Comparative short-term safety and efficacy of hypnotics: A quantitative risk-benefit analysis.

Several professional societies have provided recommendations for prescribing medications for insomnia. None has provided an integrative analysis that concurrently quantifies safety and efficacy (e.g., risk-benefit ratios). This represents an important gap for informing clinician decision-making. Accordingly, the aim of the present review is to provide such an analysis for five classes of sleep-promoting medications. Adverse event data values were extracted from the most recent FDA-approved package inserts and converted to an integer before being placebo-adjusted and standardized as a rate per 1000 (AEr). Efficacy data, pre-to-post self-reported data for active and placebo conditions were acquired from pivotal trials identified in "white papers" and systematic reviews/meta-analyses. Weighted effect sizes were calculated for subjective sleep latency, wake time after sleep onset and total sleep time, and then were averaged by medication class for each sleep continuity variable. Overall efficacy was represented by a single variable, SWT (sleep latency + wake time after sleep onset + total sleep time). Risk-benefit was represented using a simple ratio value. For safety, it was found that melatonin receptor agonists had the lowest adverse event rate (AEr = 43.1), and non-benzodiazepine benzodiazepine receptor agonists had the highest rate (AEr = 255.0). For efficacy, it was found that the pre-to-post placebo adjusted effect sizes were largest for benzodiazepines (effect size = 1.94) and smallest for melatonin receptor agonists (effect size = 0.109). For risk-benefit, histamine antagonist had the most favourable profile (risk-benefit = 69.5), while melatonin receptor agonist had the least favourable profile (risk-benefit = 395.7). Overall, the combined metric for risk-benefit suggests that treatment with a histamine antagonist is optimal and potentially represents the best first-line therapy for the medical management of insomnia.

Air travellers' experiences and understanding of jetlag and perceptions of management strategies: a qualitative study.

Jetlag is largely self-managed by the individual traveller. This paper explores the lived experiences of air travellers, their understanding of jetlag, and their perceptions of management strategies. 32 international travellers (mean age = 31, SD: 15 years; 47% female, mean flight duration = 16, SD: 6 hours) were interviewed. Interviews were recorded, transcribed verbatim and analysed using the Framework Approach. Analysis of the qualitative data revealed three emergent themes: Travel beliefs and experiences, Impact of jetlag, and Approaches to jetlag management. Participants' experience of jetlag was described in terms of the entire journey with no distinction made between circadian disruption and travel fatigue. Management strategies revolved around needs for comfort and avoiding fatigue, and were mostly guided by somatic symptom cues, prior travel experiences, or the experiential advice from others. Our findings highlight the need for traveller involvement in co-designing evidence-based interventions for jetlag to enhance their transferability into the real world. Practitioner summaryQualitative findings highlighted jetlag as encapsulating the entire journey, and not limited to post-flight circadian disruptions during international travel. Jetlag management interventions need to address issues of circadian misalignment together with travel fatigue and in-flight discomfort through behavioural and nutritional strategies. Travel context and environmental factors such as airport facilities also influenced perceived jetlag severity.

The need for sleep and circadian education in Australian high schools: incidental results from a survey of university students.

ISSUE ADDRESSED: To describe the need for high school sleep education from the perspective of undergraduate university students. METHODS: Undergraduate students who completed an online course on sleep and circadian health were surveyed 6 months after course completion. Students were asked whether a similar course would have benefited them as high school students, and about the need for sleep education in high schools. Thematic analysis of this qualitative data was carried out. RESULTS: Eighty-nine students who had attended 71 unique high schools provided responses. Eight-one per cent thought they would have benefitted from a similar course during high school and identified domains of sleep knowledge particularly relevant to high school students. They cited environmental barriers to healthy sleep present during high school and believed that sleep education could improve students' lifestyle, sleep and performance. Nineteen per cent of students said they would not have benefited, because they perceived sleeping patterns during high school to be nonmodifiable or believed that previous sleep education was sufficient. Of the respondents who did not think students would benefit, 53% would still tell their high school principal that there was a need for sleep education. CONCLUSIONS: The findings support the need for engaging sleep education for high school students. Future studies should examine the perspectives of students in high school directly, rather than undergraduate students who have already shown an interest in sleep health. SO WHAT?: Sleep health is missing from the Australian school curriculum. Online courses may be an engaging method of promoting sleep and circadian health to high school students.

Patient Perceptions of Treatment Delivery Platforms for Cognitive Behavioral Therapy for Insomnia.

OBJECTIVE: Stepped care has given rise to the proliferation of abbreviated CBT-I programs and delivery formats. This includes interventions delivered by allied health professionals and those delivered electronically through the Internet. This article aims to explore patient perceptions between electronic and face-to-face (FTF) delivery platforms for (abbreviated) CBT-I. PARTICIPANTS: Patients with insomnia from specialist sleep or psychology clinics and those from the general community in Sydney, Australia. METHOD: Semistructured interviews were conducted with patients with insomnia, guided by a schedule of questions and a choice task to explore patient perceptions of the different CBT-I treatment delivery platforms (e.g., perceived advantages and disadvantages or willingness to engage with either platform). Interviews were transcribed verbatim and analyzed using Framework Analysis. Participants also completed a battery of clinical mood and insomnia measures. RESULTS: Fifty-one interviews were conducted with patients with insomnia from specialist sleep or psychology clinics (n = 22) and the general community (n = 29). Synthesis of the qualitative data set revealed three themes pertinent to the patients' perspective toward electronic and FTF CBT-I delivery: Concepts of Efficacy, Concerns About Treatment, and Treatment on My Terms. Participants' choice to engage with either platform was also informed by diverse factors including perceived efficacy of treatment, personal commitments, lifestyle, and beliefs about sleep and insomnia. CONCLUSION: Clarifying patient treatment priorities and allaying potential concerns about engaging with an electronic treatment platform represent important steps for disseminating eCBT-I into mainstream practice.

Exploring asthma in the workplace: A triangulation of perspectives from management, employees and people with asthma.

OBJECTIVE: People with asthma spend a significant amount of time in the workplace but little is known about the current state of disease management in such contexts. The aim of the current study is to explore the experiences, attitudes and perceptions of asthma across different stakeholders in the workplace to help inform potential recommendations for workplace asthma policies. METHOD: Using purposive and convenience sampling methods, in-depth semi-structured interviews were conducted in Australia with 5 human resource personnel, 10 employees with asthma and 10 employees without asthma. Interviews were guided by a schedule of questions focusing on attitudes and experiences of people with asthma in the workplace, which were audio recorded, transcribed verbatim and thematically analysed. RESULTS: Analysis of the qualitative dataset revealed three key themes: Beliefs and Attitudes about Asthma, Asthma Solutions in the Workplace and Workplace Obstacles. Findings suggest that employees with asthma experience problems managing their asthma at work and there is a lack of workplace support in relation to asthma emergency management. CONCLUSION: Key recommendations for workplace asthma policies have been made to provide better support for employees with asthma. However, further investigation into the experience of managing asthma is required in a wider variety of occupations and work experiences to inform the development of a workplace asthma policy.

To Drug or Not to Drug: A Qualitative Study of Patients' Decision-Making Processes for Managing Insomnia.

Treatment preferences play a key role in dictating sleep health outcomes. However, patients' treatment beliefs, attitudes, and experiences that inform preference conceptualization remain an unknown phenomenon. Therefore, this study aims to explore patient perceptions toward pharmacotherapy and the nonpharmacological management of insomnia. Fifty-one patients with insomnia were recruited from specialist clinics and general community settings. Participants completed a brief questionnaire followed by an in-depth semistructured interview that was digitally recorded, transcribed verbatim, and subjected to Framework Analysis to identify emergent themes. Three key themes were identified: Resolving Insomnia, Self-Imposed Treatment Boundaries, and Treatment Uptake. Patients' illness, treatment, and psychosocial beliefs and experiences are closely linked to treatment choice. Being attuned to these influences during the clinical encounter can facilitate treatment selection that is meaningful for the patient.

Mapping the illness trajectories of insomnia: a biographical disruption?

The insomnia illness experience can be conceptualised as a form of biographical disruption. Using a critical interpretive phenomenological lens 51 in-depth semi-structured interviews were conducted with patients from specialist sleep and psychology clinics (n = 22) and the general community (n = 29). Patients' narratives revealed key phases of their illness trajectories as they recognise, rethink and respond to insomnia. Their biographical events served as reference points for both patient groups to make sense of their illness experiences as they transitioned from a perceived state of sleeplessness to clinical insomnia. The innate biological process of sleep at night and the sleep-dependent daytime psychosocial function exerted a negative bi-directional effect, creating a continuous circuit of disruption. Coping mechanisms were inspired by the participants' immediate social environment and centred on sociocultural motifs of relaxation and alertness to break the 'circuit'. Access to specialist clinic services appeared to be contingent on the richness of resources in one's social network and surrounding environment rather than the clinical severity of the disease alone. Treatment that can simultaneously target the night time and daytime consequences of insomnia resonates closely with participants' depiction of insomnia as both a physiological and a psychosocial phenomenon.

People with insomnia: experiences with sedative hypnotics and risk perception.

BACKGROUND: Sedative hypnotics form an important part of managing insomnia and are recommended for short-term use. It is standard practice for clinicians to inform the patient to use medications only 'when required', but the use of these medications is often chronic. Little is known about the impact of standard labelling/instructions on promoting appropriate medication use for managing insomnia. OBJECTIVE: To explore patient medication-taking beliefs, experiences and behavioural practices relating to the use of pharmacological/complementary sleep aids for insomnia. SETTING AND PARTICIPANTS: Specialist sleep/psychology clinics and the general community in Sydney, Australia. METHOD: Semi-structured interviews were conducted with 51 people with insomnia using a schedule of questions to gauge their experiences, beliefs and current practices relating to insomnia medication use. Interviews were audio-recorded, transcribed verbatim and subjected to Framework Analysis to identify emergent themes. RESULTS: Participants held distinctive views about the safety and efficacy of complementary and pharmacological agents but do not intuitively turn to medications to resolve their sleep complaint. Medication use was affirmed through tangible medication-taking cues due to the ambivalence in current instructions and labelling. Practices such as dosage modification, medication substitution and delaying medication use might be important drivers for psychological dependence. CONCLUSION: Current labelling and instructions do not necessarily promote the quality use of sedative hypnotics due to the variability in patient interpretations. Clarifying the timing, quantity and frequency of medication administration as well as insomnia symptom recognition would play a significant role in optimizing the role of pharmacotherapy in the management of insomnia.

Treating Insomnia: A Review of Patient Perceptions Toward Treatment.

Patient views about their treatment for insomnia often dictate outcome. This review explores the literature relating to the patients' global perceptions toward treatment for insomnia. A strategic literature search was conducted using five databases (PubMed, CINAHL, Medline, PsycINFO, and Embase). The 57 research articles included for this review were mapped out chronologically across three key stages of treatment-seeking (pretreatment appraisal, actual treatment experiences, and posttreatment evaluation). Patient perceptions played an important role across these three key stages and influenced subsequent health behaviors such as the initiation of help-seeking, treatment uptake, treatment adherence, and treatment adjustment. Patients' perceptions toward treatment were heavily grounded by their psychosocial contexts. Clinical implications and future directions for including patient-centered metrics in mainstream practice and research are discussed.

Insomnia patients' help-seeking experiences.

Timely access to appropriate treatment is important for optimizing insomnia management. To date, little is known about insomnia patients' treatment experiences or how they access and engage with the available health care resources. This study sought to capture the help-seeking experiences and behavioral patterns of patients with insomnia who are seeking or receiving specialist care. A purposive sample of 26 insomnia patients from specialist sleep and mental health clinics located in metropolitan New South Wales, Australia was recruited. Participants completed a brief questionnaire, followed by an in-depth, semi-structured interview. Interviews were digitally recorded, transcribed verbatim, and analyzed using framework analysis. Three key themes emerged from the data: patients' sleep beliefs, treatment beliefs, and accessing specialized care. The findings show that daytime symptoms arising from insomnia serve as important illness cues for patients to seek medical help. In addition, participants' treatment pathways highlight factors that prevent the widespread use of cognitive behavioral therapy for insomnia (CBT-I), including limited awareness about CBT-I, tentative referral mechanisms, limited service providers, and the high cost of CBT-I.

Primary health care practitioner perspectives on the management of insomnia: a pilot study.

This paper reports a qualitative pilot study exploring primary care health practitioners' perspectives on the management of insomnia following the extensive media coverage on the adverse effects of zolpidem in 2007-08. General practitioners and community pharmacists were recruited throughout metropolitan Sydney, New South Wales using a convenience sampling and snowballing technique. Demographic information was collected from each participant followed by a semistructured interview. In total 22 participants were interviewed, including eight general practitioners and 14 community pharmacists. Interview transcripts were analysed using 'framework analysis'. Participants' responses illuminated some of the key issues facing primary care practitioners in the management of insomnia. Practitioners perceived there to be an overreliance on pharmacotherapy among insomnia patients and inadequate support for directing patients to alternative treatment pathways if they require or prefer non-pharmacological management. Current prescribing trends appear to favour older benzodiazepines in new cases of insomnia whereas some successful sporadic users of zolpidem have continued to use zolpidem after the media coverage in 2007-08. The findings of this pilot study suggest the need to address the limitations in the management of insomnia within the current health care system, to revise and disseminate updated insomnia guidelines and to provide educational opportunities and resources to primary care practitioners concerning management options.

The insomnia patient perspective, a narrative review.

Insomnia is a common sleep disorder associated with substantial direct and indirect costs, yet there is a strong propensity among patients to self-medicate which often delays professional help. Understanding the process which underpins the initiation, engagement and adherence to insomnia treatment(s) is a vital step for understanding this phenomenon. The current paper explores how the patient perspective has been conceptualized in the research literature and its implications for insomnia treatment and health care delivery. A literature search was conducted using Embase, Medline and PsycINFO databases. Articles have been thematically organized into patient correlates of health behaviors, patient experiences and treatment attitudes. Deferral of professional help among insomnia patients is partially related to barriers embedded in the health care system and patient health beliefs.

Pharmacists' perspectives and attitudes towards the 2021 down-scheduling of melatonin in Australia using the Theoretical Domains Framework: a mixed-methods study.

BACKGROUND: In Australia, prescription melatonin became a 'Pharmacist Only Medicine' for people over 55 with insomnia from June 2021. However, little is known about pharmacists' views on melatonin down-scheduling and perceived impacts on practice. AIM: To explore Australian community pharmacists' views on and attitudes towards the down-scheduling of melatonin. METHOD: A convenience sample of community pharmacists and pharmacy interns were recruited. Participants completed a survey capturing demographic and professional practice details, and rated their knowledge, beliefs and attitudes towards melatonin. This was followed by an online semi-structured interview. Interviews were guided by a schedule of questions developed using the Theoretical Domains Framework and explored the perceived role of melatonin, preparation/response to down-scheduling, practice changes and patient interactions. Interviews continued until data saturation and were digitally recorded, transcribed verbatim and analysed using the Framework Approach. RESULTS: Twenty-four interviews were conducted with community pharmacists (n = 19) and intern pharmacists (n = 5), all practicing in metropolitan areas. Pharmacists/intern pharmacists welcomed the increased accessibility of melatonin for patients. However, pharmacists perceived a disconnect between the guidelines, supply protocols and pack sizes with practice, making it difficult to monitor patient use of melatonin. The miscommunication of eligibility also contributed to patient-pharmacist tension when supply was denied. Importantly, most participants indicated their interest in upskilling their knowledge in melatonin use in sleep, specifically formulation differences and dosage titration. CONCLUSION: While pharmacists welcomed the down-scheduling of melatonin, several challenges were noted, contributing to pharmacist-patient tensions in practice. Findings highlight the need to refine and unify melatonin supply protocols and amend pack sizes to reflect guideline recommendations as well as better educating the public about the risk-benefits of melatonin.

Baseline sleep characteristics are associated with gains in sleep duration after cognitive behavioral therapy for insomnia.

OBJECTIVE/BACKGROUND: Cognitive behavioural therapy for insomnia (CBT-I) substantially reduces total wake time (TWT) by the end of treatment. In contrast, total sleep time (TST) does not increase above baseline levels for most patients following 4-8 sessions of treatment. In the 6-12 months following CBT-I, without any further intervention, up to 64% of participants substantially increase their TST (by ≥ 30 min). The current study investigated which baseline characteristics are associated with increases in TST after CBT-I. PATIENTS/METHODS: Data were analysed from a randomised controlled trial assessing acute and maintenance CBT-I (N = 80). Linear mixed models were conducted to assess the effect of baseline characteristics on changes in TST up to 24 months after CBT-I. Baseline characteristics included age, sex, marital status, sleep continuity (derived from sleep diaries and polysomnography studies), and mental health and quality of life questionnaires. RESULTS: At baseline, self-reported sleep latency, wake after sleep onset, early morning awakenings, TWT, TST, and sleep efficiency were associated with the greatest changes in TST (p < .03 for interactions), such that patients who reported more wake/less sleep at baseline also reported the largest increases in TST. No other baseline variables were associated with changes in TST after CBT-I, including age, sex, and polysomnography-derived sleep continuity (p > .07 for interactions). CONCLUSIONS: Patients with more severe self-reported sleep difficulties and lower sleep duration at baseline showed greater improvements in TST after CBT-I. Whether more patients could increase their TST, within the context of acute treatment or following treatment, warrants investigation.

Melatonin use in children and adolescents: A scoping review of caregiver perspectives.

Despite melatonin's popularity as a pediatric sleep-aid, little has been investigated around caregivers' understanding and perception of melatonin use for their dependent. This scoping review analyzes the current literature on pediatric melatonin use, to understand how caregivers' perceptions around melatonin are shaped by their illness/medication-related beliefs, treatment experience and preferences. A literature search was conducted across Embase, Medline, PsycINFO, PubMed and Scopus, generating 184 results for screening against the inclusion criteria. Nineteen studies were retrieved, comprising of 1561 children and adolescents, aged 8.7 ± 2.3 years (range: 0-44 years), conducted primarily in the United States of America (n = 6), Canada (n = 3) and the Netherlands (n = 3). Studies were evaluated for their study design and caregiver-centered outcomes, encompassing: 1) illness/treatment-related beliefs, 2) treatment satisfaction/effectiveness, 3) treatment preference/acceptability, and 4) impact of child's sleep disturbance on caregivers' quality-of-life. Sleep disturbances necessitating melatonin use occurred alongside congenital/neurodevelopmental comorbidities in 18 studies (95%). Melatonin was commonly associated with "naturalness" and "safety". Concepts of treatment satisfaction versus effectiveness were minimally differentiated within included studies. Caregivers preferred concurrent use of melatonin and behavioral interventions for management of their dependents' sleep. Improved sleep in the dependent generally led to better quality-of-life for caregivers and their family.

Travelers' perceptions of jetlag and travel fatigue: A scoping review.

Effective management strategies for jetlag have largely been studied and evaluated through the lens of circadian science and biological rhythms. Jetlag is mostly self-managed by the individual. The most effective strategies require individuals to make behavioral changes to carefully alter sleep-wake schedules and time light exposure. However, travelers' perceptions, including their experiences, beliefs about jetlag/travel fatigue, and management expectations remain unclear. Therefore, the aim of this scoping review was to systematically synthesize the literature to understand what is currently known about travelers' perceptions of jetlag and travel fatigue. A literature search was conducted through EMBASE, PsycINFO, PubMed and Scopus generating 1164 results (2 articles known to authors), which were screened against our inclusion criteria. Twenty-two studies including data from 3952 participants were evaluated for its study design and traveler-centered outcome measures across the domains of: 1) Traveler Health Beliefs and Knowledge about Jetlag and Travel Fatigue; 2) Experience of Jetlag and Travel Fatigue 3) Traveler Priorities; 4) Self-reported Management Strategies for Jetlag and Travel Fatigue; and 5) User Experiences of Management Strategies. Synthesis of results suggests a potential mismatch between researchers' focus on circadian misalignment and travelers' focus on air travel comfort. A better understanding of the beliefs, attitudes, knowledge, satisfaction, experiences, and expectations about jetlag and travel fatigue will better enable the development of interventions that align with traveler priorities.

Evaluation of psychometric properties of patient-reported outcome measures frequently used in narcolepsy randomized controlled trials: a systematic review.

STUDY OBJECTIVES: To systematically determine subjective and objective outcome measures used to measure the efficacy of narcolepsy interventions in randomized controlled trials (RCTs) in adults and children and assess psychometric properties of patient-reported outcome measures (PROMs) used. METHODS: We searched bibliographical databases and clinical trial registries for narcolepsy RCTs and extracted objective and subjective outcome measures. If PROMs were used, we searched for psychometric studies conducted in a narcolepsy population using bibliographical databases and appraised using Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines. RESULTS: In total, 80 different outcome measures were used across 100 RCTs. Epworth Sleepiness Scale (ESS) (n = 49) and Maintenance of Wakefulness Test (n = 47) were the most frequently used outcome measures. We found 19 validation studies of 10 PROMs in narcolepsy populations. There was limited evidence for validity or responsiveness of the ESS; yet sufficient reliability (pooled ICC: 0.81-0.87). Narcolepsy Severity Scale (NSS) had sufficient reliability (pooled ICC: 0.71-0.92) and both adult and pediatric versions had sufficient discriminant validity (treated/untreated). Content validity was only evaluated in pediatric populations for ESS-CHAD and NSS-P and rated inconclusive. Quality of evidence of the psychometric studies for all scales ranged from very low to low. CONCLUSIONS: Although recognized by regulatory bodies and widely used as primary outcome measures in trials, there is surprisingly little evidence for the validity, reliability, and responsiveness of PROMs frequently used to assess treatment efficacy in narcolepsy. The field needs to establish patient-centered minimal clinically important differences for the PROMs used in these trials.

How patient centric is health policy development? The case of the Parliamentary Inquiry into Sleep Health Awareness in Australia.

Objective Parliamentary inquiries into health-related issues empower everyday Australians to contribute to the development and reform of health policy. We explored how patient and family/carers concerns are translated by this process, using a less well-known disease, narcolepsy, as an example. Methods Written submissions made to the Parliamentary Inquiry into Sleep Health Awareness in Australia 2018 by self-identified patients or family/carers with narcolepsy (n = 13) were extracted and thematically analysed using the Framework Approach. Each submission was systematically coded and abstracted into emergent themes before being evaluated against the final policy recommendations. Results Although patients and their family/carers prioritised issues that affected their daily lives (i.e. mental health sequela, workplace accommodations), the policy recommendations in the report focused mainly on issues of healthcare infrastructure, funding and engagement. Our analysis highlighted several barriers that patients and their family/carers face when contributing to this part of healthcare policy formation. Conclusions Our findings suggest that the parliamentary inquiry process in its current form is not an ideal vehicle by which patients and family/carers can contribute or influence healthcare policy. Despite calling for submissions from patients and their family/carers, the final report and subsequent health policy recommendations made by the inquiry do not appear to be patient-centric or reflective of the submissions written by these stakeholders. Increased transparency, development of processes to balance stakeholder priorities and improved accessibility for stakeholders to participate are needed if health-related parliamentary inquiries are to produce healthcare policy that ultimately meets the needs of patients and family/carers.

Does total sleep time substantially increase after cognitive behavioral therapy for insomnia?

STUDY OBJECTIVES: In most standardized approaches to cognitive behavioral therapy for insomnia, it is commonly the case that total wake time is reduced substantially during sleep restriction, but self-reported total sleep time (TST) is minimally affected. By follow-up, however, TST increases by almost 1 hour on average. A secondary analysis was undertaken to assess what percentage of participants meet or appreciably exceed baseline TST after cognitive behavioral therapy for insomnia. METHODS: Data were drawn from a randomized controlled trial assessing acute and maintenance therapies for chronic insomnia (n = 80). The present analyses assessed the percentage of participants that 1) reached (≥ 0 minute increase) and 2) appreciably exceeded (≥ 30 minutes increase) baseline TST as assessed via daily sleep diaries at posttreatment and 3, 6, 12, and 24 months following treatment. RESULTS: By the end of acute treatment, 45% of participants reached or exceeded baseline TST. By 24 months follow-up, this percentage had increased to 86%. Only 17% of participants achieved a 30-minute increase in TST by the end of acute treatment, and this proportion only increased to 58% over time. CONCLUSIONS: These findings suggest that cognitive behavioral therapy for insomnia in its current form does not appreciably increase self-reported TST in a significant proportion of patients with insomnia. Whether participants would benefit from further increases in TST warrants investigation. The further titration of sleep opportunity may be useful to accelerate increases in TST, to extend the effect to a larger subset of patients, and/or to increase the magnitude of the TST gain. CITATION: Scott H, Cheung JMY, Muench A, et al. Does total sleep time substantially increase after cognitive behavioral therapy for insomnia? J Clin Sleep Med. 2022;18(7):1823-1829.