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Diagnostics (Basel, Switzerland) Mar 2023Early detection of pre-diabetes (pre-DM) can prevent DM and related complications. This review examined studies on non-laboratory-based pre-DM risk prediction tools to... (Review)
Review
Early detection of pre-diabetes (pre-DM) can prevent DM and related complications. This review examined studies on non-laboratory-based pre-DM risk prediction tools to identify important predictors and evaluate their performance. PubMed, Embase, MEDLINE, CINAHL were searched in February 2023. Studies that developed tools with: (1) pre-DM as a prediction outcome, (2) fasting/post-prandial blood glucose/HbA1c as outcome measures, and (3) non-laboratory predictors only were included. The studies' quality was assessed using the CASP Clinical Prediction Rule Checklist. Data on pre-DM definitions, predictors, validation methods, performances of the tools were extracted for narrative synthesis. A total of 6398 titles were identified and screened. Twenty-four studies were included with satisfactory quality. Eight studies (33.3%) developed pre-DM risk tools and sixteen studies (66.7%) focused on pre-DM and DM risks. Age, family history of DM, diagnosed hypertension and obesity measured by BMI and/or WC were the most common non-laboratory predictors. Existing tools showed satisfactory internal discrimination (AUROC: 0.68-0.82), sensitivity (0.60-0.89), and specificity (0.50-0.74). Only twelve studies (50.0%) had validated their tools externally, with a variance in the external discrimination (AUROC: 0.31-0.79) and sensitivity (0.31-0.92). Most non-laboratory-based risk tools for pre-DM detection showed satisfactory performance in their study populations. The generalisability of these tools was unclear since most lacked external validation.
PubMed: 37046512
DOI: 10.3390/diagnostics13071294 -
Cephalalgia : An International Journal... Mar 2023A systematic and meta-analysis was conducted to examine the evidence of the effects of botulinum toxin A on chronic tension-type headache. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A systematic and meta-analysis was conducted to examine the evidence of the effects of botulinum toxin A on chronic tension-type headache.
METHODS
Cochrane, Embase, Ovid, ProQuest, PubMed, Scopus, Web-of-Science databases, and ClinicallTrials.gov registry were systematically searched for studies examining the effects of botulinum toxin A on tension-type headaches. The records were screened by two independent reviewers using pre-determined eligibility criteria. DerSimonian Liard random-effects meta-analyses were performed using the 'meta' package (5.2-0) in R (4.2.0). Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's Tool RoB 2 and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Clinical significance was determined using pre-defined minimal clinically important differences.
RESULTS
Eleven controlled trials were included (390 botulinum toxin A, 297 controls). Botulinum toxin A was associated with significant improvements in standardized headache intensity (-0.502 standard deviations [-0.945, -0.058]), headache frequency (-2.830 days/month [-4.082, -1.578]), daily headache duration (-0.965 [-1.860, -0.069]) and the frequency of acute pain medication use (-2.200 days/month [-3.485, -0.915]) vs controls. Botulinum toxin A-associated improvements exceeded minimal clinically important differences for headache intensity, frequency, and acute pain medication use. A 79% (28%, 150%) greater response rate was observed for botulinum toxin A vs controls in improving chronic tension-type headache. Treatment of eight chronic tension-type headache patients was sufficient to elicit a therapeutic response in one patient.
CONCLUSIONS
Corroborating the current mechanistic evidence, our meta-analysis supports the utility of botulinum toxin A for managing chronic tension-type headaches. However, due to limitations in the quality of evidence, adequately-powered high-quality controlled trials examining the effects of Botulinum toxin A on chronic tension-type headache are warranted.
REGISTRATION
Protocol preregistered in PROSPERO International Prospective Register of Systematic Reviews (CRD42020178616).
Topics: Humans; Tension-Type Headache; Botulinum Toxins, Type A; Acute Pain; Headache; Headache Disorders
PubMed: 36786349
DOI: 10.1177/03331024221150231 -
Frontiers in Neurology 2022In the landmark trials studying endovascular thrombectomy (EVT), pre-stroke dependent (PSD) patients were generally excluded. This systematic review and meta-analysis...
BACKGROUND AND PURPOSE
In the landmark trials studying endovascular thrombectomy (EVT), pre-stroke dependent (PSD) patients were generally excluded. This systematic review and meta-analysis aimed to compare the safety and efficacy of EVT between PSD and pre-stroke independent (PSI) patients.
METHODS
We searched CENTRAL, Embase, and Ovid MEDLINE up to 11 November 2021 for studies assessing PSD and PSI patients, which were separately defined as pre-stroke mRS score >2 or >1, and ≤2 or ≤1 accordingly. Two authors extracted data and assessed the risk of bias. A meta-analysis was carried out using the random-effects model. Adjusted OR and 95% CI were used to estimate adjusted pool effects. The main outcomes included favorable outcomes, successful recanalization, symptomatic intracranial hemorrhage, and 90-day mortality.
RESULTS
A total of 8,004 records met the initial search strategy, and ten studies were included in the final decision. Compared with PSI, PSD had a lower favorable outcome (OR 0.51; 95% CI, 0.33-0.79) and higher 90-day mortality (OR 3.32; 95% CI, 2.77-3.98). No significant difference was found in successful recanalization and sICH. After adjustment, only 90-day mortality (aOR 1.99; 95% CI, 1.58-2.49) remained significantly higher in PSD. Compared with PSI, PSD had lower 90-day mortality (OR, 3.10; 95% CI, 1.84-5.24). No significant difference was found regarding the favorable outcome, successful recanalization, and sICH. After adjustment, no significant difference was found in a favorable outcome, but a higher rate of 90-day mortality (aOR, 2.13; 95% CI, 1.66-2.72) remained in PSD.
CONCLUSIONS
PSD does not innately influence the EVT outcomes regarding sICH and favorable outcomes but may increase the risk of 90-day mortality. Until further evidence is available, it is reasonable to suggest EVT for patients with PSD.
PubMed: 36212663
DOI: 10.3389/fneur.2022.956958 -
MedRxiv : the Preprint Server For... Feb 2023In this review, we provide an updated assessment of available evidence on the pharmacokinetics (PK) of cannabidiol (CBD) and explore the impact of different factors on...
BACKGROUND
In this review, we provide an updated assessment of available evidence on the pharmacokinetics (PK) of cannabidiol (CBD) and explore the impact of different factors on PK outcomes.
MATERIALS AND METHODS
This systematic review and meta-regression analysis was pre-registered (PROSPERO: CRD42021269857). We systematically searched Medline, Embase, PsychInfo, and Web of Science Core Collection up to November 19, 2022. Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T , in serum or plasma. Studies of patient populations or CBD co-administration with other medications were excluded. The was used. Random-effects multivariable meta-regression analysis was conducted.
RESULTS
A total of 112 trial arms from 39 studies were included; 26 trial arms had a "Good" quality, 70 "Fair," and 16 "Poor." Eight arms used inhalation CBD, 29 oromucosal, 73 oral, and 2 intravenous. CBD formulations could be categorized to nanotech (n=14), oil-based (n=21), alcohol-based (n=10), water-based (n=12), Sativex (n=17), and Epidiolex (n=22). For single-dose studies, CBD doses ranged between 2-100mg in inhalation, 5-50mg in oromucosal, and 0.42-6000mg in oral administration. Sixty-six trial arms had only male participants or a higher number of males than females. The duration of the PK session was between 4h-164h. A higher CBD dose was associated with higher Cmax, AUC0-t, and AUC0-inf. Compared to oral administration, oromucosal administration was associated with lower Cmax, AUC0-t, and AUC0-inf. Fed status was associated with higher Cmax and AUC0-t when compared to the fasting status. A higher ratio of female participants was associated with lower Tmax in oral administration and higher Cmax.
CONCLUSION
As expected, CBD dose, route of administration, and diet were major determinants of CBD pharmacokinetics with oral routes providing higher bioavailability and nanotechnology formulations a faster onset. Though CBD appeared to have a faster onset and longer duration in females, more studies are required to delineate the role of biological sex. Factors that influence CBD PK have implications for medication development and appropriate dosing in clinical practice.
PubMed: 36778355
DOI: 10.1101/2023.02.01.23285341 -
Communications Medicine Oct 2023A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in...
BACKGROUND
A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy.
METHODS
We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review.
RESULTS
Here we show that the majority of included papers have methodological limitations precluding robust assessment of treatment effect heterogeneity. For SGLT2-inhibitors, multiple observational studies suggest lower renal function as a predictor of lesser glycaemic response, while markers of reduced insulin secretion predict lesser glycaemic response with GLP1-receptor agonists. For both therapies, multiple post-hoc analyses of randomized control trials (including trial meta-analysis) identify minimal clinically relevant treatment effect heterogeneity for cardiovascular and renal outcomes.
CONCLUSIONS
Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.
PubMed: 37794166
DOI: 10.1038/s43856-023-00359-w -
The Cochrane Database of Systematic... Sep 2015Thyroid dysfunction pre-pregnancy and during pregnancy (both hyper- and hypothyroidism) is associated with increased risk of adverse outcomes for mothers and infants in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Thyroid dysfunction pre-pregnancy and during pregnancy (both hyper- and hypothyroidism) is associated with increased risk of adverse outcomes for mothers and infants in the short- and long-term. Managing the thyroid dysfunction (e.g. thyroxine for hypothyroidism, or antithyroid medication for hyperthyroidism) may improve outcomes. The best method of screening to identify and subsequently manage thyroid dysfunction pre-pregnancy and during pregnancy is unknown.
OBJECTIVES
To assess the effects of different screening methods (and subsequent management) for thyroid dysfunction pre-pregnancy and during pregnancy on maternal and infant outcomes.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 July 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials, comparing any screening method (e.g. tool, program, guideline/protocol) for detecting thyroid dysfunction (including hypothyroidism, hyperthyroidism, and/or thyroid autoimmunity) pre-pregnancy or during pregnancy with no screening, or alternative screening methods.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility of studies, extracted and checked data accuracy, and assessed the risk of bias of included studies.
MAIN RESULTS
We included two randomised controlled trials (involving 26,408 women) - these trials were considered to be at low risk of bias. Universal screening (screening all women) versus case finding (screening only those at perceived increased risk) in pregnancy for thyroid dysfunctionOne trial (4562 women) compared universal screening with case finding for thyroid dysfunction. Before 11 weeks' gestation, women in the universal screening group, and 'high-risk' women in the case finding group had their sera tested for TSH (thyroid stimulating hormone), fT4 (free thyroxine) and TPO-Ab (thyroid peroxidase antibody); women with hypothyroidism (TSH > 2.5 mIU/litre) received levothyroxine; women with hyperthyroidism (undetectable TSH and elevated fT4) received antithyroid medication.In regards to this review's primary outcomes, compared with the case finding group, more women in the universal screening group were diagnosed with hypothyroidism (risk ratio (RR) 3.15, 95% confidence interval (CI) 1.91 to 5.20; 4562 women; GRADE: high quality evidence), with a trend towards more women being diagnosed with hyperthyroidism (RR 4.50, 95% CI 0.97 to 20.82; 4562 women; P = 0.05; GRADE: moderate quality evidence). No clear differences were seen in the risks of pre-eclampsia (RR 0.87, 95% CI 0.64 to 1.18; 4516 women; GRADE: moderate quality evidence), or preterm birth (RR 0.99, 95% CI 0.80 to 1.24; 4516 women; GRADE: high quality evidence) between groups. This trial did not report on neurosensory disability for the infant as a child.Considering this review's secondary outcomes, more women in the universal screening group received pharmacological treatment for thyroid dysfunction (RR 3.15, 95% CI 1.91 to 5.20; 4562 women). No clear differences between groups were observed for miscarriage (RR 0.90, 95% CI 0.68 to 1.19; 4516 women; GRADE: moderate quality evidence), fetal and neonatal death (RR 0.92, 95% CI 0.42 to 2.02; 4516 infants; GRADE: moderate quality evidence), or other secondary outcomes: pregnancy-induced hypertension, gestational diabetes, congestive heart failure, thyroid storm, mode of birth (caesarean section), preterm labour, placental abruption, respiratory distress syndrome, low birthweight, neonatal intensive care unit admission, or other congenital malformations. The trial did not report on a number of outcomes including adverse effects associated with the intervention. Universal screening versus no screening in pregnancy for hypothyroidismOne trial (21,846 women) compared universal screening with no screening for hypothyroidism. Before 15 + 6 weeks' gestation, women in the universal screening group had their sera tested; women who screened 'positive' (TSH > 97.5th percentile, fT4 < 2.5th percentile, or both) received levothyroxine.Considering primary review outcomes, compared with the no screening group, more women in the universal screening screened 'positive' for hypothyroidism (RR 998.18, 95% CI 62.36 to 15,978.48; 21,839 women; GRADE: high quality evidence). No data were provided for the outcome pre-eclampsia, and for preterm birth, the trial reported rates of 5.6% and 7.9% for the screening and no screening groups respectively (it was unclear if these percentages related to the entire cohort or women who screened positive). No clear difference was seen for neurosensory disability for the infant as a child (three-year follow-up IQ score < 85) (RR 0.85, 95% CI 0.60 to 1.22; 794 infants; GRADE: moderate quality evidence).More women in the universal screening group received pharmacological treatment for thyroid dysfunction (RR 1102.90, 95% CI 69.07 to 17,610.46; 1050 women); 10% had their dose lowered because of low TSH, high fT4 or minor side effects. No clear differences were observed for other secondary outcomes, including developmental delay/intellectual impairment at three years. Most of our secondary outcomes, including miscarriage, fetal or neonatal death were not reported.
AUTHORS' CONCLUSIONS
Based on the existing evidence, though universal screening for thyroid dysfunction in pregnancy increases the number of women diagnosed with hypothyroidism who can be subsequently treated, it does not clearly impact (benefit or harm) maternal and infant outcomes.While universal screening versus case finding for thyroid dysfunction increased diagnosis and subsequent treatment, we found no clear differences for the primary outcomes: pre-eclampsia or preterm birth. No clear differences were seen for secondary outcomes, including miscarriage and fetal or neonatal death; data were lacking for the primary outcome: neurosensory disability for the infant as a child, and for many secondary outcomes. Though universal screening versus no screening for hypothyroidism similarly increased diagnosis and subsequent treatment, no clear difference was seen for the primary outcome: neurosensory disability for the infant as a child (IQ < 85 at three years); data were lacking for the other primary outcomes: pre-eclampsia and preterm birth, and for the majority of secondary outcomes.For outcomes assessed using the GRADE approach the evidence was considered to be moderate or high quality, with any downgrading of the evidence based on the presence of wide confidence intervals crossing the line of no effect.More evidence is needed to assess the benefits or harms of different screening methods for thyroid dysfunction in pregnancy, on maternal, infant and child health outcomes. Future trials should assess impacts on use of health services and costs, and be adequately powered to evaluate the effects on short- and long-term outcomes.
Topics: Adult; Female; Humans; Hypothyroidism; Infant Health; Infant, Newborn; Mass Screening; Pre-Eclampsia; Preconception Care; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic; Thyroid Diseases
PubMed: 26387772
DOI: 10.1002/14651858.CD011263.pub2 -
BJOG : An International Journal of... Jul 2022Biologic medications, specifically tumour necrosis factor-α (TNF-α) inhibitors, have become increasingly prevalent in the treatment of chronic inflammatory disease... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Biologic medications, specifically tumour necrosis factor-α (TNF-α) inhibitors, have become increasingly prevalent in the treatment of chronic inflammatory disease (CID) in pregnancy.
OBJECTIVE
To determine pregnancy outcomes in women with CID exposed to biologics during pregnancy.
SEARCH STRATEGY
PubMed and EMBASE databases were searched through January 1998-July 2021.
SELECTION CRITERIA
Peer-reviewed, English-language cohort, case-control, cross-sectional studies, and case series that contained original data.
DATA COLLECTION AND ANALYSIS
Two authors independently conducted data extraction. A meta-analysis of proportions using a random-effects model was used to pool outcomes. Linear regression analysis was used to compare the mean of proportions of outcomes across exposure groups using the 'treated' group as the reference category. All studies were evaluated using an appropriate quality assessment tool. The GRADE approach was used to assess the overall certainty of evidence.
MAIN RESULTS
Thirty-five studies, describing 11 172 pregnancies, were eligible for inclusion. Analysis showed pooled proportions for congenital malformations as follows: treated 0.04 (95% CI 0.03-0.04; I = 77) versus disease-matched 0.04 (95% CI 0.03-0.05. I = 86; p = 0.238); preterm delivery treated 0.04 (95% CI 0.10-0.14; I = 88) versus disease-matched 0.10 (95% CI 0.09-0.12; I = 87; p = 0.250); severe neonatal infection: treated 0.05 (95% CI 0.03-0.07; I = 88) versus disease-matched 0.05 (95% CI 0.02-0.07; I = 94; p = 0.970); low birthweight: treated 0.10 (95% CI 0.07-0.12; I = 93) versus disease-matched 0.08 (95% CI 0.07-0.09; I = 0; p = 0.241); pooled miscarriage: treated 0.13 (95% CI 0.10-0.15; I = 77) versus disease-matched 0.08 (95% CI 0.04-0.11; I = 5; p = 0.078); pre-eclampsia; treated 0.01 (95% CI 0.01-0.02; I = 0) versus disease-matched 0.01 (95% CI 0.00-0.01; I = 0; p = 0.193). No statistical differences in proportions were observed. GRADE certainty of findings was low to very low.
CONCLUSION
We demonstrated comparable pregnancy outcomes in pregnancies exposed to biologics, disease-matched controls and CID-free pregnancies using the GRADE approach.
Topics: Biological Products; Cross-Sectional Studies; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Outcome; Premature Birth; Prenatal Care
PubMed: 35014759
DOI: 10.1111/1471-0528.17093 -
Scientific Reports Apr 2024Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with anxiety and depression. Few studies have addressed interventions for symptoms of... (Meta-Analysis)
Meta-Analysis
Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with anxiety and depression. Few studies have addressed interventions for symptoms of anxiety and depression in this population. To determine the efficacy of interventions for anxiety and depression in patients with AD. PubMed, MEDLINE, EMBASE, and PsycINFO were searched from inception to November 2023. English-language studies published in peer-reviewed journals evaluating the effect of interventions on anxiety and/or depression using validated assessment tools on patients with AD were included. Titles, abstracts, and articles were screened by at least two independent reviewers. Of 1410 references that resulted in the initial search, 17 studies were included. Fourteen of these studies are randomized controlled trials, while the other 3 studies are prospective controlled trials with pre and post-test designs. Data were extracted using a standardized extraction form, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. To accommodate trials with multiple interventions (each compared to a control group), we conducted a mixed-effects meta-analysis with the trial as a random effect. Prespecified outcomes were changes in symptoms of anxiety and depression in patients with AD as evaluated using standardized assessment tools. Of the 17 studies included in this systematic review, 7 pharmacological intervention studies with 4723 participants examining 5 different medications were included in a meta-analysis. Of these studies, only 1 study evaluated medications prescribed to treat anxiety and/or depression; the rest evaluated medications prescribed to treat AD. Meta-analysis of all the pharmacological interventions resulted in significant improvement in anxiety, depression, and combined anxiety-depression scale scores (standardized mean difference [95% CI]: - 0.29 [- 0.49 to - 0.09], - 0.27 [- 0.45 to - 0.08], - 0.27 [- 0.45 to - 0.08]) respectively. The 10 non-pharmacological studies with 2058 participants showed general improvement in anxiety but not depression. A meta-analysis of the non-pharmacological interventions was not conducted due to variable approaches and limited data. Pharmacological interventions designed to improve AD were found to improve anxiety and depression in patients with moderate-severe disease. More comprehensive studies on non-pharmacological and pharmacological interventions that primarily target anxiety and depression are needed.
Topics: Humans; Dermatitis, Atopic; Depression; Prospective Studies; Anxiety; Anxiety Disorders
PubMed: 38632375
DOI: 10.1038/s41598-024-59162-9 -
Therapeutic Advances in... 2022Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and... (Review)
Review
BACKGROUND
Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and dizziness, which have a negative impact on quality of life and treatment compliance. Available evidence for the management of clozapine-induced hypotension is scant.
OBJECTIVES
Due to limited guidance on the safety and efficacy of pharmacological treatments for clozapine-induced hypotension, we set out to systematically review and assess the evidence for the management of clozapine-induced hypotension and provide guidance to clinicians, patients, and carers.
DESIGN
We undertook a systematic review of the safety and efficacy of interventions for clozapine-induced hypotension given the limited available evidence.
DATA SOURCES AND METHODS
PubMed, Embase, PsycINFO, CINAHL, and the Cochrane trial Registry were searched from inception to November 2021 for literature on the treatment strategies for clozapine-induced hypotension and dizziness using a PROSPERO pre-registered search strategy. For orthostatic hypotension, we developed a management framework to assist in the choice of intervention.
RESULTS
We identified nine case studies and four case series describing interventions in 15 patients. Hypotension interventions included temporary clozapine dose reduction, non-pharmacological treatments, and pharmacological treatments. Midodrine, fludrocortisone, moclobemide and Bovril combination, and etilefrine were associated with improvement in symptoms or reduction in orthostatic hypotension. Angiotensin II, arginine vasopressin, and noradrenaline successfully restored and maintained mean arterial pressure in critical care situations. A paradoxical reaction of severe hypotension was reported with adrenaline use.
CONCLUSION
Orthostatic hypotension is a common side effect during clozapine titration. Following an assessment of the titration schedule, salt and fluid intake, and review of hypertensive and nonselective α1-adrenergic agents, first-line treatment should be a temporary reduction in clozapine dose or non-pharmacological interventions. If orthostatic hypotension persists, fludrocortisone should be trialled with monitoring of potassium levels and sodium and fluid intake. Midodrine may be considered second-line or where fludrocortisone is contraindicated or poorly tolerated. For patients on clozapine with hypotension in critical care settings, the use of adrenaline to maintain mean arterial pressure should be avoided.
REGISTRATION
PROSPERO (Registration No. CRD42020191530).
PubMed: 35633931
DOI: 10.1177/20451253221092931 -
Frontiers in Public Health 2023Empirical evidence has shown that light therapy (LT) can reduce depression symptoms by stimulating circadian rhythms. However, there is skepticism and inconclusive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Empirical evidence has shown that light therapy (LT) can reduce depression symptoms by stimulating circadian rhythms. However, there is skepticism and inconclusive results, along with confusion regarding dosing. The purpose of this study is to quantify light as a stimulus for the circadian system and create a dose-response relationship that can help reduce maladies among adolescents and young adults (AYAs). This will provide a reference for light exposure and neural response, which are crucial in the neuropsychological mechanism of light intervention. The study also aims to provide guidance for clinical application.
METHODS
The latest quantitative model of CL (circadian light) and CS (circadian stimulus) was adopted to quantify light dose for circadian phototransduction in youth depression-related light therapy. Articles published up to 2023 through Web of Science, Cochrane Library, Medline (OVID), CINAHL, APA PsycINFO, Embase, and Scholars were retrieved. A meta-analysis of 31 articles (1,031 subjects) was performed using Stata17.0, CMA3.0 (comprehensive meta-analysis version 3.0) software, and Python 3.9 platform for light therapy efficacy comparison and dose-response quantification.
RESULTS
Under various circadian stimulus conditions (0.1 < CS < 0.7) of light therapy (LT), malady reductions among AYAs were observed (pooled SMD = -1.59, 95%CI = -1.86 to -1.32; = -11.654, = 0.000; = 92.8%), with temporal pattern ( = 0.044) and co-medication ( = 0.000) suggested as main heterogeneity sources. For the efficacy advantage of LT with a higher circadian stimulus that is assumed to be influenced by visualization, co-medication, disease severity, and time pattern, sets of meta-analysis among random-controlled trials (RCTs) found evidence for significant efficacy of circadian-active bright light therapy (BLT) over circadian-inactive dim red light (SMD = -0.65, 95% CI = -0.96 to -0.34; = -4.101, = 0.000; = 84.9%) or circadian-active dimmer white light (SMD = -0.37, 95% CI = -0.68 to -0.06; = -2.318, = 0.02; = 33.8%), whereas green-blue, circadian-active BLT showed no significant superiority over circadian-inactive red/amber light controls (SMD = -0.21, 95% CI = -0.45 to 0.04; = -2.318, = 0.099; = 0%). Overall, circadian-active BLT showed a greater likelihood of clinical response than dim light controls, with increased superiority observed with co-medication. For pre-to-post-treatment amelioration and corresponding dose-response relationship, cumulative duration was found more influential than other categorical (co-medication, severity, study design) or continuous (CS) variables. Dose-response fitting indicated that the therapeutic effect would reach saturation among co-medicated patients at 32-42 days (900-1,000 min) and 58-59 days (1,100-1,500 min) among non-medicated AYAs. When exerting high circadian stimulus of light therapy (0.6 < CS < 0.7), there was a significantly greater effect size in 1,000-1,500 min of accumulative duration than <1,000 or >1,500 min of duration, indicating a threshold for practical guidance.
LIMITATIONS
The results have been based on limited samples and influenced by a small sample effect. The placebo effect could not be ignored.
CONCLUSIONS
Although the superiority of LT with higher circadian stimulus over dimmer light controls remains unproven, greater response potentials of circadian-active BLT have been noticed among AYAs, taking co-medication, disease severity, time pattern, and visual characteristics into consideration. The dose-response relationship with quantified circadian stimulus and temporal pattern had been elaborated under various conditions to support clinical depression treatment and LT device application in the post-pandemic era.
Topics: Adolescent; Young Adult; Humans; Phototherapy; Pandemics; Probability
PubMed: 38259764
DOI: 10.3389/fpubh.2023.1257093