids. Among the patients who used opioids, 79% (95%CI:75-83) reported side effects compared to 38% (95%CI:27-49) for non-users. Adjusting for age, sex, and pain condition, patients who used opioids were more likely to report constipation (OR:7.5; 95%CI:3.1-17.9), nausea/vomiting (OR:4.1; 95%CI:1.8-9.5), dizziness (OR:5.4; 95%CI: 2.2-13.2), drowsiness (OR:4.6; 95%CI:2.5-8.7), and weakness (OR:4.2; 95%CI:1.6-11.0) compared to non-users. A dose-response trend was observed for constipation but not for the other side effects. Nausea/vomiting (OR:2.0; 95%CI:1.1-3.6) and dizziness (OR:1.9; 95%CI:1.1-3.4) were more often associated with oxycodone than with morphine.
CONCLUSION: As observed for chronic pain treatment, side effects are highly prevalent during short-term opioid treatment for acute pain. Physicians should inform patients about those side effects and should consider prescribing laxatives.

PMID: 31182367 [PubMed - indexed for MEDLINE]

New synthetic opioids: Part of a new addiction landscape.

Neurosci Biobehav Rev. 2019 11;106:133-140

Authors: Karila L, Marillier M, Chaumette B, Billieux J, Franchitto N, Benyamina A

Abstract
Synthetic opioids (SO) are a major risk for public health across the world. These drugs can be divided into 2 categories, pharmaceutical and non-pharmaceutical fentanyls. A new generation of SO has emerged on the drug market since 2010. North America is currently facing an opioid epidemic of morbi-mortality, caused by over-prescription of opioids, illegally diverted prescribed medicines, the increasing use of heroin and the emergence of SO. Furthermore, this opioid crisis is also seen in Europe. SO are new psychoactive substances characterized by different feature such as easy availability on the Internet, low price, purity, legality, and lack of detection in laboratory tests. They have not been approved or are not recommended for human use. Opioid misuse is associated with somatic and psychiatric complications. For many substances, limited pharmacological information is available, increasing the risk of harmful adverse events. Health actors and the general population need to be clearly informed of the potential risks and consequences of the diffusion and use of SO.

PMID: 30217656 [PubMed - indexed for MEDLINE]

Lavender and dodder combined herbal syrup versus citalopram in major depressive disorder with anxious distress: A double-blind randomized trial.

J Integr Med. 2020 Jun 15;:

Authors: Firoozeei TS, Barekatain M, Karimi M, Zargaran A, Akhondzadeh S, Rezaeizadeh H

Abstract
BACKGROUND: Major depressive disorder (MDD) accompanied by anxious distress is a chronic and disabling disorder. Its conventional drug therapies often have low patient compliance due to drug-related side effects. In Persian medicine, lavender-dodder syrup is one formula often recommended for such disorders.
OBJECTIVE: This study compares the effects of lavender-dodder syrup to the standard drug, citalopram, for treating MDD with anxious distress.
DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This six-week, double-blind, randomized, clinical trial was carried out in a psychiatric outpatient clinic. During the six-week intervention period, patients in citalopram group received citalopram tablets 20 mg/d plus 5 mL placebo syrup every 12 h; patients in group B received placebo tablets once daily plus 5 mL of lavender-dodder herbal syrup every 12 h.
MAIN OUTCOME MEASURES: Primary outcome measures, depression and anxiety, were evaluated using the Hamilton Depression/Anxiety Rating Scales, and were scored at the beginning of the study and at weeks three and six. Secondary outcome measures including response to treatment and remission rates were also compared between the two groups.
RESULTS: Fifty-six participants with MDD and anxious distress were randomly assigned to two groups. Mean depression scores significantly decreased in citalopram and herbal groups at weeks three and six (time effect: P < 0.001), although the observed changes were not significantly different between the groups (intervention effect: P = 0.61). Mean anxiety scores were not significantly different between the two groups at week three (P = 0.75). However, at the end of week six, the observed decrease was significantly higher in the herbal syrup group than the citalopram group (intervention effect: P = 0.007).
CONCLUSION: The herbal syrup is an effective and tolerable supplement for treating MDD with anxious distress.
TRIAL REGISTRATION NUMBER: IRCT2016102430459N1 on Iranian Registry of Clinical Trials.

PMID: 32739466 [PubMed - as supplied by publisher]

Current etiological comprehension and therapeutic targets of acetaminophen-induced hepatotoxicity.

Pharmacol Res. 2020 Jul 29;:105102

Authors: Chowdhury A, Jahan N, Adelusi Temitope I, Wang S

Abstract
Acetaminophen (APAP) is the most popular mild analgesic and antipyretic drug used worldwide. APAP overdose leads to drug-induced hepatotoxicity and can cause hepatic failure if treatment delayed. It is adequately comprehended that the metabolism of high-dose APAP by cytochrome P450 enzymes generates N-acetyl-p-benzoquinone imine (NAPQI), a toxic metabolite, which leads to glutathione (GSH) depletion, oxidative stress, and activation of various complex molecular pathways that initiate liver injury and downstream hepatic necrosis. Administration of activated charcoal followed by N-acetylcysteine (NAC) is considered the mainstay therapy; however, including side effects and limitation of rescuing for the delayed patients where liver transplantation may be a lifesaving procedure. Many complex signal transduction pathways such as c-Jun NH2-terminal kinase (JNK), mammalian target of rapamycin (mTOR), nuclear factor (NF)-κB, and NF (erythroid-derived 2)- like 2 (Nrf2) are involved in the development of APAP hepatotoxicity, but yet hasn't been comprehensively studied; thus, the search for effective antidotes and better management strategies continues. Here, we reviewed the most current advances to elucidate the etiological factors and therapeutic targets that could provide better strategies for the management of APAP-induced hepatotoxicity.

PMID: 32738495 [PubMed - as supplied by publisher]

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[Nocebo, informed consent and doctor-patient communication].

Nervenarzt. 2020 Jul 29;:

Authors: Hansen E, Zech N, Benson S

Abstract
Negative previous experiences (conditioning), observational learning and expectations can trigger nocebo effects. They are responsible for a substantial proportion of the side effects of medical treatment, and are induced primarily by risk information for informed consent. This has been demonstrated in studies on patient groups with or without modified medical information. Drug trials in the field of neurology and psychiatry have regularly revealed side effects and drop-out also in placebo groups. The underlying neurobiological mechanisms were experimentally investigated especially for nocebo-induced hyperalgesia, whereby the specifically involved regions of the brain could be identified by functional imaging as well as changes in the dopamine, endorphin and cholecystokinin systems. Nocebo effects are specific, i.e. they are closely related to patient information and can induce or aggravate exactly the symptoms addressed. Nevertheless, informed consent is an essential part of doctor-patient communication; however, information on risks can be markedly less damaging when unnecessary repetitions are avoided, misunderstandings are recognized or resolved and several different options are given. In addition, risks should always be named together with positive aspects, such as the advantages of the appropriate treatment, the prophylactic measures applied or the early detection and treatment of developing side effects. The best protection against harm caused by information on risks is a trustful doctor-patient relationship. Poor knowledge of nocebo effects or lack of countermeasures constitute a serious threat to patients and according to the current state of knowledge could be rated as medical malpractice.

PMID: 32728796 [PubMed - as supplied by publisher]