Non-progressive breast carcinomas detected at mammography screening: a population study.

BACKGROUND: Some breast carcinomas detected at screening, especially ductal carcinoma in situ, may have limited potential for progression to symptomatic disease. To determine non-progression is a challenge, but if all screening-detected breast tumors eventually reach a clinical stage, the cumulative incidence at a reasonably high age would be similar for women with or without screening, conditional on the women being alive. METHODS: Using high-quality population data with 24 years of follow-up from the gradually introduced BreastScreen Norway program, we studied whether all breast carcinomas detected at mammography screening 50-69 years of age would progress to clinical symptoms within 85 years of age. First, we estimated the incidence rates of breast carcinomas by age in scenarios with or without screening, based on an extended age-period-cohort incidence model. Next, we estimated the frequency of non-progressive tumors among screening-detected cases, by calculating the difference in the cumulative rate of breast carcinomas between the screening and non-screening scenarios at 85 years of age. RESULTS: Among women who attended BreastScreen Norway from the age of 50 to 69 years, we estimated that 1.1% of the participants were diagnosed with a breast carcinoma without the potential to progress to symptomatic disease by 85 years of age. This proportion of potentially non-progressive tumors corresponded to 15.7% [95% CI 3.3, 27.1] of breast carcinomas detected at screening. CONCLUSIONS: Our findings suggest that nearly one in six breast carcinomas detected at screening may be non-progressive.

Cardiovascular risk factors and body composition in adults with achondroplasia.

PURPOSE: An increased cardiovascular mortality has been reported in achondroplasia. This population-based, case-control study investigated cardiovascular risk factors and body composition in Norwegian adults with achondroplasia. METHODS: We conducted anthropometric, clinical, and laboratory assessments in 49 participants with achondroplasia, of whom 40 completed magnetic resonance imaging (MRI) for body composition analysis. Controls consisted of 98 UK Biobank participants, matched for body mass index (BMI), sex, and age. RESULTS: Participants were well matched for BMI (33.3 versus 32.5 kg/m2) and sex, but achondroplasia participants were younger than controls (mean age 41.1 versus 54.3 years). Individuals with achondroplasia had lower age-adjusted mean blood pressure, total and low-density lipoprotein (LDL) cholesterol, and triglycerides compared with controls, but similar fasting glucose and HbA1c values. Age-adjusted mean visceral fat store was 1.9 versus 5.3 L (difference -2.7, 95% confidence interval [CI] -3.6 to -1.9; P < 0.001), abdominal subcutaneous fat was 6.0 versus 11.2 L (-4.7, 95% CI -5.9 to -3.4; P < 0.001), and liver fat was 2.2 versus 6.9% (-2.8, 95% CI -5.2 to -0.4; P = 0.02). CONCLUSION: Despite a high BMI, the cardiovascular risks appeared similar or lower in achondroplasia compared with controls, indicating that other factors might contribute to the increased mortality observed in this condition.

Modeling the natural history of ductal carcinoma in situ based on population data.

BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has increased substantially since the introduction of mammography screening. Nevertheless, little is known about the natural history of preclinical DCIS in the absence of biopsy or complete excision. METHODS: Two well-established population models evaluated six possible DCIS natural history submodels. The submodels assumed 30%, 50%, or 80% of breast lesions progress from undetectable DCIS to preclinical screen-detectable DCIS; each model additionally allowed or prohibited DCIS regression. Preclinical screen-detectable DCIS could also progress to clinical DCIS or invasive breast cancer (IBC). Applying US population screening dissemination patterns, the models projected age-specific DCIS and IBC incidence that were compared to Surveillance, Epidemiology, and End Results data. Models estimated mean sojourn time (MST) in the preclinical screen-detectable DCIS state, overdiagnosis, and the risk of progression from preclinical screen-detectable DCIS. RESULTS: Without biopsy and surgical excision, the majority of DCIS (64-100%) in the preclinical screen-detectable state progressed to IBC in submodels assuming no DCIS regression (36-100% in submodels allowing for DCIS regression). DCIS overdiagnosis differed substantially between models and submodels, 3.1-65.8%. IBC overdiagnosis ranged 1.3-2.4%. Submodels assuming DCIS regression resulted in a higher DCIS overdiagnosis than submodels without DCIS regression. MST for progressive DCIS varied between 0.2 and 2.5 years. CONCLUSIONS: Our findings suggest that the majority of screen-detectable but unbiopsied preclinical DCIS lesions progress to IBC and that the MST is relatively short. Nevertheless, due to the heterogeneity of DCIS, more research is needed to understand the progression of DCIS by grades and molecular subtypes.

Image quality and radiation dose in planar imaging - Image quality figure of merits from the CDRAD phantom.

PURPOSE: A contrast-detail phantom such as CDRAD is frequently used for quality assurance, optimization of image quality, and several other purposes. However, it is often used without considering the uncertainty of the results. The aim of this study was to assess two figure of merits (FOM) originating from CDRAD regarding the variations of the FOMs by dose utilized to create the x-ray image. The probability of overlapping (assessing an image acquired at a lower dose as better than an image acquired at a higher dose) was determined. METHODS: The CDRAD phantom located underneath 12, 20, and 26 cm PMMA was imaged 16 times at five dose levels using an x-ray system with a flat-panel detector. All images were analyzed by CDRAD Analyser, version 1.1, which calculated the FOM inverse image quality figure (IQFinv ) and gave contrast detail curves for each image. Inherent properties of the CDRAD phantom were used to derive a new FOM h, which describes the size of the hole with the same diameter and depth that is just visible. Data were analyzed using heteroscedastic regression of mean and variance by dose. To ease interpretation, probabilities for overlaps were calculated assuming normal distribution, with associated bootstrap confidence intervals. RESULTS: The proportion of total variability in IQFinv , explained by the dose (R2 ), was 91%, 85%, and 93% for 12, 20, and 26 cm PMMA. Corresponding results for h were 91%, 89%, and 95%. The overlap probability for different mAs levels was 1% for 0.8 vs 1.2 mAs, 5% for 1.2 vs 1.6 mAs, 10% for 1.6 vs 2.0 mAs, and 10% for 2.0 mAs vs 2.5 mAs for 12 cm PMMA. For 20 cm PMMA, it was 0.5% for 10 vs 16 mAs, 13% for 16 vs 20 mAs, 14% for 20 vs 25 mAs, and 14% for 25 vs 32 mAs. For 26 cm PMMA, the probability varied from 0% to 6% for various mAs levels. Even though the estimated probability for overlap was small, the 95% confidence interval (CI) showed relatively large uncertainties. For 12 cm PMMA, the associated CI for 0.8 vs 1.2 mAs was 0.1-3.2%, and the CI for 1.2 vs 1.6 mAs was 2.1-7.8%. CONCLUSIONS: Inverse image quality figure and h are about equally related to dose level. The FOM h, which describes the size of a hole that should be seen in the image, may be a more intuitive FOM than IQFinv . However, considering the probabilities for overlap and their confidence intervals, the FOMs deduced from the CDRAD phantom are not sensitive to dose. Hence, CDRAD may not be an optimal phantom to differentiate between images acquired at different dose levels.

Evaluating different breast tumor progression models using screening data.

BACKGROUND: Mammography screening is used to detect breast cancer at an early treatable stage, reducing breast cancer mortality. Traditionally, breast cancer has been seen as a disease with only progressive lesions, and here we examine the validity of this assumption by testing if incidence levels after introducing mammography screening can be reproduced assuming only progressive tumors. METHODS: Breast cancer incidence data 1990-2009 obtained from the initially screened Norwegian counties (Akershus, Oslo, Rogaland and Hordaland) was included, covering the time-period before, during and after the introduction of mammography screening. From 1996 women aged 50-69 were invited for biennial public screening. Using estimates of tumor growth and screening sensitivity based on pre-screening and prevalence screening data (1990-1998), we simulated incidence levels during the following period (1999-2009). RESULTS: The simulated incidence levels during the period with repeated screenings were markedly below the observed levels. The results were robust to changes in model parameters. Adjusting for hormone replacement therapy use, we obtained levels closer to the observed levels. However, there was still a marked gap, and only by assuming some tumors that undergo regressive changes or enter a markedly less detectable state, was our model able to reproduce the observed incidence levels. CONCLUSIONS: Models with strictly progressive tumors are only able to partly explain the changes in incidence levels observed after screening introduction in the initially screened Norwegian counties. More complex explanations than a time shift in detection of future clinical cancers seem to be needed to reproduce the incidence trends, questioning the basis for many over-diagnosis calculations. As data are not randomized, similar studies in other populations are wanted to exclude effect of unknown confounders.

Intermittent mild negative pressure applied to the lower limb in patients with spinal cord injury and chronic lower limb ulcers: a crossover pilot study.

STUDY DESIGN: Randomized, assessor-blinded crossover pilot study. OBJECTIVES: To explore the use of an intermittent negative pressure (INP) device for home use in addition to standard wound care (SWC) for patients with spinal cord injury (SCI) and chronic leg and foot ulcers before conducting a superiority trial. SETTING: Patient homes and outpatient clinic. METHODS: A 16-week crossover trial on 9 SCI patients (median age: 57 years, interquartile range [IQR] 52-66), with leg ulcers for 52 of weeks (IQR: 12-82) duration. At baseline, patients were allocated to treatment with INP + SWC or SWC alone. After 8 weeks, the ulcers were evaluated. To assess protocol adherence, the patients were then crossed over to the other group and were evaluated again after another 8 weeks. Lower limb INP treatment consisted of an airtight pressure chamber connected to an INP generator (alternating 10 s -40mmHg/7 s atmospheric pressure) used 2 h/day at home. Ulcer healing was assessed using a photographic wound assessment tool (PWAT) and by measuring changes in wound surface area (WSA). RESULTS: Seven of nine recruited patients adhered to a median of 90% (IQR: 80-96) of the prescribed 8-week INP-protocol, and completed the study without side effects. PWAT improvement was observed in 4/4 patients for INP + SWC vs. 2/5 patients for SWC alone (P = 0.13). WSA improved in 3/4 patients allocated to INP + SWC vs. 3/5 patients in SWC alone (P = 0.72). CONCLUSIONS: INP can be used as a home-based treatment for patients with SCI, and its efficacy should be tested in an adequately sized, preferably multicenter randomized trial.

Intermittent negative pressure applied to the lower limb increases foot macrocirculatory and microcirculatory blood flow pulsatility in people with spinal cord injury.

STUDY DESIGN: Experimental prestudy and poststudy. OBJECTIVES: Examine the acute effects of intermittent negative pressure (INP) applied to the lower limb on foot circulation in people with spinal cord injuries (SCIs). SETTING: Vascular laboratory, Oslo University Hospital. METHODS: Twenty-four people with SCI (median age 59 years, range 29-74) were exposed to lower leg INP (-40 mm Hg) using an air-tight pressure chamber connected to an INP generator. The contralateral leg was placed outside the pressure chamber. We continuously measured arterial blood flow velocity (ultrasound Doppler), skin blood flow (laser Doppler), skin temperature of the dorsum of the foot, heart rate (ECG) and systemic blood pressure (Finometer) during 5-min baseline (atmospheric pressure), followed by 10-min INP (alternating 10 s -40 mm Hg and 7 s atmospheric pressure), and 5-min post-INP (atmospheric pressure). Skin blood flow was measured on the foot placed outside the pressure chamber. A mixed effects regression model was applied to estimate the effect of INP on blood flow. To quantify flow fluctuations, we calculated cumulative up-and-down changes in arterial blood flow velocity per minute. RESULTS: Flow fluctuations increased during INP compared to baseline [32.3 cm/s/min (95% CI 26.9 to 37.7) vs. 15.2 cm/s/min (95% CI 9.8 to 20.6), P < 0.001]. Peak blood flow velocity and skin blood flow was reached 2-3 s after the onset of negative pressure and increased 33% (95% CI 16 to 46, P < 0.001) and 11% (95% CI -4.1 to 60, P = 0.14) above baseline, respectively. CONCLUSIONS: INP induced increased foot arterial blood flow fluctuations compared to baseline. SPONSORSHIPS: The Norwegian Research Council provided funding to Otivio (grant: 241589).

Changing patterns of breast cancer incidence and mortality by education level over four decades in Norway, 1971-2009.

Background: In the last century, breast cancer incidence and mortality was higher among higher versus lower educated women in developed countries. Post-millennium, incidence rates have flattened off and mortality declined. We examined breast cancer trends by education level, to see whether recent improvements in incidence and mortality rates have occurred in all education groups. Methods: We linked individual registry data on female Norwegian inhabitants aged 35 years and over during 1971­2009. Using Poisson models, we calculated absolute and relative educational differences in age-standardised breast cancer incidence and mortality over four decades. We estimated educational differences by Slope and Relative Index of Inequality, which correspond to rate difference and rate ratio, comparing the highest to lowest educated women. Results: Pre-millennium, incidence and mortality of breast cancer were significantly higher in higher versus lower educated women. Post-millennium, educational differences in breast cancer incidence and mortality attenuated. During 2000­2009, breast cancer incidence was still 38% higher for higher versus lower educated women (Relative Index of Inequality: 1.38, 95% confidence interval: 1.31­1.44), but mortality no longer varied significantly by education level (Relative Index of Inequality: 1.09, 95% confidence interval: 0.99­1.19). Among women below 50 years, however, the education gradient for mortality reversed, and mortality was 28% lower for the highest versus lowest educated women during 2000­2009 (Relative Index of Inequality: 0.72, 95% confidence interval: 0.51­0.93). Results: Post-millennium improvements in breast cancer incidence and mortality have primarily benefited higher educated women. Breast cancer mortality is now highest among the lowest educated women below 50 years.

Referral patterns, treatment and outcome of high-grade malignant bone sarcoma in Scandinavia--SSG Central Register 25 years' experience.

AIMS: The objectives of this study were to present changes in referral patterns, treatment and survival in patients with high-grade malignant bone sarcoma in Sweden and Norway based on data in the Scandinavian Sarcoma Group (SSG) Central Register. METHOD: Data on 1,437 patients with diagnosis 1986-2010 was analyzed. RESULTS: Osteosarcoma was the most frequentl diagnosis (45%), followed by Ewing sarcoma (21%) and chondrosarcoma (17%). Thirty-one percent of Swedish and 41% of Norwegian patients had tumors in the axial skeleton. Eighty-six percent of extremity tumors and 66% of axial tumors were referred to a sarcoma center prior to unplanned surgery or biopsy. During the past decade, limb salvage surgery has risen from under 50% to over 80%. Five-year overall survival in non-metastatic osteosarcoma was 70% for extremity tumors, and 35% for axial tumors. No improvement in osteosarcoma survival was observed during the last decade. Five-year survival in Ewing sarcoma improved from 50% to 69%. CONCLUSION: Referral patterns in bone sarcomas have improved. However, greater efforts should be dedicated to improving referral of patients with possible tumors in the axial skeleton to multidisciplinary teams (MDTs). Overall survival of patients with high-grade malignant bone sarcomas in Sweden and Norway is in line with other reports.

Development of the Norwegian diet index and the Norwegian lifestyle index and evaluation in a national survey.

Background: Dietary and lifestyle indices are composite tools that are used to estimate risk of health outcomes. Objective: We aimed to develop a diet and a lifestyle index assessing adherence to the national guidelines in Norway, and to investigate adherence in a nationwide survey of healthy subjects (Norkost3). Design: Cut-off values for the indices were based on the Norwegian food based dietary guidelines and national lifestyle guidelines. Adherence was evaluated in the Norkost3 (n = 1,787). Results: Twelve dietary components were included in the diet index 1) fruit and berries, 2) vegetables, 3) whole grains, 4) unsalted nuts, 5) fish, 6) low-fat dairy products, 7) margarine/oils, 8) red meat, 9) processed meat, 10) foods rich in sugar and fat, 11) drinks with added sugar, and 12) dietary supplements. Each of the components was assigned a value of 0, 0.5 or 1 corresponding to low, intermediate and high adherence, except for plant-based foods, which were assigned a value of 0, 1.5 or 3, providing a composite diet index ranging from 0 to 20 points. The five components in the lifestyle index (i.e. diet, body mass index (BMI), physical activity, tobacco and alcohol) was assigned a value of 0, 0.5 or 1, giving a final score ranging from zero to five points. In Norkost3, 49% (95% CI: 47, 52) of the participants had low adherence to the diet component, whereas only 2% (95% CI: 2, 3) achieved high adherence, although most of the subjects had high educational level. High adherence to the recommendations of BMI, tobacco and alcohol intake was observed in 50% (95% CI: 47, 52), 72% (95% CI: 70, 74) and 68% (95% CI: 66, 70) of the participants, respectively. Due to the lack of data on physical activity, adherence to this component in the lifestyle index is not presented in this study. Conclusion: The new diet and lifestyle indices assess adherence to the Norwegian food-based dietary guidelines (FBDGs) and other national lifestyle guidelines. In this study, half of the subjects had low diet and lifestyle index scores. There is a need to implement interventions to improve this by focusing on the specific lifestyle components with low adherence.

Risk of recurrent cardiovascular events in coronary artery disease patients with Type D personality.

Introduction: Data on the association between Type D personality, its traits negative affectivity (NA) and social inhibition (SI), and risk of major adverse cardiac events (MACE) in coronary outpatients is sparse. Furthermore, the associations between Type D subgroups and cardiovascular risk factors are largely unknown. Methods: We investigated i) Type D personality, NA and SI and risk of recurrent MACE, and ii) the relationship between Type D subgroups and risk factors in a coronary population. This prospective cohort study included 1083 patients` median 16 months after a myocardial infarction and/or a revascularization procedure who were followed-up for 4.2 (SD 0.4) years. Type D personality was assessed by DS14. Anxiety and depression, statin adherence, and risk factors were assessed by patients' self-report and a clinical examination with blood samples. MACE, defined as cardiovascular death, myocardial infarction, revascularization, stroke or heart failure, were obtained from hospital records from index event to end of study lasting 5.7 years. Data were analyzed by Cox proportional hazard regression. Results: In all, 352 MACE occurred in 230 patients after average 4.2 years follow-up. Higher NA score was associated with MACE after adjustment for age, risk factors and comorbidity (HR 1.02 per unit increase, 95% CI 1.00-1.05), whereas we found a weaker, not statistically significant estimated effect of higher SI score. After additional adjustment for symptoms of anxiety and depression, we found a weaker, not statistically significant association between NA and MACE (HR 1.01 per unit increase, 95% CI 0.98-1.05). Low statin adherence and smoking were more prevalent in the Type D and high NA group. Discussion: Our results indicate that the NA trait is related to worse prognosis in outpatients with coronary artery disease.

Fat infiltration in the thigh muscles is associated with symptomatic spinal stenosis and reduced physical functioning in adults with achondroplasia.

BACKGROUND: Symptomatic spinal stenosis is a prevalent complication in adults with achondroplasia. Increased muscle fat infiltration (MFI) and reduced thigh muscle volumes have also been reported, but the pathophysiology is poorly understood. We explored whether the increased MFI and reduced thigh muscle volumes were associated with the presence of symptomatic spinal stenosis and physical functioning. METHODS: MFI and thigh muscle volumes were assessed by MRI in 40 adults with achondroplasia, and compared to 80 average-statured controls, matched for BMI, gender, and age. In achondroplasia participants, the six-minute walk-test (6MWT), the 30-s sit-to-stand test (30sSTS), and a questionnaire (the IPAQ) assessed physical functioning. RESULTS: Symptomatic spinal stenosis was present in 25 of the participants (the stenosis group), while 15 did not have stenosis (the non-stenosis group). In the stenosis group, 84% (21/25) had undergone at least one spinal decompression surgery. The stenosis group had significantly higher MFI than the non-stenosis group, with an age-, gender and BMI-adjusted difference in total MFI of 3.3 percentage points (pp) (95% confidence interval [CI] 0.04 to 6.3 pp; p = 0.03). Compared to matched controls, the mean age-adjusted difference was 3.3 pp (95% CI 1.7 to 4.9 pp; p < 0.01). The non-stenosis group had MFI similar to controls (age-adjusted difference - 0.9 pp, 95% CI - 3.4 to 1.8 pp; p = 0.51). MFI was strongly correlated with the 6MWT (r = - 0.81, - 0.83, and - 0.86; all p-values < 0.01), and moderately correlated with the 30sSTS (r = - 0.56, - 0.57, and - 0.59; all p-values < 0.01). There were no significant differences in muscle volumes or physical activity level between the stenosis group and the non-stenosis group. CONCLUSION: Increased MFI in the thigh muscles was associated with the presence of symptomatic spinal stenosis, reduced functional walking capacity, and reduced lower limb muscle strength. The causality between spinal stenosis, accumulation of thigh MFI, and surgical outcomes need further study. We have demonstrated that MRI might serve as an objective muscle biomarker in future achondroplasia studies, in addition to functional outcome measures. The method could potentially aid in optimizing the timing of spinal decompression surgery and in planning of post-surgery rehabilitation.

Environmental Transformations Enhancing Dignity in an Acute Psychiatric Ward: Outcome of a User-Driven Service Design Project.

OBJECTIVES: The goal of the current project was to enhance the feeling of dignity for patients in the seclusion unit in an acute psychiatric ward through environmental design changes and to evaluate the effect of the refurbishment. BACKGROUND: Treating people with dignity is essential in all health-related work and important for our mental health. Hospital architecture and design signal values that can promote dignity. Patients who must spend time in seclusion are at their most vulnerable mental state and the often worn-down like environment can challenge the feeling of dignity. How environmental design can promote dignity in seclusion units have not been studied. METHODS: To reach suggestions for design changes enhancing dignity, we used service design that included a broad user group. The effect of design changes was evaluated by a questionnaire answered by the nursing staff during a 4-week period pre- and post refurbishment and included a control group. RESULTS: The design concepts agreed upon were a welcoming atmosphere, contact with nature, room for privacy, close contact with staff, and a designated smoking area inside the unit. The evaluation found that the environmental design changes significantly supported the patients in their situation and the staff in their work. CONCLUSION: We conclude that dignity design concepts are highly applicable also in an acute psychiatric setting and improve the situation of secluded mental health patients, which is much needed. Findings align with other environmental changes in psychiatric wards that improve the patients' well-being and reduce aggression.

Interpreting Breast Cancer Mortality Trends Related to Introduction of Mammography Screening: A Simulation Study.

Background. Several studies have evaluated the effect of mammography screening on breast cancer mortality based on overall breast cancer mortality trends, with varied conclusions. The statistical power of such trend analyses is, however, not carefully studied. Methods. We estimated how the effect of screening on overall breast cancer mortality is likely to unfold. Because a screening effect is based on earlier treatment, screening can affect only new incident cases after screening introduction. To evaluate the likelihood of detecting screening effects on overall breast cancer mortality time trends, we calculated the statistical power of joinpoint regression analysis on breast cancer mortality trends around screening introduction using simulations. Results. We found that a very gradual increase in population-level screening effect is expected due to prescreening incident cases. Assuming 25% effectiveness of a biennial screening program in reducing breast cancer mortality among women 50 to 69 y of age, the expected reduction in overall breast cancer mortality was 3% after 2 y and reached a long-term effect of 18% after 20 y. In common settings, the statistical power to detect any screening effects using joinpoint regression analysis is very low (<50%), even in an artificial setting of constant risk of baseline breast cancer mortality over time. Conclusions. Population effects of screening on breast cancer mortality emerge very gradually and are expected to be considerably lower than the effects reported in trials excluding women diagnosed before screening. Studies of overall breast cancer mortality time trends have too low statistical power to reliably detect screening effects in most populations. Implications. Researchers and policy makers evaluating mammography screening should avoid using breast cancer mortality trend analysis that does not separate pre- and postscreening incident cases. Highlights: Population-level mammography screening effects on breast cancer mortality emerge gradually following screening introduction, resulting in very low statistical power of trend analysis.Researchers and policy makers evaluating mammography screening should avoid relying on population-wide breast cancer mortality trends.Expected mammography screening effects at population level are lower than those from screening trials, as many cases of breast cancer fall outside the screening age range.

Insomnia as a predictor of recurrent cardiovascular events in patients with coronary heart disease.

Study Objectives: Insomnia is highly prevalent in patients with coronary heart disease (CHD). However, the potential effect of insomnia on the risk of recurrent major adverse cardiovascular events (MACE) remains uncertain. Methods: This prospective cohort study included 1082 consecutive patients 2-36 (mean 16) months after myocardial infarction and/or coronary revascularization. Data on clinical insomnia, coronary risk factors, and comorbidity were collected at baseline. Clinical insomnia was assessed using the Bergen Insomnia Scale (BIS). The primary composite endpoint of MACE (cardiovascular death, hospitalization due to myocardial infarction, revascularization, stroke, or heart failure) was assessed with an average follow-up of 4.2 (SD 0.3) years after baseline. Data were analyzed using Cox proportional hazard regression models stratified by prior coronary events before the index event. Results: At baseline, mean age was 62 years, 21% were females, and 45% reported clinical insomnia. A total of 346 MACE occurred in 225 patients during the follow-up period. For clinical insomnia, the relative risk of recurrent MACE was 1.62 (95% confidence interval [CI]: 1.24-2.11, p < .001) adjusted for age, gender, and previous coronary events. In a multi-adjusted analysis, including coronary risk factors, cardiovascular comorbidity, symptoms of anxiety, and depression, the relative risk was 1.41 (95% CI: 1.05-1.89, p = .023). Clinical insomnia accounted for 16% of the MACE in attributable risk fraction analyses, being third in importance after smoking (27%) and low physical activity (21%). Conclusions: Clinical insomnia was associated with increased risk of recurrent MACE. These results emphasize the importance of identifying and managing insomnia in CHD outpatients.

Estimating the natural progression of non-invasive ductal carcinoma in situ breast cancer lesions using screening data.

OBJECTIVES: In addition to invasive breast cancer, mammography screening often detects preinvasive ductal carcinoma in situ (DCIS) lesions. The natural progression of DCIS is largely unknown, leading to uncertainty regarding treatment. The natural history of invasive breast cancer has been studied using screening data. DCIS modeling is more complicated because lesions might progress to clinical DCIS, preclinical invasive cancer, or may also regress to a state undetectable by screening. We have here developed a Markov model for DCIS progression, building on the established invasive breast cancer model. METHODS: We present formulas for the probability of DCIS detection by time since last screening under a Markov model of DCIS progression. Progression rates were estimated by maximum likelihood estimation using BreastScreen Norway data from 1995-2002 for 336,533 women (including 399 DCIS cases) aged 50-69. As DCIS incidence varies by age, county, and mammography modality (digital vs. analog film), a Poisson regression approach was used to align the input data. RESULTS: Estimated mean sojourn time in preclinical, screening-detectable DCIS phase was 3.1 years (95% confidence interval: 1.3, 7.6) with a screening sensitivity of 60% (95% confidence interval: 32%, 93%). No DCIS was estimated to be non-progressive. CONCLUSION: Most preclinical DCIS lesions progress or regress with a moderate sojourn time in the screening-detectable phase. While DCIS mean sojourn time could be deduced from DCIS data, any estimate of preclinical DCIS progressing to invasive breast cancer must include data on invasive cancers to avoid strong, probably unrealistic, assumptions.

The cultivable microbiota of the human distal ileum.

OBJECTIVES: The existing literature on the microbiota of the ileum is inconsistent. To further characterize the microbiota, we analysed samples obtained directly from resected ileums used for urinary diversion after radical cystectomy. METHODS: We included 150 patients with bladder cancer operated on from March 2016 to March 2019. Samples obtained by rubbing a swab against the ileal mucosa 25 cm from the ileocecal valve were cultivated at the local laboratory. Microbial colonies were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF). RESULTS: The microbial density of the distal ileum was low. Among our samples, 79% (95% confidence interval (CI) 71%, 84%) harboured less than 1.6 × 104 cfu/mL, whereas 36% (95% CI 28%, 44%) harboured less than 1.6 × 103 cfu/mL. The flora was dominated by viridans streptococci, Candida, Actinomyces, Rothia and Lactobacillus species. Colon-related bacteria i.e. strict anaerobic bacteria, Enterobacteriales and enterococci, were recovered from 14% of the samples. Constipation was associated with increased recovery of colon-related bacteria. Antibiotic treatment prior to surgical procedures did not affect culture results. Increased age was significantly associated with more substantial fungal growth and use of proton pump inhibitors seemed to increase both bacterial and fungal growth. CONCLUSIONS: The microbiota of the human distal ileum is sparse and differs significantly from the colonic microbiota both quantitatively and by composition. These findings contradict recent metagenomics studies based on samples collected by retrograde colonoscopy and emphasize the crucial importance of adequate sampling techniques.

Obstructive sleep apnea in Norwegian adults with achondroplasia: a population-based study.

BACKGROUND: Previous studies have found a high prevalence of obstructive sleep apnea (OSA) in children with achondroplasia, but clinical studies on this complication in adults with achondroplasia are lacking. OBJECTIVES: This population-based, cross-sectional study investigated the prevalence, severity, and predictive factors of OSA in Norwegian adults with achondroplasia. METHODS: We collected clinical data on 49 participants. Participants without a preexisting diagnosis of OSA had an overnight sleep registration. OSA was defined as an apnea-hypopnea index (AHI) ≥ 5 plus characteristic clinical symptoms, or AHI ≥ 15. We used the Berlin Questionnaire to assess clinical symptoms of OSA. RESULTS: OSA was found in 59% (29/49) of the participants (95% confidence interval 44 to 73%), of whom 59% (17/29) had moderate to severe OSA (AHI ≥ 15), and 48% (14/29) were previously undiagnosed. Variables predictive of OSA were: excessive daytime sleepiness; unrested sleep; loud snoring; observed nocturnal breathing stops; hypertension; age > 40 years; and BMI > 30 kg/m2. CONCLUSION: OSA was highly prevalent in Norwegian adults with achondroplasia, which we believe is representative of this population worldwide. Follow-up of adults with achondroplasia should include assessment of symptoms and signs of OSA, with a low threshold for conducting an overnight sleep registration if findings suggestive of OSA are present.