OBJECTIVE: Chronotype, which captures a person\'s daily preferences for activity and sleep, is still a poorly researched area in epilepsy research. Finding common chronotype characteristics in people with epilepsy (PWE) and explaining possible effects on seizure management are the main goals.
METHODS: Eleven large-scale investigations from 2010 to 2023 were examined in this scoping review. These studies included 1.167 PWE and 4.657 control subjects.
RESULTS: PWE had intermediate chronotypes more often than not. Adult patients were more morning-oriented overall, while pediatric cohorts were variable. Relationships between chronotype and seizure control were limited since only two studies in adults reported this and those results conflicted. An evening-type chronotype was found to be more common in generalized epilepsy than focal. The relationship of chronotype and specific antiseizure medication (ASM) therapy was not investigated.
CONCLUSIONS: The majority of PWE displayed an intermediate chronotype, but analyses based on age showed more nuanced trends, with children displaying variable patterns, adults generally tending toward morningness, and generalized epilepsy being associated with eveningness. This review underscores the importance of more research on the complex connections between epilepsy outcomes and chronotype. It emphasizes the need to study larger samples of PWE with carefully documented seizure control and ASM therapy, including dose and timing of administration to better understand the role of chronotype on epilepsy outcomes.

High-grade gliomas are malignant brain tumors that are characteristically hard to treat because of their nature; they grow quickly and invasively through the brain tissue and develop chemoradiation resistance in adults. There is also a distinct lack of targeted treatment options in the pediatric population for this tumor type to date. Several approaches to overcome therapeutic resistance have been explored, including targeted therapy to growth pathways (ie. EGFR and VEGF inhibitors), epigenetic modulators, and immunotherapies such as Chimeric Antigen Receptor T-cell and vaccine therapies. One new promising approach relies on the timing of chemotherapy administration based on intrinsic circadian rhythms. Recent work in glioblastoma has demonstrated temporal variations in chemosensitivity and, thus, improved survival based on treatment time of day. This may be due to intrinsic rhythms of the glioma cells, permeability of the blood brain barrier to chemotherapy agents, the tumor immune microenvironment, or another unknown mechanism. We review the literature to discuss chronotherapeutic approaches to high-grade glioma treatment, circadian regulation of the immune system and tumor microenvironment in gliomas. We further discuss how these two areas may be combined to temporally regulate and/or improve the effectiveness of immunotherapies.

Hypertension remains a global health concern because of suboptimal blood pressure control despite advancements in antihypertensive treatments. Chronotherapy, defined as evening or bedtime administration of medication based on biological rhythms, is emerging as a potential strategy to improve blood pressure control and treatment outcomes. Clinical trials have investigated the potential effects of nighttime administration of antihypertensive medication in the improvement of 24 hours blood pressure control and reduction of cardiovascular risk. Implementing chronotherapy in clinical practice could have significant implications in enhancing blood pressure control and improving clinical outcomes in patients with hypertension, particularly those with resistant hypertension. However, recent trials have reported contradictory results, causing confusion in real-world practice. Herein we review, analyze, and critique the current evidence and propose suggestions regarding the clinical application and future directions of chronotherapy.

Depressive disorders in adolescents are a major health concern associated with developmental, social, and educational impairment. Bright Light Therapy (BLT) is a feasible and effective treatment for depressive disorders in adults, but few controlled trials have been conducted with children or adolescents. This scoping review focuses on the current state of knowledge for BLT in the treatment of adolescent depression. We reviewed the literature for novel data and methodologic approaches using BLT and pediatric and young adult populations.
BLT is a tolerable treatment with few side effects. However, there is a marked lack of well-powered studies to support BLT as a treatment for depressive disorders in adolescent populations. Given evidence of tolerability and positive treatment effect on depression in the adult literature, research is needed to establish the efficacy, feasibility, and acceptability of BLT in adolescents.

The timing of antihypertensive drugs administration is controversial. The aim was to compare the efficacy of dosing of antihypertensive drugs in the morning versus evening.
A PubMed, EMBASE, and clinicaltrials.gov databases search for randomized clinical trials of antihypertensive therapies where patients were randomized to morning versus evening dosing. The outcomes were ambulatory blood pressure (BP) parameters (day-time, night-time, and 24/48-hour systolic blood pressure [SBP] and diastolic blood pressure [DBP]) and cardiovascular outcomes.
Of 72 randomized controlled trials included, evening dosing significantly reduced ambulatory BP parameters: 24/48-hour SBP (mean difference [MD]=1.41 mm Hg; [95% CI, 0.48-2.34]), DBP (MD=0.60 mm Hg [95% CI, 0.12-1.08]), night-time SBP (MD=4.09 mm Hg [95% CI, 3.01-5.16]), DBP (MD, 2.57 mm Hg [95% CI, 1.92-3.22]), with a smaller reduction in day-time SBP (MD=0.94 mm Hg [95% CI, 0.01-1.87]), and DBP (MD=0.87 mm Hg [95% CI, 0.10-1.63]), and numerically lower cardiovascular events compared with morning dosing. However, when controversial data by Hermida (23 trials, 25  734 patients) were omitted (Pheterogeneity<0.05 for most outcomes), the above effect of evening dosing attenuated with no significant effect on 24/48-hour ambulatory blood pressure, day-time BP, and major adverse cardiac event and smaller reduction in night-time ambulatory SBP and DBP.
Evening dosing of antihypertensive drugs significantly reduced ambulatory BP parameters and lowered cardiovascular events but the effect was mainly driven by trials by Hermida group. Unless the intention is to specifically lower night-time BP, antihypertensive drugs should be taken at a time of day that is convenient, optimizes adherence, and minimizes undesirable effects.

The circadian clock modulates almost all vital aspects of our physiology and metabolism, including processes relevant to dentistry, such as healing, inflammation and nociception. Chronotherapy is an emerging field aiming to improve therapeutic efficacy and decrease adverse effects on health outcomes. This scoping review aimed to systematically map the evidence underpinning chronotherapy in dentistry and to identify gaps in knowledge. We conducted a systematic scoping search using four databases (Medline, Scopus, CINAHL and Embase). We identified 3908 target articles screened by two blinded reviewers, and only original animal and human studies investigating the chronotherapeutic use of drugs or interventions in dentistry were included. Of the 24 studies included, 19 were human studies and five were animal studies. Chrono-radiotherapy and chrono-chemotherapy reduced treatment side effects and improved therapeutic response, leading to higher survival rates in cancer patients. Animal studies reported that tooth movement and periodontal tissue response to orthodontic forces follow a diurnal rhythm that might influence bone metabolism. Profound and prolonged local anesthesia could be achieved when injected in the evening. Although the overall quality of the included studies was low, chronotherapy applications in dentistry seem to have favourable outcomes, especially in head and neck cancer treatments.

Outcomes for patients with high-grade glioma remain poor. Temozolomide (TMZ) is the only drug approved for first-line treatment of glioblastoma multiforme, the most aggressive form of glioma. Chronotherapy highlights the potential benefit of timed TMZ administration. This is based on pre-clinical studies of enhanced TMZ-induced glioma cytotoxicity dependent on circadian, oscillating expression of key genes involved in apoptosis, DNA damage repair, and cell-cycle mediated cell death. The current systematic review\'s primary aim was to evaluate the efficacy and toxicity of TMZ chronotherapy. A systemic review of literature following PRISMA guidelines looking at clinical outcomes on TMZ chronotherapy on gliomas was performed. The search in the English language included three databases (PubMed, EMBASE, and Cochrane) and five conferences from 1946 to April 2022. Two independent reviewers undertook screening, data extraction, and risk-of-bias assessment. A descriptive analysis was conducted due to limited data. Of the 269 articles screened, two unique studies were eligible and underwent abstraction for survival and toxicity findings. Both studies-one a retrospective cohort study (n = 166) and the other a prospective randomized feasibility study (n = 35)-were conducted by the same academic group and suggested a trend for improved overall survival, but possibly increased toxicity when TMZ was administered in the morning (vs. evening). There was limited evidence suggesting possible therapeutic value from administering TMZ in the morning, which may be consistent with the pre-clinical observations of the importance of the timing of TMZ administration in vitro. Larger, pragmatic, prospective randomized controlled trials are needed to ascertain the value of TMZ chronotherapy to provide optimized and equitable care for this population.

Sleep deprivation, alone or in combination with pharmacological treatment and as part of a chronotherapy package, is of potential use for people with major depressive episodes, however the evidence base is still conflicting. The aim of this systematic review and meta-analysis is to assess the clinical effects of sleep deprivation in comparison to any other intervention for the acute and long-term treatment of mood disorders. We searched electronic databases and trial registries (last update: 16th October 2021) for published and unpublished randomised controlled trials recruiting participants with a major depressive episode in unipolar or bipolar affective disorder. The clinical outcomes of interest were the reduction in depressive symptoms at different timepoints and the number of participants experiencing at least one side effect. Overall, 29 trials (1246 participants) were included. We did not find any difference in change in symptoms or all-cause discontinuation between interventions including SD compared to a control of the same intervention except without SD. In the included studies there were no available data for adverse events. Using the most methodologically rigorous approach, we did not find evidence that the addition of sleep deprivation to treatment packages leads to enhanced depressive outcomes.

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Several prospective studies consistently report elevated asleep blood pressure (BP) and blunted sleep-time relative systolic BP (SBP) decline (non-dipping) are jointly the most significant prognostic markers of cardiovascular disease (CVD) risk, including heart failure (HF); therefore, they, rather than office BP measurements (OBPM) and ambulatory awake and 24 h BP means, seemingly are the most worthy therapeutic targets for prevention. Published studies of the 24 h BP pattern in HF are sparse in number and of limited sample size. They report high prevalence of the abnormal non-dipper/riser 24 h SBP patterning. Despite the established clinical relevance of the asleep BP, past as do present hypertension guidelines recommend the diagnosis of hypertension rely on OBPM and, when around-the-clock ambulatory BP monitoring (ABPM) is conducted to confirm the elevated OBPM, either on the derived 24 h or \"daytime\" BP means. Additionally, hypertension guidelines do not advise the time-of-day when BP-lowering medications should be ingested, in spite of known ingestion-time differences in their pharmacokinetics and pharmacodynamics. Between 1976 and 2020, 155 unique trials of ingestion-time differences in the effects of 37 different single and 14 dual-combination hypertension medications, collectively involving 23,972 patients, were published. The vast majority (83.9%) of them found the at-bedtime/evening in comparison to upon-waking/morning treatment schedule resulted in more greatly enhanced: (i) reduction of asleep BP mean without induced sleep-time hypotension; (ii) reduction of the prevalence of the higher CVD risk non-dipper/riser 24 h BP phenotypes; (iii) improvement of kidney function, reduction of cardiac pathology, and with lower incidence of adverse effects. Most notably, no single published randomized trial found significantly better BP-lowering, particularly during sleep, or medical benefits of the most popular upon-waking/morning hypertension treatment-time scheme. Additionally, prospective outcome trials have substantiated that the bedtime relative to the upon-waking, ingestion of BP-lowering medications not only significantly reduces risk of HF but also improves overall CVD event-free survival time.