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The Cochrane Database of Systematic... May 2022Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently,... (Review)
Review
BACKGROUND
Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently, synthesis inhibitors of oestrogen (such as letrozole) have also been used to enhance efficacy. The most widely researched drugs are prostaglandins (such as misoprostol, which has a strong uterotonic effect), mifepristone, mifepristone with prostaglandins, and letrozole with prostaglandins. More evidence is needed to identify the best dosage, regimen, and route of administration to optimise patient outcomes. This is an update of a review last published in 2011.
OBJECTIVES
To compare the effectiveness and side effects of different medical methods for first trimester abortion.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Global Health, and LILACs on 28 February 2021. We also searched Clinicaltrials.gov and the World Health Organization's (WHO) International Clinical Trials Registry Platform, and reference lists of retrieved papers.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) that compared different medical methods for abortion before the 12th week of gestation. The primary outcome is failure to achieve complete abortion. Secondary outcomes are mortality, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the method.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected and evaluated studies for inclusion, and assessed the risk of bias. We processed data using Review Manager 5 software. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 99 studies in the review (58 from the original review and 41 new studies). 1. Combined regimen mifepristone/prostaglandin Mifepristone dose: high-dose (600 mg) compared to low-dose (200 mg) mifepristone probably has similar effectiveness in achieving complete abortion (RR 1.07, 95% CI 0.87 to 1.33; I = 0%; 4 RCTs, 3494 women; moderate-certainty evidence). Prostaglandin dose: 800 µg misoprostol probably reduces abortion failure compared to 400 µg (RR 0.63, 95% CI 0.51 to 0.78; I= 0%; 3 RCTs, 4424 women; moderate-certainty evidence). Prostaglandin timing: misoprostol administered on day one probably achieves more success on complete abortion than on day three (RR 1.94, 95% CI 1.05 to 3.58; 1489 women; 1 RCT; moderate-certainty evidence). Administration strategy: there may be no difference in failure of complete abortion with self-administration at home compared with hospital administration (RR 1.63, 95% CI 0.68 to 3.94; I = 84%; 2263 women; 4 RCTs; low-certainty evidence), but failure may be higher when administered by nurses in hospital compared to by doctors in hospital (RR 2.69, 95% CI 1.39 to 5.22; I = 66%; 3 RCTs, 3056 women; low-certainty evidence). Administration route: oral misoprostol probably leads to more failures than the vaginal route (RR 2.38, 95% CI 1.46 to 3.87; I = 39%; 3 RCTs, 1704 women; moderate-certainty evidence) and may be associated with more frequent side effects such as nausea (RR 1.14, 95% CI 1.03 to 1.26; I = 0%; 2 RCTs, 1380 women; low-certainty evidence) and diarrhoea (RR 1.80 95% CI 1.49 to 2.17; I = 0%; 2 RCTs, 1379 women). Compared with the vaginal route, complete abortion failure is probably lower with sublingual (RR 0.68, 95% CI 0.22 to 2.11; I = 59%; 2 RCTs, 3229 women; moderate-certainty evidence) and may be lower with buccal administration (RR 0.71, 95% CI 0.34 to 1.46; I = 0%; 2 RCTs, 479 women; low-certainty evidence), but sublingual or buccal routes may lead to more side effects. Women may experience more vomiting with sublingual compared to buccal administration (RR 1.33, 95% CI 1.01 to 1.77; low-certainty evidence). 2. Mifepristone alone versus combined regimen The efficacy of mifepristone alone in achieving complete abortion compared to combined mifepristone/prostaglandin up to 12 weeks is unclear (RR of failure 3.25, 95% CI 0.81 to 13.09; I = 83%; 3 RCTs, 273 women; very low-certainty evidence). 3. Prostaglandin alone versus combined regimen Nineteen studies compared prostaglandin alone to a combined regimen (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate). Compared to any of the combination regimens, misoprostol alone may increase the risk for failure to achieve complete abortion (RR of failure 2.39, 95% CI 1.89 to 3.02; I = 64%; 18 RCTs, 3471 women; low-certainty evidence), and with more diarrhoea. 4. Prostaglandin alone (route of administration) Oral misoprostol alone may lead to more failures in complete abortion than the vaginal route (RR 3.68, 95% CI 1.56 to 8.71, 2 RCTs, 216 women; low-certainty evidence). Failure to achieve complete abortion may be slightly reduced with sublingual compared with vaginal (RR 0.69, 95% CI 0.37 to 1.28; I = 87%; 5 RCTs, 2705 women; low-certainty evidence) and oral administration (RR 0.58, 95% CI 0.11 to 2.99; I = 66%; 2 RCTs, 173 women). Failure to achieve complete abortion may be similar or slightly higher with sublingual administration compared to buccal administration (RR 1.11, 95% CI 0.71 to 1.74; 1 study, 401 women).
AUTHORS' CONCLUSIONS
Safe and effective medical abortion methods are available. Combined regimens (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate) may be more effective than single agents (prostaglandin alone or mifepristone alone). In the combined regimen, the dose of mifepristone can probably be lowered to 200 mg without significantly decreasing effectiveness. Vaginal misoprostol is probably more effective than oral administration, and may have fewer side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all studies were conducted in settings with good access to emergency services, which may limit the generalisability of these results.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Spontaneous; Diarrhea; Drug Therapy, Combination; Estradiol; Female; Humans; Letrozole; Methotrexate; Mifepristone; Misoprostol; Oxytocics; Pregnancy; Pregnancy Trimester, First; Prostaglandins; Tamoxifen
PubMed: 35608608
DOI: 10.1002/14651858.CD002855.pub5 -
Cannabis and Cannabinoid Research Aug 2023This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Bibliographic and clinical trial registries were searched for... (Review)
Review
This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Bibliographic and clinical trial registries were searched for interventional human trials using cutaneously administered CBD or reported plasma CBD concentrations (any species). Eight of 544 articles fitted the selection criteria: 3 placebo-controlled randomized and 5 single-arm trials. Eleven more studies were found in clinical trial databases but not accessible. Symptoms targeted were dermatopathologies or safety (two studies), pain (two), and behavior (one). Doses were 50-250 mg or 0.075-1.0% CBD, but coformulated with other ingredients. Risk of bias was high and reporting deficiencies further compromised data reliability. Diverse methodologies and formulations hampered syntheses for CBD dose, efficacy, and safety. Plasma CBD levels in dogs and rodents were 0.01-5 μM translating to <100 nM free, unbound CBD in humans. Adverse events were uncommon and mild, but meaningless without CBD's contribution to efficacy data. Achievable CBD plasma concentrations ∼100 nM can interact predominantly with high-affinity CBD targets, for example, TRPA1 and TRPM8 membrane channels that are abundantly expressed in pathological conditions. Even if reached, higher CBD concentrations on less susceptible targets risk complex and unsafe CBD therapy. A conceptual framework is proposed where dermal capillary loops create sinking for topical CBD demonstrating parallels between topical and transdermal CBD administration. Users risk generalizing inadequately designed trials to all CBD preparations. New clinical trials are urgently needed: they must demonstrate that outcomes are solely from CBD pharmacology, are reliable, unbiased, safe, and comparable. Measurements of sustained plasma CBD levels are mandatory, irrespective of administration route for successful translation from systems that express human molecular targets. Placebos must be appropriate. Transcutaneous and topical formulations need preliminary studies to optimize CBD skin penetration. Then, users can rationally balance efficacy against potential harms and cost-effectiveness of CBD formulations.
Topics: Humans; Animals; Dogs; Cannabidiol; Reproducibility of Results; Pain; Administration, Cutaneous; Seizures
PubMed: 35605018
DOI: 10.1089/can.2021.0154 -
European Journal of Clinical... May 2021Ketamine has rapid-onset antidepressant effects in patients with treatment-resistant depression. Common side effects include dissociation (a sense of detachment from...
PURPOSE
Ketamine has rapid-onset antidepressant effects in patients with treatment-resistant depression. Common side effects include dissociation (a sense of detachment from reality) and increases in systolic and diastolic blood pressure. The objective of this structured review was to examine the effect of ketamine formulation and route of administration on its pharmacokinetics, safety and tolerability, to identify formulation characteristics and routes of administration that might minimise side effects.
METHODS
This was a structured review of published ketamine pharmacokinetics, safety and tolerability data for any ketamine formulation. The ratio of ketamine:norketamine was calculated from reported C values, as a measure of first pass metabolism. The effect of formulation and route of administration on safety was evaluated by measuring mean changes in systolic blood pressure and tolerability by changes in dissociation ratings. Data were correlated using Spearman's method.
RESULTS
A total of 41 treatment arms were identified from 21 publications, and included formulation development studies in healthy volunteers, and studies in clinical populations (patients undergoing anaesthesia, or being treated for pain or depression). Ketamine:norketamine ratios were strongly positively correlated with change in dissociation ratings (r = 0.89) and change in blood pressure (r = 0.96), and strongly negatively correlated with ketamine T (r = - 0.87; p < 0.00001 for all). Ketamine T strongly positively correlated with a change in dissociation ratings (r = - 0.96) and change in blood pressure (r = - 0.99; p < 0.00001 for all).
CONCLUSION
Ketamine formulations that maximize first pass metabolism and delay T will be better tolerated and safer than formulations which lack those characteristics.
Topics: Antidepressive Agents; Dissociative Disorders; Drug Administration Routes; Drug Delivery Systems; Humans; Hypertension; Ketamine; Metabolic Clearance Rate
PubMed: 33210159
DOI: 10.1007/s00228-020-03047-z -
Current Drug Discovery Technologies 2022Turmeric (Curcuma longa L.) is a popular spice containing curcumin that is responsible for its therapeutic effects. Curcumin with anti-inflammatory, antioxidant,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Turmeric (Curcuma longa L.) is a popular spice containing curcumin that is responsible for its therapeutic effects. Curcumin with anti-inflammatory, antioxidant, anti-cancer, and antimicrobial activities has led to a lot of research focusing on it over the years. This systematic review aimed to evaluate research on the anti-Plasmodium berghei activity of curcumin and its derivatives.
METHODS
Our study was performed according to PRISMA guidelines and was recorded in the database of a systematic review and preclinical meta-analysis of CAMARADESNC3Rs (SyRF). The search was performed in five databases, namely Scopus, PubMed, Web of Science, EMBASE, and Google Scholar, from 2010 to 2020. The following keywords were searched: "Plasmodium berghei", "Medicinal Plants", "Curcumin", "Concentration", Animals kind", "Treatment Durations", "Routes of Administration" and "in vivo".
RESULTS
Of the 3,500 papers initially obtained, 14 articles were reliable and were thus scrutinized. Animal models were included in all studies. The most commonly used animal strain was Albino (43%), followed by C57BL/6 (22%). The other studies used various murine strains, including BALB/c (14%) and ICR (7%). Two (14%) studies did not mention the strain of animal model used. Curcumin alone or in combination with other compounds depending on the dose used, route of administration, and animal model showed a moderate to strong anti-Plasmodium berghei effect.
CONCLUSION
According to the studies, curcumin has anti-malarial effects on Plasmodium berghei, and, however, its effect on human Plasmodium is unclear. Due to the side effects and drug resistance of current drugs in the treatment of human malaria, the use of new compounds with few or no side effects, such as curcumin, is recommended as an alternative or complementary treatment.
Topics: Animals; Anti-Inflammatory Agents; Antimalarials; Curcumin; Malaria; Mice; Plasmodium berghei
PubMed: 35293297
DOI: 10.2174/1570163819666220315140736 -
Vaccine Feb 2021There are a myriad of vaccine schedules for rabies pre- (PrEP) and post-exposure prophylaxis (PEP) that differ in the number and timedoses, number of visits, length of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are a myriad of vaccine schedules for rabies pre- (PrEP) and post-exposure prophylaxis (PEP) that differ in the number and timedoses, number of visits, length of schedule, and route of administration. The objective of this study was to systematically review the evidence and investigate how thedifferences in schedules influence titres over time.
METHODS
Four databaseswere searched from inception to January 2020 for rabies PrEP and PEP studies. Adose-response meta-analysis was utilised to pool geometric mean titres (GMT) over time. Subgroup analyses by route of administration, age group, and schedule were conducted.
RESULTS
80 studies met the inclusion criteria and contributed with 191 datasets and 12,413 participants. Both intradermal (ID) and intramuscular (IM) PrEP/PEP produce adequate GMTs. Significantly lower GMT levels were achieved in older (>50yrs) compared to younger (<50yrs) participants. Short 1-week schedules were as effective as longer schedules that can take between 3 and 12 weeks to complete.
CONCLUSIONS
Several effective ID and IM schedules were identified, the selection of a schedule should take into account the patient's needs, costs, availability to return for subsequent doses, and the time required to complete the schedule. Older individuals warrant special attention as they develop lower antibody response.
Topics: Aged; Antibodies, Viral; Humans; Injections, Intradermal; Injections, Intramuscular; Post-Exposure Prophylaxis; Rabies; Rabies Vaccines; Vaccination
PubMed: 33478786
DOI: 10.1016/j.vaccine.2021.01.023 -
Farmacia Hospitalaria : Organo Oficial... May 2024To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and... (Review)
Review
PURPOSE
To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety.
METHODS
Systematic review on the databases PubMed, ISI Web of Science, SCOPUS and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1,040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included.
RESULTS
NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischemia and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA.
CONCLUSIONS
Peripheral infusions of NA could be a safe and beneficial option in early resuscitation provided that a number of guidelines are followed that reduce the likelihood of complications associated with this route.
PubMed: 38724402
DOI: 10.1016/j.farma.2024.04.003 -
Naunyn-Schmiedeberg's Archives of... Feb 2023Terbutaline is used for the management of bronchospasm associated with asthma, bronchitis, emphysema, and chronic obstructive pulmonary disease. A systematic review... (Review)
Review
Terbutaline is used for the management of bronchospasm associated with asthma, bronchitis, emphysema, and chronic obstructive pulmonary disease. A systematic review would be beneficial to assess the impact of routes of administration, stereoisomerism, disease states, smoking, age, exercise, and chronobiology on pharmacokinetics (PK) of terbutaline in humans. PubMed and Google Scholar databases were searched to screen all the relevant articles consisting of at least one of the PK parameters after administration of oral, inhaled, and intravenous (IV) terbutaline in humans. Oral studies of terbutaline depicted a linear relationship between plasma concentration (C) and the administered dose. The IV studies demonstrated multi-exponential behavior for disposition and renal clearance. Higher systemic availability was observed with inhaled as compared to oral route, and chrono-pharmacokinetic behavior was notable. Time to reach maximum plasma concentration (T) was prolonged, and maximum plasma concentration (C) was lowered after exercise. The primary route of excretion in chronic kidney disease (CKD) patients is reported to be nonrenal. In pregnant women, the C of terbutaline is lowered and clearance is increased. The addition of theophylline to terbutaline did not affect the PK of terbutaline; hence, both can be used without dose adjustment. This review summarizes all the available PK parameters of terbutaline, and it may be helpful for researchers in the development and evaluation of PK models as well as in designing optimal dosage regimens in different clinical conditions.
Topics: Pregnancy; Humans; Female; Terbutaline; Asthma; Theophylline; Kinetics; Administration, Intravenous
PubMed: 36227333
DOI: 10.1007/s00210-022-02304-5 -
The Journal of Arthroplasty Nov 2022Platelet-rich plasma (PRP) usage in orthopedics continues to rise, despite guidelines suggesting non-superiority to comparative cohorts. Therefore, we performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Platelet-rich plasma (PRP) usage in orthopedics continues to rise, despite guidelines suggesting non-superiority to comparative cohorts. Therefore, we performed a systematic review and meta-analysis on PRP efficacy using two clinical assessments: (1) Visual Analog Scale and (2) Western Ontario and McMaster Universities Osteoarthritis Index. We assessed consistency and clinical relevancy by determining study heterogeneity (eg, sample sizes, ages, body mass index, arthritic severities, etc.). Comparative cohorts were: (A) hyaluronic acid (HA); (B) corticosteroid (CS); (C) normal saline (NS); and (D) exercise therapy. We performed sub-analyses of structural changes assessed on ultrasound, radiograph, or magnetic resonance imaging .
METHODS
We utilized PubMed, Cochrane Library, and Embase databases up to December 1, 2021, according to Preferred Reporting Items for Systematic-Reviews and Meta-Analyses guidelines. Twenty-four studies met criteria, with comparisons to: HA (n = 11); CS (n = 6); NS (n = 5); and exercise therapy (n = 3). Seven studies assessed structural changes. Evaluations utilized a methodological scoring system. I statistics and forest plots pooled analyses and delineated study results.
RESULTS
PRP led to Visual Analog Scale and Western Ontario and McMaster Universities Osteoarthritis Index improvements in most studies when compared to HA, CS, and NS (P ≤ .05). Comparison to exercise therapy resulted in inconclusive findings (P ≥ .05). However, substantial heterogeneity (I ≥ 76%) was reported due to study variability. No differences were found when assessing structural changes or cartilage thickness by magnetic resonance imaging (standardized mean difference -0.01 [-0.19, 0.18], P = .91).
CONCLUSIONS
PRP may be associated with pain and functional improvements but was not clinically relevant (inconsistent study- and patient-metrics). In addition, PRP did not confer superiority when assessing knee-related structural changes.
Topics: Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis, Knee; Platelet-Rich Plasma; Saline Solution; Treatment Outcome
PubMed: 35537610
DOI: 10.1016/j.arth.2022.05.014 -
Drug Design, Development and Therapy 2024The aim of this review was to provide all the pharmacokinetic data for semaglutide in humans concerning its pharmacokinetics after subcutaneously and oral applications... (Review)
Review
PURPOSE
The aim of this review was to provide all the pharmacokinetic data for semaglutide in humans concerning its pharmacokinetics after subcutaneously and oral applications in healthy and diseased populations, to provide recommendations for clinical use.
METHODOLOGY
The PubMed and Embase databases were searched to screen studies associated with the pharmacokinetics of semaglutide. The pharmacokinetic parameters included area under the curve plasma concentrations (AUC), maximal plasma concentration (C), time to C, half-life (t), and clearance. The systematic literature search retrieved 17 articles including data on pharmacokinetic profiles after subcutaneously and oral applications of semaglutide, and at least one of the above pharmacokinetic parameter was reported in all included studies.
RESULTS
Semaglutide has a predictable pharmacokinetic profile with a long t that allows for once-weekly subcutaneous administration. The AUC and C of both oral and subcutaneous semaglutide increased with dose. Food and various dosing conditions including water volume and dosing schedules can affect the oral semaglutide exposure. There are limited drug-drug interactions and no dosing adjustments in patients with upper gastrointestinal disease, renal impairment or hepatic impairment. Body weight may affect semaglutide exposure, but further studies are needed to confirm this.
CONCLUSION
This review encompasses all the pharmacokinetic data for subcutaneous and oral semaglutide in both healthy and diseased participants. The existing pharmacokinetic data can assist in developing and evaluating pharmacokinetic models of semaglutide and will help clinicians predict semaglutide dosages. In addition, it can also help optimize future clinical trials.
Topics: Glucagon-Like Peptides; Humans; Administration, Oral; Injections, Subcutaneous; Hypoglycemic Agents; Drug Interactions
PubMed: 38952487
DOI: 10.2147/DDDT.S470826 -
Expert Review of Clinical Immunology 2023Phototherapy has been one of the first and still frequently used treatment modality for psoriasis. In the last decades, different types of lasers have been used for the...
INTRODUCTION
Phototherapy has been one of the first and still frequently used treatment modality for psoriasis. In the last decades, different types of lasers have been used for the treatment of psoriasis and other inflammatory skin diseases with variable success.
AREAS COVERED
Efficacy and safety of laser devices and intense pulsed light for the treatment of psoriasis. The literature search was conducted using the bibliographic databases MEDLINE, EMBASE, and Cochrane. Search terms included 'laser' AND 'psoriasis,' 'IPL' AND 'psoriasis,' 'intense pulsed light' AND 'psoriasis.'
EXPERT OPINION
Due to its high efficacy and safety profile, 308-nm Excimer laser retains its specific place in the treatment of plaque psoriasis as a first- or second-line therapy in mild disease or as an adjuvant treatment in case of partial response to systemic treatments in moderate-to-severe disease. Vascular lasers remain a last line therapy that can be tried in patients with recalcitrant limited plaques or nail affection. They are easy to apply and have a very good safety profile and tolerability, but the efficacy is limited. Fractional ablative lasers for application of laser-assisted drug delivery appear interesting and a topic for further research. When using lasers for psoriasis, a good pre-treatment is mandatory.
Topics: Humans; Phototherapy; Psoriasis; Dermatitis; Administration, Cutaneous; Treatment Outcome
PubMed: 37079360
DOI: 10.1080/1744666X.2023.2205640