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JAMA Nov 2023Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality.
OBJECTIVE
To compare efficacy and comparative efficacy of therapies for alcohol use disorder.
DATA SOURCES
PubMed, the Cochrane Library, the Cochrane Central Trials Registry, PsycINFO, CINAHL, and EMBASE were searched from November 2012 to September 9, 2022 Literature was subsequently systematically monitored to identify relevant articles up to August 14, 2023, and the PubMed search was updated on August 14, 2023.
STUDY SELECTION
For efficacy outcomes, randomized clinical trials of at least 12 weeks' duration were included. For adverse effects, randomized clinical trials and prospective cohort studies that compared drug therapies and reported health outcomes or harms were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers evaluated each study, assessed risk of bias, and graded strength of evidence. Meta-analyses used random-effects models. Numbers needed to treat were calculated for medications with at least moderate strength of evidence for benefit.
MAIN OUTCOMES AND MEASURES
The primary outcome was alcohol consumption. Secondary outcomes were motor vehicle crashes, injuries, quality of life, function, mortality, and harms.
RESULTS
Data from 118 clinical trials and 20 976 participants were included. The numbers needed to treat to prevent 1 person from returning to any drinking were 11 (95% CI, 1-32) for acamprosate and 18 (95% CI, 4-32) for oral naltrexone at a dose of 50 mg/d. Compared with placebo, oral naltrexone (50 mg/d) was associated with lower rates of return to heavy drinking, with a number needed to treat of 11 (95% CI, 5-41). Injectable naltrexone was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, -4.99 days; 95% CI, -9.49 to -0.49 days) Adverse effects included higher gastrointestinal distress for acamprosate (diarrhea: risk ratio, 1.58; 95% CI, 1.27-1.97) and naltrexone (nausea: risk ratio, 1.73; 95% CI, 1.51-1.98; vomiting: risk ratio, 1.53; 95% CI, 1.23-1.91) compared with placebo.
CONCLUSIONS AND RELEVANCE
In conjunction with psychosocial interventions, these findings support the use of oral naltrexone at 50 mg/d and acamprosate as first-line pharmacotherapies for alcohol use disorder.
Topics: Humans; Acamprosate; Alcohol Drinking; Alcoholism; Drug-Related Side Effects and Adverse Reactions; Naltrexone; Prospective Studies; Quality of Life; United States; Alcohol Deterrents; Psychosocial Intervention
PubMed: 37934220
DOI: 10.1001/jama.2023.19761 -
Journal of Nanobiotechnology Jan 2024Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins,... (Review)
Review
Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies.
Topics: Humans; Exosomes; Tissue Distribution; Drug Delivery Systems; Extracellular Vesicles; Neoplasms; Pharmaceutical Preparations
PubMed: 38172932
DOI: 10.1186/s12951-023-02259-6 -
Public Health Aug 2023To determine the effect of recreational cannabis legalization (RCL) and/or recreational cannabis commercialization (RCC) on emergency department (ED) visits,... (Review)
Review
OBJECTIVE
To determine the effect of recreational cannabis legalization (RCL) and/or recreational cannabis commercialization (RCC) on emergency department (ED) visits, hospitalizations, and deaths due to substance use, injury, and mental health among those aged 11 years and older.
METHODS
A systematic review of six electronic databases up to February 1, 2023. Original, peer-reviewed articles with interrupted time series or before and after designs were included. Four independent reviewers screened articles and assessed risk of bias. Outcomes with 'critical' risk of bias were excluded. Protocol registered on PROSPERO (# CRD42021265183).
RESULTS
After screening and risk of bias assessment, 29 studies were included which examined ED visits or hospitalizations for cannabis use or alcohol (N = 10), opioid mortality (N = 3), motor vehicle fatalities or injury (N = 11), and intentional injury/mental health (N = 5). Rates or number of cannabis-related hospitalizations increased after RCL in Canada and the USA. Immediate increases in rates of cannabis-related ED visits were found after both RCL and RCC in Canada. Rates of traffic fatalities increased after RCL and RCC in certain jurisdictions in the USA.
CONCLUSIONS
RCL was associated with increased rates of cannabis-related hospitalizations. RCL and/or RCC was associated with increased rates of cannabis-related ED visits, consistently shown across sex and age groups. The effect on fatal motor vehicle incidents was mixed, with observed increases found after RCL and/or RCC. The effect of RCL or RCC on opioids, alcohol, intentional injury, and mental health is not clear. These results inform population health initiatives and international jurisdictions considering RCL implementation.
Topics: Humans; Cannabis; Mental Health; Carcinoma, Renal Cell; Substance-Related Disorders; Analgesics, Opioid; Legislation, Drug; Ethanol; Kidney Neoplasms
PubMed: 37429043
DOI: 10.1016/j.puhe.2023.06.012 -
World Neurosurgery Apr 2024Traumatic spinal cord injury (TSCI) is a debilitating neurological condition with significant long-term consequences on the mental health and well-being of affected... (Review)
Review
BACKGROUND
Traumatic spinal cord injury (TSCI) is a debilitating neurological condition with significant long-term consequences on the mental health and well-being of affected individuals. We aimed to investigate anxiety and depression in individuals with pediatric-onset TSCI.
METHODS
PubMed, Scopus, and Web of Science databases were searched from inception to December 20th, 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and studies were included according to the eligibility criteria.
RESULTS
A total of 1013 articles were screened, and 18 studies with 4234 individuals were included in the final review. Of these, 1613 individuals (38.1%) had paraplegia, whereas 1658 (39.2%) had tetraplegia. A total of 1831 participants (43.2%) had complete TSCI, whereas 1024 (24.2%) had incomplete TSCI. The most common etiology of TSCI with 1545 people (36.5%) was motor vehicle accidents. The youngest mean age at the time of injury was 5.92 ± 4.92 years, whereas the oldest was 14.6 ± 2.8 years. Patient Health Questionnaire-9 was the most common psychological assessment used in 9 studies (50.0%). Various risk factors, including pain in 4 studies (22.2%), reduced sleep quality, reduced functional independence, illicit drug use, incomplete injury, hospitalization, reduced quality of life, and duration of injury in 2 (11.1%) studies, each, were associated with elevated anxiety and depression.
CONCLUSIONS
Different biopsychosocial risk factors contribute to elevated rates of anxiety and depression among individuals with pediatric-onset TSCI. Individuals at risk of developing anxiety and depression should be identified, and targeted support should be provided. Future large-scale studies with long-term follow-up are required to validate and extend these findings.
Topics: Child; Humans; Infant; Child, Preschool; Depression; Quality of Life; Spinal Cord Injuries; Paraplegia; Anxiety
PubMed: 38143027
DOI: 10.1016/j.wneu.2023.12.092 -
Contact Lens & Anterior Eye : the... Feb 2024To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED). (Review)
Review
PURPOSE
To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED).
METHODS
A systematic review that included full-length randomized controlled studies (RCTs), as well as post hoc analyses of RCTs reporting new findings on OC-01 VNS treatment in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The search period included studies published between December 2021 and September 2023. The Cochrane risk of bias tool was used to analyze the quality of the studies selected.
RESULTS
A total of 8 studies were included in this systematic review. OC-01 VNS treatment achieved higher improvement than vehicle in all reported variables. The mean differences between both groups were in favor of OC-01 VNS treatment and were as follow: eye dryness score base on a visual analogue scale (EDS-VAS) of -7.5 ± 2.2 points [-11.6 to -5.6], Schirmer test (ST) with anesthesia of 6.6 ± 2.3 mm [4.9 to 11.8] and total corneal fluorescein staining (tCFS) of -1.2 ± 0.01 points [-1.2 to -1.1]. Similar improvements were reported with OC-01 VNS 0.03 mg and 0.06 mg. Adverse events (AEs) were 15.5 ± 19.4 % [-13 to 80.5] higher in the OC-01 VNS group with an overall adherence > 93 %.
CONCLUSIONS
OC-01 VNS improves dry eye symptoms and signs with a satisfactory tolerability. Therefore, OC-01 VNS seems to be a safe and effective treatment that could be recommended in patients with DED. This new treatment could be particularly useful in those patients who have difficulties with the administration of traditional topical therapies.
Topics: Humans; Dry Eye Syndromes; Fluorescein; Nasal Sprays; Tears; Varenicline
PubMed: 38065797
DOI: 10.1016/j.clae.2023.102097 -
Addiction Biology Jan 2024Driving is a critical everyday task necessitating the rapid and seamless integration of dynamic visually derived information to guide neurobehaviour. Biological markers... (Review)
Review
Driving is a critical everyday task necessitating the rapid and seamless integration of dynamic visually derived information to guide neurobehaviour. Biological markers are frequently employed to detect Δ9-tetrahydrocannabinol (THC) consumption among drivers during roadside tests, despite not necessarily indicating impairment. Characterising THC-specific alterations to oculomotor behaviour may offer a more sensitive measure for indexing drug-related impairment, necessitating discrimination between acute THC effects, chronic use and potential tolerance effects. The present review aims to synthesise current evidence on the acute and chronic effects of THC on driving-relevant oculomotor behaviour. The review was prospectively registered (10.17605/OSF.IO/A4H9W), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines informed reporting standards. Overall, 20 included articles comprising 12 experimental acute dosing trials, 5 cross-sectional chronic use studies and 3 roadside epidemiological studies examined the effects of cannabis/THC on oculomotor parameters including saccadic activity gaze behaviour, nystagmus, smooth pursuit and eyelid/blink characteristics. Acute THC consumption selectively impacts oculomotor control, notably increasing saccadic latency and inaccuracy and impairing inhibitory control. Chronic cannabis users, especially those with early age of use onset, display enduring oculomotor deficits that affect visual scanning efficiency. The presence of eyelid tremors appears to be a reliable indicator of cannabis consumption while remaining distinct from direct impairment associated with visual attention and motor control. Cannabis selectively influences oculomotor activity relevant to driving, highlighting the role of cannabinoid systems in these processes. Defining cannabis/THC-specific changes in oculomotor control may enhance the precision of roadside impairment assessments and vehicle safety systems to detect drug-related impairment and assess driving fitness.
Topics: Cannabis; Dronabinol; Cross-Sectional Studies; Cannabinoids; Cannabinoid Receptor Agonists
PubMed: 38221807
DOI: 10.1111/adb.13359 -
Biomedicines Feb 2024In light of the unsuccessful traditional therapies for Parkinson's disease (PD) overmany years, there is an unmet need for the development of novel therapies to... (Review)
Review
In light of the unsuccessful traditional therapies for Parkinson's disease (PD) overmany years, there is an unmet need for the development of novel therapies to alleviate the symptoms of PD retardation or halt the progression of the disease itself. This systematic review aims to critically update some of the most promising novel treatments including gene therapy, cell-based therapies, targeted drug delivery, and neuroprotective agents, focusing on their challenges, limitations and future directions in PD research. Gene therapy in PD is encouraging, with AAV-based approaches targeting neurotrophic factors, dopamine production, and neuronal circuits in animal and clinical trials. A promising approach to targeted drug delivery for PD involves the use of nanotechnology to create drug delivery vehicles that can traverse the blood-brain barrier and deliver medications specifically to the regions of the brain affected by PD. Neuroprotective agents are compounds that have the ability to protect neurons from degeneration and death, and they hold great promise for the evolution of disease-modifying treatments for PD. Magnetic field therapy is a promising non-invasive method that promotes neural plasticity in PD. The establishment of standardized protocols for animal and human studies, safety, ethical considerations, and cost-effectiveness are the major challenges for the future research of novel PD therapies. The development of novel therapies for PD represents a promising path toward to effective personalized disease-modifying treatments for PD.
PubMed: 38540162
DOI: 10.3390/biomedicines12030549 -
Wounds : a Compendium of Clinical... Feb 2024Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound...
BACKGROUND
Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound care remains limited.
OBJECTIVE
To conduct a comprehensive review to assess the efficacy of topical phenytoin compared with standard and alternative treatments for different wound types.
MATERIALS AND METHODS
The authors last searched Cochrane Library, PubMed, PubMed Central, and MEDLINE in June 2023. All English-language human RCTs and NRCTs from any time were included. The RoB 2 was used to assess quality of randomized trials, and the ROBINS-I was used to assess the quality of nonrandomized trials. Studies with a low risk of bias or some concerns in no more than 1 domain were included. Data collected and analyzed included wound type, interventions, sample size, outcome measures, and adverse effects.
RESULTS
The search yielded 101 studies, of which 17 RCTs and 8 NRCTs were eligible for inclusion. Of the included studies, 56% had a low risk of bias in all domains. The sample sizes varied between 20 and 130 (median, 60), with a total sample size of 1653 patients. Phenytoin improved wound healing in 17 of the 24 studies that evaluated it (71%), increased granulation tissue in 9 of the 10 studies that evaluated it (90%), provided analgesic effects in 7 of the 13 studies that evaluated it (54%), and inhibited bacterial contaminants in 6 of the 8 studies that evaluated it (75%). Adverse effects were rare (29%), minimal, and transient.
CONCLUSION
Phenytoin enhances wound healing and offers analgesic and antibacterial properties with minimal adverse effects. Further research is needed on optimal dosage of phenytoin, as well as frequency, delivery vehicles, and effects on other postoperative wounds.
BACKGROUND
Although phenytoin's potential benefits in wound healing, pain relief, and infection control across various wound types have been previously reported, its use in wound care remains limited.
OBJECTIVE
To conduct a comprehensive review to assess the efficacy of topical phenytoin compared with standard and alternative treatments for different wound types.
MATERIALS AND METHODS
The authors last searched Cochrane Library, PubMed, PubMed Central, and MEDLINE in June 2023. All English-language human RCTs and NRCTs from any time were included. The RoB 2 was used to assess quality of randomized trials, and the ROBINS-I was used to assess the quality of nonrandomized trials. Studies with a low risk of bias or some concerns in no more than 1 domain were included. Data collected and analyzed included wound type, interventions, sample size, outcome measures, and adverse effects.
RESULTS
The search yielded 101 studies, of which 17 RCTs and 8 NRCTs were eligible for inclusion. Of the included studies, 56% had a low risk of bias in all domains. The sample sizes varied between 20 and 130 (median, 60), with a total sample size of 1653 patients. Phenytoin improved wound healing in 17 of the 24 studies that evaluated it (71%), increased granulation tissue in 9 of the 10 studies that evaluated it (90%), provided analgesic effects in 7 of the 13 studies that evaluated it (54%), and inhibited bacterial contaminants in 6 of the 8 studies that evaluated it (75%). Adverse effects were rare (29%), minimal, and transient.
CONCLUSION
Phenytoin enhances wound healing and offers analgesic and antibacterial properties with minimal adverse effects. Further research is needed on optimal dosage of phenytoin, as well as frequency, delivery vehicles, and effects on other postoperative wounds.
Topics: Humans; Phenytoin; Anti-Bacterial Agents; Wound Healing; Analgesics; Pain
PubMed: 38479432
DOI: No ID Found