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Frontiers in Aging Neuroscience 2023To conduct a meta-analysis of the effectiveness and safety of ginkgo biloba preparations combined with donepezil hydrochloride vs. donepezil for the treatment of...
OBJECTIVE
To conduct a meta-analysis of the effectiveness and safety of ginkgo biloba preparations combined with donepezil hydrochloride vs. donepezil for the treatment of Alzheimer's disease (AD).
METHODS
Three English databases (Cochrane Library, PubMed, EMBASE), and four Chinese databases [the China National Knowledge Infrastructure (CKNI), the Chinese Biomedical Literature database (CBM), the Chongqing VIP database, and WANFANG DATA)] were manually searched for literature published from the respective dates of inception of the databases to December 2022. The randomized controlled trials (RCTs) of ginkgo biloba preparations with donepezil hydrochloride vs. donepezil for the treatment of AD were included. Relevant literature was screened, and the data in the included studies were extracted for quality assessment according to the Risk of bias tool. The RevMan 5.3 software was used for meta-analysis.
RESULTS
A total of 1,642 participants were enrolled in the 18 RCTs. Of these, 842 were in the experimental group (ginkgo biloba preparations combined with donepezil hydrochloride) and 800 were in the control group (donepezil). The overall methodological quality of the included RCTs is poor due to the high risks of blindness and allocation concealment. The meta-analysis results showed statistically significant differences in several outcomes including Risk Ratio (RR) in change for clinical effectiveness rate (1.23, 95% CI 1.13, 1.34, < 0.00001), mean difference (MD) in change for Mini-Mental State Examination score (3.02, 95% CI 2.14, 3.89, < 0.00001), Activity of Daily Living Scale score (-4.56, 95% CI -5.09, -4.03, < 0.00001), Hasegawa Dementia Scale score (2.04, 95% CI 1.74, 2.34, < 0.00001), Montreal Cognitive Assessment score (2.38, 95% CI 0.72, 4.06, = 0.005), between the experimental and control groups. But there is no statistically significant difference in change for adverse reaction (0.91, 95% CI 0.58, 1.42, = 0.69).
CONCLUSION
Ginkgo biloba preparations plus donepezil can improve clinical effectiveness rate and vocabulary memory outcomes. However, more relevant high-quality RCTs are needed in the future to validate these results.
SYSTEMATIC REVIEW REGISTRATION
Identifier CRD42022378970.
PubMed: 36960422
DOI: 10.3389/fnagi.2023.1124710 -
Cancer Medicine May 2023Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including... (Review)
Review
BACKGROUND
Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including quality of life and survival. This systematic review aimed to identify and describe interventions used to ameliorate (improve) or prevent cognitive impairments in adults with brain tumours.
METHODS
We performed a literature search of the Ovid MEDLINE, PsychINFO and PsycTESTS databases from commencement until September 2021.
RESULTS
In total, 9998 articles were identified by the search strategy; an additional 14 articles were identified through other sources. Of these, 35 randomised and nonrandomised studies were deemed to meet the inclusion/exclusion criteria of our review and were subsequently included for evaluation. A range of interventions were associated with positive effects on cognition, including pharmacological agents such as memantine, donepezil, methylphenidate, modafinil, ginkgo biloba and shenqi fuzheng, and nonpharmacological interventions such as general and cognitive rehabilitation, working memory training, Goal Management Training, aerobic exercise, virtual reality training combined with computer-assisted cognitive rehabilitation, hyperbaric oxygen therapy and semantic strategy training. However, most identified studies had a number of methodological limitations and were judged to be at moderate-to-high risk of bias. In addition, it remains unclear whether and to what extent the identified interventions lead to durable cognitive benefits after cessation of the intervention.
CONCLUSION
The 35 studies identified in this systematic review have indicated potential cognitive benefits for a number of pharmacological and nonpharmacological interventions in patients with brain tumours. Study limitations were identified and further studies should focus on improved study reporting, methods to reduce bias and minimise participant drop-out and withdrawal where possible, and consider standardisation of methods and interventions across studies. Greater collaboration between centres could result in larger studies with standardised methods and outcome measures, and should be a focus of future research in the field.
Topics: Adult; Humans; Quality of Life; Cognitive Dysfunction; Cognition; Cognition Disorders; Brain Neoplasms
PubMed: 36880363
DOI: 10.1002/cam4.5760 -
Journal of Ethnopharmacology Jun 2023Alzheimer's disease (AD) is a degenerative disease of the central nervous system (CNS) with insidious onset. AD is also the most common cause of dementia. Compound... (Meta-Analysis)
Meta-Analysis
Clinical efficacy and safety of compound Congrong Yizhi Capsules on Alzheimer's disease in mainland China: A systematic review with trial sequential analysis and GRADE assessment.
ETHNOPHARMACOLOGICAL RELEVANCE
Alzheimer's disease (AD) is a degenerative disease of the central nervous system (CNS) with insidious onset. AD is also the most common cause of dementia. Compound Congrong Yizhi Capsules (CCYC), a traditional Chinese medicine compound developed by the team of Beijing University of Chinese Medicine, has been widely used to treat AD.
AIM OF THIS STUDY
To systematically evaluate the clinical efficacy and safety of CCYC for AD by meta-analysis, Trial Sequential Analysis (TSA) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
METHODS
This study was registered at PROSPERO (CRD42022295496). Randomized controlled trials (RCTs) of CCYC as the treatment for AD published before December 1, 2021 were retrieved from 4 Chinses databases, 4 English databases and 2 clinical trials registration systems. RevMan 5.4 and STATA 17.0 was used to conduct the meta-analysis of the included studies, the quality of outcomes was rated by the GRADE system, the TSA was conducted by TSA 0.9.5.10 software.
RESULTS
Seven studies were included, and the total sample size was 746. Meta-analysis showed that 6 months of treatment with CCYC plus conventional western medicine treatments (CTs) improved MMSE scores compared with CTs alone (WMD: 4.32, 95% CI: 3.23, 5.42), and TSA confirmed that more trials in the future will not reverse the result. Among which, CCYC combined with donepezil can significantly improve MMSE scores (WMD: 3.54, 95% CI: 2.86, 4.22). CCYC combined with olanzapine also showed good effect on both MMSE (WMD: 6.49, 95% CI: 5.54, 7.44) and ADL scores (WMD: 5.23, 95% CI: 4.63, 5.83). No serious adverse events were reported. The strengths of the evidences above are MODERATE.
CONCLUSION
CCYC combined with cognition-modifying western medicine can improve cognitive function, mental behavioural symptoms, and activities of daily living in AD patients with good safety.
Topics: Humans; Alzheimer Disease; GRADE Approach; Plant Extracts; Treatment Outcome
PubMed: 36731808
DOI: 10.1016/j.jep.2023.116208 -
Journal of Alzheimer's Disease : JAD 2023Choline alphoscerate (alpha glyceryl phosphorylcholine, α-GPC) is a choline-containing phospholipid used as a medicine or nutraceutical to improve cognitive function... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Choline alphoscerate (alpha glyceryl phosphorylcholine, α-GPC) is a choline-containing phospholipid used as a medicine or nutraceutical to improve cognitive function impairment occurring in neurological conditions including adult-onset dementia disorders. Despite its 1985 marketing authorization, there are still discrepancies between countries regarding its approval as a prescription medicine and discussions about its effectiveness.
OBJECTIVE
This study aimed to evaluate the efficacy of the α-GPC compound for treating cognitive impairment in patients with adult-onset neurological disorders.
METHODS
Relevant studies were identified by searching PubMed, Web of Science, and Embase. Studies that evaluated the effects of α-GPC alone or in combination with other compounds on adult-onset cognitive impairment reporting cognition, function, and behavior were considered. We assessed the risk of bias of selected studies using the Cochrane risk of bias tool.
RESULTS
A total of 1,326 studies and 300 full-text articles were screened. We included seven randomized controlled trials (RCTs) and one prospective cohort study that met our eligibility criteria. We found significant effects of α-GPC in combination with donepezil on cognition [4 RCTs, mean difference (MD):1.72, 95% confidence interval (CI): 0.20 to 3.25], functional outcomes [3 RCTs, MD:0.79, 95% CI: 0.34 to 1.23], and behavioral outcomes [4 RCTs; MD: -7.61, 95% CI: -10.31 to -4.91]. We also observed that patients who received α-GPC had significantly better cognition than those who received either placebo or other medications [MD: 3.50, 95% CI: 0.36 to 6.63].
CONCLUSION
α-GPC alone or in combination with donepezil improved cognition, behavior, and functional outcomes among patients with neurological conditions associated with cerebrovascular injury.
Topics: Humans; Donepezil; Glycerylphosphorylcholine; Cognitive Dysfunction; Cognition Disorders; Cognition; Randomized Controlled Trials as Topic
PubMed: 36683513
DOI: 10.3233/JAD-221189 -
The Cochrane Database of Systematic... Nov 2022Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of... (Review)
Review
BACKGROUND
Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 12, 2014.
OBJECTIVES
To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adults treated with cranial irradiation.
SEARCH METHODS
For this review update we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, and PsycInfo via Ovid to 12 September 2022.
SELECTION CRITERIA
We included randomised controlled (RCTs) trials that evaluated pharmacological or non-pharmacological interventions in cranial irradiated adults, with objective cognitive functioning as a primary or secondary outcome measure.
DATA COLLECTION AND ANALYSIS
Two review authors (MK, JD) independently extracted data from selected studies and carried out a risk of bias assessment. Cognitive function, fatigue and mood outcomes were reported. No data were pooled.
MAIN RESULTS
Eight studies met the inclusion criteria and were included in this updated review. Six were from the original version of the review, and two more were added when the search was updated. Nineteen further studies were assessed as part of this update but did not fulfil the inclusion criteria. Of the eight included studies, four studies investigated "prevention" of cognitive problems (during radiotherapy and follow-up) and four studies investigated "amelioration" (interventions to treat cognitive impairment as a late complication of radiotherapy). There were five pharmacological studies (two studies on prevention and three in amelioration) and three non-pharmacological studies (two on prevention and one in amelioration). Due to differences between studies in the interventions being evaluated, a meta-analysis was not possible. Studies in early radiotherapy treatment phase (five studies) Pharmacological studies in the "early radiotherapy treatment phase" were designed to prevent or ameliorate cognitive deficits and included drugs used in dementia (memantine) and fatigue (d-threo-methylphenidate hydrochloride). Non-pharmacological studies in the "early radiotherapy treatment phase" included a ketogenic diet and a two-week cognitive rehabilitation and problem-solving programme. In the memantine study, the primary cognitive outcome of memory at six months did not reach significance, but there was significant improvement in overall cognitive function compared to placebo, with similar adverse events across groups. The d-threo-methylphenidate hydrochloride study found no statistically significant difference between arms, with few adverse events. The study of a calorie-restricted ketogenic diet found no effect, although a lower than expected calorie intake in the control group complicates interpretation of the results. The study investigating the utility of a rehabilitation program did not carry out a statistical comparison of cognitive performance between groups. Studies in delayed radiation or late effect phase (four studies) The "amelioration" pharmacological studies to treat cognitive complications of radiotherapy included drugs used in dementia (donepezil) or psychostimulants (methylphenidate and modafinil). Non-pharmacological measures included cognitive rehabilitation and problem solving (Goal Management Training). These studies included patients with cognitive problems at entry who had "stable" brain cancer. The donepezil study did not find an improvement in the primary cognitive outcome of overall cognitive performance, but did find improvement in an individual test of memory, compared to placebo; adverse events were not reported. A study comparing methylphenidate with modafinil found improvements in cognitive function in both the methylphenidate and modafinil arms; few adverse events were reported. Another study comparing two different doses of modafinil combined treatment arms and found improvements across all cognitive tests, however, a number of adverse events were reported. Both studies were limited by a small sample size. The Goal Management Training study suggested a benefit of the intervention, a behavioural intervention that combined mindfulness and strategy training, on executive function and processing speed. There were a number of limitations across studies and few were without high risks of bias.
AUTHORS' CONCLUSIONS
In this update, limited additional evidence was found for the treatment or amelioration of cognitive deficits in adults treated with cranial irradiation. As concluded in the original review, there is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation. There is supportive evidence that donepezil, methylphenidate and modafinil may have a role in treating cognitive deficits in adults with brain tumours who have been treated with cranial irradiation; patient withdrawal affected the statistical power of these studies. Further research that tries to minimise the withdrawal of consent, and subsequently reduce the requirement for imputation procedures, may offer a higher certainty of evidence. There is evidence from only a single small study to support non-pharmacological interventions in the amelioration of cognitive deficits. Further research is required.
Topics: Adult; Humans; Modafinil; Donepezil; Memantine; Quality of Life; Cognitive Dysfunction; Cranial Irradiation; Cognition; Methylphenidate; Brain Neoplasms; Fatigue; Dementia
PubMed: 36427235
DOI: 10.1002/14651858.CD011335.pub3 -
Health Science Reports Nov 2022Dementia is becoming a major global public health menace in the aging population affecting 47 million people globally. Dementia has no cure and effective interventions....
BACKGROUND AND AIMS
Dementia is becoming a major global public health menace in the aging population affecting 47 million people globally. Dementia has no cure and effective interventions. Treatment of dementia is a big problem. The most common symptomatic medications for cognition, behavior, and global functioning among patients with dementia currently are cholinesterase inhibitors and memantine. However, Information on the effectiveness of cholinesterase inhibitors for dementia is conflicting and controversial. Thus, this makes it difficult for decision-makers, healthcare providers, patients, and caregivers to decide on the most effective intervention. The current meta-analysis sought to investigate the efficacy of pharmacologic interventions to improve cognitive and behavioral symptoms in people with living dementia.
METHODS
This current systematic review and meta-analysis used the preferred reporting items for systematic reviews and meta-analyses to ensure accuracy and comprehensiveness. The Cochrane MEDLINE, Database of Systematic Reviews, and other databases were thoroughly searched for relevant studies. We selected Studies such as randomized controlled trials published in English with a sample size of at least 20 subjects. We selected and applied the random-effects meta-analysis as the most preferred model because of the heterogeneity across studies. The computation of the weighted effect size was based on the result from the test of heterogeneity.
RESULTS
Twenty-two studies were finally used in the meta-analysis. The study subjects who received donepezil 5 mg/day, donepezil 10 mg/day, and galantamine 24 mg/day had improved cognition symptoms (ADAS-cog) score of -1.46 (95% CI = -2.24, -0.68, = 3.67, < 0.001), -2.31 (95% CI = -3.30, -1.31, = 5.45, < 0.001) and -3.04 (95% CI = -4.16, -1.92, = 5.31, < 0.001) respectively.
CONCLUSION
The current meta-analysis suggests significant benefits of cholinesterase inhibitors such as donepezil (5 and 10 mg/day) and galantamine on cognitive symptoms.
PubMed: 36381407
DOI: 10.1002/hsr2.913 -
Ageing Research Reviews Dec 2022Dementia is a progressive neurodegenerative syndrome that has no cure. Although a significant proportion of people with dementia progress into the severe stages of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dementia is a progressive neurodegenerative syndrome that has no cure. Although a significant proportion of people with dementia progress into the severe stages of the disease, evidence on the clinical effectiveness of treatments for people with severe dementia remains limited.
AIMS
To systematically review the effectiveness of pharmacological and non-pharmacological treatments for people living with severe dementia and assess the quality of the evidence.
METHOD
We searched MEDLINE, EMBASE, PsycINFO, CINAHL and online clinical trial registers up to January 2022, for Randomised Controlled Trials (RCT) in people living with severe dementia. Quality and risk of bias were assessed independently by two authors.
RESULTS
A total of 30 trials met our inclusion criteria of which 14 evaluated the effectiveness of pharmacological treatments, and 16 evaluated a non-pharmacological intervention. Pharmacological treatments: Meta-analyses indicated that pharmacological treatments (donepezil: 10 mg, 5 mg; galantamine: 24 mg; memantine: 10 mg) are associated with better outcomes compared to placebo for: severity of symptoms (standardized mean difference (SMD) 0.37, 95% CI 0.26-0.48; 4 studies; moderate-certainty evidence), activities of daily living (SMD 0.15, 95% CI 0.04-0.26; 5 studies; moderate-certainty evidence), and clinical impression of change (Relative Risk (RR) 1.34, 95% CI 1.14-1.57; 4 studies; low-certainty evidence). Pharmacological treatments were also more likely to reduce mortality compared to placebo (RR 0.60, 95% CI 0.40-0.89; 6 studies; low-certainty evidence). Non-pharmacological treatments: Five trials were included in the meta-analyses of non-pharmacological interventions (multi-sensory stimulation, needs assessment, and activities-based interventions); results showed that non-pharmacological interventions may reduce neuropsychiatric symptoms of dementia compared to usual care (SMD -0.33, 95% CI -0.59 to -0.06; low certainty evidence).
CONCLUSIONS
There is moderate-certainty evidence that pharmacological treatments may decrease disease severity and improve function for people with severe dementia. Non-pharmacological treatments are probably effective in reducing neuropsychiatric symptoms but the quality of evidence remains low. There is an urgent need for high-quality evidence for other outcomes and for developing service-user informed interventions for this under-served group.
Topics: Humans; Dementia; Activities of Daily Living; Memantine; Treatment Outcome
PubMed: 36243355
DOI: 10.1016/j.arr.2022.101758 -
Medicine Oct 2022Gunao-Yizhi decoction has the effects of supplementing intelligence, strengthening marrow, resolving phlegm, and reducing turbidity. It is clinically used for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gunao-Yizhi decoction has the effects of supplementing intelligence, strengthening marrow, resolving phlegm, and reducing turbidity. It is clinically used for the treatment of vascular dementia (VaD). However, there is still a lack of systematic evaluation of its efficacy and safety. This review conducted a systematic review of the current evidence on the efficacy and safety of Gunao-Yizhi decoction combined with donepezil for VaD.
METHODS
China National Knowledge Infrastructure (CNKI), Wanfang database (Wanfang), Chinese Science and Technology Periodical Database (VIP), China Biology Medicine disc (CBM), MEDLINE, EMBASE, and Cochrane Library were searched for randomized controlled trials on Gunao-Yizhi decoction combined with donepezil for VaD. RevMan 5.3 software was used for data analysis.
RESULTS
Twelve studies were obtained, including 1036 patients. Compared with donepezil alone, meta-analysis showed that Gunao-Yizhi decoction combined with donepezil could improve clinical efficacy, mini-mental state examination (MMSE) score, Hasegawa dementia scale (HDS), increase the level of superoxide dismutase (SOD) in serum, and reduce the level of malonaldehyde dismutas (MDA) in serum. The GRADE system was adopted to evaluate the outcome index. Clinical efficiency and the MMSE score were evaluated as very-low-quality evidence. HDS score, serum SOD level, and serum MDA level were evaluated as low-quality evidence.
CONCLUSION
Gunao-Yizhi decoction combined with donepezil has a significant prevalence in the treatment of vascular dementia, with no increase in adverse events. Gunao-Yizhi decoction can be recommended for routine use in the treatment of VaD.
Topics: Dementia, Vascular; Donepezil; Drugs, Chinese Herbal; Humans; Malondialdehyde; Superoxide Dismutase
PubMed: 36221397
DOI: 10.1097/MD.0000000000030971 -
Frontiers in Neuroscience 2022The mainstay of therapy for many neurodegenerative dementias still relies on acetylcholinesterase inhibitors (AChEI); however, there is debate on various aspects of such...
BACKGROUND
The mainstay of therapy for many neurodegenerative dementias still relies on acetylcholinesterase inhibitors (AChEI); however, there is debate on various aspects of such treatment. A huge body of literature exists on possible predictors of response, but a comprehensive review is lacking. Therefore, our aim is to perform a systematic review of the predictors of response to AChEI in neurodegenerative dementias, providing a categorization and interpretation of the results.
METHODS
We conducted a systematic review of the literature up to December 31, 2021, searching five different databases and registers, including studies on rivastigmine, donepezil, and galantamine, with clearly defined criteria for the diagnosis of dementia and the response to AChEI therapy. Records were identified through the string: . The results were presented narratively.
RESULTS
We identified 1,994 records in five different databases; after exclusion of duplicates, title and abstract screening, and full-text retrieval, 122 studies were finally included.
DISCUSSION
The studies show high heterogeneity in duration, response definition, drug dosage, and diagnostic criteria. Response to AChEI seems associated with correlates of cholinergic deficit (hallucinations, fluctuating cognition, substantia innominate atrophy) and preserved cholinergic neurons (faster alpha on REM sleep EEG, increased anterior frontal and parietal lobe perfusion after donepezil); white matter hyperintensities in the cholinergic pathways have shown inconsistent results. The K-variant of butyrylcholinesterase may correlate with better response in late stages of disease, while the role of polymorphisms in other genes involved in the cholinergic system is controversial. Factors related to drug availability may influence response; in particular, low serum albumin (for donepezil), CYP2D6 variants associated with reduced enzymatic activity and higher drug doses are the most consistent predictors, while AChEI concentration influence on clinical outcomes is debatable. Other predictors of response include faster disease progression, lower serum cholesterol, preserved medial temporal lobes, apathy, absence of concomitant diseases, and absence of antipsychotics. Short-term response may predict subsequent cognitive response, while higher education might correlate with short-term good response (months), and long-term poor response (years). Age, gender, baseline cognitive and functional levels, and APOE relationship with treatment outcome is controversial.
PubMed: 36203811
DOI: 10.3389/fnins.2022.998224 -
Medicine Aug 2022Vascular dementia (VaD) is a comprehensive syndrome related to the damage of cognitive function and various cerebral vascular illnesses. VaD is also generally recognized... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vascular dementia (VaD) is a comprehensive syndrome related to the damage of cognitive function and various cerebral vascular illnesses. VaD is also generally recognized as the second most common type of dementia after Alzheimer disease, contributing to 30% of the dementia population in Asia and developing countries. The ability of donepezil hydrochloride and nimodipine had been respectively proven in improving cognitive function in vascular dementia. However, whether the combined application of both drugs contribute to better efficacy remains as a research hotspot. Studies had shown definite satisfactory result with such combination, however evidence-based evaluation of the efficacy is still lacking. Therefore, meta-analysis is employed in this study to evaluate the efficacy and safety of using donepezil hydrochloride combined with nimodipine in treating VaD to provide references for clinical treatments. The efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia is systematically reviewed to provide evidence-based references for clinical applications.
METHODS
Both Chinese and English databases were searched from the start till August, 2020 for any RCT regarding the combined use of the 2 drugs in treating vascular dementia. Two investigators would later evaluate and screened out research and data based on an improved Jaded scale. Software Rev Man 5.3.0 was employed to carry out meta-analysis on clinical effificacy, mini-mental state examination (MMSE) ratings, activity of daily living (ADL) ratings, and clinical dementia scale (CDR) ratings.
RESULTS
Donepezil hydrochloride combined with nimodipine had demonstrated satisfactory efficacy on the treatment of vascular dementia. Improvements were namely spotted on MMSE scale, ADL scale, and CDR scale, with the utmost efficacy by 12 weeks after intervention.
CONCLUSIONS
Donepezil hydrochloride combined with nimodipine had good efficacy in the treatment of patients with vascular dementia, mainly in terms of improving the Simple MMSE scores, the ability to use daily living scale (ADL) scores and the CDR, and the best results were obtained after 12 weeks of intervention. Such conclusion should be cautiously evaluated.
Topics: Alzheimer Disease; Dementia, Vascular; Donepezil; Humans; Mental Status and Dementia Tests; Nimodipine
PubMed: 35945739
DOI: 10.1097/MD.0000000000029307