-
The American Journal of Emergency... Jan 2021Due to the healthcare burden associated with migraines, prompt and effective treatment is vital to improve patient outcomes and ED workflow. This was a prospective,... (Randomized Controlled Trial)
Randomized Controlled Trial
Due to the healthcare burden associated with migraines, prompt and effective treatment is vital to improve patient outcomes and ED workflow. This was a prospective, randomized, double-blind trial. Adults who presented to the ED with a diagnosis of migraine from August of 2019 to March of 2020 were included. Pregnant patients, or with renal impairment were excluded. Patients were randomized to receive intravenous magnesium, prochlorperazine, or metoclopramide. The primary outcome was change in pain from baseline on a numeric rating scale (NRS) evaluated at 30 min after initiation of infusion of study drug. Secondary outcomes included NRS at 60 and 120 min, ED length of stay, necessity for rescue analgesia, and adverse effects. A total of 157 patients were analyzed in this study. Sixty-one patients received magnesium, 52 received prochlorperazine, and 44 received metoclopramide. Most patients were white females, and the median age was 36 years. Hypertension and migraines were the most common comorbidities, with a third of the patients reporting an aura. There was a median decrease in NRS at 30 min of three points across all three treatment arms. The median decrease in NRS (IQR) at 60 min was -4 (2-6) in the magnesium group, -3 (2-5) in the metoclopramide group, and -4.5 (2-7) in the prochlorperazine group (p = 0.27). There were no statistically significant differences in ED length of stay, rescue analgesia, or adverse effects. Reported adverse effects were dizziness, anxiety, and akathisia. No significant difference was observed in NRS at 30 min between magnesium, metoclopramide and prochlorperazine.
Topics: Administration, Intravenous; Adult; Double-Blind Method; Female; Humans; Magnesium; Male; Metoclopramide; Middle Aged; Migraine Disorders; Patient Satisfaction; Prochlorperazine; Prospective Studies; Severity of Illness Index; Time Factors
PubMed: 33041146
DOI: 10.1016/j.ajem.2020.09.033 -
Computational and Structural... 2020The status quo for combating uprising antibacterial resistance is to employ synergistic combinations of antibiotics. Nevertheless, the currently available combination...
The status quo for combating uprising antibacterial resistance is to employ synergistic combinations of antibiotics. Nevertheless, the currently available combination therapies are fast becoming untenable. Combining antibiotics with various FDA-approved non-antibiotic drugs has emerged as a novel strategy against otherwise untreatable multi-drug resistant (MDR) pathogens. The apex of this study was to investigate the mechanisms of antibacterial synergy of the combination of polymyxin B with the phenothiazines against the MDR Gram-negative pathogens Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. The synergistic antibacterial effects were tested using checkerboard and static time-kill assays. Electron microscopy (EM) and untargeted metabolomics were used to ascertain the mechanism(s) of the antibacterial synergy. The combination of polymyxin B and the phenothiazines showed synergistic antibacterial activity in checkerboard and static time-kill assays at clinically relevant concentrations against both polymyxin-susceptible and polymyxin-resistant isolates. EM revealed that the polymyxin B-prochlorperazine combination resulted in greater damage to the bacterial cell compared to each drug monotherapy. In metabolomics, at 0.5 h, polymyxin B monotherapy and the combination (to a greatest extent) disorganised the bacterial cell envelope as manifested by a major perturbation in bacterial membrane lipids (glycerophospholipids and fatty acids), peptidoglycan and lipopolysaccharide (LPS) biosynthesis. At the late time exposure (4 h), the aforementioned effects (except LPS biosynthesis) perpetuated mainly with the combination therapy, indicating the disorganising bacterial membrane biogenesis is potentially behind the mechanisms of antibacterial synergy. In conclusion, the study highlights the potential usefulness of the combination of polymyxin B with phenothiazines for the treatment of polymyxin-resistant Gram-negative infections (e.g. CNS infections).
PubMed: 32952938
DOI: 10.1016/j.csbj.2020.08.008 -
European Journal of Pharmacology Nov 2020In 2020 the whole world focused on antivirus drugs towards SARS-CoV-2. Most of the researchers focused on drugs used in other viral infections or malaria. We have not... (Review)
Review
In 2020 the whole world focused on antivirus drugs towards SARS-CoV-2. Most of the researchers focused on drugs used in other viral infections or malaria. We have not seen such mobilization towards one topic in this century. The whole situation makes clear that progress needs to be made in antiviral drug development. The first step to do it is to characterize the potential antiviral activity of new or already existed drugs on the market. Phenothiazines are antipsychotic agents used previously as antiseptics, anthelminthics, and antimalarials. Up to date, they are tested for a number of other disorders including the broad spectrum of viruses. The goal of this paper was to summarize the current literature on activity toward RNA-viruses of such drugs like chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine. We identified 49 papers, where the use of the phenothiazines for 23 viruses from different families were tested. Chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine possess anti-viral activity towards different types of viruses. These drugs inhibit clathrin-dependent endocytosis, cell-cell fusion, infection, replication of the virus, decrease viral invasion as well as suppress entry into the host cells. Additionally, since the drugs display activity at nontoxic concentrations they have therapeutic potential for some viruses, still, further research on animal and human subjects are needed in this field to verify cell base research.
Topics: Animals; Antipsychotic Agents; Antiviral Agents; Betacoronavirus; COVID-19; Chlorpromazine; Coronavirus Infections; Fluphenazine; Humans; Pandemics; Perphenazine; Phenothiazines; Pneumonia, Viral; Prochlorperazine; RNA Viruses; SARS-CoV-2; Thioridazine; COVID-19 Drug Treatment
PubMed: 32949606
DOI: 10.1016/j.ejphar.2020.173553 -
Paediatric and Perinatal Epidemiology Jan 2021Although nausea and vomiting of pregnancy (NVP) is common, the secular and demographic trends of NVP and its treatments are not well-studied.
BACKGROUND
Although nausea and vomiting of pregnancy (NVP) is common, the secular and demographic trends of NVP and its treatments are not well-studied.
OBJECTIVES
To describe the prevalence and patterns of first-trimester NVP and selected treatments among controls in the National Birth Defects Prevention Study (NBDPS).
METHODS
National Birth Defects Prevention Study is a population-based case-control study of birth defects in the United States (1997-2011). We collected self-reported data about NVP and use of commonly reported pharmacological and herbal/natural treatments (ondansetron, promethazine, pyridoxine, metoclopramide, doxylamine succinate, ginger, phosphorated carbohydrate solution, and prochlorperazine) from mothers of non-malformed control infants. We estimated the prevalence of NVP and selected treatments and examined secular and demographic trends (education, race/ethnicity, and maternal age) for such use, adjusting for study centre.
RESULTS
Among 10 540 mothers of controls, 7393 women (70.1%) reported first-trimester NVP, and 12.2% of those used one or more of the commonly reported treatments. Specific treatment use varied after adjustment for study centre (ondansetron: 3.4%; promethazine: 4.2%; pyridoxine: 3.2%; metoclopramide: 0.7%; doxylamine succinate: 1.7%; ginger: 1.0%; phosphorated carbohydrate solution: 0.4%; and prochlorperazine: 0.3%). Treatment use increased for each agent over the study period. Women with more years of education reported more NVP and treatment use. White (72%), Hispanic (71%), and other race (73%) women reported more NVP than Black women (67%); White women used selected NVP treatments most frequently, and Black women used them more than Hispanic women. Though women aged 25-34 years reported more NVP (72%) than younger (69%) or older (67%) women, the frequency of medication use was similar among women aged 25-34 and ≥35, and lower among women aged <25 years.
CONCLUSIONS
National Birth Defects Prevention Study controls reported NVP at frequencies similar to those previously reported. Of note, we observed an increase in use of selected treatments over time, and variations in NVP and treatments by study site and demographic factors.
Topics: Antiemetics; Case-Control Studies; Female; Humans; Infant; Nausea; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Vomiting
PubMed: 32623767
DOI: 10.1111/ppe.12705 -
Trials Jul 2020PRIMARY OBJECTIVE: To determine whether chemoprophylaxis with hydroxychloroquine versus placebo increases time to contracting coronavirus disease 2019 (COVID-19) in...
ChemoPROphyLaxIs with hydroxychloroquine For covId-19 infeCtious disease (PROLIFIC) to prevent covid-19 infection in frontline healthcare workers: A structured summary of a study protocol for a randomised controlled trial.
OBJECTIVES
PRIMARY OBJECTIVE: To determine whether chemoprophylaxis with hydroxychloroquine versus placebo increases time to contracting coronavirus disease 2019 (COVID-19) in frontline healthcare workers.
SECONDARY OBJECTIVES
1) To determine whether chemoprophylaxis with daily versus weekly dosing of hydroxychloroquine increases time to contracting COVID-19 disease in frontline healthcare workers. 2) To compare the number of COVID-19 cases between each trial arm on the basis of positive tests (as per current clinical testing methods and/or serology) 3) To compare the percentage of COVID-19 positive individuals with current testing methods versus serologically-proven COVID-19 in each trial arm 4) To compare COVID-19 disease severity in each trial arm 5) To compare recovery time from COVID-19 infection in each trial arm EXPLORATORY OBJECTIVES: 1) To determine compliance (as measured by trough pharmacokinetic hydroxychloroquine levels) on COVID-19 positive tests 2) To determine if genetic factors determine susceptibility to COVID-19 disease or response to treatment 3) To determine if blood group determines susceptibility to COVID-19 disease 4) To compare serum biomarkers of COVID-19 disease in each arm TRIAL DESIGN: Double-blind, multi-centre, 2-arm (3:3:2 ratio) randomised placebo-controlled trial PARTICIPANTS: National Health Service (NHS) workers who have direct patient contact delivering care to patients with COVID-19. Participants in the trial will be recruited from a number of NHS hospitals directly caring for patients with COVID-19.
INCLUSION CRITERIA
To be included in the trial the participant MUST: 1) Have given written informed consent to participate 2) Be aged 18 years to 70 years 3) Not previously have been diagnosed with COVID-19 4) Work in a high-risk secondary or tertiary healthcare setting (hospitals accepting COVID-19 patients) with direct patient-facing care EXCLUSION CRITERIA: The presence of any of the following will mean participants are ineligible: 1) Known COVID-19 positive test at baseline (if available) 2) Symptomatic for possible COVID-19 at baseline 3) Known hypersensitivity reaction to hydroxychloroquine, chloroquine or 4-aminoquinolines 4) Known retinal disease 5) Known porphyria 6) Known chronic kidney disease (CKD; eGFR<30ml/min) 7) Known epilepsy 8) Known heart failure or conduction problems 9) Known significant liver disease (Gilbert's syndrome is permitted) 10) Known glucose-6-phosphate dehydrogenase (G6PD) deficiency 11) Currently taking any of the following contraindicated medications: Digoxin, Chloroquine, Halofantrine, Amiodarone, Moxifloxacin, Cyclosporin, Mefloquine, Praziquantel, Ciprofloxacin, Clarithromycin, Prochlorperazine, Fluconazole 12) Currently taking hydroxychloroquine or having a clinical indication for taking hydroxychloroquine 13) Currently breastfeeding 14) Unable to be followed-up during the trial 15) Current or future involvement in the active treatment phase of other interventional research studies (excluding observational/non-interventional studies) before study follow-up visit 16) Not able to use or have access to a modern phone device/web-based technology 17) Any other clinical reason which may preclude entry in the opinion of the investigator INTERVENTION AND COMPARATOR: Interventions being evaluated are: A) Daily hydroxychloroquine or B) Weekly hydroxychloroquine or C) Placebo The maximum treatment period is approximately 13 weeks per participant. Hydroxychloroquine-identical matched placebo tablets will ensure that all participants are taking the same number and dosing regimen of tablets across the three trial arms. There is no variation in the dose of hydroxychloroquine by weight. The dosing regimen for the three arms of the study (A, B, C) are described in further detail below. Arm A: Active Hydroxychloroquine (- daily dosing and placebo-matched hydroxychloroquine - weekly dosing). Form: Tablets Route: Oral. Dose and Frequency: Active hydroxychloroquine: Days 1-2: Loading phase - 400mg (2 x 200mg tablets) taken twice a day for 2 days Days 3 onwards: Maintenance Phase - 200mg (1 x 200mg tablet) taken once daily, every day for 90 days (~3 months) Matched Placebo hydroxychloroquine: Days 3 onwards: Maintenance Phase - 2 tablets taken once a week on the same day each week (every 7 day) for 90 days (~3 months) Arm B: Active Hydroxychloroquine (- weekly dosing and placebo matched hydroxychloroquine - daily dosing.) Form: Tablets Route: Oral. Dose and Frequency: Active hydroxychloroquine: Days 1-2: Loading Phase - 400mg (2 x 200mg tablets) taken twice daily for 2 days Days 3 onwards: Maintenance Phase - 400mg (2 x 200mg tablets) taken once a week on the same day each week (every 7 day) for 90 days (~3 months) Matched Placebo hydroxychloroquine: Days 3 onwards: Maintenance Phase - 1 tablet taken once daily for 90 days (~3 months) Arm C: Matched placebo Hydroxychloroquine (- daily dosing and matched placebo hydroxychloroquine - weekly dosing.) Form: Table. Route: Oral. Frequency: Matched placebo hydroxychloroquine - daily dosing: Days 1-2: Loading Phase - 2 tablets taken twice daily for 2 days Days 3 onwards: Maintenance Phase - 1 tablet taken once daily for 90 days (~3 months) Matched placebo hydroxychloroquine - weekly dosing: Days 3 onwards: Maintenance Phase - 2 tablets taken once a week on the same day each week (every 7th day) for 90 days (~3 months) A schematic of the dosing schedule can be found in the full study protocol (Additional File 1).
MAIN OUTCOMES
Time to diagnosis of positive COVID-19 disease (defined by record of date of symptoms onset and confirmed by laboratory test) RANDOMISATION: Participants will be randomised to either hydroxychloroquine dosed daily with weekly placebo, HCQ dosed weekly with daily placebo, or placebo dosed daily and weekly. Randomisation will be in a 3:3:2 ratio [hydroxychloroquine-(daily), hydroxychloroquine-(weekly), placebo], using stratified block randomisation. Random block sizes will be used, and stratification will be by study site.
BLINDING (MASKING)
Participants and trial investigators consenting participants, delivering trial assessments and procedures will be blinded to intervention.
NUMBERS TO BE RANDOMISED (SAMPLE SIZE)
A sufficient number of participants will be enrolled so that approximately 1000 participants in total will have data suitable for the primary statistical analysis. It is anticipated that approximately 1,200 participants will need to be enrolled in total, to allow for a 20% dropout over the period of the trial. This would result in approximately 450:450:300 participants randomised to hydroxychloroquine daily, hydroxychloroquine weekly+daily matched placebo or matched-placebo daily and weekly.
TRIAL STATUS
V 1.0, 7 April 2020 EU Clinical Trials Register EudraCT Number: 2020-001331-26 Date of registration: 14 April 2020 Trial registered before first participant enrolment. Trial site is Cambridge University Hospitals NHS Foundation Trust. Recruitment started on 11 May 2020. It is anticipated that the trial will run for 12 months. The recruitment end date cannot yet be accurately predicted.
FULL PROTOCOL
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).
Topics: Adolescent; Adult; Aged; Antiviral Agents; Betacoronavirus; COVID-19; COVID-19 Testing; Chemoprevention; Clinical Laboratory Techniques; Coronavirus Infections; Drug Administration Schedule; England; Female; Health Personnel; Host-Pathogen Interactions; Humans; Hydroxychloroquine; Male; Medication Adherence; Middle Aged; Occupational Health; Pandemics; Pneumonia, Viral; Protective Factors; Randomized Controlled Trials as Topic; Remission Induction; Risk Assessment; Risk Factors; SARS-CoV-2; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult; COVID-19 Drug Treatment
PubMed: 32616067
DOI: 10.1186/s13063-020-04543-4 -
PeerJ 2020Medulloblastoma (MB) is the most common intracranial malignant tumor in children. The genes and pathways involved in the pathogenesis of MB are relatively unknown. We...
BACKGROUND
Medulloblastoma (MB) is the most common intracranial malignant tumor in children. The genes and pathways involved in the pathogenesis of MB are relatively unknown. We aimed to identify potential biomarkers and small-molecule drugs for MB.
METHODS
Gene expression profile data sets were obtained from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were identified using the Limma package in R. Functional annotation, and cell signaling pathway analysis of DEGs was carried out using DAVID and Kobas. A protein-protein interaction network was generated using STRING. Potential small-molecule drugs were identified using CMap.
RESULT
We identified 104 DEGs (29 upregulated; 75 downregulated). Gene ontology analysis showed enrichment in the mitotic cell cycle, cell cycle, spindle, and DNA binding. Cell signaling pathway analysis identified cell cycle, HIF-1 signaling pathway, and phospholipase D signaling pathway as key pathways. SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were the prominent hub genes and their expression level were verified by RT-qPCR. Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB. The five hub genes may be targets for diagnosis and treatment of MB, and the small-molecule compounds are promising drugs for effective treatment of MB.
CONCLUSION
In this study we obtained five hub genes of MB, SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were confirmed as hub genes. Meanwhile, Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB.
PubMed: 32328342
DOI: 10.7717/peerj.8670 -
Schizophrenia Research Jun 2020To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across four continents.
AIM
To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across four continents.
METHODS
Individually linked health data in Denmark (2000-2012), Finland (2005-2014), Iceland (2004-2017), Norway (2005-2015), Sweden (2006-2015), Germany (2006-2015), Australia (New South Wales, 2004-2012), Hong Kong (2001-2015), UK (2006-2016), and the US (Medicaid, 2000-2013, and IBM MarketScan, 2012-2015) were used. Using a uniformed approach, we estimated the prevalence of antipsychotic use as the proportion of pregnancies where a woman filled at least one antipsychotic prescription within three months before pregnancy until birth. For the Nordic countries, data were meta-analyzed to investigate maternal characteristics associated with the use of antipsychotics.
RESULTS
We included 8,394,343 pregnancies. Typical antipsychotic use was highest in the UK (4.4%) whereas atypical antipsychotic use was highest in the US Medicaid (1.5%). Atypical antipsychotic use increased over time in most populations, reaching 2% in Australia (2012) and US Medicaid (2013). In most countries, prochlorperazine was the most commonly used typical antipsychotic and quetiapine the most commonly used atypical antipsychotic. Use of antipsychotics decreased across the trimesters of pregnancy in all populations except Finland. Antipsychotic use was elevated among smokers and those with parity ≥4 in the Nordic countries.
CONCLUSION
Antipsychotic use during pregnancy varied considerably between populations, partly explained by varying use of the typical antipsychotic prochlorperazine, which is often used for nausea and vomiting in early pregnancy. Increasing usage of atypical antipsychotics among pregnant women reflects the pattern that was previously reported for the general population.
Topics: Antipsychotic Agents; Australia; Female; Finland; Germany; Hong Kong; Humans; Norway; Pregnancy; Sweden; United States
PubMed: 32295750
DOI: 10.1016/j.schres.2020.03.048 -
Case Reports in Neurology 2020The clinical presentation of repetitive choreiform involuntary movements of the anterior abdominal wall was first introduced as "belly dancer's dyskinesia." Etiologies...
The clinical presentation of repetitive choreiform involuntary movements of the anterior abdominal wall was first introduced as "belly dancer's dyskinesia." Etiologies of this rare condition include idiopathic causes, medication inducement, or post-abdominal surgery. We report a case of orobuccal stereotypic movements and abdominal wall dyskinesia secondary to prochlorperazine intake. The movements began 2 weeks after cessation of prochlorperazine. The patient took this dopamine receptor-blocking medication for 6 months to treat nausea due to chemotherapy. To our knowledge, abdominal wall dyskinesia as a tardive syndrome of prochlorperazine has not been previously reported.
PubMed: 32231546
DOI: 10.1159/000504336 -
The American Journal on Addictions Jul 2020Highly potent synthetic opioids (HPSO) are increasingly responsible for opioid overdose deaths in the United States.
BACKGROUND AND OBJECTIVES
Highly potent synthetic opioids (HPSO) are increasingly responsible for opioid overdose deaths in the United States.
METHODS
In an open-label, uncontrolled trial to test the feasibility of extended-release buprenorphine (BXR) injection treatment of heroin-using individuals with opioid use disorder testing positive for HPSO, participants were enrolled and began an induction with sublingual BXR (n = 5). During the induction, ancillary medications (clonidine, clonazepam, zolpidem, and prochlorperazine) were provided for breakthrough opioid withdrawal symptoms.
RESULTS
Two participants received the BXR injection on the second day of the induction and three participants on the third day.
DISCUSSION AND CONCLUSION
All five participants were retained at least 1-month postinduction.
SCIENTIFIC SIGNIFICANCE
It may be feasible to provide BXR treatment to HPSO-positive heroin users rapidly to achieve clinical stabilization. (Am J Addict 2020;00:00-00).
Topics: Adult; Buprenorphine; Delayed-Action Preparations; Female; Heroin Dependence; Humans; Induction Chemotherapy; Injections; Male; Middle Aged; Narcotic Antagonists; Psychotropic Drugs; Substance Withdrawal Syndrome; Treatment Outcome
PubMed: 32167629
DOI: 10.1111/ajad.13018