The effect of sleep restriction therapy for insomnia on REM sleep fragmentation: A secondary analysis of a randomised controlled trial

REM sleep fragmentation is hypothesised to be a reliable feature of insomnia, which may contribute to emotion dysregulation. Sleep restriction therapy (SRT), an effective intervention for insomnia, has the potential to reduce REM sleep fragmentation through its manipulation of basic sleep-wake processes. We performed secondary data analysis of a randomised controlled trial to examine whether SRT reduces REM sleep fragmentation in comparison to a matched control arm. Participants (n=56; 39 female, mean age=40.78±9.08 yr.) were randomly allocated to 4 weeks of SRT or 4 weeks of time in bed regularisation. Ambulatory polysomnographic recordings were performed at baseline, week-1, and week-4. Arousals during REM and NREM sleep were scored blind to group allocation. The following REM sleep fragmentation index was the primary outcome: index 1 = (REM arousals + REM awakenings + NREM intrusions) / REM duration in hrs. Secondary outcomes were two further indices of REM sleep fragmentation: index 2 = (REM arousals + REM awakenings) / REM duration in hrs; and index 3 = REM arousals / REM duration in hrs. A NREM fragmentation index was also calculated (NREM arousals / NREM duration in hrs). Linear-mixed models were fitted to assess between-group differences. There was no significant group difference for the primary REM fragmentation index at week 1 (p=0.097, d=-0.31) or week 4 (p=0.741, d=-0.06). There was some indication that secondary indices of REM fragmentation decreased more in the SRT group relative to control at week-1 (index 2: p=0.023, d=-0.46; index 3: p=0.051, d=-0.39), but not at week-4 (ds0.13). No group-effects were found for arousals during NREM sleep. We did not find clear evidence that SRT modifies REM sleep fragmentation. Small-to-medium effect sizes in the hypothesised direction, across several indices of REM fragmentation during early treatment, demands further investigation in future studies

The effect of single‐component sleep restriction therapy on depressive symptoms: A systematic review and meta‐analysis

Summary: Sleep restriction therapy is a behavioural component within cognitive behavioural therapy for insomnia and is an effective standalone treatment for insomnia, but its effect on depressive symptoms remains unclear. This review aimed to synthesise and evaluate the impact of single‐component sleep restriction therapy on depressive symptoms relative to a control intervention. We searched electronic databases and sleep‐related journals for randomised controlled trials and uncontrolled clinical trials, published from 1 January 1986 until 19 August 2023, that delivered sleep restriction therapy to adults with insomnia. Random‐effects meta‐analysis of standardised mean differences and Cochrane risk of bias assessment were performed on randomised controlled trials, while uncontrolled clinical trials were discussed narratively. The meta‐analysis was pre‐registered on PROSPERO (ID: CRD42020191803). We identified seven randomised controlled trials (N = 1102) and two uncontrolled clinical trials (N = 22). Findings suggest that sleep restriction therapy is associated with a medium effect for improvement in depressive symptoms at post‐treatment (N c = 6, g = −0.45 [95% confidence interval = −0.70 to −0.21], p < 0.001) and a small effect at follow‐up (N c = 4, g = −0.31 [95% confidence interval = −0.45 to −0.16], p < 0.001). Five of the seven included randomised controlled trials were judged to have a high risk of bias. Standalone sleep restriction therapy appears to be efficacious for improving depressive symptoms at post‐treatment and follow‐up. However, conclusions are tentative due to the small number of trials and because none of the trials was performed in a population with clinically defined depression. Large‐scale trials are needed to test the effect of sleep restriction therapy in patients experiencing depression and insomnia. Findings also highlight the need to improve the standardisation and reporting of sleep restriction therapy procedures, and to design studies with more rigorous control arms to reduce potential bias

Nurse-delivered sleep restriction therapy to improve insomnia disorder in primary care: the HABIT RCT

Background: Insomnia is a prevalent and distressing sleep disorder. Multicomponent cognitive–behavioural therapy is the recommended first-line treatment, but access remains extremely limited, particularly in primary care where insomnia is managed. One principal component of cognitive–behavioural therapy is a behavioural treatment called sleep restriction therapy, which could potentially be delivered as a brief single-component intervention by generalists in primary care. Objectives: The primary objective of the Health-professional Administered Brief Insomnia Therapy trial was to establish whether nurse-delivered sleep restriction therapy in primary care improves insomnia relative to sleep hygiene. Secondary objectives were to establish whether nurse-delivered sleep restriction therapy was cost-effective, and to undertake a process evaluation to understand intervention delivery, fidelity and acceptability. Design: Pragmatic, multicentre, individually randomised, parallel-group, superiority trial with embedded process evaluation. Setting: National Health Service general practice in three regions of England. Participants: Adults aged ≥ 18 years with insomnia disorder were randomised using a validated web-based randomisation programme. Interventions: Participants in the intervention group were offered a brief four-session nurse-delivered behavioural treatment involving two in-person sessions and two by phone. Participants were supported to follow a prescribed sleep schedule with the aim of restricting and standardising time in bed. Participants were also provided with a sleep hygiene leaflet. The control group received the same sleep hygiene leaflet by e-mail or post. There was no restriction on usual care. Main outcome measures: Outcomes were assessed at 3, 6 and 12 months. Participants were included in the primary analysis if they contributed at least one post-randomisation outcome. The primary end point was self-reported insomnia severity with the Insomnia Severity Index at 6 months. Secondary outcomes were health-related and sleep-related quality of life, depressive symptoms, work productivity and activity impairment, self-reported and actigraphy-defined sleep, and hypnotic medication use. Cost-effectiveness was evaluated using the incremental cost per quality-adjusted life-year. For the process evaluation, semistructured interviews were carried out with participants, nurses and practice managers or general practitioners. Due to the nature of the intervention, both participants and nurses were aware of group allocation. Results: We recruited 642 participants (n = 321 for sleep restriction therapy; n = 321 for sleep hygiene) between 29 August 2018 and 23 March 2020. Five hundred and eighty participants (90.3%) provided data at a minimum of one follow-up time point; 257 (80.1%) participants in the sleep restriction therapy arm and 291 (90.7%) participants in the sleep hygiene arm provided primary outcome data at 6 months. The estimated adjusted mean difference on the Insomnia Severity Index was −3.05 (95% confidence interval −3.83 to −2.28; p  Limitations: While we recruited a clinical sample, 97% were of white ethnic background and 50% had a university degree, which may limit generalisability to the insomnia population in England. Conclusions: Brief nurse-delivered sleep restriction therapy in primary care is clinically effective for insomnia disorder, safe, and likely to be cost-effective. Future work: Future work should examine the place of sleep restriction therapy in the insomnia treatment pathway, assess generalisability across diverse primary care patients with insomnia, and consider additional methods to enhance patient engagement with treatment. Trial registration: This trial is registered as ISRCTN42499563. Funding: The award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/84/01) and is published in full in Health Technology Assessment; Vol. 28, No. 36. See the NIHR Funding and Awards website for further award information

Nurse-delivered sleep restriction therapy in primary care for adults with insomnia disorder: a mixed-methods process evaluation

Background Sleep restriction therapy (SRT) is a behavioural therapy for insomnia. Aim To conduct a process evaluation of a randomised controlled trial comparing SRT delivered by primary care nurses plus a sleep hygiene booklet with the sleep hygiene booklet only for adults with insomnia disorder. Design and setting A mixed-methods process evaluation in a general practice setting. Method Semi-structured interviews were conducted in a purposive sample of patients receiving SRT, the practice nurses who delivered the therapy, and also GPs or practice managers at the participating practices. Qualitative data were explored using framework analysis, and integrated with nurse comments and quantitative data, including baseline Insomnia Severity Index score and serial sleep efficiency outcomes to investigate the relationships between these. Results In total, 16 patients, 13 nurses, six practice managers, and one GP were interviewed. Patients had no previous experience of behavioural therapy, needed flexible appointment times, and preferred face-to-face consultations; nurses felt prepared to deliver SRT, accommodating patient concerns, tailoring therapy, and negotiating sleep timings despite treatment complexity and delays between training and intervention delivery. How the intervention produced change was explored, including patient and nurse interactions and patient responses to SRT. Difficulties maintaining SRT, negative attitudes towards treatment, and low self-efficacy were highlighted. Contextual factors, including freeing GP time, time constraints, and conflicting priorities for nurses, with suggestions for alternative delivery options, were raised. Participants who found SRT a positive process showed improvements in sleep efficiency, whereas those who struggled did not. Conclusion SRT was successfully delivered by practice nurses and was generally well received by patients, despite some difficulties delivering and applying the intervention in practice

Elective Tracheotomy in Patients Receiving Mandibular Reconstructions: Reduced Postoperative Ventilation Time and Lower Incidence of Hospital-Acquired Pneumonia

Elective tracheotomy (ET) secures the airway and prevents adverse airway-related events as unplanned secondary tracheotomy (UT), prolonged ventilation (PPV) or nosocomial infection. The primary objective of this study was to identify factors predisposing for airway complications after reconstructive lower ja surgery. We reviewed records of patients undergoing mandibulectomy and microvascular bone reconstruction (N = 123). Epidemiological factors, modus of tracheotomy regarding ET and UT, postoperative ventilation time and occurrence of hospital-acquired pneumonia HAP were recorded. Predictors for PPV and HAP, ET and UT were identified. A total of 82 (66.7%) patients underwent tracheotomy of which 12 (14.6%) were performed as UT. A total of 52 (42.3%) patients presented PPV, while 19 (15.4%) developed HAP. Increased operation time (OR 1.004, p = 0.005) and a difficult airway (OR 2.869, p = 0.02) were predictors, while ET reduced incidence of PPV (OR 0.054, p = 0.006). A difficult airway (OR 4.711, p = 0.03) and postoperative delirium (OR 6.761, p = 0.01) increased UT performance. HAP increased with anesthesia induction time (OR 1.268, p = 0.001) and length in ICU (OR 1.039, p = 0.009) while decreasing in ET group (HR 0.32, p = 0.02). OR for ET increased with mounting CCI (OR 1.462, p = 0.002) and preoperative radiotherapy (OR 2.8, p = 0.018). ET should be strongly considered in patients with increased CCI, preoperative radiotherapy and prolonged operation time. ET shortened postoperative ventilation time and reduced HAP

A quantitative PCR (TaqMan) assay for pathogenic Leptospira spp

BACKGROUND: Leptospirosis is an emerging infectious disease. The differential diagnosis of leptospirosis is difficult due to the varied and often "flu like" symptoms which may result in a missed or delayed diagnosis. There are over 230 known serovars in the genus Leptospira. Confirmatory serological diagnosis of leptospirosis is usually made using the microscopic agglutination test (MAT) which relies on the use of live cultures as the source of antigen, often performed using a panel of antigens representative of local serovars. Other techniques, such as the enzyme linked immunosorbent assay (ELISA) and slide agglutination test (SAT), can detect different classes of antibody but may be subject to false positive reactions and require confirmation of these results by the MAT. METHODS: The polymerase chain reaction (PCR) has been used to detect a large number of microorganisms, including those of clinical significance. The sensitivity of PCR often precludes the need for isolation and culture, thus making it ideal for the rapid detection of organisms involved in acute infections. We employed real-time (quantitative) PCR using TaqMan chemistry to detect leptospires in clinical and environmental samples. RESULTS AND CONCLUSIONS: The PCR assay can be applied to either blood or urine samples and does not rely on the isolation and culture of the organism. Capability exists for automation and high throughput testing in a clinical laboratory. It is specific for Leptospira and may discriminate pathogenic and non-pathogenic species. The limit of detection is as low as two cells

Nurse delivered Sleep Restriction Therapy for adults with Insomnia Disorder: process evaluation

Background: Sleep Restriction Therapy (SRT) is a behavioural therapy for insomnia. Aim: To conduct a process evaluation of a randomised controlled trial comparing SRT delivered by primary care nurses plus sleep hygiene booklet with sleep hygiene booklet only for adults with Insomnia Disorder. Design and setting: Mixed methods process evaluation. Methods: We used semi-structured interviews of a purposive sample of patients receiving SRT, practice nurses delivering it, and general practitioners (GPs) or practice managers. Qualitative data were explored using Framework Analysis, and integrated with nurse comments and quantitative data, including baseline Insomnia Severity Index score and serial sleep efficiency outcomes to investigate relationships between these. Results: We interviewed 16 patients, 13 nurses, 6 practice managers and 1 GP. Patients had no previous experience of behavioural therapy, needed flexible appointment times, and preferred face-to-face consultations; nurses felt prepared to deliver SRT, accommodating patient concerns, tailoring therapy, and negotiating sleep timings, despite treatment complexity and delays between training and intervention delivery. We explored how the intervention produced change, including patient and nurse interactions and patient responses to SRT. Difficulties maintaining SRT, negative attitudes towards treatment, and low self-efficacy were highlighted. Contextual factors, including freeing GP time, time constraints and conflicting priorities for nurses, with suggestions for alternative delivery options. Participants who found SRT a positive process showed improvements in sleep efficiency, whilst those that struggled did not. Conclusion: SRT was successfully delivered by practice nurses and was generally well received by patients, despite some difficulties delivering and applying the intervention in practice

Clinical and cost-effectiveness of nurse-delivered sleep restriction therapy for insomnia in primary care (HABIT): a pragmatic, superiority, open-label, randomised controlled trial.

Background Insomnia is prevalent and distressing but access to the first-line treatment, cognitive behavioural therapy (CBT), is extremely limited. We aimed to assess the clinical and cost-effectiveness of sleep restriction therapy, a key component of CBT, which has the potential to be widely implemented. Methods We did a pragmatic, superiority, open-label, randomised controlled trial of sleep restriction therapy versus sleep hygiene. Adults with insomnia disorder were recruited from 35 general practices across England and randomly assigned (1:1) using a web-based randomisation programme to either four sessions of nurse-delivered sleep restriction therapy plus a sleep hygiene booklet or a sleep hygiene booklet only. There was no restriction on usual care for either group. Outcomes were assessed at 3 months, 6 months, and 12 months. The primary endpoint was self-reported insomnia severity at 6 months measured with the insomnia severity index (ISI). The primary analysis included participants according to their allocated group and who contributed at least one outcome measurement. Cost-effectiveness was evaluated from the UK National Health Service and personal social services perspective and expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. The trial was prospectively registered (ISRCTN42499563). Findings Between Aug 29, 2018, and March 23, 2020 we randomly assigned 642 participants to sleep restriction therapy (n=321) or sleep hygiene (n=321). Mean age was 55·4 years (range 19–88), with 489 (76·2%) participants being female and 153 (23·8%) being male. 580 (90·3%) participants provided data for at least one outcome measurement. At 6 months, mean ISI score was 10·9 (SD 5·5) for sleep restriction therapy and 13·9 (5·2) for sleep hygiene (adjusted mean difference –3·05, 95% CI –3·83 to –2·28; p<0·0001; Cohen's d –0·74), indicating that participants in the sleep restriction therapy group reported lower insomnia severity than the sleep hygiene group. The incremental cost per QALY gained was £2076, giving a 95·3% probability that treatment was cost-effective at a cost-effectiveness threshold of £20 000. Eight participants in each group had serious adverse events, none of which were judged to be related to intervention. Interpretation Brief nurse-delivered sleep restriction therapy in primary care reduces insomnia symptoms, is likely to be cost-effective, and has the potential to be widely implemented as a first-line treatment for insomnia disorder

Stöd till inkubator- och accelerationsprogram i det enterpenörella ekosystemet med COVID-19 : En kollektiv fallstudie för Tyskland

The aim of this thesis paper is to analyse the support of incubator and accelerator programs inthe German entrepreneurial ecosystem with the impact of COVID-19. Incubator and accelerator programs have been established across multiple innovation hubs worldwide over the last decade. They have become a substantial support system for entrepreneurship providing help for young companies to innovate. The benefits offered usually include access to capital, network, mentorship and office space in exchange for equity or to simply foster innovation. With a lot of uncertainties deriving from the current pandemic, entrepreneurship has an increasingly relevant role to ensure a flourishing economy in the future. As the world is adapting to new circumstances, incubators and accelerators need to reevaluate their support to startups as well. The literature review consists of relevant literature by elaborating on the existing entrepreneurial ecosystem theories. It further discusses incubators and accelerators and the German entrepreneurial market before introducing the theoretical framework for the paper. As part of the research, this thesis uses a collective case study method by conducting interviews with startup founders and employees of incubator and accelerator programs in Germany. The qualitative data collection will undergo a deductive reasoning approach to analyse the research phenomenon and to contribute to the field of entrepreneurship. After introducing each company from the collective case study, the empirical findings systematically lay out the data from the interviews by separating the data into a section for incubators and accelerators and a section for startups. The data highlights relevant changes regarding the support of the programs with and without the impact of COVID-19. The discussion chapter points out the findings by comparing the data with the literature and the theoretical framework. The findings are broken down into subsections that point out the importance of the support programs as well as the proposed changes in the offerings. Concluded, changes can be made in the area of mentorships and coachings as there is a need for more individuality. Also regular feedback cycles, a higher capital support and the change to a hybrid model with a remote and on-site structure as well as the use of software to stay connected are possibilities for accelerators and incubators to help the startups.Syftet med denna uppsats är att analysera stödet av inkubator och accelerationsprogram i det tyska enterepenörella ekosystemet och hur det påverkats av COVID-19. Inkubator och acceleratorprogrammen har etablerats under olika innovationscenter över hela världen det senaste decenniet. De har blivit ett betydande stödsystem för entrepenörskap som ska ge stöttning åt nystartade företag för att hjälpa dom bli innovativa. Förmånerna är tillgång till kapital, nätverk, mentorsskap och lokaler, detta sker i utbyte mot delägarskap eller att bidra till att främja innovation. Med osäkerheten orsakat av den nuvarande pandemin, har entrepenörskap en mycket viktig roll för att säkerställa en uppåtgående ekonomi i framtiden. Då världen anpassar sig till nya omständigheter, behöver inkubationer och accelerationer se över stödet till startup företag. Litteraturöversikten innehåller relevant litteratur som utarbetarde redan existerande teorier inom det entrepenörella ekosystemet. Vidare diskuteras inkubatorer och accelerationer och den tyska entrepönerella marknaden, följt av introduktionen av det teoretiska ramverket för uppsatsen. Som en del av forskningen används en kollektivtfallstudie metod där det genomförts intervjuer med start up grundare och anställda på inkubator och accelerator program i Tyskland. Den kvalitativa inhämtningen av data genomgår ett slutligt resonemang för att analysera forskningsfenomenet och bidra till forskningsområdet entrepenörskap. Efter att ha introducerat varje företag för den utvalda fallstudien, visas datasystematisk med de empiriska resultaten från intervjuerna. Detta görs igenom att separera data i två sektioner. En för inkubatorer och accelationer, och en sektion för start ups. Uppgifterna belyser relevanta förändringar när det gäller stödet till programmen med och utan inverkan av COVID-19. I diskussionskapitlet pekas resultaten ut genom att uppgifterna jämförs medlitteraturen och den teoretiska ramen. Resultaten delas upp i under avsnitt som pekar ut stödprogrammens betydelse samt de föreslagna förändringarna i utbudet. Slutsatsen är att förändringar kan göras inom området mentorskap och coachning eftersom det finns ett behov av mer individualitet. Regelbundna feedbackcykler, ett högre kapitalstöd och en övergång tillen hybridmodell med en struktur på distans och på plats samt användning av programvara föratt hålla kontakten är möjligheter för acceleratorer och inkubatorer att hjälpa nystartade företag