Giant cell arteritis: incidence and phenotypic distribution in Western Norway 2013-2020.

Objectives: There is an increasing awareness of the spectrum of phenotypes in giant cell arteritis (GCA). However, there is sparse evidence concerning the phenotypic distribution which may be influenced by both genetic background and the environment. We established a cohort of all GCA-patients in the Bergen Health Area (Western Norway), to describe the phenotypic distribution and whether phenotypes differ with regards to incidence and clinical features. Methods: This is a retrospective cohort study including all GCA-patients in the Bergen Health Area from 2013-2020. Data were collected by reviewing patient records, and patients considered clinically likely GCA were included if they fulfilled at least one set of classification criteria. Temporal artery biopsy (TAB) and imaging results were used to classify the patients according to phenotype. The phenotype "cranial GCA" was used for patients with a positive TAB or halo sign on temporal artery ultrasound. "Non-cranial GCA" was used for patients with positive findings on FDG-PET/CT, MRI-, or CT angiography, or wall thickening indicative of vasculitis on ultrasound of axillary arteries. Patients with features of both these phenotypes were labeled "mixed." Patients that could not be classified due to negative or absent examination results were labeled "unclassifiable". Results: 257 patients were included. The overall incidence of GCA was 20.7 per 100,000 persons aged 50 years or older. Overall, the cranial phenotype was dominant, although more than half of the patients under 60 years of age had the non-cranial phenotype. The diagnostic delay was twice as long for patients of non-cranial and mixed phenotype compared to those of cranial phenotype. Headache was the most common clinical feature (78% of patients). Characteristic clinic features occurred less frequently in patients of non-cranial phenotype compared to cranial phenotype. Conclusion: The overall incidence for GCA was comparable to earlier reports from this region. The cranial phenotype dominated although the non-cranial phenotype was more common in patients under 60 years of age. The diagnostic delay was longer in patients with the non-cranial versus cranial phenotype, indicating a need for examination of non-cranial arteries when suspecting GCA.

Measuring implementation: development of the implementation process assessment tool (IPAT).

BACKGROUND: Implementation science comprises a large set of theories suggesting interacting factors at different organisational levels. Development of literature syntheses and frameworks for implementation have contributed to comprehensive descriptions of implementation. However, corresponding instruments for measuring these comprehensive descriptions are currently lacking. The present study aimed to develop an instrument measuring care providers' perceptions of an implementation effort, and to explore the instrument's psychometric properties. METHODS: Based on existing implementation literature, a questionnaire was designed with items on individual and team factors and on stages of change in an implementation process. The instrument was tested in a Norwegian study on implementation of evidence based practices for psychosis. Item analysis, factor structure, and internal consistency at baseline were examined. RESULTS: The 27-item Implementation Process Assessment Tool (IPAT) revealed large variation between mean score of the items. The total scale scores were widely dispersed across respondents. Internal consistency for the total scale was high (Cronbach's alpha: .962), and all but one item contributed positively to the construct. The results indicated four underlying constructs: individual stages for behavioural change, individual activities and perceived support, collective readiness and support, and individual perceptions of the intervention. CONCLUSIONS: The IPAT appears to be a feasible instrument for investigating the implementation process from the perspective of those making the change. It can enable examination of the relative importance of factors thought to be essential for implementation outcomes. It may also provide ongoing feedback for leaders tailoring support for teams to improve implementation. However, further research is needed to detect the instrument's properties later in the implementation process and in different contexts. TRIAL REGISTRATION: ClinicalTrials.gov code NCT03271242 (retrospective registered September 5, 2017).

Survival and death causes of patients with giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study.

BACKGROUND: Our objective was to determine the survival and causes of death in a large and well-characterized cohort of patients with giant cell arteritis (GCA). METHODS: This is a hospital-based, retrospective, observational cohort study including patients diagnosed with GCA in Western Norway during 1972-2012. Patients were identified through computerized hospital records using the International Classification of Diseases (ICD)-coding system. Medical records were reviewed. Patients were randomly assigned population controls matched on age, sex, and geography from the Central Population Registry of Norway (CPRN). Date and cause of death were obtained from the Norwegian Cause of Death Registry (NCoDR). The survival was analyzed using Kaplan-Meier methods with the Gehan-Breslow test and the causes of death using cumulative incidence and Cox models for competing risks. RESULTS: We identified 881 cases with a clinical diagnosis of GCA of which 792 fulfilled the American College of Rheumatology (ACR) 1990 classification criteria. Among those fulfilling the ACR criteria, 528 were also biopsy-verified. Cases were matched with 2577 population controls. A total of 490 (56%) GCA patients and 1517 (59%) controls died during the study period. We found no difference in the overall survival of GCA patients compared to controls, p = 0.413. The most frequent underlying causes of death in both groups were diseases of the circulatory system followed by cancer. GCA patients had increased risk of dying of circulatory disease (HR 1.31, 95% CI 1.13-1.51, p < 0.001) but lower risk of dying of cancer (HR 0.56, 95% CI 0.42-0.73, p < 0.001) compared to population controls. CONCLUSIONS: We found no difference in the overall survival of GCA patients compared to matched controls, but there were differences in the distribution of underlying death causes.

Adherence to the Healthy Nordic Food Index and the incidence of acute myocardial infarction and mortality among patients with stable angina pectoris.

BACKGROUND: The Healthy Nordic Food Index (HNFI) has been associated with beneficial effects on markers of cardiovascular disease (CVD). Whether such effects are present among patients with established coronary heart disease is unknown. In the present study, we investigated the association between adherence to the HNFI and the risk of acute myocardial infarction (AMI) (fatal or nonfatal) and death among patients with stable angina pectoris. METHODS: In the Western Norway B-vitamin Intervention Trial, participants completed a 169-item semi-quantitative food frequency questionnaire. The HNFI was calculated from six food groups (fish, cabbage, apples/pears, root vegetables, whole grain bread and oatmeal), scoring 0-6. Three adherence groups were defined: 0-1 points (low), 2-3 points (medium) or 4-6 points (high). Cox regression analyses investigated associations between adherence to the HNFI and outcomes. RESULTS: Among 2019 men (79.7%) and women with mean age of 61.7 years, 307 patients experienced an AMI event during a median (25th and 75th percentiles) follow-up of 7.5 (6.3 and 8.7) years. Median follow-up for total mortality was 10.5 (9.3 and 11.7) years; 171 patients died from CVD and 380 from any cause. No association between HNFI and the risk of AMI was detected. However, the HNFI was associated with a reduced risk of all-cause death, both by linear estimates [hazard ratio (95% confidence interval = 0.91 (0.84-0.98)] and by comparison of the highest with the lowest adherence group [hazard ratio (95% confidence interval = 0.70 (0.52-0.95)]. CONCLUSIONS: The results of the present study suggest that a Healthy Nordic diet may reduce mortality in patients with established CVD.

Correction to: Incidence of giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study.

Following publication of the original article [1], the authors reported an error.

Maternal exercise, season and sex modify the daily fetal heart rate rhythm.

AIM: The knowledge on biological rhythms is rapidly expanding. We aimed to define the longitudinal development of the daily (24-hour) fetal heart rate rhythm in an unrestricted, out-of-hospital setting and to examine the effects of maternal physical activity, season and fetal sex. METHODS: We recruited 48 women with low-risk singleton pregnancies. Using a portable monitor for continuous fetal electrocardiography, fetal heart rate recordings were obtained around gestational weeks 24, 28, 32 and 36. Daily rhythms in fetal heart rate and fetal heart rate variation were detected by cosinor analysis; developmental trends were calculated by population-mean cosinor and multilevel analysis. RESULTS: For the fetal heart rate and fetal heart rate variation, a significant daily rhythm was present in 122/123 (99.2%) and 116/121 (95.9%) of the individual recordings respectively. The rhythms were best described by combining cosine waves with periods of 24 and 8 hours. With increasing gestational age, the magnitude of the fetal heart rate rhythm increased, and the peak of the fetal heart rate variation rhythm shifted from a mean of 14:25 (24 weeks) to 20:52 (36 weeks). With advancing gestation, the rhythm-adjusted mean value of the fetal heart rate decreased linearly in females (P < .001) and nonlinearly in males (quadratic function, P = .001). At 32 and 36 weeks, interindividual rhythm diversity was found in male fetuses during higher maternal physical activity and during the summer season. CONCLUSION: The dynamic development of the daily fetal heart rate rhythm during the second half of pregnancy is modified by fetal sex, maternal physical activity and season.

Incidence of giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study.

BACKGROUND: Giant cell arteritis (GCA) is the most common systemic vasculitis in persons older than 50 years. The highest incidence rates of the disease have been reported in Scandinavian countries. Our objective was to determine the epidemiology of GCA in an expected high-incidence region during a 41-year period. METHODS: This is a hospital-based, retrospective, cohort study. Patients diagnosed with GCA in Bergen health area during 1972-2012 were identified through computerized hospital records (n = 1341). Clinical information was extracted from patients' medical journals, which were reviewed by a standardized method. We excluded patients if data were unavailable (n = 253), if the reviewing rheumatologist found GCA to be an implausible diagnosis (n = 207) or if the American College of Rheumatology (ACR) 1990 classification criteria for GCA were not fulfilled (n = 89). Descriptive methods were used to characterize the sample. Incidence was analyzed by graphical methods and Poisson regression. RESULTS: A total of 792 patients were included. The average annual cumulative incidence of GCA was 16.7 (95% CI 15.5-18.0) per 100,000 of the population ≥ 50 years old. The corresponding incidence for biopsy-verified GCA was 11.2 (95% CI 10.2-12.3). The annual cumulative incidence increased with time in the period 1972-1992 (relative risk (RR) 1.1, p < 0.001) but not in 1993-2012 (RR 1.0, p = 0.543). The incidence was higher in women compared to men (average annual incidence 37.7 (95% CI 35.8-39.6) vs. 14.3 (95% CI 13.2-15.5), p < 0.001) with women having a twofold to threefold higher incidence rate throughout the study period. Average annual incidence increased with age until the 7th decade of life in both sexes throughout the study period (2.8 (95% CI 2.3-3.3) for age <60, 15.5 (95% CI 14.4-16.8) for age 60-69, 34.5 (95% CI 32.8-36.4) for age 70-79 and 26.8 (95% CI 25.3-28.4) for age ≥80 years, p < 0.001 for all age adjustments). CONCLUSIONS: Our study confirms an incidence of GCA comparable to previous reports on Scandinavian populations. Our results show increasing incidence from 1972 through 1992, after which the incidence has levelled out.

Inter-rater reliability of professional-caregiver-reported life events in adults with intellectual disabilities.

BACKGROUND: The inter-rater reliability (IRR) of the measure of life events in adults with intellectual disabilities was investigated. METHOD: Two staff members for each of 79 adults with intellectual disabilities (ID) living in group homes used a checklist to report the adults' exposure to and intensity of life events over the previous 12 months. The IRR was estimated with intraclass correlation analysis (ICC). The factors of the level of ID, number of years the rater knew the rated person and quality of community care were investigated for possible associations with level of reliability. RESULTS: The ICC values for the occurrence of life events were .44-.80 depending on the category of life events. In general, intensity measures showed lower ICC values. When the rater had known the person rated for 2 or more years or the quality of community care was high, the ICC values increased, whereas lower levels of ID were associated with lower ICC values. CONCLUSIONS: Inter-rater reliability in general was found to be acceptable. Further development and research are needed to improve the reliability of life event measures for more severe ID.

Results after surgical treatment of liver metastases in patients with high-grade gastroenteropancreatic neuroendocrine carcinomas.

BACKGROUND: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce. The aim of this study was to evaluate the results of curatively intended resection/radiofrequency ablation (RFA) of liver metastases in patients with metastatic GEP-NEC. METHODS: 32 patients with a diagnosis of high-grade gastroenteropancreatic neuroendocrine neoplasm (Ki-67 > 20%) and with intended curative resection/RFA of liver metastases, were identified among 840 patients from two Nordic GEP-NEC registries. Tumor morphology (well vs poor differentiation) was reassessed. Overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier analyses for the entire cohort and for subgroups. RESULTS: Median OS after resection/RFA of liver metastases was 35.9 months (95%-CI: 20.6-51.3) with a five-year OS of 43%. The median PFS was 8.4 months (95%-CI: 3.9-13). Four patients (13%) were disease-free after 5 years. Two patients had well-differentiated morphology (NET G3) and 20 patients (63%) had Ki-67 ≥ 55%. A Ki-67 < 55% and receiving adjuvant chemotherapy were statistically significant factors of improved OS after liver resection/RFA. CONCLUSION: This study shows a long median and long term survival after liver surgery/RFA for these selected metastatic GEP-NEC patients, particularly for the group with a Ki-67 in the relatively lower G3 range. Our findings indicate a possible role for surgical treatment of liver metastases in the management of this patient population.

Oral health among children with congenital heart defects in Western Norway.

AIM: This was to describe oral health in children with congenital heart defects (CHD), to evaluate association of different background variables with oral health, and to compare caries prevalence at dentine level with caries data in the general population. METHODS: In this cross-sectional study, 5-year-old children in Western Norway with a need for lifelong follow-up due to CHD were invited to participate (n = 100). Children born in 2005, 2006, and 2007 underwent a comprehensive oral health examination during the period 2010-2012. Caries prevalence at the dentine level was compared with data available for 5-year-old children from the general population of Western Norway (n = 18,974). RESULTS: The response rate was 67 %. Caries prevalence in children with CHD at d1-5mft was 37.3 % and at d3-5mft 25.4 %. Few children (n = 4) had experienced fillings, indicating an unmet need for operative treatment. Enamel lesions (d1-2s) exceeded dentine lesions (d3-5s) in the study group, 60 % versus 40 %, indicating a significant need of non-operative treatment. At dentine level, caries prevalence in children with CHD was significantly higher than in children in the general population (25.4 versus 18.3 %). Erosion was more prevalent than caries (50.7 versus 37.3 %). In total, 37.3 % of all children had d3-5mfs caries, erosion (grades 3 or 4), developmental defects of enamel (DDE) with post-eruptive breakdown of enamel and exposure into dentine, or combinations of the diagnoses. Investigated background factors did not significantly affect caries, erosion, or DDE. CONCLUSION: More than a third of the children with CHD were found to have an oral health status that may imply risk for systemic hazardous effects.

Self-reported diabetes self-management competence and support from healthcare providers in achieving autonomy are negatively associated with diabetes distress in adults with Type 1 diabetes.

AIM: To investigate the associations of self-perceived competence in diabetes management and autonomy support from healthcare providers with diabetes distress in adults with Type 1 diabetes mellitus that is not optimally controlled [HbA(1c) ≥ 64 mmol/mol (8.0%)]. METHODS: This cross-sectional study comprised blood sampling and three self-report questionnaires, the Problem Areas in Diabetes scale, the Perceived Competence in Diabetes Scale and a measure of autonomy support by healthcare providers, the Health Care Climate Questionnaire. We fitted blockwise linear regression models to assess the associations between Problem Areas in Diabetes score and the variables of interest (autonomy support and perceived diabetes competence), controlling for clinical and sociodemographic variables. RESULTS: Of the study sample [n = 178; mean age 36.7 (±10.7) years], 31.5% had long-term complications and 43.2% reported elevated (≥40) Problem Areas in Diabetes scores. A significant negative association was found between autonomy support and Problem Areas in Diabetes score (B = -3.61, P = 0.001), indicating that lower autonomy support was associated with greater diabetes distress. When perceived competence was controlled, it mediated the association of autonomy support with diabetes distress, reducing it to non-significance. There was a significant negative association between perceived competence and Problem Areas in Diabetes score (B = -8.89, P < 0.001), indicating that lower perceived competence was associated with greater perceived distress. CONCLUSIONS: There was an indirect (fully mediated) relationship between autonomy support and diabetes distress; autonomy support was associated with increased perceived competence, which, in turn, was associated with reduced distress. Healthcare providers' communication styles enhancing perceived competence through autonomy support may contribute to effective treatment for people with Type 1 diabetes and suboptimum glycaemic control.

IP-10 differentiates between active and latent tuberculosis irrespective of HIV status and declines during therapy.

OBJECTIVES: Biomarkers for diagnosis and therapy efficacy in tuberculosis (TB) are requested. We have studied biomarkers that may differentiate between active and latent TB infection (LTBI), the influence of HIV infection and changes during anti-TB chemotherapy. METHODS: Thirty-eight plasma cytokines, assessed by multiplex and enzyme immunoassays, were analyzed in patients with active TB before and during 24 weeks of anti-TB chemotherapy (n = 65), from individuals with LTBI (n = 34) and from QuantiFERON-TB (QFT) negative controls (n = 65). The study participants were grouped according to HIV status. RESULTS: Plasma levels of the CXC chemokine IP-10 and soluble TNF receptor type 2 (sTNFr2) significantly differentiated active TB from the LTBI group, irrespective of HIV status. In the HIV-infected group the sensitivity and specificity was 100% for IP-10 with a cut-off of 2547 pg/mL. Plasma IP-10 declined gradually during anti-TB chemotherapy (12-24 weeks, p = 0.002) to a level comparable to LTBI and QFT negative control groups. sTNFr2 fluctuated throughout therapy, but was decreased after 12-24 weeks (p = 0.006). CONCLUSIONS: IP-10 distinguished with high accuracy active TB from LTBI irrespective of HIV infection and declined during anti-TB chemotherapy. Plasma IP-10 may serve as a diagnostic biomarker to differentiate between the stages of TB infection and for monitoring therapy efficacy.

Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study.

BACKGROUND: As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. PATIENTS AND METHODS: Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic hospitals. RESULTS: The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-67<55% was by receiver operating characteristic analysis the best cut-off value concerning correlation to the response rate. Patients with Ki-67<55% had a lower response rate (15% versus 42%, P<0.001), but better survival than patients with Ki-67≥55% (14 versus 10 months, P<0.001). Platinum schedule did not affect the response rate or survival. The most important negative prognostic factors for survival were poor performance status (PS), primary colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels. CONCLUSIONS: Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67<55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.

Autonomic symptoms and dopaminergic treatment in de novo Parkinson's disease.

OBJECTIVES: Autonomic symptoms are present in early stages of Parkinson's disease (PD), but evidence on how they are influenced by dopaminergic treatment remains unclear. The aim of this study was to investigate the impact of dopaminergic treatment on autonomic symptoms in early PD in a population-based cohort. METHODS: A total of 171 drug-naive patients with PD were investigated at diagnosis and 12 months later. Orthostatic blood pressure was measured, and autonomic symptoms were assessed by a preliminary version of the Movement Disorders Society-sponsored new version of the Unified Parkinson's Disease Rating Scale (range 0-4). RESULTS: In the 82% using dopaminergic treatment after 1 year, constipation and orthostatic blood pressure drop increased. There was a tendency towards increased orthostatic dizziness and urinary dysfunction. Dysphagia scores were reduced, and this was associated with higher levodopa-equivalent daily dose. CONCLUSIONS: Dopaminergic treatment during the first year after initiation seems to have only a minor impact on autonomic symptoms in early PD. It may increase constipation and orthostatic dizziness, while dysphagia can improve. Autonomic symptoms remained mild after 1 year of dopaminergic treatment.

Management of latent tuberculous infection in Norway in 2009: a descriptive cross-sectional study.

SETTING: Despite a steep increase in the number of individuals treated for latent tuberculous infection (LTBI), few data are available on how treatment is implemented. OBJECTIVE: To obtain baseline information on initiation and completion of treatment for LTBI in Norway in 2009. DESIGN: A descriptive cross-sectional study. RESULTS: All 721 patients treated for LTBI in 2009 in Norway were included, of whom 607 (84%) completed treatment. The treatment regimen generally consisted of 3 months of rifampicin and isoniazid. The three main reasons for starting treatment were: 1) countries of origin with high tuberculosis (TB) prevalence, 2) a positive tuberculin skin test, and 3) a positive interferon gamma release assay. The use of directly observed treatment varied by health region and age. The majority of the 34 medical specialists interviewed saw a need for new national guidelines to improve the selection of high-risk patients with LTBI. CONCLUSIONS: Management of LTBI is in accordance with current guidelines, with a high completion rate. More targeted selection of which patients should be offered preventive treatment is required, and new guidelines and tools to enhance risk assessment are necessary.

T regulatory cells and immune activation in Mycobacterium tuberculosis infection and the effect of preventive therapy.

Mycobacterium tuberculosis (TB) often causes persistent infection and many immune cell subsets and regulatory mechanisms may operate throughout the various stages of infection. We have studied dendritic cell (DC) subsets, regulatory T cells (Treg) and the expression of activation and apoptosis markers on CD4+ and CD8+ T cells in blood from patients with active TB (n=20), subjects with positive QuantiFERON-TB GOLD (QFT) test (LTBI, latent TB infection) (n=20) before and after 3 months of preventive anti-tuberculous therapy and from QFT-negative controls (n=28). The frequency of CD4+ CD25+ CD127⁻ Treg was highest in the group with active TB (P=0.001), but also increased in the LTBI group (P=0.006) compared to controls. The highest level of activated T cells, defined as CD38+ HLA-DR+ cells, was found in the active TB group, for the CD4+ T cell subset positively correlated to the level of CD25+ CD127⁻ Treg (P<0.001, r=0.4268). After 3 months of preventive therapy, there was an increase in the fraction of foxp3+ Treg, but no differences in markers of activation or apoptosis. In conclusion, there seems to be an increased level of immune activation and Treg in both latent and active TB infection that is only modestly influenced by preventive therapy.

Sleep detection with an accelerometer actigraph: comparisons with polysomnography.

Two validation studies were conducted to optimize the sleep-detection algorithm of the Actillume. The first study used home recordings of postmenopausal women (age range: 51 to 77 years), which were analyzed to derive the optimal algorithm for detecting sleep and wakefulness from wrist activity data, both for nocturnal in-bed recordings and considering the entire 24 h. The second study explored the optimal algorithm to score in-bed recordings of healthy young adults (age range: 19 to 34 years) monitored in the laboratory. In Study I, the algorithm for in-bed recordings (n=39) showed a minute-by-minute agreement of 85% between Actillume and polysomnography (PSG), a correlation of.98, and a mean measurement error (ME) of 21 min for estimates of sleep duration. Using the same algorithm to score 24-h recordings with Webster's rules, an agreement of 89%, a correlation of.90, and 1 min ME were observed. A different algorithm proved optimal to score in-bed recordings (n=31) of young adults, yielding an agreement of 91%, a correlation of.92, and an ME of 5 min. The strong correlations and agreements between sleep estimates from Actillume and PSG in both studies suggest that the Actillume can reliably monitor sleep and wakefulness both in community-residing elderly and healthy young adults in the laboratory. However, different algorithms are optimal for individuals with different characteristics.

Sleep-wake patterns among postmenopausal women: a 24-hour unattended polysomnographic study.

BACKGROUND: Circadian sleep-wake profiles in postmenopausal women were examined to explore relationships between nocturnal and out-of-bed sleep. METHODS: Twenty-one home recordings were obtained with unattended polysomnography from women ranging from 56 to 77 years of age. RESULTS: While maintaining their daily routines, volunteers slept an average of 439 minutes throughout the 24-hour recordings. Ten percent of the accumulated sleep time was recorded out of bed. CONCLUSIONS: Greater age was associated with more afternoon-evening sleep. Sleep was also frequently observed shortly after volunteers arose from bed in the morning.

Circadian sleep, illumination, and activity patterns in women: influences of aging and time reference.

Patterns of sleep, illumination, and activity of women of different ages were continuously monitored in their natural environments with a wrist activity monitor. Partial correlation analyses were performed to determine relationships between age and sleep and several circadian rhythm measures including the amplitudes, mesors, and timings of sleep, of illumination, and of activity. We found no age-related decline in actigraphic sleep duration. Age was not a significant correlate of circadian rhythm parameters of sleep. Moreover, no age effects were found on daily illumination exposure or on the circadian timing of illumination and activity patterns. However, the level and amplitude of the circadian activity rhythm showed a gradual decline with aging, independent of the time reference (i.e., Daylight Saving Time versus Standard Time) when recordings were obtained. As expected, significant associations were observed between local time reference and the level and timing of peak of illumination patterns. However, changes in local time reference were not significantly and consistently associated with actigraphic sleep or activity measures.

Mortality hazard associated with prescription hypnotics.

BACKGROUND: The American Cancer Society's Cancer Prevention Study II was a large survey designed primarily to examine cancer risks such as cigarette smoking. From the same survey and methods, data on usage of "prescription sleeping pills" in 1982 were examined. METHODS: Standardized mortality ratios were computed. Because sleeping pill use could be a proxy for other risk factors, cox proportional hazards models were computed to control for possible confounding factors as extensively as the data permitted. RESULTS: Men and women who reported taking prescription sleeping pills 30+ times in the past month had standardized mortality ratios of 3.18 and 2.82, respectively; controlling for 10-year age groups (p < 0.001). The standardized mortality ratios for usage 1-29 times/month were 1.8 and 1.48, respectively (p < 0.001). In proportional hazards models that controlled for 30 other risk factors and comorbidities simultaneously, the excess mortality risk associated with usage 30+ times per month remained significant, but hazard ratios were reduced to 1.35 for men and 1.22 for women. CONCLUSIONS: Use of hypnotics was associated with excess mortality. This methodology could not determine if hypnotic compounds caused the risks associated with their use, nor could the risks of individual compounds be determined. Since millions of Americans are currently taking hypnotics, long-term controlled trials are urgently needed to further guide both patients and physicians.