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The American Journal of Geriatric... Jan 2024Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may exert positive effects in patients with depression. Our aim was to conduct a... (Meta-Analysis)
Meta-Analysis Review
AIM/HYPOTHESIS
Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may exert positive effects in patients with depression. Our aim was to conduct a systematic review and meta-analysis to examine the antidepressant effects of GLP-1RAs.
METHODS
Randomized controlled trials and prospective cohort studies investigating the effects of GLP-1RAs versus placebo or other antidiabetic therapies on depressive symptoms were searched for using multiple electronic sources (CENTRAL, PubMed, EMBASE, PsycINFO, World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, China Network Knowledge Infrastructure, China Biomedical Database, Wan Fang data, and Chinese Scientific Journals Database) from inception to February 16, 2023. We utilized a random effects model to analyze standardized mean differences for the change in depression rating scales comparing GLP-1RA treated groups with control treated groups.
RESULTS
The meta-analysis comprising 2,071 participants included 5 randomized controlled trials and 1 prospective cohort study. The meta-analysis indicated that the change from baseline in depression rating scale scores decreased significantly when patients received treatment with GLP-1RAs compared to control treatments (SMD = -0.12, 95% CI [-0.21, -0.03], p <0.01, I = 0%, p = 0.52). The subgroup analysis showed that the effects of GLP-1RAs on depressive symptoms were consistent in patients with Type 2 diabetes mellitus (SMD = -0.12, 95% CI [-0.21, -0.03], p <0.01, I = 2%, p = 0.40).
CONCLUSIONS
Adults treated with GLP-1RAs showed significant reductions in the depression rating scale scores compared to those treated with control substances. Our findings suggest that GLP-1RAs may be a potential treatment for alleviating depressive symptoms in humans.
Topics: Humans; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor Agonists; Prospective Studies; Hypoglycemic Agents; Antidepressive Agents
PubMed: 37684186
DOI: 10.1016/j.jagp.2023.08.010 -
Nutrients Oct 2020Citicoline is a chemical compound involved in the synthesis of cell membranes. It also has other, not yet explained functions. Research on the use of citicoline is...
Citicoline is a chemical compound involved in the synthesis of cell membranes. It also has other, not yet explained functions. Research on the use of citicoline is conducted in neurology, ophthalmology, and psychiatry. Citicoline is widely available as a dietary supplement. It is often used to enhance cognitive functions. In our article, accessible databases were searched for articles regarding citicoline use in neurological diseases. This article has a systemic review form. After rejecting non-eligible reports, 47 remaining articles were reviewed. The review found that citicoline has been proven to be a useful compound in preventing dementia progression. It also enhances cognitive functions among healthy individuals and improves prognosis after stroke. In an animal model of nerve damage and neuropathy, citicoline stimulated regeneration and lessened pain. Among patients who underwent brain trauma, citicoline has an unclear clinical effect. Citicoline has a wide range of effects and could be an essential substance in the treatment of many neurological diseases. Its positive impact on learning and cognitive functions among the healthy population is also worth noting.
Topics: Animals; Brain Injuries, Traumatic; Cognition; Cytidine Diphosphate Choline; Dementia; Disease Models, Animal; Humans; Meta-Analysis as Topic; Nervous System Diseases; Neuralgia; Neurotransmitter Agents; Peripheral Nervous System; Stroke
PubMed: 33053828
DOI: 10.3390/nu12103113 -
Nutrients May 2020Nitric oxide related ergogenic aids such as arginine (Arg) have shown to impact positively on sport performance through several physiological and metabolic mechanisms.... (Meta-Analysis)
Meta-Analysis
Nitric oxide related ergogenic aids such as arginine (Arg) have shown to impact positively on sport performance through several physiological and metabolic mechanisms. However, research results have shown to be controversial. The great differences regarding required metabolic pathways and physiological demands between aerobic and anaerobic sport disciplines could be the reasons. The aim of this systematic review and meta-analysis was to evaluate the effects of Arg supplementation on aerobic (≤VOmax) and anaerobic (>VOmax) performance. Likewise, to show the effective dose and timing of this supplementation. A structured search was carried out in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and PICOS guidelines in PubMed/MEDLINE, Web of Science (WOS), and Scopus databases from inception to January 2020. Eighteen studies were included which compare Arg supplementation with placebo in an identical situation and testing its effects on aerobic and anaerobic performance tests. Trials analyzing supplementation with other supplements were removed and there was not athlete's level, gender, ethnicity, or age filters. The performed meta-analysis included 15 studies and random effects model and pooled standardized mean differences (SMD) were used according to Hedges' g. Results revealed that Arg supplementation could improve aerobic (SMD, 0.84; 95% CI, 0.12 to 1.56; magnitude of SMD (MSMD), large; I2, 89%; = 0.02) and anaerobic (SMD, 0.24; 95% CI, 0.05 to 0.43; MSMD, small; I2, 0%; = 0.01) performance tests. In conclusion, acute Arg supplementation protocols to improve aerobic and anaerobic performance should be adjusted to 0.15 g/kg of body weight ingested between 60-90 min before. Moreover, chronic Arg supplementation should include 1.5-2 g/day for 4-7 weeks in order to improve aerobic performance, and 10-12 g/day for 8 weeks to enhance anaerobic performance.
Topics: Aerobiosis; Anaerobiosis; Arginine; Athletic Performance; Body Weight; Dietary Supplements; Energy Metabolism; Female; Humans; Male; Nitric Oxide; Performance-Enhancing Substances
PubMed: 32370176
DOI: 10.3390/nu12051300 -
The Cochrane Database of Systematic... Apr 2020Lumbosacral radicular pain (commonly called sciatica) is a syndrome involving patients who report radiating leg pain. Epidural corticosteroid injections deliver a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lumbosacral radicular pain (commonly called sciatica) is a syndrome involving patients who report radiating leg pain. Epidural corticosteroid injections deliver a corticosteroid dose into the epidural space, with the aim of reducing the local inflammatory process and, consequently, relieving the symptoms of lumbosacral radicular pain. This Cochrane Review is an update of a review published in Annals of Internal Medicine in 2012. Some placebo-controlled trials have been published recently, which highlights the importance of updating the previous review.
OBJECTIVES
To investigate the efficacy and safety of epidural corticosteroid injections compared with placebo injection on pain and disability in patients with lumbosacral radicular pain.
SEARCH METHODS
We searched the following databases without language limitations up to 25 September 2019: Cochrane Back and Neck group trial register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, International Pharmaceutical Abstracts, and two trial registers. We also performed citation tracking of included studies and relevant systematic reviews in the field.
SELECTION CRITERIA
We included studies that compared epidural corticosteroid injections of any corticosteroid drug to placebo injections in patients with lumbosacral radicular pain. We accepted all three anatomical approaches (caudal, interlaminar, and transforaminal) to delivering corticosteroids into the epidural space. We considered trials that included a placebo treatment as delivery of an inert substance (i.e. one with no pharmacologic activity), an innocuous substance (e.g. normal saline solution), or a pharmacologically active substance but not one considered to provide sustained benefit (e.g. local anaesthetic), either into the epidural space (i.e. to mimic epidural corticosteroid injection) or adjacent spinal tissue (i.e. subcutaneous, intramuscular, or interspinous tissue). We also included trials in which a local anaesthetic with a short duration of action was used as a placebo and injected together with corticosteroid in the intervention group.
DATA COLLECTION AND ANALYSIS
Two authors independently performed the screening, data extraction, and 'Risk of bias' assessments. In case of insufficient information, we contacted the authors of the original studies or estimated the data. We grouped the outcome data into four time points of assessment: immediate (≤ 2 weeks), short term (> 2 weeks but ≤ 3 months), intermediate term (> 3 months but < 12 months), and long term (≥ 12 months). We assessed the overall quality of evidence for each outcome and time point using the GRADE approach.
MAIN RESULTS
We included 25 clinical trials (from 29 publications) investigating the effects of epidural corticosteroid injections compared to placebo in patients with lumbosacral radicular pain. The included studies provided data for a total of 2470 participants with a mean age ranging from 37.3 to 52.8 years. Seventeen studies included participants with lumbosacral radicular pain with a diagnosis based on clinical assessment and 15 studies included participants with mixed duration of symptoms. The included studies were conducted mainly in North America and Europe. Fifteen studies did not report funding sources, five studies reported not receiving funding, and five reported receiving funding from a non-profit or government source. Eight trials reported data on pain intensity, 12 reported data on disability, and eight studies reported data on adverse events. The duration of the follow-up assessments ranged from 12 hours to 1 year. We considered eight trials to be of high quality because we judged them as having low risk of bias in four out of the five bias domains. We identified one ongoing trial in a trial registry. Epidural corticosteroid injections were probably slightly more effective compared to placebo in reducing leg pain at short-term follow-up (mean difference (MD) -4.93, 95% confidence interval (CI) -8.77 to -1.09 on a 0 to 100 scale; 8 trials, n = 949; moderate-quality evidence (downgraded for risk of bias)). For disability, epidural corticosteroid injections were probably slightly more effective compared to placebo in reducing disability at short-term follow-up (MD -4.18, 95% CI -6.04 to -2.17, on a 0 to 100 scale; 12 trials, n = 1367; moderate-quality evidence (downgraded for risk of bias)). The treatment effects are small, however, and may not be considered clinically important by patients and clinicians (i.e. MD lower than 10%). Most trials provided insufficient information on how or when adverse events were assessed (immediate or short-term follow-up) and only reported adverse drug reactions - that is, adverse events that the trialists attributed to the study treatment. We are very uncertain that epidural corticosteroid injections make no difference compared to placebo injection in the frequency of minor adverse events (risk ratio (RR) 1.14, 95% CI 0.91 to 1.42; 8 trials, n = 877; very low quality evidence (downgraded for risk of bias, inconsistency and imprecision)). Minor adverse events included increased pain during or after the injection, non-specific headache, post-dural puncture headache, irregular periods, accidental dural puncture, thoracic pain, non-local rash, sinusitis, vasovagal response, hypotension, nausea, and tinnitus. One study reported a major drug reaction for one patient on anticoagulant therapy who had a retroperitoneal haematoma as a complication of the corticosteroid injection.
AUTHORS' CONCLUSIONS
This study found that epidural corticosteroid injections probably slightly reduced leg pain and disability at short-term follow-up in people with lumbosacral radicular pain. In addition, no minor or major adverse events were reported at short-term follow-up after epidural corticosteroid injections or placebo injection. Although the current review identified additional clinical trials, the available evidence still provides only limited support for the use of epidural corticosteroid injections in people with lumbosacral radicular pain as the treatment effects are small, mainly evident at short-term follow-up and may not be considered clinically important by patients and clinicians (i.e. mean difference lower than 10%). According to GRADE, the quality of the evidence ranged from very low to moderate, suggesting that further studies are likely to play an important role in clarifying the efficacy and tolerability of this treatment. We recommend that further trials should attend to methodological features such as appropriate allocation concealment and blinding of care providers to minimise the potential for biased estimates of treatment and harmful effects.
Topics: Adrenal Cortex Hormones; Adult; Anesthetics, Local; Humans; Injections, Epidural; Lumbosacral Region; Middle Aged; Randomized Controlled Trials as Topic; Sciatica
PubMed: 32271952
DOI: 10.1002/14651858.CD013577 -
The Cochrane Database of Systematic... Aug 2018Attention deficit hyperactivity disorder (ADHD) is a childhood-onset disorder characterised by inattention, hyperactivity, and impulsivity. ADHD can persist into... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a childhood-onset disorder characterised by inattention, hyperactivity, and impulsivity. ADHD can persist into adulthood and can affects individuals' social and occupational functioning, as well as their quality of life and health. ADHD is frequently associated with other mental disorders such as substance use disorders and anxiety and affective disorders. Amphetamines are used to treat adults with ADHD, but uncertainties about their efficacy and safety remain.
OBJECTIVES
To examine the efficacy and safety of amphetamines for adults with ADHD.
SEARCH METHODS
In August 2017, we searched CENTRAL, MEDLINE, Embase, PsycINFO, 10 other databases, and two trials registers, and we ran citation searches for included studies. We also contacted the corresponding authors of all included studies, other experts in the field, and the pharmaceutical company, Shire, and we searched the reference lists of retrieved studies and reviews for other published, unpublished, or ongoing studies. For each included study, we performed a citation search in Web of Science to identify any later studies that may have cited it.
SELECTION CRITERIA
We searched for randomised controlled trials comparing the efficacy of amphetamines (at any dose) for ADHD in adults aged 18 years and over against placebo or an active intervention.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data from each included study. We used the standardised mean difference (SMD) and the risk ratio (RR) to assess continuous and dichotomous outcomes, respectively. We conducted a stratified analysis to determine the influence of moderating variables. We assessed trials for risk of bias and drew a funnel plot to investigate the possibility of publication bias. We rated the quality of the evidence using the GRADE approach, which yielded high, moderate, low, or very low quality ratings based on evaluation of within-trial risk of bias, directness of evidence, heterogeneity of data; precision of effect estimates, and risk of publication bias.
MAIN RESULTS
We included 19 studies that investigated three types of amphetamines: dexamphetamine (10.2 mg/d to 21.8 mg/d), lisdexamfetamine (30 mg/d to 70 mg/d), and mixed amphetamine salts (MAS; 12.5 mg/d to 80 mg/d). These studies enrolled 2521 participants; most were middle-aged (35.3 years), Caucasian males (57.2%), with a combined type of ADHD (78.8%). Eighteen studies were conducted in the USA, and one study was conducted in both Canada and the USA. Ten were multi-site studies. All studies were placebo-controlled, and three also included an active comparator: guanfacine, modafinil, or paroxetine. Most studies had short-term follow-up and a mean study length of 5.3 weeks.We found no studies that had low risk of bias in all domains of the Cochrane 'Risk of bias' tool, mainly because amphetamines have powerful subjective effects that may reveal the assigned treatment, but also because we noted attrition bias, and because we could not rule out the possibility of a carry-over effect in studies that used a cross-over design.Sixteen studies were funded by the pharmaceutical industry, one study was publicly funded, and two studies did not report their funding sources.Amphetamines versus placeboSeverity of ADHD symptoms: we found low- to very low-quality evidence suggesting that amphetamines reduced the severity of ADHD symptoms as rated by clinicians (SMD -0.90, 95% confidence interval (CI) -1.04 to -0.75; 13 studies, 2028 participants) and patients (SMD -0.51, 95% CI -0.75 to -0.28; six studies, 120 participants).Retention: overall, we found low-quality evidence suggesting that amphetamines did not improve retention in treatment (risk ratio (RR) 1.06, 95% CI 0.99 to 1.13; 17 studies, 2323 participants).Adverse events: we found that amphetamines were associated with an increased proportion of patients who withdrew because of adverse events (RR 2.69, 95% CI 1.63 to 4.45; 17 studies, 2409 participants).Type of amphetamine: we found differences between amphetamines for the severity of ADHD symptoms as rated by clinicians. Both lisdexamfetamine (SMD -1.06, 95% CI -1.26 to -0.85; seven studies, 896 participants; low-quality evidence) and MAS (SMD -0.80, 95% CI -0.93 to -0.66; five studies, 1083 participants; low-quality evidence) reduced the severity of ADHD symptoms. In contrast, we found no evidence to suggest that dexamphetamine reduced the severity of ADHD symptoms (SMD -0.24, 95% CI -0.80 to 0.32; one study, 49 participants; very low-quality evidence). In addition, all amphetamines were efficacious in reducing the severity of ADHD symptoms as rated by patients (dexamphetamine: SMD -0.77, 95% CI -1.14 to -0.40; two studies, 35 participants; low-quality evidence; lisdexamfetamine: SMD -0.33, 95% CI -0.65 to -0.01; three studies, 67 participants; low-quality evidence; MAS: SMD -0.45, 95% CI -1.02 to 0.12; one study, 18 participants; very low-quality evidence).Dose at study completion: different doses of amphetamines did not appear to be associated with differences in efficacy.Type of drug-release formulation: we investigated immediate- and sustained-release formulations but found no differences between them for any outcome.Amphetamines versus other drugsWe found no evidence that amphetamines improved ADHD symptom severity compared to other drug interventions.
AUTHORS' CONCLUSIONS
Amphetamines improved the severity of ADHD symptoms, as assessed by clinicians or patients, in the short term but did not improve retention to treatment. Amphetamines were associated with higher attrition due to adverse events. The short duration of studies coupled with their restrictive inclusion criteria limits the external validity of these findings. Furthermore, none of the included studies had an overall low risk of bias. Overall, the evidence generated by this review is of low or very low quality.
Topics: Adult; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic
PubMed: 30091808
DOI: 10.1002/14651858.CD007813.pub3 -
The Cochrane Database of Systematic... Nov 2015Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children with ADHD find... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children with ADHD find it difficult to pay attention, they are hyperactive and impulsive.Methylphenidate is the drug most often prescribed to treat children and adolescents with ADHD but, despite its widespread use, this is the first comprehensive systematic review of its benefits and harms.
OBJECTIVES
To assess the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD.
SEARCH METHODS
In February 2015 we searched six databases (CENTRAL, Ovid MEDLINE, EMBASE, CINAHL, PsycINFO, Conference Proceedings Citations Index), and two trials registers. We checked for additional trials in the reference lists of relevant reviews and included trials. We contacted the pharmaceutical companies that manufacture methylphenidate to request published and unpublished data.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing methylphenidate versus placebo or no intervention in children and adolescents aged 18 years and younger with a diagnosis of ADHD. At least 75% of participants needed to have an intellectual quotient of at least 70 (i.e. normal intellectual functioning). Outcomes assessed included ADHD symptoms, serious adverse events, non-serious adverse events, general behaviour and quality of life.
DATA COLLECTION AND ANALYSIS
Seventeen review authors participated in data extraction and risk of bias assessment, and two review authors independently performed all tasks. We used standard methodological procedures expected within Cochrane. Data from parallel-group trials and first period data from cross-over trials formed the basis of our primary analyses; separate analyses were undertaken using post-cross-over data from cross-over trials. We used Trial Sequential Analyses to control for type I (5%) and type II (20%) errors, and we assessed and downgraded evidence according to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach for high risk of bias, imprecision, indirectness, heterogeneity and publication bias.
MAIN RESULTS
The studies.We included 38 parallel-group trials (5111 participants randomised) and 147 cross-over trials (7134 participants randomised). Participants included individuals of both sexes, at a boys-to-girls ratio of 5:1, and participants' ages ranged from 3 to 18 years across most studies (in two studies ages ranged from 3 to 21 years). The average age across all studies was 9.7 years. Most participants were from high-income countries.The duration of methylphenidate treatment ranged from 1 to 425 days, with an average duration of 75 days. Methylphenidate was compared to placebo (175 trials) or no intervention (10 trials). Risk of Bias.All 185 trials were assessed to be at high risk of bias. Primary outcomes. Methylphenidate may improve teacher-rated ADHD symptoms (standardised mean difference (SMD) -0.77, 95% confidence interval (CI) -0.90 to -0.64; 19 trials, 1698 participants; very low-quality evidence). This corresponds to a mean difference (MD) of -9.6 points (95% CI -13.75 to -6.38) on the ADHD Rating Scale (ADHD-RS; range 0 to 72 points; DuPaul 1991a). A change of 6.6 points on the ADHD-RS is considered clinically to represent the minimal relevant difference. There was no evidence that methylphenidate was associated with an increase in serious (e.g. life threatening) adverse events (risk ratio (RR) 0.98, 95% CI 0.44 to 2.22; 9 trials, 1532 participants; very low-quality evidence). The Trial Sequential Analysis-adjusted intervention effect was RR 0.91 (CI 0.02 to 33.2).
SECONDARY OUTCOMES
Among those prescribed methylphenidate, 526 per 1000 (range 448 to 615) experienced non-serious adverse events, compared with 408 per 1000 in the control group. This equates to a 29% increase in the overall risk of any non-serious adverse events (RR 1.29, 95% CI 1.10 to 1.51; 21 trials, 3132 participants; very low-quality evidence). The Trial Sequential Analysis-adjusted intervention effect was RR 1.29 (CI 1.06 to 1.56). The most common non-serious adverse events were sleep problems and decreased appetite. Children in the methylphenidate group were at 60% greater risk for trouble sleeping/sleep problems (RR 1.60, 95% CI 1.15 to 2.23; 13 trials, 2416 participants), and 266% greater risk for decreased appetite (RR 3.66, 95% CI 2.56 to 5.23; 16 trials, 2962 participants) than children in the control group.Teacher-rated general behaviour seemed to improve with methylphenidate (SMD -0.87, 95% CI -1.04 to -0.71; 5 trials, 668 participants; very low-quality evidence).A change of seven points on the Child Health Questionnaire (CHQ; range 0 to 100 points; Landgraf 1998) has been deemed a minimal clinically relevant difference. The change reported in a meta-analysis of three trials corresponds to a MD of 8.0 points (95% CI 5.49 to 10.46) on the CHQ, which suggests that methylphenidate may improve parent-reported quality of life (SMD 0.61, 95% CI 0.42 to 0.80; 3 trials, 514 participants; very low-quality evidence).
AUTHORS' CONCLUSIONS
The results of meta-analyses suggest that methylphenidate may improve teacher-reported ADHD symptoms, teacher-reported general behaviour, and parent-reported quality of life among children and adolescents diagnosed with ADHD. However, the low quality of the underpinning evidence means that we cannot be certain of the magnitude of the effects. Within the short follow-up periods typical of the included trials, there is some evidence that methylphenidate is associated with increased risk of non-serious adverse events, such as sleep problems and decreased appetite, but no evidence that it increases risk of serious adverse events.Better designed trials are needed to assess the benefits of methylphenidate. Given the frequency of non-serious adverse events associated with methylphenidate, the particular difficulties for blinding of participants and outcome assessors point to the advantage of large, 'nocebo tablet' controlled trials. These use a placebo-like substance that causes adverse events in the control arm that are comparable to those associated with methylphenidate. However, for ethical reasons, such trials should first be conducted with adults, who can give their informed consent.Future trials should publish depersonalised individual participant data and report all outcomes, including adverse events. This will enable researchers conducting systematic reviews to assess differences between intervention effects according to age, sex, comorbidity, type of ADHD and dose. Finally, the findings highlight the urgent need for large RCTs of non-pharmacological treatments.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Female; Humans; Male; Methylphenidate; Randomized Controlled Trials as Topic
PubMed: 26599576
DOI: 10.1002/14651858.CD009885.pub2 -
Neuroscience and Biobehavioral Reviews Sep 2019There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a...
There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data - emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.
Topics: Addiction Medicine; Humans; Outcome Assessment, Health Care; Practice Guidelines as Topic; Substance-Related Disorders; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation
PubMed: 31271802
DOI: 10.1016/j.neubiorev.2019.06.007 -
The Cochrane Database of Systematic... May 2020Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use.
OBJECTIVES
To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification.
MAIN RESULTS
Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome.
AUTHORS' CONCLUSIONS
Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used.
Topics: Administration, Oral; Body Weight; Breast Feeding; Domperidone; Female; Galactogogues; Humans; Infant; Infant, Newborn; Lactation; Metoclopramide; Milk, Human; Mothers; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Sulpiride; Thyrotropin-Releasing Hormone
PubMed: 32421208
DOI: 10.1002/14651858.CD011505.pub2 -
BMJ Open Jul 2019The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain...
OBJECTIVE
The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain injury (TBI).
METHODS
We performed a search strategy in PubMed, OvidMEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Google Scholar, Directory of Open Access Journals, LILACS, Web of Science and Prospero (up to 10 December 2018) for published and unpublished evidence on the risks and benefits of 9 prespecified medications classes used to control agitated behaviours following TBI. We included all randomised controlled trials, quasi-experimental and observational studies examining the effects of medications administered to control agitated behaviours in TBI patients. Included studies were classified into three mutually exclusive categories: (1) agitated behaviour was the presenting symptom; (2) agitated behaviour was not the presenting symptom, but was measured as an outcome variable; and (3) safety of pharmacological interventions administered to control agitated behaviours was measured.
RESULTS
Among the 181 articles assessed for eligibility, 21 studies were included. Of the studies suggesting possible benefits, propranolol reduced maximum intensities of agitation per week and physical restraint use, methylphenidate improved anger measures following 6 weeks of treatment, valproic acid reduced weekly agitated behaviour scale ratings and olanzapine reduced irritability, aggressiveness and insomnia between weeks 1 and 3 of treatment. Amantadine showed variable effects and may increase the risk of agitation in the critically ill. In three studies evaluating safety outcomes, antipsychotics were associated with an increased duration of post-traumatic amnesia (PTA) in unadjusted analyses. Small sample sizes, heterogeneity and an unclear risk of bias were limits.
CONCLUSIONS
Propranolol, methylphenidate, valproic acid and olanzapine may offer some benefit; however, they need to be further studied. Antipsychotics may increase the length of PTA. More studies on tailored interventions and continuous evaluation of safety and efficacy throughout acute, rehabilitation and outpatient settings are needed.
PROSPERO REGISTRATION NUMBER
CRD42016033140.
Topics: Antipsychotic Agents; Brain Injuries, Traumatic; Humans; Psychomotor Agitation; Psychoses, Substance-Induced; Randomized Controlled Trials as Topic
PubMed: 31289093
DOI: 10.1136/bmjopen-2019-029604 -
The Cochrane Database of Systematic... Dec 2020The prevalence of substance use, both prescribed and non-prescribed, is increasing in many areas of the world. Substance use by women of childbearing age contributes to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of substance use, both prescribed and non-prescribed, is increasing in many areas of the world. Substance use by women of childbearing age contributes to increasing rates of neonatal abstinence syndrome (NAS). Neonatal opioid withdrawal syndrome (NOWS) is a newer term describing the subset of NAS related to opioid exposure. Non-pharmacological care is the first-line treatment for substance withdrawal in newborns. Despite the widespread use of non-pharmacological care to mitigate symptoms of NAS, there is not an established definition of, and standard for, non-pharmacological care practices in this population. Evaluation of safety and efficacy of non-pharmacological practices could provide clear guidance for clinical practice.
OBJECTIVES
To evaluate the safety and efficacy of non-pharmacological treatment of infants at risk for, or having symptoms consistent with, opioid withdrawal on the length of hospitalization and use of pharmacological treatment for symptom management. Comparison 1: in infants at risk for, or having early symptoms consistent with, opioid withdrawal, does non-pharmacological treatment reduce the length of hospitalization and use of pharmacological treatment? Comparison 2: in infants receiving pharmacological treatment for symptoms consistent with opioid withdrawal, does concurrent non-pharmacological treatment reduce duration of pharmacological treatment, maximum and cumulative doses of opioid medication, and length of hospitalization?
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search CENTRAL (2019, Issue 10); Ovid MEDLINE; and CINAHL on 11 October 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs), quasi-RCTs, and cluster trials.
SELECTION CRITERIA
We included trials comparing single or bundled non-pharmacological interventions to no non-pharmacological treatment or different single or bundled non-pharmacological interventions. We assessed non-pharmacological interventions independently and in combination based on sufficient similarity in population, intervention, and comparison groups studied. We categorized non-pharmacological interventions as: modifying environmental stimulation, feeding practices, and support of the mother-infant dyad. We presented non-randomized studies identified in the search process narratively.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Primary outcomes in infants at risk for, or having early symptoms consistent with, opioid withdrawal included length of hospitalization and pharmacological treatment with one or more doses of opioid or sedative medication. Primary outcomes in infants receiving opioid treatment for symptoms consistent with opioid withdrawal included length of hospitalization, length of pharmacological treatment with opioid or sedative medication, and maximum and cumulative doses of opioid medication.
MAIN RESULTS
We identified six RCTs (353 infants) in which infants at risk for, or having symptoms consistent with, opioid withdrawal participated between 1975 and 2018. We identified no RCTs in which infants receiving opioid treatment for symptoms consistent with opioid withdrawal participated. The certainty of evidence for all outcomes was very low to low. We also identified and excluded 34 non-randomized studies published between 2005 and 2018, including 29 in which infants at risk for, or having symptoms consistent with, opioid withdrawal participated and five in which infants receiving opioid treatment for symptoms consistent with opioid withdrawal participated. We identified seven preregistered interventional clinical trials that may qualify for inclusion at review update when complete. Of the six RCTs, four studies assessed modifying environmental stimulation in the form of a mechanical rocking bed, prone positioning, non-oscillating waterbed, or a low-stimulation nursery; one study assessed feeding practices (comparing 24 kcal/oz to 20 kcal/oz formula); and one study assessed support of the maternal-infant dyad (tailored breastfeeding support). There was no evidence of a difference in length of hospitalization in the one study that assessed modifying environmental stimulation (mean difference [MD) -1 day, 95% confidence interval [CI) -2.82 to 0.82; 30 infants; very low-certainty evidence) and the one study of support of the maternal-infant dyad (MD -8.9 days, 95% CI -19.84 to 2.04; 14 infants; very low-certainty evidence). No studies of feeding practices evaluated the length of hospitalization. There was no evidence of a difference in use of pharmacological treatment in three studies of modifying environmental stimulation (typical risk ratio [RR) 1.00, 95% CI 0.86 to 1.16; 92 infants; low-certainty evidence), one study of feeding practices (RR 0.92, 95% CI 0.63 to 1.33; 49 infants; very low-certainty evidence), and one study of support of the maternal-infant dyad (RR 0.50, 95% CI 0.13 to 1.90; 14 infants; very low-certainty evidence). Reported secondary outcomes included neonatal intensive care unit (NICU) admission, days to regain birth weight, and weight nadir. One study of support of the maternal-infant dyad reported NICU admission (RR 0.50, 95% CI 0.13 to 1.90; 14 infants; very low-certainty evidence). One study of feeding practices reported days to regain birth weight (MD 1.10 days, 95% CI 2.76 to 0.56; 46 infants; very low-certainty evidence). One study that assessed modifying environmental stimulation reported weight nadir (MD -0.28, 95% CI -1.15 to 0.59; 194 infants; very low-certainty evidence) and one study of feeding practices reported weight nadir (MD -0.8, 95% CI -2.24 to 0.64; 46 infants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
We are uncertain whether non-pharmacological care for opioid withdrawal in newborns affects important clinical outcomes including length of hospitalization and use of pharmacological treatment based on the six included studies. The outcomes identified for this review were of very low- to low-certainty evidence. Combined analysis was limited by heterogeneity in study design and intervention definitions as well as the number of studies. Many prespecified outcomes were not reported. Although caregivers are encouraged by experts to optimize non-pharmacological care for opioid withdrawal in newborns prior to initiating pharmacological care, we do not have sufficient evidence to inform specific clinical practices. Larger well-designed studies are needed to determine the effect of non-pharmacological care for opioid withdrawal in newborns.
Topics: Beds; Breast Feeding; Environment Design; Humans; Hypnotics and Sedatives; Infant Equipment; Infant, Newborn; Intensive Care Units, Neonatal; Length of Stay; Narcotics; Neonatal Abstinence Syndrome; Nurseries, Infant; Opiate Substitution Treatment; Patient Positioning; Prone Position; Randomized Controlled Trials as Topic
PubMed: 33348423
DOI: 10.1002/14651858.CD013217.pub2