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Sleep Medicine Reviews Jun 2023The consumption of caffeine in response to insufficient sleep may impair the onset and maintenance of subsequent sleep. This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Review
The consumption of caffeine in response to insufficient sleep may impair the onset and maintenance of subsequent sleep. This systematic review and meta-analysis investigated the effect of caffeine on the characteristics of night-time sleep, with the intent to identify the time after which caffeine should not be consumed prior to bedtime. A systematic search of the literature was undertaken with 24 studies included in the analysis. Caffeine consumption reduced total sleep time by 45 min and sleep efficiency by 7%, with an increase in sleep onset latency of 9 min and wake after sleep onset of 12 min. Duration (+6.1 min) and proportion (+1.7%) of light sleep (N1) increased with caffeine intake and the duration (-11.4 min) and proportion (-1.4%) of deep sleep (N3 and N4) decreased with caffeine intake. To avoid reductions in total sleep time, coffee (107 mg per 250 mL) should be consumed at least 8.8 h prior to bedtime and a standard serve of pre-workout supplement (217.5 mg) should be consumed at least 13.2 h prior to bedtime. The results of the present study provide evidence-based guidance for the appropriate consumption of caffeine to mitigate the deleterious effects on sleep.
Topics: Humans; Caffeine; Sleep; Polysomnography; Coffee; Sleep Deprivation
PubMed: 36870101
DOI: 10.1016/j.smrv.2023.101764 -
Cureus Dec 2021Attention-deficit hyperactivity disorder (ADHD) affects multiple cognitive domains, including impaired attention, hyperactivity, and increased impulsivity. According to... (Review)
Review
Attention-deficit hyperactivity disorder (ADHD) affects multiple cognitive domains, including impaired attention, hyperactivity, and increased impulsivity. According to the CDC, 9.4% of children between 2 and 17 years old have been diagnosed with ADHD. Neurotransmitters such as noradrenaline and dopamine have been suggested as crucial players in the pathophysiology of ADHD and are often targets of modern medication. Adenosine receptors types A1 and A2a in the brain are inhibited by caffeine: a stimulant known to augment attention by increasing cholinergic and dopaminergic transmission. The cognitive function of attention is also enhanced by the amino acid: L-theanine. The mechanism of action is that it behaves like a glutamate reuptake inhibitor while also acting in the hippocampus as a competitive low-affinity glutamate receptor antagonist. It's also shown to have a neuroprotective effect by its action on the gamma aminobutyric acid (GABA)-A receptors. Our systematic review investigates the literature and clinical trials on the cognitive-enhancing effects of caffeine and L-theanine.
PubMed: 35111479
DOI: 10.7759/cureus.20828 -
Sleep Medicine Reviews Feb 2017Caffeine is the most widely consumed psychoactive substance in the world. It is readily available in coffee and other foods and beverages, and is used to mitigate... (Review)
Review
Caffeine is the most widely consumed psychoactive substance in the world. It is readily available in coffee and other foods and beverages, and is used to mitigate sleepiness, enhance performance, and treat apnea in premature infants. This review systematically explores evidence from epidemiological studies and randomized controlled trials as to whether coffee and caffeine have deleterious effects on sleep. Caffeine typically prolonged sleep latency, reduced total sleep time and sleep efficiency, and worsened perceived sleep quality. Slow-wave sleep and electroencephalographic (EEG) slow-wave activity were typically reduced, whereas stage-1, wakefulness, and arousals were increased. Dose- and timing-response relationships were established. The sleep of older adults may be more sensitive to caffeine compared to younger adults. Pronounced individual differences are also present in young people, and genetic studies isolated functional polymorphisms of genes implicated in adenosine neurotransmission and metabolism contributing to individual sensitivity to sleep disruption by caffeine. Most studies were conducted in male adults of Western countries, which limits the generalizability of the findings. Given the importance of good sleep for general health and functioning, longitudinal investigations aimed at establishing possible causal relationships among coffee- and caffeine-induced changes in sleep quality and health development are warranted.
Topics: Age Factors; Caffeine; Coffee; Epidemiologic Studies; Humans; Randomized Controlled Trials as Topic; Sleep; Sleep Initiation and Maintenance Disorders; Sleep Stages; Wakefulness
PubMed: 26899133
DOI: 10.1016/j.smrv.2016.01.006 -
Clinical Microbiology and Infection :... Sep 2022The benefits of remdesivir in the treatment of hospitalized patients with COVID-19 remain debated with the National Institutes of Health and the World Health... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The benefits of remdesivir in the treatment of hospitalized patients with COVID-19 remain debated with the National Institutes of Health and the World Health Organization providing contradictory recommendations for and against use.
OBJECTIVES
To evaluate the role of remdesivir for hospitalized inpatients as a function of oxygen requirements.
DATA SOURCES
Beginning with our prior systematic review, we searched MEDLINE using PubMed from 15 January 2021 through 5 May 2022.
STUDY ELIGIBILITY CRITERIA
Randomised controlled trials; all languages.
PARTICIPANTS
All hospitalized adults with COVID-19.
INTERVENTIONS
Remdesivir, in comparison to either placebo, or standard of care.
ASSESSMENT OF RISK OF BIAS
We used the ROB-2 criteria.
METHODS OF DATA SYNTHESIS
The primary outcome was mortality, stratified by oxygen use (none, supplemental oxygen without mechanical ventilation, and mechanical ventilation). We conducted a frequentist random effects meta-analysis on the risk ratio scale and, to contextualize the probabilistic benefits, we also performed a Bayesian random effects meta-analysis on the risk difference scale. A ≥1% absolute risk reduction was considered clinically important.
RESULTS
We identified eight randomized trials, totaling 10 751 participants. The risk ratio for mortality comparing remdesivir vs. control was 0.77 (95% CI, 0.5-1.19) in the patients who did not require supplemental oxygen; 0.89 (95% CI, 0.79-0.99) for nonventilated patients requiring oxygen; and 1.08 (95% CI, 0.88-1.31) in the setting of mechanical ventilation. Using neutral priors, the probabilities that remdesivir reduces mortality were 76.8%, 93.8%, and 14.7%, respectively. The probability that remdesivir reduced mortality by ≥ 1% was 77.4% for nonventilated patients requiring oxygen.
CONCLUSIONS
Based on this meta-analysis, there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy. Treatment guidelines should be re-evaluated.
Topics: Adenosine Monophosphate; Adult; Alanine; Bayes Theorem; Humans; Oxygen; SARS-CoV-2; United States; COVID-19 Drug Treatment
PubMed: 35598856
DOI: 10.1016/j.cmi.2022.04.018 -
Rheumatology (Oxford, England) Jun 2021To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening.
METHODS
A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared with the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesized via narrative review.
RESULTS
Sixty-nine studies were included in the meta-analysis. DM subtype (RR 2.21), older age (WMD 11.19), male sex (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73) and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. PM (RR 0.49) and clinically amyopathic DM (RR 0.44) subtypes, Raynaud's phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD -1189.96) or lactate dehydrogenase (WMD -336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. CT scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers.
CONCLUSION
Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients.
Topics: Adenosine Triphosphatases; Age Factors; Antibodies, Antinuclear; Creatine Kinase; DNA-Binding Proteins; Deglutition Disorders; Dermatomyositis; Female; Guidelines as Topic; Humans; L-Lactate Dehydrogenase; Lung Diseases, Interstitial; Male; Myositis; Neoplasms; Publication Bias; Raynaud Disease; Risk; Sex Factors; Skin Ulcer; Tomography, X-Ray Computed; Transcription Factors
PubMed: 33599244
DOI: 10.1093/rheumatology/keab166 -
Nutrients Aug 2021Caffeine (1,3,7-trimethylxanthine) is one of the most common substances used by athletes to enhance their performance during competition. Evidence suggests that the...
Caffeine (1,3,7-trimethylxanthine) is one of the most common substances used by athletes to enhance their performance during competition. Evidence suggests that the performance-enhancing properties of caffeine can be obtained by employing several forms of administration, namely, capsules/tablets, caffeinated drinks (energy drinks and sports drinks), beverages (coffee), and chewing gum. However, caffeinated drinks have become the main form of caffeine administration in sport due to the wide presence of these products in the market. The objective of this systematic review is to evaluate the different effects of caffeinated drinks on physical performance in various sports categories such as endurance, power-based sports, team sports, and skill-based sports. A systematic review of published studies was performed on scientific databases for studies published from 2000 to 2020. All studies included had blinded and cross-over experimental designs, in which the ingestion of a caffeinated drink was compared to a placebo/control trial. The total number of studies included in this review was 37. The analysis of the included studies revealed that both sports drinks with caffeine and energy drinks were effective in increasing several aspects of sports performance when the amount of drink provides at least 3 mg of caffeine per kg of body mass. Due to their composition, caffeinated sports drinks seem to be more beneficial to consume during long-duration exercise, when the drinks are used for both rehydration and caffeine supplementation. Energy drinks may be more appropriate for providing caffeine before exercise. Lastly, the magnitude of the ergogenic benefits obtained with caffeinated drinks seems similar in women and men athletes. Overall, the current systematic review provides evidence of the efficacy of caffeinated drinks as a valid form for caffeine supplementation in sport.
Topics: Athletes; Athletic Performance; Caffeine; Central Nervous System Stimulants; Energy Drinks; Female; Humans; Male; Performance-Enhancing Substances
PubMed: 34578821
DOI: 10.3390/nu13092944 -
Journal of Asthma and Allergy 2023Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their... (Review)
Review
BACKGROUND
Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their effects on AHR can provide valuable information about the underlying disease pathophysiology. This review summarizes the available evidence regarding the effects of biologics on allergen-specific and non-allergen-specific airway responses in patients with asthma.
METHODS
We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including risk-of-bias assessment. PubMed and Ovid were searched for studies published between January 1997 and December 2021. Eligible studies were randomized, placebo-controlled trials that assessed the effects of biologics on AHR, early allergic response (EAR) and/or late allergic response (LAR) in patients with asthma.
RESULTS
Thirty studies were identified for inclusion. Bronchoprovocation testing was allergen-specific in 18 studies and non-allergen-specific in 12 studies. Omalizumab reduced AHR to methacholine, acetylcholine or adenosine monophosphate (3/9 studies), and reduced EAR (4/5 studies) and LAR (2/3 studies). Mepolizumab had no effect on AHR (3/3 studies), EAR or LAR (1/1 study). Tezepelumab reduced AHR to methacholine or mannitol (3/3 studies), and reduced EAR and LAR (1/1 study). Pitrakinra reduced LAR, with no effect on AHR (1/1 study). Etanercept reduced AHR to methacholine (1/2 studies). No effects were observed for lebrikizumab, tocilizumab, efalizumab, IMA-638 and anti-OX40 ligand on AHR, EAR or LAR; benralizumab on LAR; tralokinumab on AHR; and Ro-24-7472 on AHR or LAR (all 1/1 study each). No dupilumab or reslizumab studies were identified.
CONCLUSION
Omalizumab and tezepelumab reduced EAR and LAR to allergens. Tezepelumab consistently reduced AHR to methacholine or mannitol. These findings provide insights into AHR mechanisms and the precise effects of asthma biologics. Furthermore, findings suggest that tezepelumab broadly targets allergen-specific and non-allergic forms of AHR, and the underlying cells and mediators involved in asthma.
PubMed: 37496824
DOI: 10.2147/JAA.S410592 -
American Journal of Cardiovascular... Jul 2023The intravenous double-syringe technique (DST) of adenosine administration is the first-line treatment for stable supraventricular tachycardia (SVT). Alternatively, the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The intravenous double-syringe technique (DST) of adenosine administration is the first-line treatment for stable supraventricular tachycardia (SVT). Alternatively, the single-syringe technique (SST) was recently found to be potentially beneficial in several studies. This study aimed to perform a meta-analysis of the SST versus the DST of adenosine administration for the treatment of SVT.
METHODS
We assessed EMBASE, PubMed, Cochrane, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) and non-randomized studies of intervention (NRSIs) comparing the DST to the SST of adenosine administration in patients with SVT. Outcomes included termination rate, termination rate at first dose, total administered dose, adverse effects, and discharge rate.
RESULTS
We included four studies (three RCTs and one NRSI) with a total of 178 patients, of whom 99 underwent the SST of adenosine administration. No significant difference was found between treatment groups regarding termination rate, termination rate restricted to RCTs, total administered dose, and discharge rate. Termination rate at first dose (odds ratio 2.87; confidence interval 1.11-7.41; p = 0.03; I = 0%) was significantly increased in patients who received the SST. Major adverse effects were observed in only one study.
CONCLUSIONS
The SST is probably as safe as the DST and at least as effective for SVT termination, SVT termination at first dose, and discharge rate from the emergency department. However, definitive superiority of one technique is not feasible given the limited sample size.
REGISTRATION
PROSPERO identifier nº CRD42022345125.
Topics: Humans; Adenosine; Syringes; Tachycardia, Supraventricular; Emergency Service, Hospital; Administration, Intravenous
PubMed: 37162718
DOI: 10.1007/s40256-023-00581-w -
BMJ (Clinical Research Ed.) Jul 2020To compare the effects of treatments for coronavirus disease 2019 (covid-19). (Comparative Study)
Comparative Study
OBJECTIVE
To compare the effects of treatments for coronavirus disease 2019 (covid-19).
DESIGN
Living systematic review and network meta-analysis.
DATA SOURCES
WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis.
STUDY SELECTION
Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.
METHODS
After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.
RESULTS
463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty).
CONCLUSION
Corticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19.
SYSTEMATIC REVIEW REGISTRATION
This review was not registered. The protocol is publicly available in the supplementary material.
READERS' NOTE
This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Betacoronavirus; COVID-19; Centers for Disease Control and Prevention, U.S.; China; Coronavirus Infections; Databases, Factual; Drug Combinations; Evidence-Based Medicine; Glucocorticoids; Humans; Hydroxychloroquine; Lopinavir; Network Meta-Analysis; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Respiration, Artificial; Ritonavir; SARS-CoV-2; Severity of Illness Index; Standard of Care; Treatment Outcome; United States; COVID-19 Drug Treatment
PubMed: 32732190
DOI: 10.1136/bmj.m2980 -
Neurological Sciences : Official... Sep 2022This study aimed to compare the safety profile of high-efficacy disease-modifying therapies (DMTs) natalizumab, fingolimod, alemtuzumab, cladribine, ocrelizumab,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to compare the safety profile of high-efficacy disease-modifying therapies (DMTs) natalizumab, fingolimod, alemtuzumab, cladribine, ocrelizumab, ofatumumab, ozanimod, as well as a potentially high-efficacy DMT, ponesimod, in adult patients with relapsing-remitting multiple sclerosis (RRMS).
METHODS
A systematic review with frequentist network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We included randomized controlled trials (RCTs) with at least 48-week follow-up investigating the use of natalizumab, fingolimod, alemtuzumab, cladribine, ocrelizumab, ofatumumab, ozanimod, and ponesimod, as well as other DMTs, in adult patients with RRMS. Eligible studies were identified by two reviewers in MEDLINE (via PubMed), EMBASE, and Cochrane Library. The Cochrane Collaboration tool to assess the risk of bias for RCTs was used.
RESULTS
A total of 33 RCTs were included in the systematic review and NMA. A higher rate of adverse events (AEs) was revealed for alemtuzumab versus all other high-efficacy DMTs; for alemtuzumab (average probability of an event: 98.2%) versus placebo (86.2%); for cladribine (3.5 mg; 90.5%) versus ozanimod (1 mg; 84.2%) and placebo; as well as for ocrelizumab (95.5%) versus ozanimod, ofatumumab (88.9%), fingolimod (87.4%), natalizumab (82.8%), and placebo. No significant differences were found between drugs in terms of serious AEs except for cladribine (3.5 mg, 17.3%) versus ocrelizumab (10.3%) and ofatumumab (16.6%) versus ocrelizumab. Significant differences in AEs leading to the discontinuation of study drug were found only for ponesimod (10.1%) versus alemtuzumab (12 mg, 3.0%) and placebo (4.2%). No differences were found in terms of upper respiratory tract infections, nasopharyngitis, fatigue, and nausea between individual high-efficacy DMTs as well as between DMTs and placebo. The results of the NMA indicated a higher risk of infections for alemtuzumab (12 mg) versus ocrelizumab, for cladribine (3.5 mg) versus ofatumumab and placebo, and for ofatumumab versus placebo. For serious infections and urinary tract infections, a significant increase was found only for alemtuzumab (12 mg) versus ocrelizumab, while no differences were found between the other DMTs or between DMTs and placebo. Headache was more common for alemtuzumab (12 mg) as compared with all the other high-efficacy DMTs and placebo, as well as for cladribine versus natalizumab and fingolimod versus natalizumab.
CONCLUSION
The commonly reported AEs are generally similar among high-efficacy DMTs. However, based on P scores for most analyzed endpoints, natalizumab and ocrelizumab were shown to be the safest DMTs. Considering the limitations of indirect comparisons, further research is needed to confirm our findings, preferably head-to-head RCTs and large observational studies.
Topics: Adult; Alemtuzumab; Cladribine; Fingolimod Hydrochloride; Humans; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Network Meta-Analysis
PubMed: 35713731
DOI: 10.1007/s10072-022-06197-3