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ERJ Open Research Jan 2021Despite evidence that opioids might relieve chronic breathlessness, physicians may still be reluctant to prescribe them due to safety concerns. By contrast,...
BACKGROUND
Despite evidence that opioids might relieve chronic breathlessness, physicians may still be reluctant to prescribe them due to safety concerns. By contrast, benzodiazepine (BDZ) prescribing often seeks to reduce chronic breathlessness despite no evidence of net benefit. Prescribing patterns and indications for these medications in severe interstitial lung disease (ILD) are unknown. Here, our objective was to evaluate the indications, medications and temporal patterns of BDZ and opioid prescriptions in people with oxygen-dependent ILD.
METHODS
This was an observational, population-based, longitudinal study of adults starting long-term oxygen therapy (LTOT) for ILD between 2005 and 2014 in the Swedish National Registry for Respiratory Failure (Swedevox). People dispensed BDZs (n=2000) and opioids (n=2000) from 6 months before start of LTOT throughout follow-up (first of death or study end) were analysed.
RESULTS
Of 1635 included patients, 651 (39.8%) received BDZs and 710 (43.4%) received opioids during the study period; 373 (22.8%) patients received both. The most frequently prescribed BDZs and opioids were oxazepam (85.6%) and oxycodone (28.7%), respectively. Indications for breathlessness were uncommon for BDZs (1.4%) and opioids (6.4%). During the last year of life, opioid indications for breathlessness increased from 2.5% (12-10 months before death) to 10.2% in the last 3 months of life (p=0.048).
CONCLUSIONS
In oxygen-dependent ILD, opioids are rarely prescribed for breathlessness even in the last months of life, when chronic breathlessness often increases in prevalence and intensity.
PubMed: 33569492
DOI: 10.1183/23120541.00716-2020 -
The Cochrane Database of Systematic... Dec 2020Anxiety in relation to surgery is a well-known problem. Melatonin offers an alternative treatment to benzodiazepines for ameliorating this condition in the preoperative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anxiety in relation to surgery is a well-known problem. Melatonin offers an alternative treatment to benzodiazepines for ameliorating this condition in the preoperative and postoperative periods.
OBJECTIVES
To assess the effects of melatonin on preoperative and postoperative anxiety compared to placebo or benzodiazepines.
SEARCH METHODS
We searched the following databases on 10 July 2020: CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science. For ongoing trials and protocols, we searched clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform.
SELECTION CRITERIA
We included randomized, placebo-controlled or standard treatment-controlled (or both) studies that evaluated the effects of preoperatively administered melatonin on preoperative or postoperative anxiety. We included adult patients of both sexes (15 to 90 years of age) undergoing any kind of surgical procedure for which it was necessary to use general, regional, or topical anaesthesia.
DATA COLLECTION AND ANALYSIS
One review author conducted data extraction in duplicate. Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimens, preoperative anxiety outcome measures, and postoperative anxiety outcome measures.
MAIN RESULTS
We included 27 randomized controlled trials (RCTs), involving 2319 participants, that assessed melatonin for treating preoperative anxiety, postoperative anxiety, or both. Twenty-four studies compared melatonin with placebo. Eleven studies compared melatonin to a benzodiazepine (seven studies with midazolam, three studies with alprazolam, and one study with oxazepam). Other comparators in a small number of studies were gabapentin, clonidine, and pregabalin. No studies were judged to be at low risk of bias for all domains. Most studies were judged to be at unclear risk of bias overall. Eight studies were judged to be at high risk of bias in one or more domain, and thus, to be at high risk of bias overall. Melatonin versus placebo Melatonin probably results in a reduction in preoperative anxiety measured by a visual analogue scale (VAS, 0 to 100 mm) compared to placebo (mean difference (MD) -11.69, 95% confidence interval (CI) -13.80 to -9.59; 18 studies, 1264 participants; moderate-certainty evidence), based on a meta-analysis of 18 studies. Melatonin may reduce immediate postoperative anxiety measured on a 0 to 100 mm VAS compared to placebo (MD -5.04, 95% CI -9.52 to -0.55; 7 studies, 524 participants; low-certainty evidence), and may reduce delayed postoperative anxiety measured six hours after surgery using the State-Trait Anxiety Inventory (STAI) (MD -5.31, 95% CI -8.78 to -1.84; 2 studies; 73 participants; low-certainty evidence). Melatonin versus benzodiazepines (midazolam and alprazolam) Melatonin probably results in little or no difference in preoperative anxiety measured on a 0 to 100 mm VAS (MD 0.78, 95% CI -2.02 to 3.58; 7 studies, 409 participants; moderate-certainty evidence) and there may be little or no difference in immediate postoperative anxiety (MD -2.12, 95% CI -4.61 to 0.36; 3 studies, 176 participants; low-certainty evidence). Adverse events Fourteen studies did not report on adverse events. Six studies specifically reported that no side effects were observed, and the remaining seven studies reported cases of nausea, sleepiness, dizziness, and headache; however, no serious adverse events were reported. Eleven studies measured psychomotor and cognitive function, or both, and in general, these studies found that benzodiazepines impaired psychomotor and cognitive function more than placebo and melatonin. Fourteen studies evaluated sedation and generally found that benzodiazepine caused the highest degree of sedation, but melatonin also showed sedative properties compared to placebo. Several studies did not report on adverse events; therefore, it is not possible to conclude with certainty, from the data on adverse effects collected in this review, that melatonin is better tolerated than benzodiazepines.
AUTHORS' CONCLUSIONS
When compared with placebo, melatonin given as premedication (as tablets or sublingually) probably reduces preoperative anxiety in adults (measured 50 to 120 minutes after administration), which is potentially clinically relevant. The effect of melatonin on postoperative anxiety compared to placebo (measured in the recovery room and six hours after surgery) was also evident but was much smaller, and the clinical relevance of this finding is uncertain. There was little or no difference in anxiety when melatonin was compared with benzodiazepines. Thus, melatonin may have a similar effect to benzodiazepines in reducing preoperative and postoperative anxiety in adults.
Topics: Adult; Aged; Aged, 80 and over; Alprazolam; Anti-Anxiety Agents; Anxiety; Bias; Clonidine; Drug Administration Schedule; Humans; Melatonin; Midazolam; Middle Aged; Oxazepam; Postoperative Care; Postoperative Complications; Preoperative Care; Publication Bias; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 33319916
DOI: 10.1002/14651858.CD009861.pub3 -
Journal of Neural Transmission (Vienna,... Jan 2021To reduce potentially inappropriate medications, the FORTA (Fit fOR The Aged) concept classifies drugs in terms of their suitability for geriatric patients with...
To reduce potentially inappropriate medications, the FORTA (Fit fOR The Aged) concept classifies drugs in terms of their suitability for geriatric patients with different labels, namely A (indispensable), B (beneficial), C (questionable), and D (avoid). The aims of our study were to assess the medication appropriateness in PD inpatients applying the FORTA list and drug-drug interaction software, further to assess the adequacy of FORTA list for patients with PD. We retrospectively collected demographic data, comorbidities, laboratory values, and the medication from the discharge letters of 123 geriatric inpatients with PD at the university hospital of Hannover Medical School. Patients suffered on average from 8.2 comorbidities. The majority of the medication was labeled A (60.6% of PD-specific and 40.9% of other medication) or B (22.3% of PD-specific and 26.9% of other medication). Administered drugs labeled with D were amantadine, clozapine, oxazepam, lorazepam, amitriptyline, and clonidine. Overall, 545 interactions were identified, thereof 11.9% severe interactions, and 1.7% contraindicated combinations. 81.3% of patients had at least one moderate or severe interaction. The FORTA list gives rational recommendations for PD-specific and other medication, especially for general practitioners. Considering the demographic characteristics and the common multimorbidity of geriatric PD patients, this study underlines the importance of awareness, education, and preventive interventions to increase drug safety.
Topics: Aged; Comorbidity; Humans; Parkinson Disease; Pharmaceutical Preparations; Polypharmacy; Retrospective Studies
PubMed: 33263172
DOI: 10.1007/s00702-020-02276-x -
Cells Nov 2020The constitutive androstane receptor (CAR) is the essential regulator of genes involved both in xenobiotic and endobiotic metabolism. Diazepam has been shown as a potent...
The constitutive androstane receptor (CAR) is the essential regulator of genes involved both in xenobiotic and endobiotic metabolism. Diazepam has been shown as a potent stimulator of CAR nuclear translocation and is assumed as an indirect CAR activator not interacting with the CAR cavity. In this study, we sought to determine if diazepam is a ligand directly interacting with the CAR ligand binding domain (LBD) and if it regulates its target genes in a therapeutically relevant concentration. We used different CAR constructs in translocation and luciferase reporter assays, recombinant CAR-LBD in a TR-FRET assay, and target genes induction studied in primary human hepatocytes (PHHs), HepaRG cells, and in CAR humanized mice. We also used in silico docking and CAR-LBD mutants to characterize the interaction of diazepam and its metabolites with the CAR cavity. Diazepam and its metabolites such as nordazepam, temazepam, and oxazepam are activators of CAR+Ala in translocation and two-hybrid assays and fit the CAR cavity in docking experiments. In gene reporter assays with CAR3 and in the TR-FRET assay, only diazepam significantly interacts with CAR-LBD. Diazepam also promotes up-regulation of CYP2B6 in PHHs and in HepaRG cells. However, in humanized CAR mice, diazepam significantly induces neither nor genes nor does it regulate critical genes involved in glucose and lipids metabolism and liver proliferation. Thus, we demonstrate that diazepam interacts with human CAR-LBD as a weak ligand, but it does not significantly affect expression of tested CAR target genes in CAR humanized mice.
Topics: Adult; Animals; Cell Line; Cell Proliferation; Constitutive Androstane Receptor; Diazepam; Female; Genes, Reporter; Hepatocytes; Humans; Ligands; Liver; Male; Mice; Middle Aged; Protein Domains; Protein Transport; Receptors, Cytoplasmic and Nuclear
PubMed: 33255185
DOI: 10.3390/cells9122532 -
The Science of the Total Environment Jan 2021Pharmaceutically active compounds (PhACs) are ubiquitous in the aquatic environment worldwide and considered emerging contaminants. Their effects on growth, behavior,...
Pharmaceutically active compounds (PhACs) are ubiquitous in the aquatic environment worldwide and considered emerging contaminants. Their effects on growth, behavior, and physiological processes of aquatic organisms have been identified even at very low concentrations. Ecotoxicological investigations have primarily focused on single compound exposure, generally at a range of concentrations. In the natural environment, pollutants seldom occur in isolation, but little is known about the effects and risks of combinations of chemicals. This study aimed to investigate the effects of concurrent exposure to six psychoactive PhACs on locomotory behavior and life history traits of clonal marbled crayfish Procambarus virginalis. Crayfish were exposed to ~1 μg L of the antidepressants sertraline, citalopram, and venlafaxine; the anxiolytic oxazepam; the opioid tramadol; and the widely abused psychostimulant methamphetamine. In the absence of shelter, exposed crayfish moved significantly shorter distances and at lower velocity and showed significantly less activity than controls. With available shelter, exposed crayfish moved significantly more distance, showed higher activity, and spent a significantly more time outside the shelter than controls. Molting, mortality, and spawning frequency did not vary significantly between the groups. Hemolymph glucose level did not vary among groups and was not correlated with observed behaviors. Results suggest that environmental concentrations of the tested compounds in combination can alter the behavior of non-target aquatic organisms as individual exposure of these compounds, which may lead to disruption of ecosystem processes due to their reduced caution in polluted conditions. Further research is needed using varied chemical mixtures, exposure systems, and habitats, considering molecular and physiological processes connected to behavior alterations.
Topics: Animals; Aquatic Organisms; Astacoidea; Ecosystem; Methamphetamine; Pharmaceutical Preparations; Water Pollutants, Chemical
PubMed: 32882544
DOI: 10.1016/j.scitotenv.2020.141383 -
3 Biotech Jul 2020In the present study, a new strain of LW-03 was isolated from the bulbs of The isolated endophytic strain LW-03 exhibited excellent antifungal activity against common...
In the present study, a new strain of LW-03 was isolated from the bulbs of The isolated endophytic strain LW-03 exhibited excellent antifungal activity against common plant pathogens, such as , and . The growth inhibition percentage of was 74.56 ± 2.35%, which was the highest, followed by , , and were 71.91 ± 2.87%, 69.54 ± 2.73%, and 65.13 ± 1.91%, respectively. The ethyl acetate fraction revealed a number of bioactive compounds and several of which were putatively identified as antimicrobial agents, such as 4-hydroxy-2-nonenylquinoline -oxide, sphingosine ceramides like cer(d18:0/16:0(2OH)), cer(d18:0/16:0), and cer(d18:1/0:0), di-peptides, tri-peptide, cyclopeptides [cyclo(D-Trp-L-Pro)], [cyclo (Pro-Phe)], dehydroabietylamine, oxazepam, 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine like compound (PC(0:0/20:4), phosphatidylethanolamine (PE(18:1/0:0)), 3-Hydroxyoctadecanoic acid, 7.alpha.,27-Dihydroxycholesterol, -Acetyl-d-mannosamine, p-Hydroxyphenyllactic acid, Phytomonic acid, and 2-undecenyl-quinoloin-4 (1H). The LW-03 strain exhibits multiple plant growth-promoting traits, including the production of organic acids, ACC deaminase, indole-3-acetic acid (IAA), siderophores, and nitrogen fixation activity. The beneficial effects of the endophytic strain LW-03 on the growth of two lily varieties were further evaluated under greenhouse conditions. Our results revealed plant growth-promoting activity in inoculated plants relative to non-inoculated control plants. The broad-spectrum antifungal activity and multiple plant growth-promoting properties of LW-03 make it an important player in the development of biological fertilizers and sustainable agricultural biological control strategies.
PubMed: 32612899
DOI: 10.1007/s13205-020-02294-2 -
Tidsskrift For Den Norske Laegeforening... Jun 2020Benzodiazepines are also used as intoxicants. This can be dangerous, particularly in multi-substance abuse. We describe cases of acute poisoning related to substance...
BACKGROUND
Benzodiazepines are also used as intoxicants. This can be dangerous, particularly in multi-substance abuse. We describe cases of acute poisoning related to substance abuse of benzodiazepines in patients at the main A&E clinic in Oslo.
MATERIAL AND METHOD
We included all patients treated for substance abuse poisoning with benzodiazepines and/or z-hypnotics at the Oslo Accident and Emergency Outpatient Clinic from 1 October 2013 to 30 September 2015. The patients were found through a retrospective review of the A&E clinic's registers. Data were taken from patient records. Diagnosis of the toxic agent was based on the attending doctor's recorded clinical evaluation.
RESULTS
Of 1 037 cases, 787 (76 %) were men. The median age was 36 (interquartile range 28-46, range 14-78). Clonazepam (Rivotril) was the most frequently occurring drug, with 575 cases (55 %), followed by diazepam (Stesolid, Valium, Vival) 158 (15 %), alprazolam (Xanor) 125 (12 %) and oxazepam (Sobril) 94 (9 %). Zopiclone (Imovane, Zopitin) and zolpidem (Stilnoct) occurred rarely, in 25 (2 %) and 11 (1 %) cases, respectively. Benzodiazepines were combined with other intoxicants in 936 (90 %) cases, most frequently heroin 484 (47 %), ethanol 321 (31 %) and amphetamine 199 (19 %).
INTERPRETATION
In substance abuse poisoning, benzodiazepines were very often combined with other intoxicants, most frequently opioids, ethanol and/or amphetamine.
Topics: Adult; Analgesics, Opioid; Benzodiazepines; Female; Humans; Hypnotics and Sedatives; Male; Poisoning; Retrospective Studies; Substance-Related Disorders
PubMed: 32602327
DOI: 10.4045/tidsskr.20.0035 -
Chemosphere Nov 2020The occurrence and distribution of 111 organic micropollutants (OMPs) were evaluated in water and sediment samples from Lake Mälaren, Sweden, using a liquid...
The occurrence and distribution of 111 organic micropollutants (OMPs) were evaluated in water and sediment samples from Lake Mälaren, Sweden, using a liquid chromatography-tandem mass spectrometry method. The partitioning of contaminants between lake compartments was estimated using solid water distribution coefficients (K) and organic carbon-water partitioning coefficients (K). In total, 30 and 24 OMPs were detected in lake water and sediment, respectively. Concentrations ranged from low ng/L to 89 ng/L (lamotrigine) in lake water and from low ng/g dry weight (dw) to 28 ng/g dw (citalopram) in sediment. Carbamazepine, lamotrigine, caffeine, and tolyltriazole were the dominant compounds in Lake Mälaren samples (both water and sediment). Seventeen OMPs were detected in both water and sediment samples, including carbamazepine, DEET, tolyltriazole, bicalutamide, caffeine, lamotrigine, and cetirizine. Log K values varied between 0.84 for lamotrigine and 4.4 for citalopram, while log K values varied between 2.1 for lamotrigine and 5.9 for citalopram. These results indicate that sorption to sediment plays a minor role in removal of all OMPs analyzed in the aqueous phase except for citalopram and cetirizine, which showed high sorption potential. The environmental risks of OMPs were assessed based on the RQ values. The worst-case scenario for environmental risk assessment was conducted using the maximum measured environment concentration. For most of the target OMPs, including tolyltriazole, bicalutamide, fexofenadine, oxazepam, cetirizine, and diclofenac, the RQ values were below 0.01, indicating low or no risk to lake ecosystems.
Topics: Ecosystem; Ecotoxicology; Environmental Monitoring; Geologic Sediments; Lakes; Sweden; Water Pollutants, Chemical
PubMed: 32535449
DOI: 10.1016/j.chemosphere.2020.127293 -
Neurobiology of Sleep and Circadian... May 2020Multiple sclerosis (MS) is an autoimmune disease of the nervous system which appears with de-myelination of the central nervous system. Sleep disorder and fatigue are...
BACKGROUND
Multiple sclerosis (MS) is an autoimmune disease of the nervous system which appears with de-myelination of the central nervous system. Sleep disorder and fatigue are very common in MS patients and are part of the main debilitating factors in patients. The present study was conducted to survey sleep quality and fatigue in MS patients.
METHODS
A descriptive-analytical study was conducted on 87 MS patients, who were referred to the Kermanshah MS Center in 2017. Data collection tools include a demographics form, fatigue severity scale, and Pittsburg sleep quality inventory. The questionnaires were self-reporting. The collected data was analyzed in SPSS23.
RESULTS
The mean age of the participants was 35.50±9.25 years and the majority of the participants were married (54; 62.1%). Quality of sleep was related to family history of MS and history of using medications (antidepressants like tricyclics, MAOIs, SSRIs, and SNRIs and anxiety drugs such as diazepam, oxazepam, and alprazolam (p < 0.05). Moreover, there was a significant relationship between length of sleep and history of using medicines (p < 0.05). Finally, the results showed that there was a strong statistical relationship between performance during the day and fatigue (p < 0.05).
CONCLUSIONS
The results recommend holding relaxation and exercise courses by nurses to ease fatigue in MS patients. Clinics can also play a more effective role by being more supportive and holding more efficient training programs. The program is taught by the researchers.
TRIAL REGISTRATION
This study was carried out following the permission from Ethics Committee, Department of Research and Technology, Kermanshah University of Medical Sciences (approval number: KUMS.REC.1395.680).
PubMed: 32455178
DOI: 10.1016/j.nbscr.2020.100050 -
Open Medicine (Warsaw, Poland) 2019Münchausen syndrome can be characterized by simulated illness, pathological lying and wandering from place to place (the patient typically presents to numerous...
Münchausen syndrome can be characterized by simulated illness, pathological lying and wandering from place to place (the patient typically presents to numerous hospitals). Individuals with elevated blood pressure due to non-adherence to medication have the so-called pseudo-resistant hypertension. A 45-year-old woman was admitted to hospital on an emergency basis because of a hypertensive crisis. Despite combination antihypertensive treatment, normalization of blood pressure was not achieved and a device to produce a therapeutic arteriovenous fi stula was implanted. Aft er the procedure, a signifi cant increase in pulmonary artery pressure was observed and closure of the fistula was performed by implantation of the stent graft . The suspicion was raised that the patient had not been taking her prescribed medications. Therefore, blood samples were taken and the serum was analyzed for presence of the prescribed drugs (atorvastatin, bisoprolol, chlorthalidone, clonidine, doxazosin, furosemide, nitrendipine, oxazepam and valsartan). The results confirmed suspected failure of the patient to take the prescribed medications. Münchausen syndrome is usually first suspected when inexplicable laboratory test results are noted. To our knowledge, this is the first reported case of Münchausen syndrome with pseudo-resistant hypertension leading to the implantation of a device to produce a therapeutic arteriovenous fi stula.
PubMed: 31737783
DOI: 10.1515/med-2019-0094