Comparative effectiveness of non-pharmacological interventions on sleep in individuals with chronic musculoskeletal pain: A systematic review with network meta-analysis.

This network meta-analysis aimed to estimate the comparative effectiveness of non-pharmacological interventions on sleep in individuals with chronic musculoskeletal pain. Seven databases were systematically searched up to February 2023. A random-effects network meta-analysis in a frequentist framework was performed to synthesize continuous data as standardized mean differences (SMD) along with a 95% confidence interval (95% CI). A total of 15,641 records were identified, and 107 randomized controlled trials involving 8,121 participants were included. Of 14 identified interventions, eight were significantly more effective than passive control in improving sleep quality at immediate post-intervention (SMDs = 0.67-0.74), with cognitive behavioral therapy (CBT) being the most effective treatment (SMD = 0.74, 95% CI: 0.45-1.03). Only CBT demonstrated sustained effects at short-term (SMD = 1.56; 95% CI: 0.62-2.49) and mid-term (SMD = 1.23; 95% CI: 0.44-2.03) follow-ups. Furthermore, CBT significantly improved subjective (SMD = 0.64; 95% CI: 0.25-1.03) and objective (SMD = 0.30; 95% CI: 0.01-0.59) sleep efficiency compared with passive control at immediate post-intervention. Our findings support CBT as the first-line treatment for improving sleep in individuals with chronic musculoskeletal pain, given its superior effectiveness across multiple sleep outcomes and its sustainable effects until mid-term follow-up. However, the certainty of evidence for these interventions in improving sleep quality was very low to low.

Effectiveness of Exercise, Cognitive Behavioral Therapy, and Pharmacotherapy on Improving Sleep in Adults with Chronic Insomnia: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Despite the well-established treatment effectiveness of exercise, cognitive behavioral therapy for insomnia (CBT-I), and pharmacotherapy on improving sleep, there have been no studies to compare their long-term effectiveness, which is of clinical importance for sustainable management of chronic insomnia. This study compared the long-term effectiveness of these three interventions on improving sleep in adults with chronic insomnia. MEDLINE, PsycINFO, Embase, and SPORTDiscus were searched for eligible reports. Trials that investigated the long-term effectiveness of these three interventions on improving sleep were included. The post-intervention follow-up of the trial had to be ≥6 months to be eligible. The primary outcome was the long-term effectiveness of the three interventions on improving sleep. Treatment effectiveness was the secondary outcome. A random-effects network meta-analysis was carried out using a frequentist approach. Thirteen trials were included in the study. After an average post-intervention follow-up period of 10.3 months, both exercise (SMD, -0.29; 95% CI, -0.57 to -0.01) and CBT-I (-0.48; -0.68 to -0.28) showed superior long-term effectiveness on improving sleep compared with control. Temazepam was the only included pharmacotherapy, which demonstrated superior treatment effectiveness (-0.80; -1.25 to -0.36) but not long-term effectiveness (0.19; -0.32 to 0.69) compared with control. The findings support the use of both exercise and CBT-I for long-term management of chronic insomnia, while temazepam may be used for short-term treatment.

Familial α-synucleinopathy spectrum features in patients with psychiatric REM sleep behaviour disorder.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the earliest and most specific prodromes of the α-synucleinopathies including Parkinson's disease (PD). It remains uncertain whether RBD occurring in the context of psychiatric disorders (psy-RBD), although very common, is merely a benign epiphenomenon of antidepressant treatment, or whether it harbours an underlying α-synucleinopathy. We hypothesised that patients with psy-RBD demonstrate a familial predisposition to an α-synucleinopathy. METHODS: In this case-control-family study, a combination of family history and family study method was used to measure the α-synucleinopathy spectrum features, which included RBD, neurodegenerative prodromal markers and clinical diagnoses of neurodegenerative disorders. We compared the risk of α-synucleinopathy spectrum features in the first-degree relatives (FDRs) of patients with psy-RBD, psychiatric controls and healthy controls. RESULTS: There was an increase of α-synucleinopathy spectrum features in the psy-RBD-FDRs, including possible and provisional RBD (adjusted HR (aHR)=2.02 and 6.05, respectively), definite RBD (adjusted OR=11.53) and REM-related phasic electromyographic activities, prodromal markers including depression (aHR=4.74) and probable subtle parkinsonism, risk of prodromal PD and clinical diagnosis of PD/dementia (aHR=5.50), as compared with healthy-control-FDRs. When compared with psychiatric-control-FDRs, psy-RBD-FDRs consistently presented with a higher risk for the diagnosis and electromyographic features of RBD, diagnosis of PD/dementia (aHR=3.91) and risk of prodromal PD. In contrast, psychiatric controls only presented with a familial aggregation of depression. CONCLUSION: Patients with psy-RBD are familially predisposed to α-synucleinopathy. The occurrence of RBD with major depression may signify a subtype of major depressive disorders with underlying α-synucleinopathy neurodegeneration. TRIAL REGISTRATION NUMBER: NCT03595475.

Clinical and neuroimaging markers of neurodegeneration in first-degree relatives of patients with REM sleep behavior disorder with and without isolated rapid eye movement sleep without atonia: A case-control clinical and dopamine PET study.

OBJECTIVES: The current study aimed to examine the neurodegenerative implication of isolated REM sleep without atonia (RSWA) among first-degree relatives of patients with REM sleep behaviour disorder (RBD). METHODS: This cross-sectional case-control study recruited three groups of subjects: First-degree relatives of RBD patients with isolated RSWA (n = 17), first-degree relatives of RBD patients without isolated RSWA (n = 18), and normal controls who did not have any RWSA and family history of RBD (n = 15). Prodromal Parkinson's Disease likelihood ratio by the updated MDS Research Criteria and striatal dopaminergic transmission function of the subjects as assessed by triple-tracer (18F-DOPA, 11C-Raclopride, and 18F-FDG) PET/CT scan were used as proxy markers of neurodegeneration. RESULTS: In contrary to our hypothesis, the three groups did not differ in their pre- or post-striatal dopaminergic transmission function, and their Prodromal Parkinson's Disease likelihood ratio. However, they differed significantly in their frequency of a having first-degree relatives with Parkinson's disease or dementia of Lewy body (first-degree relativess with RSWA vs first degree relatives without RSWA vs normal controls = 58.8% vs 22.2% vs 0%, p = 0.001). CONCLUSION: FDRs of RBD patients with isolated RSWA did not have increased neurodegenerative markers compared to FDRs of RBD patients without isolated RSWA and normal control, despite an paradoxical increase in frequency of Parkinson's disease or dementia of Lewy body among their family compared to FDRs of RBD patients without isolated RSWA. Further longitudinal follow-up study will be needed to ascertain their long-term prognosis.

Effects of Tai Chi and cognitive behavioral therapy for insomnia on improving sleep in older adults: Study protocol for a non-inferiority trial.

Background: Insomnia is a prevailing health problem among older adults. Tai Chi, a popular mind-body exercise practiced by older people in various oriental communities, has been shown to improve sleep. However, Tai Chi has not been directly compared to cognitive behavioral therapy for insomnia (CBT-I), which is the first-line non-pharmacological treatment for insomnia in older adults. This study aims to examine whether Tai Chi is non-inferior to CBT-I as a treatment for insomnia in older adults. Methods: This is a single-center, assessor-blinded, non-inferiority randomized controlled trial comparing Tai Chi and CBT-I in 180 older adults aged ≥50 years with chronic insomnia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Participants will be randomly assigned to either the Tai Chi or CBT-I group. Interventions will last for 3 months with a 12-month follow-up. The primary outcome is self-perceived insomnia severity measured by Insomnia Severity Index (ISI) at 3 months and at 15 months. The secondary outcomes include the remission rate of chronic insomnia, insomnia treatment response, subjective sleep quantity and quality, 7-day actigraphy, 7-day sleep diary, sleep medication, health-related quality of life, mental health, body balance and lower extremity function, adverse events, habitual physical activity, and dietary intake. Measurements will be conducted at baseline, 3 months, and 15 months by outcome assessors who are blinded to the group allocation. Discussion: This will be the first non-inferiority randomized controlled trial to compare the efficacy and long-term outcomes of Tai Chi versus CBT-I for treating insomnia in older adults. This study will be of clinical importance as it supports the use of Tai Chi as an alternative non-pharmacological approach for insomnia treatment and sustainable management.

The differential effects of sleep deprivation on pain perception in individuals with or without chronic pain: A systematic review and meta-analysis.

Many experimental sleep deprivation (SD) studies were conducted to clarify the causal relationship between sleep and pain. This systematic review and meta-analysis aimed to update the evidence regarding the effects of different experimental SD paradigms on various pain outcomes. Five databases were searched from their inception to June 2022. Separate random-effects models were used to estimate the pooled effect sizes (ES) of different experimental SD paradigms on various pain outcomes. Thirty-one studies involving 699 healthy individuals and 47 individuals with chronic pain were included. For healthy individuals, limited evidence substantiated that total SD significantly reduced pain threshold and tolerance (ES 0.74-0.95), while moderate evidence supported that partial SD significantly increased spontaneous pain intensity (ES 0.30). Very limited to moderate evidence showed that sleep fragmentation significantly increased peripheral and central sensitization in healthy individuals (ES 0.42-0.79). Further, there was very limited evidence that total or partial SD significantly aggravated spontaneous pain intensity in people with chronic pain. Our results accentuated that different SD paradigms differentially increased subjective pain intensity and worsened peripheral/central pain sensitization in healthy individuals, whereas the corresponding findings in people with chronic pain remain uncertain. Further rigorous studies are warranted to quantify their relationships in clinical populations.

Adjunctive bright light treatment with gradual advance in unipolar major depressive disorder with evening chronotype - A randomized controlled trial.

BACKGROUND: Unipolar non-seasonal depressed patients with concomitant evening chronotype were associated with poor clinical outcomes and higher non-remission rate. This study aims to examine the efficacy of adjunctive bright light therapy with gradual timing advance in a randomized, assessor and prescriber-blinded controlled trial. METHOD: Participants were randomly allocated to receive 5 weeks of either bright white light therapy (BLT) or dim red light (DRL) with the same advancement protocol. Participants were followed up till 5 months after treatment. Primary outcomes included (i) remission rate and (ii) the severity of depression. The analysis was conducted using Kaplan-Meier survival analysis, Cox proportional hazard analysis and linear mixed models. RESULTS: A total of 93 participants (46.4 ± 11.7 years old, 80% female) were randomized. The cumulative remission rate for the BLT and the DRL groups was 67.4% and 46.7%, respectively. Time to remission was shorter for the BLT group relative to the DRL group (log-rank test p = 0.024). Cox proportional hazard survival analysis showed that patients in the BLT group had a higher probability of achieving remission relative to patients in the DRL group [hazard ratio = 1.9 (95% CI = 1.1- 3.4), p = 0.026]. Further sensitivity analysis demonstrated greater improvement in 17-Hamilton Depression Score (group × time interaction, p = 0.04) in the BLT group for those who were adherent to light therapy. CONCLUSIONS: The use of bright light therapy with gradual advance protocol is an effective adjunctive treatment resulting in quicker and a higher rate of remission of depression in patients with non-seasonal unipolar depression and evening-chronotype.

Prevalence and correlates of REM sleep behaviour disorder in patients with major depressive disorder: a two-phase study.

OBJECTIVE: To investigate the prevalence and clinical correlates of video polysomnography (vPSG)-confirmed rapid eye movement sleep behaviour disorder (RBD) in patients with major depressive disorder (MDD). METHODS: This is a clinic-based two-phase epidemiological study. In phase 1, patients with MDD were screened by a validated questionnaire, RBD Questionnaire-Hong Kong (RBDQ-HK). In phase 2, a subsample of both the screen-positive (RBDQ-HK >20) and screen-negative patients with MDD underwent further clinical and sleep assessment (vPSG) to confirm the diagnosis of RBD (MDD+RBD). Poststratification weighting method was used to estimate the prevalence of MDD+RBD. The total likelihood ratio and the probability of prodromal Parkinson's disease (PD) were calculated from prodromal markers and risk factors, as per the Movement Disorder Society research criteria. RESULTS: A total of 455 patients with MDD were screened (median age (IQR)=52.66 (15.35) years, 77.58% woman, 43.74% positive). Eighty-one patients underwent vPSG and 12 of them were confirmed MDD+RBD. The prevalence of MDD+RBD was estimated to be 8.77% (95% CI: 4.33% to 16.93%), with possibly male predominance. MDD+RBD were associated with colour vision and olfaction deficit and a higher probability for prodromal PD. CONCLUSIONS: Almost 9% of patients with MDD in the psychiatric outpatient clinic has vPSG-confirmed RBD. Comorbid MDD+RBD may represent a subtype of MDD with underlying α-synucleinopathy neurodegeneration. Systematic screening of RBD symptoms and necessity of vPSG confirmation should be highlighted for capturing this MDD subtype with a view to enhance personalised treatment and future neuroprotection to prevent neurodegeneration.

Effectiveness and Mechanisms of Mindfulness Training for School Teachers in Difficult Times: A Randomized Controlled Trial.

OBJECTIVES: Research in recent years has shown that mindfulness-based interventions can enhance teachers' mental and physical health. However, the existing studies were predominantly conducted in Western, educated, industrialized, rich, and democratic (WEIRD) societies. As a randomized controlled trial in a non-WEIRD society, the present study examined the effectiveness and mechanisms of mindfulness training for Hong Kong teachers in difficult times. METHODS: Teachers from primary and secondary schools (n = 186) were randomly assigned to mindfulness training (eight-week .b Foundations) or waitlist control condition. They completed online self-report surveys on measures of well-being, emotion management, and mindfulness in teaching at baseline, post-intervention, and two-month follow-up. RESULTS: The intervention group reported significantly higher levels of life satisfaction, positive affect, general health, along with significantly lower levels of insomnia, stress, and negative affect than the control group at post-test and two-month follow-up. The effect sizes were medium to large (η p 2 = 0.06 to 0.14). More importantly, teachers' baseline well-being had a significant moderating effect on the intervention effectiveness. Those with a lower baseline in well-being benefitted more than their counterparts with a higher baseline. In addition, teachers' emotion management was found to be the mediator through which mindfulness training enhanced teachers' well-being. Such improvement in well-being also predicted higher levels of mindfulness in teaching. CONCLUSIONS: This study provides evidence on the efficacy of mindfulness training for teachers beyond WEIRD societies. It suggests the universality and practicality of mindfulness training in enhancing teachers' well-being and reducing their distress in difficult times.

Sexual behaviors and intention for cervical screening among HPV-vaccinated young Chinese females.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) vaccination and cervical screening prevent cervical cancer effectively. However, there are concerns whether vaccination leads to high-risk sexual behaviors and less intention for cervical screening. We aimed to evaluate the influence of HPV vaccination on high-risk sexual behaviors, and intention for cervical screening among young Chinese females. We also reported the latest HPV vaccination uptake in Hong Kong. METHODS: A population-based survey was conducted between September 2016 and January 2017. Subjects were school-age girls from twenty-five secondary schools (in-school) and community females between 18 and 27 years (out-school). Demographics, vaccine-related attitudes, intention for cervical screening and participants' sexual behaviors were examined. RESULTS: We surveyed 2260 females from in-school (n = 1664) and out-school (n = 596) settings. 11.5% in-school and 23.5% out-school participants received at least one dose of HPV vaccine. Vaccination was not associated with age (in-school Odds Ratio [OR] 0.99, p = 0.87; out-school OR 1, p = 0.94), ethnicity (in-school OR 0.82, p = 0.72; out-school OR 0, p = 0.98), maternal education (in-school OR for secondary school 1.19, p = 0.43; for post-secondary school 1.28, p = 0.48), underage sex (in-school OR 1.22, p = 0.80; out-school OR 0.63, p = 0.67), earlier sexual exposure (in-school ß 0.01, p = 0.99; out-school ß 0.13, p = 0.68), multiple sex partners (in-school OR 3.27, p = 0.22; out-school OR 1.16, p = 0.43), and unprotected sex (in-school OR 1.14, p = 0.78; out-school OR 0.60, p = 0.10). Out-school females with higher personal education level was associated with higher vaccine uptake (post-secondary OR 3.4, p < 0.001; bachelor's degree or above OR 3.71, p < 0.001). More vaccinated females intended for cervical screening (in-school 23.6% vs. 21.1%; out-school 53.6% vs. 43.6%). Costs and knowledge were important factors for non-vaccination and non-intention for cervical screening. CONCLUSIONS: HPV vaccination was not associated with earlier and high risk sexual behavior among Chinese young females. Vaccinated Chinese young females had a higher intention for cervical screening.

Get screened: a randomized trial of the incremental benefits of reminders, recall, and outreach on cancer screening.

BACKGROUND: Rates of breast cancer (BC) and colorectal cancer (CRC) screening are particularly low among poor and minority patients. Multifaceted interventions have been shown to improve cancer-screening rates, yet the relative impact of the specific components of these interventions has not been assessed. Identifying the specific components necessary to improve cancer-screening rates is critical to tailor interventions in resource limited environments. OBJECTIVE: To assess the relative impact of various components of the reminder, recall, and outreach (RRO) model on BC and CRC screening rates within a safety net practice. DESIGN: Pragmatic randomized trial. PARTICIPANTS: Men and women aged 50-74 years past due for CRC screen and women aged 40-74 years past due for BC screening. INTERVENTIONS: We randomized 1,008 patients to one of four groups: (1) reminder letter; (2) letter and automated telephone message (Letter + Autodial); (3) letter, automated telephone message, and point of service prompt (Letter + Autodial + Prompt); or (4) letter and personal telephone call (Letter + Personal Call). MAIN MEASURES: Documentation of mammography or colorectal cancer screening at 52 weeks following randomization. KEY RESULTS: Compared to a reminder letter alone, Letter + Personal Call was more effective at improving screening rates for BC (17.8 % vs. 27.5 %; AOR 2.2, 95 % CI 1.2-4.0) and CRC screening (12.2 % vs. 21.5 %; AOR 2.0, 95 % CI 1.1-3.9). Compared to letter alone, a Letter + Autodial + Prompt was also more effective at improving rates of BC screening (17.8 % vs. 28.2 %; AOR 2.1, 95 % CI 1.1-3.7) and CRC screening (12.2 % vs. 19.6 %; AOR 1.9, 95 % CI 1.0-3.7). Letter + Autodial was not more effective than a letter alone at improving screening rates. CONCLUSIONS: The addition of a personal telephone call or a patient-specific provider prompt were both more effective at improving mammogram and CRC screening rates compared to a reminder letter alone. The use of automated telephone calls, however, did not provide any incremental benefit to a reminder letter alone.

Randomized, controlled trial of a multimodal intervention to improve cancer screening rates in a safety-net primary care practice.

BACKGROUND: Cancer screening rates are suboptimal for low-income patients. OBJECTIVE: To assess an intervention to increase cancer screening among patients in a safety-net primary care practice. DESIGN: Patients at an inner-city family practice who were overdue for cancer screening were randomized to intervention or usual care. Screening rates at 1 year were compared using the chi-square test, and multivariable analysis was performed to adjust for patient factors. SUBJECTS: All average-risk patients at an inner-city family practice overdue for mammography or colorectal cancer (CRC) screening. Patients' ages were 40 to 74 years (mean 53.9, SD 8.7) including 40.8 % African Americans, 4.2 % Latinos, 23.2 % with Medicaid and 10.9 % without any form of insurance. INTERVENTION: The 6-month intervention to promote cancer screening included letters, automated phone calls, prompts and a mailed Fecal Immunochemical Testing (FIT) Kit. MAIN MEASURES: Rates of cancer screening at 1 year. KEY RESULTS: Three hundred sixty-six patients overdue for screening were randomly assigned to intervention (n = 185) or usual care (n = 181). Primary analysis revealed significantly higher rates of cancer screening in intervention subjects: 29.7 % vs. 16.7 % for mammography (p = 0.034) and 37.7 % vs. 16.7 % for CRC screening (p = 0.0002). In the intervention group, 20 % of mammography screenings and 9.3 % of CRC screenings occurred at the early assessment, while the remainder occurred after repeated interventions. Within the CRC intervention group 44 % of screened patients used the mailed FIT kit. On multivariable analysis the CRC screening rates remained significantly higher in the intervention group, while the breast cancer screening rates were not statistically different. CONCLUSIONS: A multimodal intervention significantly increased CRC screening rates among patients in a safety-net primary care practice. These results suggest that relatively inexpensive letters and automated calls can be combined for a larger effect. Results also suggest that mailed screening kits may be a promising way to increase average-risk CRC screening.

Residual sleep disturbances in patients remitted from major depressive disorder: a 4-year naturalistic follow-up study.

STUDY OBJECTIVES: To investigate the prevalence and clinical, psychosocial, and functional correlates of residual sleep disturbances in remitted depressed outpatients. DESIGN: A 4-yr prospective observational study in a cohort of psychiatric outpatients with major depressive disorder was conducted with a standardized diagnostic psychiatric interview and a packet of questionnaires, including a sleep questionnaire, Hospital Anxiety and Depression Scale, NEO personality inventory, and Short Form-12 Health Survey. SETTINGS: A university-affiliated psychiatric outpatient clinic. INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: Four hundred twenty-one depressed outpatients were recruited at baseline, and 371 patients (mean age 44.6 ± 10.4 yr, female 81.8%; response rate 88.1%) completed the reassessments, in which 41% were classified as remitted cases. One year prevalence of frequent insomnia at baseline and follow-up in remitted patients was 38.0% and 19.3%, respectively. One year prevalence of frequent nightmares at baseline and follow-up was 24.0% and 9.3%, respectively. Remitted patients with residual insomnia were more likely to be divorced (P < 0.05) and scored higher on the anxiety subscale (P < 0.05). Remitted patients with residual nightmares were younger (P < 0.05) and scored higher on neuroticism (P < 0.05) and anxiety subscales (P < 0.01). Residual insomnia and nightmares were associated with various aspects of impaired quality of life. Residual nightmares was associated with suicidal ideation (odds ratio = 8.40; 95% confidence interval 1.79-39.33). CONCLUSIONS: Residual sleep disturbances, including insomnia and nightmares, were commonly reported in remitted depressed patients with impaired quality of life and suicidal ideation. A constellation of psychosocial and personality factors, baseline sleep disturbances, and comorbid anxiety symptoms may account for the residual sleep disturbances. Routine assessment and management of sleep symptoms are indicated in the integrated management of depression.

A multimodal intervention to promote mammography and colorectal cancer screening in a safety-net practice.

BACKGROUND: There are limited data regarding interventions designed to improve cancer screening rates in safety-net practices with "real world" patients. OBJECTIVE: To examine the impact of a multimodal intervention on mammography and colorectal cancer (CRC) screening rates in a safety-net practice caring for underserved patients. METHODS: At an inner-city family medicine practice, all patients past due for mammography or CRC screening were assigned to receive or not receive a screening promotion intervention based on their medical record number. The 12-month intervention included outreach to patients (tailored letters, automated and personal phone calls) and point-of-care patient and clinician prompts. The trial was registered at clinicaltrials.gov, NCT00818857. RESULTS: We enrolled 469 participants aged 40 to 74 years, including 28% African Americans, 5% Latinos, 25% with Medicaid, and 10% without any form of insurance. Participants in the intervention group showed statistically significantly higher rates of cancer screening; rates were 41% vs 16.8% for mammography and 28.8% vs 10% for CRC screening. These findings were confirmed in multivariable analysis. Similar relative improvements in screening were seen across race, ethnicity, socioeconomic status, and insurance groups. DISCUSSION: A multimodal intervention shows promise for improving rates of mammography and colorectal cancer screening within a safety-net practice. Further study will identify the most cost-effective components of the intervention.

Nocturnal sleep disturbances as a predictor of suicide attempts among psychiatric outpatients: a clinical, epidemiologic, prospective study.

OBJECTIVE: Nocturnal sleep disturbances, including insomnia and recurrent nightmares, represent common distressing sleep complaints that might have important prognostic and therapeutic implications in psychiatric patients. The present study aimed at investigating nocturnal sleep disturbances in relation to the risk of suicide attempts in a consecutive cohort of psychiatric outpatients. METHOD: Participants attending a psychiatric outpatient clinic in Hong Kong were recruited into the study with a detailed sleep questionnaire assessment. The questionnaire was distributed between May and June 2006. Relevant clinical information, with a comprehensive clinical history of patients since their attendance at psychiatric services and 1 year after completion of their questionnaires, was reviewed. RESULTS: The final study population consisted of 1,231 psychiatric outpatients with a mean age of 42.5 years (SD = 11.3; range, 18-65). Both frequent insomnia and recurrent nightmares were significantly and independently associated with an increased incidence of suicide attempts 1 year after questionnaire assessment (insomnia: OR = 6.96; 95% CI, 1.21-39.97; recurrent nightmares: OR = 8.17; 95% CI, 1.06-63.13) and an increase in lifetime prevalence of suicide attempts (insomnia: OR = 1.55; 95% CI, 1.06-2.25; recurrent nightmares: OR = 2.43; 95% CI, 1.51-3.91). Comorbid insomnia and nightmares had increased odds of lifetime prevalence (OR = 2.43; 95% CI, 1.53-3.85) and 1-year incidence of suicidal risk (OR = 17.08; 95% CI, 2.64-110.40). Antidepressants, particularly selective serotonin reuptake inhibitors (OR = 1.52; 95% CI, 1.02-2.25), serotonin-norepinephrine reuptake inhibitors (OR = 2.10; 95% CI, 1.15-3.83), heterocyclics (OR = 2.78; 95% CI, 1.21-6.42), and non-benzodiazepine hypnotics (OR = 1.54; 95% CI, 1.02-2.33) were independently associated with recurrent nightmares after adjustment for confounding variables. CONCLUSIONS: Nocturnal sleep disturbances, particularly frequent insomnia and recurrent nightmares, were independently associated with enhanced suicidal risk among psychiatric patients. Future studies are warranted to investigate the underlying pathophysiologic mechanism and interventional responses.

Localized expression of small RNA inhibitors in human cells.

Several types of small RNAs have been proposed as gene expression repressors with great potential for use in gene therapy. RNA polymerase III (pol III) provides an ideal means of expressing small RNAs in cells because its normal products are small, highly structured RNAs that are found in a variety of subcellular compartments. We have designed cassettes that use human pol III promoters for the high-level expression of small RNAs in the cytoplasm, nucleoplasm, and nucleolus. The levels and subcellular destinations of the transcripts are compared for transcripts expressed using the U6 small nuclear RNA (snRNA), 5S ribosomal RNA (rRNA), and the 7SL RNA component of the signal recognition particle. The most effective location for a particular inhibitory RNA is not necessarily predictable; thus these cassettes allow testing of the same RNA insert in multiple subcellular locations. Several small interfering RNA (siRNA) inserts were tested for efficacy. An siRNA insert that reduces lamin expression when transcribed from the U6 snRNA promoter in the nucleus has no effect on lamin expression when transcribed from 5S rRNA and 7SL RNA-based cassettes and found in the nucleolus and cytoplasm. To test further the generality of U6-driven siRNA inhibitors, siRNAs targeting HIV were tested by co-transfection with provirus in cell culture. Although the degree of HIV-1 inhibition varied among inserts, results show that the U6 cassette provides a means of expressing an siRNA-like inhibitor of HIV gene expression.