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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 -
The Annals of Pharmacotherapy Oct 2023To review the available literature regarding the treatment effects and efficacy of benzonatate needed to better inform patients, providers, and regulators evaluating its... (Review)
Review
OBJECTIVE
To review the available literature regarding the treatment effects and efficacy of benzonatate needed to better inform patients, providers, and regulators evaluating its role in modern medical therapies.
DATA SOURCES
Comprehensive literature searches were conducted in PubMed, Embase (Elsevier), Cochrane Library, and Scopus for original research articles evaluating the effectiveness, tolerability, and safety profile of benzonatate from January 1956 through August 2022.
STUDY SELECTION AND DATA EXTRACTION
The identified studies were screened for relevance and then assessed for inclusion through a full-text review, data extraction, and quality assessment by multiple reviewers using the online software Covidence.
DATA SYNTHESIS
The selection process resulted in 37 articles consisting of 21 cohort studies, 5 experimental studies, and 11 case studies and series. Initial clinical studies exploring potential therapeutic benefits collected data from very small populations and limited clinical settings. Safety is primarily assessed in terms of toxicity due to overdose or inappropriate use. Quality assessment raised concerns for high degrees of biases primarily related to the limited sample size, data collection, generalizability, and study design.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
This review reveals substantial limitations within existing evidence pertaining to the safety and clinical effectiveness of benzonatate and thus, a need for large observational studies or randomized trials to better characterize its role and value in modern medical practice.
CONCLUSIONS
Rising safety concerns should bring closer scrutiny upon the prescription of benzonatate whose approval is founded upon evidence that would not stand up to current regulatory review.
Topics: Humans; Butylamines; Drug Overdose; Text Messaging
PubMed: 36688284
DOI: 10.1177/10600280221135750 -
Anesthesia and Analgesia Jul 2023Pain after thoracic surgery is of moderate-to-severe intensity and can cause increased postoperative distress and affect functional recovery. Opioids have been central...
Pain after thoracic surgery is of moderate-to-severe intensity and can cause increased postoperative distress and affect functional recovery. Opioids have been central agents in treating pain after thoracic surgery for decades. The use of multimodal analgesic strategies can promote effective postoperative pain control and help mitigate opioid exposure, thus preventing the risk of developing persistent postoperative pain. This practice advisory is part of a series developed by the Society of Cardiovascular Anesthesiologists (SCA) Quality, Safety, and Leadership (QSL) Committee's Opioid Working Group. It is a systematic review of existing literature for various interventions related to the preoperative and intraoperative pain management of thoracic surgical patients and provides recommendations for providers caring for patients undergoing thoracic surgery. This entails developing customized pain management strategies for patients, which include preoperative patient evaluation, pain management, and opioid use-focused education as well as perioperative use of multimodal analgesics and regional techniques for various thoracic surgical procedures. The literature related to this field is emerging and will hopefully provide more information on ways to improve clinically relevant patient outcomes and promote recovery in the future.
Topics: Humans; Pain Management; Analgesics, Opioid; Pain, Postoperative; Opioid-Related Disorders; Thoracic Surgical Procedures; Analgesics
PubMed: 37079466
DOI: 10.1213/ANE.0000000000006441 -
JAMA Network Open Sep 2023The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested.
OBJECTIVES
To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group.
DATA SOURCE AND STUDY SELECTION
Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece).
DATA EXTRACTION AND SYNTHESIS
Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines.
MAIN OUTCOMES AND MEASURES
The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group.
RESULTS
The analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses.
CONCLUSIONS AND RELEVANCE
This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.
Topics: Humans; Female; Aged; Male; Blood Pressure; Antihypertensive Agents; Longitudinal Studies; Hypertension; Dementia
PubMed: 37698858
DOI: 10.1001/jamanetworkopen.2023.33353 -
International Journal of Molecular... Dec 2023Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high... (Review)
Review
Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high prevalence and social burden of addiction are indisputable; however, the available intervention is insufficient. The modulation of gene expression and aberrant adaptation of neural networks are attributed to the changes in brain functions under repeated exposure to addictive substances. Considerable studies have demonstrated that miRNAs are strong modulators of post-transcriptional gene expression in substance addiction. The emerging role of microRNA (miRNA) provides new insights into many biological and pathological processes in the central nervous system: their variable expression in different regions of the brain and tissues may play a key role in regulating the pathophysiological events of addiction. This work provides an overview of the current literature on miRNAs involved in addiction, evaluating their impaired expression and regulatory role in neuroadaptation and synaptic plasticity. Clinical implications of such modulatory capacities will be estimated. Specifically, it will evaluate the potential diagnostic role of miRNAs in the various stages of drug and substance addiction. Future perspectives about miRNAs as potential novel therapeutic targets for substance addiction and abuse will also be provided.
Topics: Humans; MicroRNAs; Substance-Related Disorders; Behavior, Addictive; Brain
PubMed: 38069445
DOI: 10.3390/ijms242317122 -
The American Journal of Emergency... Jul 2023Alcohol Withdrawal Syndrome (AWS) among patients with chronic and heavy alcohol consumption can range from mild to severe and is associated with high morbidity and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcohol Withdrawal Syndrome (AWS) among patients with chronic and heavy alcohol consumption can range from mild to severe and is associated with high morbidity and mortality. Currently, treating AWS with benzodiazepines is the standard of care, but phenobarbital has also been hypothesized to be an effective first-line treatment due to its pharmacological properties and mechanism of action. We conducted a meta-analysis to review relevant literature and compare the clinical outcomes for patients diagnosed with AWS in ED and ICU settings.
METHODS
We performed a literature search in in the PubMed, Scopus, and Web of Science databases from inception to June 30, 2022. Randomized trials and observational (prospective or retrospective) studies were eligible if they included adult patients who presented in the ED and were treated in the ED and/or the intensive care unit (ICU) with a diagnosis of AWS. The primary outcome was the rate of intubation among patients who received phenobarbital, compared with benzodiazepines. Secondary outcomes such as rates of seizures, hospital, and ICU length of stay (LOS), also were included. The PROSPERO registration is CRD42022318862.
RESULTS
We included twelve studies (1934 patients) in our analysis. Of the 1934 patients in these studies, 765 (41.7%) were treated with phenobarbital and 1169 (58.3%) were treated with other modalities for alcohol withdrawal. Treating AWS patients with phenobarbital did not affect their risk for intubation, as the risk for intubation was similar between the phenobarbital and the control group (RR 0.70, 95% CI 0.36-1.38, P = 0.31). In addition, patients who were treated with phenobarbital were found to have similar rates of seizures (RR 0.73, 95% CI 0.29-1.89) and length of stay in the hospital (Standardized Mean Difference -0.02, 95% CI -0.26, 0.21) or the ICU (SMD -0.02, 95% CI -0.21, 0.25) when compared with patients receiving benzodiazepines.
CONCLUSIONS
Management of patients with AWS with phenobarbital is associated with similar rates of intubation, length of stay in the ICU, or length of stay in the hospital as treatment with benzodiazepines. However, due to the inclusion of mostly observational studies and a significant level of heterogeneity among the studies assessed in this review, additional trials with strong methodology are needed.
Topics: Adult; Humans; Substance Withdrawal Syndrome; Alcoholism; Retrospective Studies; Prospective Studies; Phenobarbital; Benzodiazepines; Seizures
PubMed: 37060631
DOI: 10.1016/j.ajem.2023.04.002 -
Neuropsychopharmacology : Official... Mar 2024While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated.... (Meta-Analysis)
Meta-Analysis
While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated. Neuromodulation (NM) methods, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) may address SUDs by targeting addiction neurocircuitry. We evaluated the efficacy of NM to improve behavioral outcomes in SUDs. A systematic literature search was performed on MEDLINE, PsychINFO, and PubMed databases and a list of search terms for four key concepts (SUD, rTMS, tDCS, DBS) was applied. Ninety-four studies were identified that examined the effects of rTMS, tDCS, and DBS on substance use outcomes (e.g., craving, consumption, and relapse) amongst individuals with SUDs including alcohol, tobacco, cannabis, stimulants, and opioids. Meta-analyses were performed for alcohol and tobacco studies using rTMS and tDCS. We found that rTMS reduced substance use and craving, as indicated by medium to large effect sizes (Hedge's g > 0.5). Results were most encouraging when multiple stimulation sessions were applied, and the left dorsolateral prefrontal cortex (DLPFC) was targeted. tDCS also produced medium effect sizes for drug use and craving, though they were highly variable and less robust than rTMS; right anodal DLPFC stimulation appeared to be most efficacious. DBS studies were typically small, uncontrolled studies, but showed promise in reducing misuse of multiple substances. NM may be promising for the treatment of SUDs. Future studies should determine underlying neural mechanisms of NM, and further evaluate extended treatment durations, accelerated administration protocols and long-term outcomes with biochemical verification of substance use.
Topics: Humans; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation; Substance-Related Disorders; Behavior, Addictive; Craving; Prefrontal Cortex
PubMed: 38086901
DOI: 10.1038/s41386-023-01776-0 -
Neuroscience and Biobehavioral Reviews Sep 2023Recent lifestyle changes have resulted in tremendous peer pressure and mental stress, and increased the incidences of chronic psychological disorders; like addiction,... (Review)
Review
Recent lifestyle changes have resulted in tremendous peer pressure and mental stress, and increased the incidences of chronic psychological disorders; like addiction, depression and anxiety (ADA). In this context, the stress-tolerance levels vary amongst individuals and genetic factors play prominent roles. Vulnerable individuals may often be drawn towards drug-addiction to combat stress. This systematic review critically appraises the relationship of various genetic factors linked with the incidences of ADA development. For coherence, we focused solely on cocaine as a substance of abuse in this study. Online scholarly databases were used to screen pertinent literature using apt keywords; and the final retrieval included 42 primary-research articles. The major conclusion drawn from this systematic analysis states that there are 51 genes linked with the development of ADA; and 3 (BDNF, PERIOD2 and SLC6A4) of them are common to all the three aspects of ADA. Further, inter-connectivity analyses of the 51 genes further endorsed the central presence of BDNF and SLC6A4 genes in the development of ADA disorders. The conclusions derived from this systematic study pave the way for future studies for the identification of diagnostic biomarkers and drug targets; and for the development of novel and effective therapeutic regimens against ADA.
Topics: Humans; Cocaine-Related Disorders; Depression; Brain-Derived Neurotrophic Factor; Anxiety; Anxiety Disorders; Cocaine; Serotonin Plasma Membrane Transport Proteins
PubMed: 37271299
DOI: 10.1016/j.neubiorev.2023.105270 -
Phytomedicine : International Journal... Sep 2023Liver diseases have a negative impact on global health and are a leading cause of death worldwide. Chlorogenic acids (CGAs), a family of esters formed between certain... (Review)
Review
BACKGROUND
Liver diseases have a negative impact on global health and are a leading cause of death worldwide. Chlorogenic acids (CGAs), a family of esters formed between certain trans-cinnamic acids and quinic acid, are natural polyphenols abundant in coffee, tea, and a variety of traditional Chinese medicines (TCMs). They are reported to have good hepatoprotective effects against various liver diseases.
PURPOSE
This review aims to analyze the available literature on the hepatoprotective effect of CGAs, with particular emphasis on their mechanisms.
METHODS
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed and Web of Science databases were adopted to retrieve all relevant literature on CGAs for liver disease from 2013 to March 2023.
RESULTS
Research has indicated that CGAs play a crucial role in improving different types of liver diseases, including drug-induced liver injury (DILI), alcoholic liver disease (ALD), metabolic (dysfunction)-associated fatty liver disease (MAFLD), cholestatic liver disease (CLD), liver fibrosis, and liver cancer. CGAs display remarkable antioxidant and anti-inflammatory effects by activating erythroid 2-related factor 2 (Nrf2) and inhibiting toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathways. Some important molecules such as AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), and other key physiological processes like intestinal barrier and gut microbiota have also been discovered to participate in CGAs-provided amelioration on various liver diseases.
CONCLUSION
In this review, different studies indicate that CGAs have an excellent protective effect against various liver diseases associated with various signaling pathways.
Topics: Humans; Chlorogenic Acid; Polyphenols; Antioxidants; Liver Diseases, Alcoholic; Nucleotidyltransferases; Liver
PubMed: 37453191
DOI: 10.1016/j.phymed.2023.154961 -
Journal of Attention Disorders Oct 2023The two most prevalent neurodevelopmental disorders-Attention Deficit Hyperactivity Disorder (ADHD) and Autism (ASD)-(ASD/ADHD) strongly impact individuals' functions.... (Review)
Review
BACKGROUND
The two most prevalent neurodevelopmental disorders-Attention Deficit Hyperactivity Disorder (ADHD) and Autism (ASD)-(ASD/ADHD) strongly impact individuals' functions. This is worsened when individuals are undiagnosed and risks such as increased imprisonments, depression or drug misuse are often observed. This systematic review synthesizes the risks associated with late/undiagnosed ASD/ADHD.
METHODS
Four databases were searched (Medline, Scopus, PsychInfor, and Embase). Published studies exploring the impact of undiagnosed ASD/ADHD were included. Exclusion criteria included, lack of diagnosis status, studies not solely on ASD or ADHD, gray literature and studies not in English. The findings were summarize through a narrative synthesis.
RESULTS
Seventeen studies were identified, 14 on ADHD and three on ASD. The narrative synthesis identified three main themes: (1) Health, (2) Offending behavior, and (3) Day-to-day impact. The risks highlighted a significant impact on mental wellbeing and social interactions, higher risks of substance abuse, accidents and offending behavior as well as lower levels of income and education.
DISCUSSION
The findings suggest that undiagnosed ASD/ADHD is linked to many risks and negative outcomes affecting individuals, their families, and the wider society. The restricted number of studies on ASD are a limitation to the generalization of these findings Implications for research and practice are discussed, highlighting the importance of screening and acknowledging the possibility of ASD/ADHD in many settings such as psychiatric and forensic.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Autistic Disorder; Autism Spectrum Disorder; Narration
PubMed: 37341291
DOI: 10.1177/10870547231176862