-
Thorax May 2019Conventional measures to evaluate COPD may fail to capture systemic problems, particularly musculoskeletal weakness and cardiovascular disease. Identifying these... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Conventional measures to evaluate COPD may fail to capture systemic problems, particularly musculoskeletal weakness and cardiovascular disease. Identifying these manifestations and assessing their association with clinical outcomes (ie, mortality, exacerbation and COPD hospital admission) is of increasing clinical importance.
OBJECTIVE
To assess associations between 6 min walk distance (6MWD), heart rate, fibrinogen, C reactive protein (CRP), white cell count (WCC), interleukins 6 and 8 (IL-6 and IL-8), tumour necrosis factor-alpha, quadriceps maximum voluntary contraction, sniff nasal inspiratory pressure, short physical performance battery, pulse wave velocity, carotid intima-media thickness and augmentation index and clinical outcomes in patients with stable COPD.
METHODS
We systematically searched electronic databases (August 2018) and identified 61 studies, which were synthesised, including meta-analyses to estimate pooled HRs, following Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
Shorter 6MWD and elevated heart rate, fibrinogen, CRP and WCC were associated with higher risk of mortality. Pooled HRs were 0.80 (95% CI 0.73 to 0.89) per 50 m longer 6MWD, 1.10 (95% CI 1.02 to 1.18) per 10 bpm higher heart rate, 3.13 (95% CI 2.14 to 4.57) per twofold increase in fibrinogen, 1.17 (95% CI 1.06 to 1.28) per twofold increase in CRP and 2.07 (95% CI 1.29 to 3.31) per twofold increase in WCC. Shorter 6MWD and elevated fibrinogen and CRP were associated with exacerbation, and shorter 6MWD, higher heart rate, CRP and IL-6 were associated with hospitalisation. Few studies examined associations with musculoskeletal measures.
CONCLUSION
Findings suggest 6MWD, heart rate, CRP, fibrinogen and WCC are associated with clinical outcomes in patients with stable COPD. Use of musculoskeletal measures to assess outcomes in patients with COPD requires further investigation.
TRIAL REGISTRATION NUMBER
CRD42016052075.
Topics: Biomarkers; Exercise Test; Hemodynamics; Humans; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Severity of Illness Index
PubMed: 30617161
DOI: 10.1136/thoraxjnl-2018-211855 -
Journal of Sport and Health Science May 2022There is controversial evidence regarding the effect of acute resistance exercise (ARE) on heart rate variability (HRV) parameters, which indicates the activities of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is controversial evidence regarding the effect of acute resistance exercise (ARE) on heart rate variability (HRV) parameters, which indicates the activities of the cardiac autonomic nervous system. The aim of this study was to perform a systematic review and meta-analysis of the literature on the effect of ARE on HRV parameters and identify its possible moderating factors.
METHODS
The PubMed-Medline, Web of Science, SPORTDiscus, and Cochrane Library databases were searched. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) declaration was followed, and the methodological quality of the studies was evaluated. The level of significance was set at p ≤ 0.05. Twenty-six studies met the inclusion criteria. Main effect analyses between pre- and post-test interventions demonstrated an increase in normalized units low frequency (p < 0.001; standardized mean difference (SMD) = 0.78; 95% confidence interval (95%CI): 0.46‒1.11) and low frequency/high frequency ratio (p < 0.001; SMD = 0.82; 95%CI: 0.64‒0.99) and a decrease in standard deviation of the normal-to-normal (NN) interval (p < 0.001; SMD = -0.58; 95%CI: -0.85 to -0.30), root mean square of the successive differences (p < 0.001; SMD = -1.01; 95%CI: -1.29 to -0.74), and normalized units high frequency (p < 0.001; SMD: -1.08; 95%CI: -1.43 to -0.73) following ARE in healthy individuals range: 15 ± 1 to 48 ± 2 years; mean ± SD).
RESULTS
There were differences between the subgroups in the number of sets used in an exercise (p = 0.05) for root mean square of the successive differences, as well as for exercise intensity (p = 0.01) and rest between sets (p = 0.05) for normalized units high frequency. Interestingly, there were differences between the subgroups in training volume for root mean square of the successive differences (p = 0.01), normalized units high frequency (p = 0.003) and normalized units low frequency (p = 0.02).
CONCLUSION
Overall, there was a withdrawal of cardiac parasympathetic and activation of cardiac sympathetic modulations following ARE, and these changes were greater with higher training volume ∼30 min after ARE in healthy individuals. Furthermore, the number of sets, intensity, and rest between sets affected HRV parameters. However, gender, body mass index, and training status did not influence the changes in HRV parameters as a response to ARE.
Topics: Autonomic Nervous System; Exercise; Heart Rate; Humans; Resistance Training; Rest
PubMed: 33246163
DOI: 10.1016/j.jshs.2020.11.008 -
The Cochrane Database of Systematic... Jun 2013Patients awaiting surgical procedures often experience significant anxiety. Such anxiety may result in negative physiological manifestations, slower wound healing,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients awaiting surgical procedures often experience significant anxiety. Such anxiety may result in negative physiological manifestations, slower wound healing, increased risk of infection, and may complicate the induction of anaesthesia and impede postoperative recovery. To reduce patient anxiety, sedatives and anti-anxiety drugs are regularly administered before surgery. However, these often have negative side effects and may prolong patient recovery. Therefore, increasing attention is being paid to a variety of non-pharmacological interventions for reduction of preoperative anxiety such as music therapy and music medicine interventions. Interventions are categorized as 'music medicine' when passive listening to pre-recorded music is offered by medical personnel. In contrast, music therapy requires the implementation of a music intervention by a trained music therapist, the presence of a therapeutic process, and the use of personally tailored music experiences. A systematic review was needed to gauge the efficacy of both music therapy and music medicine interventions for reduction of preoperative anxiety.
OBJECTIVES
To examine the effects of music interventions with standard care versus standard care alone on preoperative anxiety in surgical patients.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE (1950 to August 2012), CINAHL (1980 to August 2012), AMED (1985 to April 2011; we no longer had access to AMED after this date), EMBASE (1980 to August 2012), PsycINFO (1967 to August 2012), LILACS (1982 to August 2012), Science Citation Index (1980 to August 2012), the specialist music therapy research database (March 1 2008; database is no longer functional), CAIRSS for Music (to August 2012), Proquest Digital Dissertations (1980 to August 2012), ClinicalTrials.gov (2000 to August 2012), Current Controlled Trials (1998 to August 2012), and the National Research Register (2000 to September 2007). We handsearched music therapy journals and reference lists, and contacted relevant experts to identify unpublished manuscripts. There was no language restriction.
SELECTION CRITERIA
We included all randomized and quasi-randomized trials that compared music interventions and standard care with standard care alone for reducing preoperative anxiety in surgical patients.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted the data and assessed the risk of bias. We contacted authors to obtain missing data where needed. Where possible, results were presented in meta analyses using mean differences and standardized mean differences. Post-test scores were used. In cases of significant baseline differences, we used change scores.
MAIN RESULTS
We included 26 trials (2051 participants). All studies used listening to pre-recorded music. The results suggested that music listening may have a beneficial effect on preoperative anxiety. Specifically, music listening resulted, on average, in an anxiety reduction that was 5.72 units greater (95% CI -7.27 to -4.17, P < 0.00001) than that in the standard care group as measured by the Stait-Trait Anxiety Inventory (STAI-S), and -0.60 standardized units (95% CI -0.90 to -0.31, P < 0.0001) on other anxiety scales. The results also suggested a small effect on heart rate and diastolic blood pressure, but no support was found for reductions in systolic blood pressure, respiratory rate, and skin temperature. Most trials were assessed to be at high risk of bias because of lack of blinding. Blinding of outcome assessors is often impossible in music therapy and music medicine studies that use subjective outcomes, unless in studies in which the music intervention is compared to another treatment intervention. Because of the high risk of bias, these results need to be interpreted with caution.None of the studies included wound healing, infection rate, time to discharge, or patient satisfaction as outcome variables. One large study found that music listening was more effective than the sedative midazolam in reducing preoperative anxiety and equally effective in reducing physiological responses. No adverse effects were identified.
AUTHORS' CONCLUSIONS
This systematic review indicates that music listening may have a beneficial effect on preoperative anxiety. These findings are consistent with the findings of three other Cochrane systematic reviews on the use of music interventions for anxiety reduction in medical patients. Therefore, we conclude that music interventions may provide a viable alternative to sedatives and anti-anxiety drugs for reducing preoperative anxiety.
Topics: Anxiety; Blood Pressure; Heart Rate; Humans; Music Therapy; Preoperative Care; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 23740695
DOI: 10.1002/14651858.CD006908.pub2 -
Sensors (Basel, Switzerland) May 2021Recently, there has been an increase in the production of devices to monitor mental health and stress as means for expediting detection, and subsequent management of... (Review)
Review
Recently, there has been an increase in the production of devices to monitor mental health and stress as means for expediting detection, and subsequent management of these conditions. The objective of this review is to identify and critically appraise the most recent smart devices and wearable technologies used to identify depression, anxiety, and stress, and the physiological process(es) linked to their detection. The MEDLINE, CINAHL, Cochrane Central, and PsycINFO databases were used to identify studies which utilised smart devices and wearable technologies to detect or monitor anxiety, depression, or stress. The included articles that assessed stress and anxiety unanimously used heart rate variability (HRV) parameters for detection of anxiety and stress, with the latter better detected by HRV and electroencephalogram (EGG) together. Electrodermal activity was used in recent studies, with high accuracy for stress detection; however, with questionable reliability. Depression was found to be largely detected using specific EEG signatures; however, devices detecting depression using EEG are not currently available on the market. This systematic review highlights that average heart rate used by many commercially available smart devices is not as accurate in the detection of stress and anxiety compared with heart rate variability, electrodermal activity, and possibly respiratory rate.
Topics: Heart Rate; Mental Health; Monitoring, Physiologic; Reproducibility of Results; Wearable Electronic Devices
PubMed: 34065620
DOI: 10.3390/s21103461 -
Tropical Medicine & International... Aug 2022To investigate risk factors for mortality in dengue. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate risk factors for mortality in dengue.
METHODS
We performed a systematic review and meta-analysis searching MEDLINE, Embase, SciELO, LILACS Bireme, and OpenGrey databases to identify eligible observational studies of patients with dengue, of both genders, aged 14 years or older, that analysed risk factors associated with mortality and reported adjusted risk measures with their respective confidence intervals (CIs). We estimated the pooled weighted mean difference and 95% CIs with a DerSimonian and Laird random-effects model. We assessed the methodological quality using the Newcastle-Ottawa Scale.
RESULTS
Of 1,170 citations reviewed, 18 papers, with a total of 25,851 patients, were included in the systematic review and 12 in the meta-analysis. Severe hepatitis (OR 29.222, 95% CI 3.876-220.314), dengue shock syndrome (OR 23.575, 95% CI 3.664-151.702), altered mental status (OR 3.76, 95% CI 1.67-8.42), diabetes mellitus (OR 3.698, 95% CI 1.196-11.433), and higher pulse rate (OR 1.039, 95% CI 1.011-1.067) are associated with mortality in patients with dengue. All studies included were classified as having a high quality.
CONCLUSIONS
Proper identification and management of these risk factors should be considered to improve patient outcomes and reduce the hidden burden of this neglected tropical disease. Future well-designed studies are needed to investigate the association of other clinical, radiological, and laboratorial findings with mortality in dengue, as well as to develop prognostic models based on the risk factors found in our study.
Topics: Dengue; Diabetes Mellitus; Female; Humans; Male; Risk Factors
PubMed: 35761748
DOI: 10.1111/tmi.13797 -
Psychiatry and Clinical Neurosciences Jul 2022Patients with anxiety disorders (AD) have been found to have lower heart rate variability (HRV) than healthy individuals in some studies, but this was inconsistent.... (Meta-Analysis)
Meta-Analysis Review
AIMS
Patients with anxiety disorders (AD) have been found to have lower heart rate variability (HRV) than healthy individuals in some studies, but this was inconsistent. Furthermore, the influence of distinct diagnoses, study design, and demographic factors on the results was not comprehensively examined.
METHODS
We gathered studies comparing HRV in patients with AD and in healthy controls. The parasympathetic activity in the hierarchical order principle was adopted in the main analysis. We adopted the random effects model to calculate the standardized mean difference.
RESULTS
Of the 7805 screened studies, 99 were included in the quantitative analysis, with a total of 4897 AD patients and 5559 controls finally entered the meta-analysis. AD patients had a significantly lower resting-state HRV for parasympathetic activity compared to control (Hedges' g = -0.3897). For the diagnostic subgroup analysis relative to the controls, resting-state HRV was significantly lower in post-traumatic stress disorder, panic disorder, generalized anxiety disorder, and social anxiety disorder patients. HRV reactivity (all reactivity data, data on physiological challenge, and psychological challenge) did not show significant inter-group differences between AD patients and healthy subjects.
CONCLUSIONS
The results supported that patients with AD had significantly lower resting-state HRV than the healthy population, but no alterations were found for HRV reactivity.
Topics: Anxiety; Anxiety Disorders; Heart Rate; Humans; Panic Disorder; Stress Disorders, Post-Traumatic
PubMed: 35340102
DOI: 10.1111/pcn.13356 -
The Cochrane Database of Systematic... Mar 2018Health outcomes are improved when newborn babies with critical congenital heart defects (CCHDs) are detected before acute cardiovascular collapse. The main screening... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Health outcomes are improved when newborn babies with critical congenital heart defects (CCHDs) are detected before acute cardiovascular collapse. The main screening tests used to identify these babies include prenatal ultrasonography and postnatal clinical examination; however, even though both of these methods are available, a significant proportion of babies are still missed. Routine pulse oximetry has been reported as an additional screening test that can potentially improve detection of CCHD.
OBJECTIVES
• To determine the diagnostic accuracy of pulse oximetry as a screening method for detection of CCHD in asymptomatic newborn infants• To assess potential sources of heterogeneity, including:○ characteristics of the population: inclusion or exclusion of antenatally detected congenital heart defects;○ timing of testing: < 24 hours versus ≥ 24 hours after birth;○ site of testing: right hand and foot (pre-ductal and post-ductal) versus foot only (post-ductal);○ oxygen saturation: functional versus fractional;○ study design: retrospective versus prospective design, consecutive versus non-consecutive series; and○ risk of bias for the "flow and timing" domain of QUADAS-2.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2) in the Cochrane Library and the following databases: MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Health Services Research Projects in Progress (HSRProj), up to March 2017. We searched the reference lists of all included articles and relevant systematic reviews to identify additional studies not found through the electronic search. We applied no language restrictions.
SELECTION CRITERIA
We selected studies that met predefined criteria for design, population, tests, and outcomes. We included cross-sectional and cohort studies assessing the diagnostic accuracy of pulse oximetry screening for diagnosis of CCHD in term and late preterm asymptomatic newborn infants. We considered all protocols of pulse oximetry screening (eg, different saturation thresholds to define abnormality, post-ductal only or pre-ductal and post-ductal measurements, test timing less than or greater than 24 hours). Reference standards were diagnostic echocardiography (echocardiogram) and clinical follow-up, including postmortem findings, mortality, and congenital anomaly databases.
DATA COLLECTION AND ANALYSIS
We extracted accuracy data for the threshold used in primary studies. We explored between-study variability and correlation between indices visually through use of forest and receiver operating characteristic (ROC) plots. We assessed risk of bias in included studies using the QUADAS-2 tool. We used the bivariate model to calculate random-effects pooled sensitivity and specificity values. We investigated sources of heterogeneity using subgroup analyses and meta-regression.
MAIN RESULTS
Twenty-one studies met our inclusion criteria (N = 457,202 participants). Nineteen studies provided data for the primary analysis (oxygen saturation threshold < 95% or ≤ 95%; N = 436,758 participants). The overall sensitivity of pulse oximetry for detection of CCHD was 76.3% (95% confidence interval [CI] 69.5 to 82.0) (low certainty of the evidence). Specificity was 99.9% (95% CI 99.7 to 99.9), with a false-positive rate of 0.14% (95% CI 0.07 to 0.22) (high certainty of the evidence). Summary positive and negative likelihood ratios were 535.6 (95% CI 280.3 to 1023.4) and 0.24 (95% CI 0.18 to 0.31), respectively. These results showed that out of 10,000 apparently healthy late preterm or full-term newborn infants, six will have CCHD (median prevalence in our review). Screening by pulse oximetry will detect five of these infants as having CCHD and will miss one case. In addition, screening by pulse oximetry will falsely identify another 14 infants out of the 10,000 as having suspected CCHD when they do not have it.The false-positive rate for detection of CCHD was lower when newborn pulse oximetry was performed longer than 24 hours after birth than when it was performed within 24 hours (0.06%, 95% CI 0.03 to 0.13, vs 0.42%, 95% CI 0.20 to 0.89; P = 0.027).Forest and ROC plots showed greater variability in estimated sensitivity than specificity across studies. We explored heterogeneity by conducting subgroup analyses and meta-regression of inclusion or exclusion of antenatally detected congenital heart defects, timing of testing, and risk of bias for the "flow and timing" domain of QUADAS-2, and we did not find an explanation for the heterogeneity in sensitivity.
AUTHORS' CONCLUSIONS
Pulse oximetry is a highly specific and moderately sensitive test for detection of CCHD with very low false-positive rates. Current evidence supports the introduction of routine screening for CCHD in asymptomatic newborns before discharge from the well-baby nursery.
Topics: Asymptomatic Diseases; Data Accuracy; False Positive Reactions; Heart Defects, Congenital; Humans; Infant, Newborn; Oximetry; Sensitivity and Specificity
PubMed: 29494750
DOI: 10.1002/14651858.CD011912.pub2 -
CNS Drugs Jun 2014Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of... (Review)
Review
BACKGROUND
Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD).
METHODS
A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]).
RESULTS
In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX.
CONCLUSIONS
The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Clinical Trials, Phase III as Topic; Dextroamphetamine; Dose-Response Relationship, Drug; Humans; Lisdexamfetamine Dimesylate; Prodrugs; Randomized Controlled Trials as Topic; Time Factors
PubMed: 24788672
DOI: 10.1007/s40263-014-0166-2 -
PloS One 2021Cardiac autonomic neuropathy is a common complication of type 2 diabetes mellitus (T2DM), that can be measured through heart rate variability (HRV)-known to be decreased... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiac autonomic neuropathy is a common complication of type 2 diabetes mellitus (T2DM), that can be measured through heart rate variability (HRV)-known to be decreased in T2DM. Physical exercise can improve HRV in healthy population, however results are under debate in T2DM. We conducted a systemic review and meta-analysis to assess the effects of physical exercise on HRV in T2DM patients.
METHOD
PubMed, Cochrane, Embase, and ScienceDirect databases were searched for all studies reporting HRV parameters in T2DM patients before and after exercise training, until September 20th 2020, without limitation to specific years. We conducted random-effects meta-analysis stratified by type of exercise for each of the HRV parameters: RR-intervals (or Normal to Normal intervals-NN), standard deviation of RR intervals (SDNN), percentage of adjacent NN intervals varying by more than 50 milliseconds (pNN50), root mean square of successive RR-intervals differences (RMSSD), total power, Low Frequency (LF), High Frequency (HF) and LF/HF ratio. Sensitivity analyses were computed on studies with the highest quality.
RESULTS
We included 21 studies (9 were randomized) for a total of 523 T2DM patients: 472 had an exercise training and 151 were controls (no exercise). Intervention was endurance (14 studies), resistance (2 studies), endurance combined with resistance (4 studies), and high intensity interval training (HIIT) (4 studies). After exercise training, all HRV parameters improved i.e. an increase in SDNN (effect size = 0.59, 95%CI 0.26 to 0.93), RMSSD (0.62, 0.28 to 0.95), pNN50 (0.62, 0.23 to 1.00), HF (0.58, -0.16 to 0.99), and a decrease in LF (-0.37, -0.69 to -0.05) and LF/HF (-0.52, -0.79 to -0.24). There were no changes in controls. Stratification by type of exercise showed an improvement in most HRV parameters (SDNN, RMSSD, pNN50, LF, HF, LF/HF) after endurance training, whereas mostly LF/HF was improved after both resistance training and HIIT. Supervised training improved most HRV parameters. Duration and frequency of training did not influence the benefits on HRV.
CONCLUSION
Exercise training improved HRV parameters in T2DM patients which may reflect an improvement in the activity of the autonomic nervous system. The level of proof is the highest for endurance training. Supervised training seemed beneficial.
Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Endurance Training; Exercise; Female; Heart; Heart Rate; High-Intensity Interval Training; Humans; Male; Randomized Controlled Trials as Topic; Resistance Training
PubMed: 33999947
DOI: 10.1371/journal.pone.0251863 -
CNS Drugs Mar 2017Many children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular Effects of Stimulant and Non-Stimulant Medication for Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of Trials of Methylphenidate, Amphetamines and Atomoxetine.
BACKGROUND
Many children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be associated with cardiovascular effects. It is important to identify whether mean group effects translate into clinically relevant increases for some individual patients, and/or increase the risk for serious cardiovascular adverse events such as stroke or sudden death.
OBJECTIVES
To evaluate potential cardiovascular effects of these treatments, we conducted a systematic review and meta-analysis of the effects of methylphenidate (MPH), amphetamines (AMP), and atomoxetine (ATX) on diastolic and systolic blood pressure (DBP, SBP) and heart rate (HR) in children and adolescents with ADHD.
METHODS
We conducted systematic searches in electronic databases (PsychINFO, EMBASE and Medline) to identify published trials which involved individuals who were (i) diagnosed with ADHD and were aged between 0-18 years; (ii) treated with MPH, AMP or ATX and (iii) had their DBP and SBP and/or HR measured at baseline (pre) and the endpoint (post) of the study treatment. Studies with an open-label design or a double-blind randomised control design of any duration were included. Statistical analysis involved calculating differences between pre- and post-treatment measurements for the various cardiovascular parameters divided by the pooled standard deviation. Further, we assessed the percentage of clinically relevant increased BP or HR, or documented arrhythmias.
RESULTS
Eighteen clinical trials met the inclusion criteria (10 for MPH, 5 for AMP, and 7 for ATX) with data from 5837 participants (80.7% boys) and average duration of 28.7 weeks (range 4-96 weeks). All three medications were associated with a small, but statistically significant pre-post increase of SBP (MPH: standard mean difference [SMD] 0.25, 95% confidence interval [CI] 0.08-0.42, p < 0.01; AMP: SMD 0.09, 95% CI 0.03-0.15, p < 0.01; ATX: SMD 0.16, 95% CI 0.04-0.27, p = 0.01). MPH did not have a pre-post effect on DBP and HR. AMP treatment was associated with a small but statistically significant pre-post increase of DBP (SMD 0.16, CI 0.03-0.29, p = 0.02), as was ATX treatment (SMD 0.22, CI 0.10-0.34, p < 0.01). AMP and ATX were associated with a small to medium statistically significant pre-post increase of HR (AMP: SMD 0.37, CI 0.13-0.60, p < 0.01; ATX: SMD 0.43, CI 0.26-0.60, p < 0.01). The head-to-head comparison of the three medications did not reveal significant differences. Sensitivity analyses revealed that AMP studies of <18 weeks reported higher effect sizes on DBP compared with longer duration studies (F(1) = 19.55, p = 0.05). Further, MPH studies published before 2007 reported higher effect sizes on SBP than studies after 2007 (F(1) = 5.346, p = 0.05). There was no effect of the following moderators: type of medication, doses, sample size, age, gender, type of ADHD, comorbidity or dropout rate. Participants on medication reported 737 (12.6%) other cardiovascular effects. Notably, 2% of patients discontinued their medication treatment due to any cardiovascular effect. However, in the majority of patients, the cardiovascular effects resolved spontaneously, medication doses were changed or the effects were not considered clinically relevant. There were no statistically significant differences between the medication treatments in terms of the severity of cardiovascular effects.
CONCLUSIONS
Statistically significant pre-post increases of SBP, DBP and HR were associated with AMP and ATX treatment in children and adolescents with ADHD, while MPH treatment had a statistically significant effect only on SBP in these patients. These increases may be clinically significant for a significant minority of individuals that experience larger increases. Since increased BP and HR in general are considered risk factors for cardiovascular morbidity and mortality during adult life, paediatric patients using ADHD medication should be monitored closely and regularly for HR and BP.
Topics: Adolescent; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous System Stimulants; Child; Child, Preschool; Clinical Trials as Topic; Heart Rate; Humans; Infant; Methylphenidate; Psychotropic Drugs
PubMed: 28236285
DOI: 10.1007/s40263-017-0410-7