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European Neuropsychopharmacology : the... Apr 2024Sleep medications often carry residual effects potentially affecting driving safety, warranting network meta-analysis (NMA).... (Meta-Analysis)
Meta-Analysis
Residual effects of medications for sleep disorders on driving performance: A systematic review and network meta-analysis of randomized controlled trials: NMA driving and hypnotics.
Sleep medications often carry residual effects potentially affecting driving safety, warranting network meta-analysis (NMA). PubMed/EMBASE/TRID/Clinicaltrials.gov/WHO-ICTRP/WebOfScience were inquired for randomized controlled trials of hypnotic driving studies in persons with insomnia and healthy subjects up to 05/28/2023, considering the vehicle's standard deviation of lateral position - SDLP (Standardized Mean Difference/SMD) and driving impairment rates on the first morning (co-primary outcomes) and endpoint. Risk-of-bias, global/local inconsistencies were measured, and CINeMA was used to assess the confidence in the evidence. Of 4,805 identified records, 26 cross-over RCTs were included in the systematic review, of which 22 entered the NMA, focusing on healthy subjects only. After a single administration, most molecules paralleled the placebo, outperforming zopiclone regarding SDLP. In contrast, ramelteon 8 mg, daridorexant 100 mg, zolpidem 10 mg bedtime, zolpidem middle-of-the-night 10 mg and 20 mg, mirtazapine 15-30 mg, and triazolam 0.5 mg performed significantly worse than placebo. Lemborexant 2.5-5 mg, suvorexant 15-20 mg, and zolpidem 3.5 mg middle-of-the-night associated with lower impairment than zopiclone. Repeated administration (maximum follow-up time of ten days) caused fewer residual effects than acute ones, except for flurazepam. Heterogeneity and inconsistency were negligible. Confidence in the evidence was low/very low. Sensitivity analyses confirmed the main analyses. Most FDA-approved hypnotics overlapped placebo at in-label doses, outperforming zopiclone. Repeated administration for 15 days or less reduced residual effects, warranting further research on the matter.
Topics: Humans; Hypnotics and Sedatives; Zolpidem; Network Meta-Analysis; Automobile Driving; Psychomotor Performance; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Piperazines; Azabicyclo Compounds
PubMed: 38401406
DOI: 10.1016/j.euroneuro.2024.01.011 -
The Cochrane Database of Systematic... Feb 2016People with chronic plaque psoriasis often have lesions on the scalp. Hair makes the scalp difficult to treat and the adjacent facial skin is particularly sensitive to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with chronic plaque psoriasis often have lesions on the scalp. Hair makes the scalp difficult to treat and the adjacent facial skin is particularly sensitive to topical treatments.
OBJECTIVES
To assess the efficacy and safety of topical treatments for scalp psoriasis.
SEARCH METHODS
We searched the following databases up to August 2015: the Cochrane Skin Group Specialised Register, CENTRAL (2015, Issue 7), MEDLINE (from 1946), EMBASE (from 1974) and LILACS (from 1982). We also searched five trials registers, screened abstracts of six psoriasis-specific conferences and checked the reference lists of included studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) with a parallel-group, cross-over or within-patient design of topical treatments for people of all ages with scalp psoriasis.
DATA COLLECTION AND ANALYSIS
Two authors independently carried out study selection, data extraction and 'Risk of bias' assessment. Disagreements were settled by reference to a third author.To assess the quality of evidence, we focused on the following outcomes: 'clearance' or 'response' as assessed by the investigator global assessment (IGA), improvement in quality of life, adverse events requiring withdrawal of treatment and 'response' as assessed by the patient global assessment (PGA).We expressed the results of the single studies as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes, and mean differences (MD) with 95% CI for continuous outcomes. If studies were sufficiently homogeneous, we meta-analysed the data by using the random-effects model. Where it was not possible to calculate a point estimate for a single study, we described the data qualitatively. We also presented the number needed to treat to benefit (NNTB).We categorised topical corticosteroids according to the German classification of corticosteroid potency as mild, moderate, high and very high.
MAIN RESULTS
We included 59 RCTs with a total of 11,561 participants. Thirty studies were either conducted or sponsored by the manufacturer of the study medication. The risk of bias varied considerably among the included studies. For instance, most authors did not state the randomisation method and few addressed allocation concealment. Most findings were limited to short-term treatments, since most studies were conducted for less than six months. Only one trial investigated long-term therapy (12 months). Although we found a wide variety of different interventions, we limited the grading of the quality of evidence to three major comparisons: steroid versus vitamin D, two-compound combination of steroid and vitamin D versus steroid monotherapy and versus vitamin D.In terms of clearance, as assessed by the IGA, steroids were better than vitamin D (RR 1.82; 95% CI 1.52 to 2.18; four studies, 2180 participants, NNTB = 8; 95% CI 7 to 11; moderate quality evidence). Statistically, the two-compound combination was superior to steroid monotherapy, however the additional benefit was small (RR 1.22; 95% CI 1.08 to 1.36; four studies, 2474 participants, NNTB = 17; 95% CI 11 to 41; moderate quality evidence). The two-compound combination was more effective than vitamin D alone (RR 2.28; 95% CI 1.87 to 2.78; four studies, 2008 participants, NNTB = 6; 95% CI 5 to 7; high quality evidence).In terms of treatment response, as assessed by the IGA, corticosteroids were more effective than vitamin D (RR 2.09; 95% CI 1.80 to 2.41; three studies, 1827 participants; NNTB = 4; 95% CI 4 to 5; high quality evidence). The two-compound combination was better than steroid monotherapy, but the additional benefit was small (RR 1.15; 95% CI 1.06 to 1.25; three studies, 2444 participants, NNTB = 13; 95% CI 9 to 24; moderate quality evidence). It was also more effective than vitamin D alone (RR 2.31; 95% CI 1.75 to 3.04; four studies, 2222 participants, NNTB = 3; 95% CI 3 to 4; moderate quality evidence).Reporting of quality of life data was poor and data were insufficient to be included for meta-analysis.Steroids caused fewer withdrawals due to adverse events than vitamin D (RR 0.22; 95% CI 0.11 to 0.42; four studies, 2291 participants; moderate quality evidence). The two-compound combination and steroid monotherapy did not differ in the number of adverse events leading withdrawal (RR 0.88; 95% CI 0.42 to 1.88; three studies, 2433 participants; moderate quality evidence). The two-compound combination led to fewer withdrawals due to adverse events than vitamin D (RR 0.19; 95% CI 0.11 to 0.36; three studies, 1970 participants; high quality evidence). No study reported the type of adverse event requiring withdrawal.In terms of treatment response, as assessed by the PGA, steroids were more effective than vitamin D (RR 1.48; 95% CI 1.28 to 1.72; three studies, 1827 participants; NNTB = 5; 95% CI 5 to 7; moderate quality evidence). Statistically, the two-compound combination was better than steroid monotherapy, however the benefit was not clinically important (RR 1.13; 95% CI 1.06 to 1.20; two studies, 2226 participants; NNTB = 13; 95% CI 9 to 26; high quality evidence). The two-compound combination was more effective than vitamin D (RR 1.76; 95% CI 1.46 to 2.12; four studies, 2222 participants; NNTB = 4; 95% CI 3 to 6; moderate quality evidence).Common adverse events with these three interventions were local irritation, skin pain and folliculitis. Systemic adverse events were rare and probably not drug-related.In addition to the results of the major three comparisons we found that the two-compound combination, steroids and vitamin D monotherapy were more effective than the vehicle. Steroids of moderate, high and very high potency tended to be similarly effective and well tolerated. There are inherent limitations in this review concerning the evaluation of salicylic acid, tar, dithranol or other topical treatments.
AUTHORS' CONCLUSIONS
The two-compound combination as well as corticosteroid monotherapy were more effective and safer than vitamin D monotherapy. Given the similar safety profile and only slim benefit of the two-compound combination over the steroid alone, monotherapy with generic topical steroids may be fully acceptable for short-term therapy.Future RCTs should investigate how specific therapies improve the participants' quality of life. Long-term assessments are needed (i.e. 6 to 12 months).
Topics: Administration, Topical; Chronic Disease; Dermatologic Agents; Humans; Psoriasis; Randomized Controlled Trials as Topic; Scalp Dermatoses; Steroids; Vitamin D
PubMed: 26915340
DOI: 10.1002/14651858.CD009687.pub2 -
The Cochrane Database of Systematic... Feb 2017Blepharokeratoconjunctivitis (BKC) is a type of inflammation of the surface of the eye and eyelids that involves changes of the eyelids, dysfunction of the meibomian... (Review)
Review
BACKGROUND
Blepharokeratoconjunctivitis (BKC) is a type of inflammation of the surface of the eye and eyelids that involves changes of the eyelids, dysfunction of the meibomian glands, and inflammation of the conjunctiva and cornea. Chronic inflammation of the cornea can lead to scarring, vascularisation and opacity. BKC in children can cause significant symptoms including irritation, watering, photophobia and loss of vision from corneal opacity, refractive error or amblyopia.Treatment of BKC is directed towards modification of meibomian gland disease and the bacterial flora of lid margin and conjunctiva, and control of ocular surface inflammation. Although both topical and systemic treatments are used to treat people with BKC, this Cochrane review focuses on topical treatments.
OBJECTIVES
To assess and compare data on the efficacy and safety of topical treatments (including antibiotics, steroids, immunosuppressants and lubricants), alone or in combination, for BKC in children from birth to 16 years.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE ( January 1946 to 11 July 2016), Embase (January 1980 to 11 July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 July 2016. We searched the reference lists of identified reports and the Science Citation Index to identify any additional reports of studies that met the inclusion criteria.
SELECTION CRITERIA
We searched for randomised controlled trials that involved topical treatments in children up to 16 years of age with a clinical diagnosis of BKC. We planned to include studies that evaluated a single topical medication versus placebo, a combination of treatments versus placebo, and those that compared two or multiple active treatments. We planned to include studies in which participants received additional treatments, such as oral antibiotics, oral anti-inflammatories, warm lid compresses and lid margin cleaning.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the results of the literature search (titles and abstracts) to identify studies that met the inclusion criteria of the review and applied standards as expected for Cochrane reviews. We graded the certainty of the evidence using GRADE.
MAIN RESULTS
We included one study from the USA that met the inclusion criteria. In the study, 137 children aged zero to six years old with blepharoconjunctivitis were randomised to treatment in one of four trial arms (loteprednol etabonate/tobramycin combination, loteprednol etabonate alone, tobramycin alone or placebo) for 15 days, with assessments on days 1, 3, 7 and 15. We judged the study to be at high risk of attrition bias and bias due to selective outcome reporting. The study did not report the number of children with improvement in symptoms nor with total or partial success as measured by changes in clinical symptoms.All children showed a reduction in blepharoconjunctivitis grade score, but there was no evidence of important differences between groups. Visual acuity was not fully reported but the authors stated that there was no change in visual acuity in any of the treatment groups. The study reported ocular and non ocular adverse events but was underpowered to detect differences between the groups. Ocular adverse events were as follows: loteprednol/tobramycin 1/34 (eye pain); loteprednol 4/35 (eye pain, conjunctivitis, eye discharge, eye inflammation); tobramycin 0/34; placebo (vehicle) 0/34. The evidence was limited for all these outcomes and we judged it to be very low certainty.There was no information on clinical signs (aside from grade score), disease progression or quality of life.
AUTHORS' CONCLUSIONS
There is no high-quality evidence of the safety and efficacy of topical treatments for BKC, which resulted in uncertainty about the indications and effectiveness of topical treatment. Clinical trials are required to test efficacy and safety of current and any future treatments. Outcome measures need to be developed which can capture both objective clinical and patient-reported aspects of the condition and treatments.
Topics: Administration, Topical; Anti-Allergic Agents; Anti-Bacterial Agents; Blepharitis; Child; Child, Preschool; Conjunctiva; Eyelids; Humans; Infant; Infant, Newborn; Keratoconjunctivitis; Loteprednol Etabonate; Randomized Controlled Trials as Topic; Tobramycin
PubMed: 28170093
DOI: 10.1002/14651858.CD011965.pub2 -
The Annals of Pharmacotherapy Feb 2021Hydrogen peroxide 40% (HP40) was approved by the US Food and Drug Administration for topical treatment of seborrheic keratosis (SK) in December 2017. This article will...
OBJECTIVE
Hydrogen peroxide 40% (HP40) was approved by the US Food and Drug Administration for topical treatment of seborrheic keratosis (SK) in December 2017. This article will review phase II and III clinical trials to assess the drug's efficacy, safety, and clinical application.
DATA SOURCES
A systematic literature review was performed using the terms "Eskata AND seborrheic keratosis," and "hydrogen peroxide AND seborrheic keratosis" in the OVID MEDLINE, PubMed, Cochrane Library, EMBASE, and Web of Science databases. ClinicalTrials.gov was searched to identify ongoing or nonpublished studies.
STUDY SELECTION AND DATA ABSTRACTION
Articles written in English between January 2000 and mid-June 2020 discussing phase II and phase III clinical trials were evaluated.
DATA SYNTHESIS
In 2 phase III clinical trials, 4% and 8% of patients treated with HP40 had a Physician Lesion Assessment score of zero for all 4 SKs, respectively, compared with 0% in both vehicle groups at the primary end point of day 106 ( < 0.01; < 0.0001).
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
HP40, although less effective, has a better safety profile than other treatment options. It should be especially considered for treatment of facial SKs, where it is most efficacious and where other treatment modalities, such as cryotherapy, are more challenging.
CONCLUSIONS
HP40 is a new, safe alternative treatment for SKs, although it is expensive and only modestly effective, both of which somewhat limit its overall utility. HP40 is a promising topical alternative, particularly for cosmetically sensitive locations, such as the face.
Topics: Administration, Topical; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Female; Humans; Hydrogen Peroxide; Keratosis, Seborrheic; Oxidants; Randomized Controlled Trials as Topic; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 32646224
DOI: 10.1177/1060028020941793 -
Drug Development and Industrial Pharmacy May 2024TheDES are formed by mixing a Hydrogen Bond Donor (HBD) and a Hydrogen Bond Acceptor (HBA) in appropriate molar ratios. These solvents have been shown to enhance drug... (Review)
Review
OBJECTIVE
TheDES are formed by mixing a Hydrogen Bond Donor (HBD) and a Hydrogen Bond Acceptor (HBA) in appropriate molar ratios. These solvents have been shown to enhance drug solubility, permeability, and delivery. The main objective of the present article is to review these advantages of TheDES.
SIGNIFICANCE
TheDES show unique properties, such as low toxicity, biodegradability, improved bioavailability and enhanced drug delivery of poorly soluble active pharmaceutical ingredients. They are also biocompatible in nature which makes them a promising candidate for various therapeutic applications, including drug formulations, drug delivery and other biomedical uses. The development and utilization of TheDES shows significant advancement in pharmaceutical research, providing new opportunities for improving drug delivery.
METHODS
The current study was carried out by conducting a systematic literature review that identified relevant papers from indexed databases. Numerous studies and research are cited and quoted in this article to demonstrate the effectiveness of TheDES in enhancing drug solubility, permeability, and delivery. All chosen articles were selected considering their significance, quality, and approach to addressing issues.
RESULT
As a result, various TheDES were identified that can be formulated in different ways: one component can act as a vehicle for an API, either HBD or HBA can be an API, both HBD and HBA can be APIs, or the individual components of DES are not therapeutically active but the resulting DES possesses therapeutic activity. Additionally, TheDES were also recognized to enhance drug delivery and solubility for different APIs, including NSAIDs, anesthetic drugs, antifungals, and others.
Topics: Solubility; Deep Eutectic Solvents; Drug Delivery Systems; Permeability; Humans; Drug Compounding; Hydrogen Bonding; Chemistry, Pharmaceutical; Biological Availability; Pharmaceutical Preparations; Solvents
PubMed: 38634708
DOI: 10.1080/03639045.2024.2345131 -
Environmental Health Perspectives Apr 2019A causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our knowledge, no systematic reviews have summarized the most recently published evidence and no analyses have examined the dose-response relation.
OBJECTIVE
We investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia.
METHODS
We searched all case-control and cohort studies that have investigated the risk of childhood leukemia in relation to exposure either to motorized traffic and related contaminants, based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or to measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. We carried out a meta-analysis of all eligible studies, including nine studies published since the last systematic review and, when possible, we fit a dose-response curve using a restricted cubic spline regression model.
RESULTS
We found 29 studies eligible to be included in our review. In the dose-response analysis, we found little association between disease risk and traffic indicators near the child's residence for most of the exposure range, with an indication of a possible excess risk only at the highest levels. In contrast, benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 y of age, and when exposure assessment at the time of diagnosis was used. Exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels.
DISCUSSION
Overall, the epidemiologic literature appears to support an association between benzene and childhood leukemia risk, with no indication of any threshold effect. A role for other measured and unmeasured pollutants from motorized traffic is also possible. https://doi.org/10.1289/EHP4381.
Topics: Air Pollutants; Air Pollution; Child; Child, Preschool; Dose-Response Relationship, Drug; Environmental Exposure; Female; Humans; Infant; Infant, Newborn; Leukemia; Male; Vehicle Emissions
PubMed: 31017485
DOI: 10.1289/EHP4381 -
The Cochrane Database of Systematic... 2000Infection with head lice is a widespread condition in developed and developing countries. Infection occurs most commonly in children, but also affects adults. If left... (Review)
Review
BACKGROUND
Infection with head lice is a widespread condition in developed and developing countries. Infection occurs most commonly in children, but also affects adults. If left untreated the condition can become intensely irritating and skin infections may occur if the bites are scratched.
OBJECTIVES
The aim of this review was to assess the effects of interventions for head lice.
SEARCH STRATEGY
Trials register of The Cochrane Infectious Diseases Group; Medline; Embase; Science Citation Index; Biosis and Toxline; reference lists of relevant articles; pharmaceutical companies producing pediculicides (published and unpublished trials); UK and US Regulatory Authorities.
SELECTION CRITERIA
Randomised trials (published and unpublished) or trials using alternate allocation were sought which compared pediculicides with the same and different formulations of other pediculicides, and pediculicides with physical methods.
DATA COLLECTION AND ANALYSIS
Of the 70 identified studies, only three met the inclusion criteria and one is awaiting assessment. Two reviewers independently assessed trial quality. One reviewer extracted the data.
MAIN RESULTS
We found no evidence that any one pediculicide has greater effect than another. The two studies comparing malathion and permethrin with their respective vehicles showed a higher cure rate for the active ingredient than the vehicle. The third study comparing synergised pyrethrins with permethrin showed their effects to be equivalent. Adverse effects were reported in a number of trials and were all minor, although reporting quality varied between trials.
REVIEWER'S CONCLUSIONS
Permethrin, synergised pyrethrin and malathion were effective in the treatment of head lice. However, the emergence of drug resistance since these trials were conducted means there is no direct contemporary evidence of the comparative effectiveness of these products. The 'best' choice will now depend on local resistance patterns. There is currently no evidence from trials to indicate the effectiveness of physical methods, such as combing/'BugBusting' or other chemical control methods such as the use of herbal treatments, when used in the curative treatment of head lice. Future trials should take into account the methodological recommendations that arise from this review.
Topics: Adult; Animals; Antiparasitic Agents; Carbaryl; Health Education; Humans; Hygiene; Lice Infestations; Malathion; Pediculus; Permethrin; Phytotherapy; Pyrethrins; Scalp Dermatoses
PubMed: 10796608
DOI: 10.1002/14651858.CD001165 -
The Cochrane Database of Systematic... 2001Infection with head lice is a widespread condition in developed and developing countries. Infection occurs most commonly in children, but also affects adults. If left... (Review)
Review
BACKGROUND
Infection with head lice is a widespread condition in developed and developing countries. Infection occurs most commonly in children, but also affects adults. If left untreated the condition can become intensely irritating and skin infections may occur if the bites are scratched.
OBJECTIVES
The aim of this review was to assess the effects of interventions for head lice.
SEARCH STRATEGY
Trials register of The Cochrane Infectious Diseases Group; Medline; Embase; Science Citation Index; Biosis and Toxline; reference lists of relevant articles; pharmaceutical companies producing pediculicides (published and unpublished trials); UK and US Regulatory Authorities.
SELECTION CRITERIA
Randomised trials (published and unpublished) or trials using alternate allocation were sought which compared pediculicides with the same and different formulations of other pediculicides, and pediculicides with physical methods.
DATA COLLECTION AND ANALYSIS
Of the 71 identified studies, only four met the inclusion criteria. Two reviewers independently assessed trial quality. One reviewer extracted the data.
MAIN RESULTS
We found no evidence that any one pediculicide has greater effect than another. The two studies comparing malathion and permethrin with their respective vehicles showed a higher cure rate for the active ingredient than the vehicle. Another study comparing synergised pyrethrins with permethrin showed their effects to be equivalent. A comparative trial of malathion lotion vs combing, showed combing to be ineffective for the cureative treatment of head lice infection. Adverse effects were reported in a number of trials and were all minor, although reporting quality varied between trials.
REVIEWER'S CONCLUSIONS
Permethrin, synergised pyrethrin and malathion were effective in the treatment of head lice. However, the emergence of drug resistance since these trials were conducted means there is no direct contemporary evidence of the comparative effectiveness of these products. The 'best' choice will now depend on local resistance patterns. Physical treatment methods(BugBusting) were shown ot be ineffective to treat head lice. No evidence exists regarding other chemical control methods such as the use of herbal treatments, when used in the curative treatment of head lice. Future trials should take into account the methodological recommendations that arise from this review.
Topics: Adult; Animals; Antiparasitic Agents; Carbaryl; Health Education; Humans; Hygiene; Lice Infestations; Malathion; Pediculus; Permethrin; Phytotherapy; Pyrethrins; Randomized Controlled Trials as Topic; Scalp Dermatoses
PubMed: 11686980
DOI: 10.1002/14651858.CD001165 -
Osteoarthritis and Cartilage Sep 2014Studies using animal models are important in drug development, but often poorly predict treatment results in man. We investigated factors that may impact on the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Studies using animal models are important in drug development, but often poorly predict treatment results in man. We investigated factors that may impact on the magnitude of the analgesic treatment effect in animal models of osteoarthritis (OA) pain.
DESIGN
Systematic review of studies that measured behavioural pain outcomes in small animal models of OA, and tested drugs which reduce OA pain in man. Standardised mean difference (SMD) and 95% confidence intervals (CIs) were calculated using random effects meta-analysis for selected models and drugs.
RESULTS
Most studies used rat models (42/50) and chemical methods of OA induction (39/50). Analgesic treatment effect (SMD) was most commonly measured between drug- and vehicle treated rats with knee OA. Meta-analysis was carried out for 102 such comparisons from 26 studies. The pooled SMD was 1.36 (95% CI = 1.15-1.57). Non-steroidal anti-inflammatory drugs (NSAIDs) were associated with smaller SMDs than opioids (z = -3.25, P = 0.001). Grip strength gave larger SMDs than assessment of static weight bearing (z = -4.60, P < 0.001), mechanically-evoked pain (z = -3.83, P = 0.001) and movement-evoked pain (z = -5.23, P < 0.001), and SMDs for mechanically-evoked pain were larger than for movement-evoked pain (z = -2.78, P = 0.006). Studies that reported structural evaluation of OA phenotype were associated with smaller SMDs (z = -2.45, P = 0.014). Publication was significantly biased towards positive findings.
CONCLUSION
Attention to study-level moderators and publication bias may improve the ability of research using animal models to predict whether analgesic agents will reduce arthritis pain in man.
Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Drug Evaluation, Preclinical; Evidence-Based Medicine; Osteoarthritis; Pain; Rats; Research Design
PubMed: 25008207
DOI: 10.1016/j.joca.2014.06.015 -
Forensic Science International Nov 2021Past research on cannabis has been limited in scope to THC potencies lower than legally available and efforts to integrate the effects into models of driving performance... (Review)
Review
Past research on cannabis has been limited in scope to THC potencies lower than legally available and efforts to integrate the effects into models of driving performance have not been attempted to date. The purpose of this systematic review is to understand the implications for modeling driving performance and describe future research needs. The risk of motor vehicle crashes increases 2-fold after smoking marijuana. Driving during acute cannabis intoxication impairs concentration, reaction time, along with a variety of other necessary driving-related skills. Changes to legislation in North America and abroad have led to an increase in cannabis' popularity. This has given rise to more potent strains, with higher THC concentrations than ever before. There is also rising usage of novel ingestion methods other than smoking, such as oral cannabis products (e.g., brownies, infused drinks, candies), vaping, and topicals. The PRISMA guidelines were followed to perform a systematic search of the PubMed database for peer-reviewed literature. Search terms were combined with keywords for driving performance: driving, performance, impairment. Grey literature was also reviewed, including congressional reports, committee reports, and roadside surveys. There is a large discrepancy between the types of cannabis products sold and what is researched. Almost all studies that used inhalation as the mode of ingestion with cannabis that is around 6% THC. This pales in comparison to the more potent strains being sold today which can exceed 20%. Which is to say nothing of extracts, which can contain 60% or more THC. Experimental protocol is another gap in research that needs to be filled. Methodologies that involve naturalistic (real world) driving environments, smoked rather than vaporized cannabis, and non-lab certified products introduce uncontrollable variables. When considering the available literature and the implications of modeling the impacts of cannabis on driving performance, two critical areas emerge that require additional research: The first is the role of cannabis potency. Second is the route of administration. Does the lower peak THC level result in smaller impacts on performance? How long does potential impairment last along the longer time-course associated with different pharmacokinetic profiles. It is critical for modeling efforts to understand the answers to these questions, accurately model the effects on driver performance, and by extension understand the risk to the public.
Topics: Analgesics; Automobile Driving; Cannabinoid Receptor Agonists; Cannabis; Dronabinol; Hallucinogens; Marijuana Smoking; Psychomotor Performance
PubMed: 34634690
DOI: 10.1016/j.forsciint.2021.110902