Fit-for-Purpose Ki-67 Immunohistochemistry Assays for Breast Cancer.

New therapies are being developed for breast cancer, and in this process, some "old" biomarkers are reutilized and given a new purpose. It is not always recognized that by changing a biomarker's intended use, a new biomarker assay is created. The Ki-67 biomarker is typically assessed by immunohistochemistry (IHC) to provide a proliferative index in breast cancer. Canadian laboratories assessed the analytical performance and diagnostic accuracy of their Ki-67 IHC laboratory-developed tests (LDTs) of relevance for the LDTs' clinical utility. Canadian clinical IHC laboratories enrolled in the Canadian Biomarker Quality Assurance Pilot Run for Ki-67 in breast cancer by invitation. The Dako Ki-67 IHC pharmDx assay was employed as a study reference assay. The Dako central laboratory was the reference laboratory. Participants received unstained slides of breast cancer tissue microarrays with 32 cases and performed their in-house Ki-67 assays. The results were assessed using QuPath, an open-source software application for bioimage analysis. Positive percent agreement (PPA, sensitivity) and negative percent agreement (NPA, specificity) were calculated against the Dako Ki-67 IHC pharmDx assay for 5%, 10%, 20%, and 30% cutoffs. Overall, PPA and NPA varied depending on the selected cutoff; participants were more successful with 5% and 10%, than with 20% and 30% cutoffs. Only 4 of 16 laboratories had robust IHC protocols with acceptable PPA for all cutoffs. The lowest PPA for the 5% cutoff was 85%, for 10% was 63%, for 20% was 14%, and for 30% was 13%. The lowest NPA for the 5% cutoff was 50%, for 10% was 33%, for 20% was 50%, and for 30% was 57%. Despite many years of international efforts to standardize IHC testing for Ki-67 in breast cancer, our results indicate that Canadian clinical LDTs have a wide analytical sensitivity range and poor agreement for 20% and 30% cutoffs. The poor agreement was not due to the readout but rather due to IHC protocol conditions. International Ki-67 in Breast Cancer Working Group (IKWG) recommendations related to Ki-67 IHC standardization cannot take full effect without reliable fit-for-purpose reference materials that are required for the initial assay calibration, assay performance monitoring, and proficiency testing.

Long-term exposure to fine particle elemental components and lung cancer incidence in the ELAPSE pooled cohort.

BACKGROUND: An association between long-term exposure to fine particulate matter (PM2.5) and lung cancer has been established in previous studies. PM2.5 is a complex mixture of chemical components from various sources and little is known about whether certain components contribute specifically to the associated lung cancer risk. The present study builds on recent findings from the "Effects of Low-level Air Pollution: A Study in Europe" (ELAPSE) collaboration and addresses the potential association between specific elemental components of PM2.5 and lung cancer incidence. METHODS: We pooled seven cohorts from across Europe and assigned exposure estimates for eight components of PM2.5 representing non-tail pipe emissions (copper (Cu), iron (Fe), and zinc (Zn)), long-range transport (sulfur (S)), oil burning/industry emissions (nickel (Ni), vanadium (V)), crustal material (silicon (Si)), and biomass burning (potassium (K)) to cohort participants' baseline residential address based on 100 m by 100 m grids from newly developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). RESULTS: The pooled study population comprised 306,550 individuals with 3916 incident lung cancer events during 5,541,672 person-years of follow-up. We observed a positive association between exposure to all eight components and lung cancer incidence, with adjusted HRs of 1.10 (95% CI 1.05, 1.16) per 50 ng/m3 PM2.5 K, 1.09 (95% CI 1.02, 1.15) per 1 ng/m3 PM2.5 Ni, 1.22 (95% CI 1.11, 1.35) per 200 ng/m3 PM2.5 S, and 1.07 (95% CI 1.02, 1.12) per 200 ng/m3 PM2.5 V. Effect estimates were largely unaffected by adjustment for nitrogen dioxide (NO2). After adjustment for PM2.5 mass, effect estimates of K, Ni, S, and V were slightly attenuated, whereas effect estimates of Cu, Si, Fe, and Zn became null or negative. CONCLUSIONS: Our results point towards an increased risk of lung cancer in connection with sources of combustion particles from oil and biomass burning and secondary inorganic aerosols rather than non-exhaust traffic emissions. Specific limit values or guidelines targeting these specific PM2.5 components may prove helpful in future lung cancer prevention strategies.

Effect of Secular Trend, Age, and Length of Follow-up on Optimum Body Mass Index From 1985 Through 2015 in a Large Austrian Cohort.

BACKGROUND: Obesity and its health consequences will dominate health care systems in many countries during the next decades. However, the body mass index (BMI) optimum in relation to all-cause mortality is still a matter of debate. MATERIAL AND METHODS: Data of the Vorarlberg Health Monitoring & Prevention Program (VHM&PP, 1985-2005) and data provided by the Main Association of Austrian Social Security Institutions (MAASSI, 2005-2015) were analyzed. Information was available on age, sex, smoking status, measured height and weight, and mortality. Generalized additive models were used to model mortality as a function of BMI, calendar time, age, and follow-up. RESULTS: In MAASSI (N = 282,216, 46.0% men), men and women were on average 2.7 years older than in VHM&PP (N = 185,361, 46.1% men). Average BMI was slightly higher in men (26.1 vs 25.7 kg/m2) but not in women (24.6 vs 24.7 kg/m2). We found an interactive effect of age and follow-up on the BMI optimum. Over age 35 years in men and 55 years in women, the BMI optimum decreased with length of follow-up. While keeping covariates fixed, BMI optimum increased slightly between 1985 and 2015 in men and women, 24.9 (95% CI, 23.9-25.9) to 26.4 (95% CI, 25.3-27.3), and 22.4 (95% CI, 21.7-23.1) to 23.3 (95% CI, 22.6-24.5) kg/m2, respectively. CONCLUSION: Age and length of follow-up have a pronounced effect on the BMI associated with the lowest all-cause mortality. After controlling for age and length of follow-up, the BMI optimum increased slightly over 30 years in this large study sample.

Fibroepithelial lesions of the breast: a comprehensive morphological and outcome analysis of a large series.

Mammary fibroepithelial lesions encompass a wide spectrum of tumors ranging from an indolent fibroadenoma to potentially fatal malignant phyllodes tumor. The criteria used for their classification based on morphological assessment are often challenging to apply and there is no consensus as to what constitutes an adequate resection margin. We studied a retrospective cohort of 213 fibroepithelial lesions in 178 patients (80 fibroadenomas with unusual features and 133 phyllodes tumors: 63 benign, 41 borderline, and 29 malignant) in order to describe the spectrum of changes within each group, with special emphasis on margin evaluation. Outcome data were available for 153 fibroepithelial lesions in 139 patients (median 56 months, range 3-249 months). Positive final margin (tumor transected), age < 50 years and a predominantly myxoid stroma were statistically significant predictors of local recurrence, while age > 50, stromal overgrowth, diffuse marked atypia, necrosis and mitotic index of ≥ 10 per 10 HPF were predictive of distant metastases. Tumors with satellite/bulging nodules were at a significantly higher risk to have a final positive resection margin. Our findings highlight important aspects of the interpretation and reporting of fibroepithelial lesions: the amount of myxoid stroma and the presence of satellite nodules are clinically relevant and should be routinely assessed and reported; infiltrative border might not be a prerequisite for the diagnosis of malignant phyllodes tumor, while the presence of tumor necrosis, massive stromal overgrowth or mitotic index of ≥ 25 per 10 HPF is diagnostic of malignant phyllodes tumor. On the other hand, increased mitotic index outside of the range of the World Health Organization guidelines in the absence of other worrisome features should be treated with caution, as it can be found in benign tumors.

Large intragenic deletion of CDC73 (exons 4-10) in a three-generation hyperparathyroidism-jaw tumor (HPT-JT) syndrome family.

BACKGROUND: Inactivating mutations of CDC73 cause Hyperparathyroidism-Jaw Tumour syndrome (HPT-JT), Familial Isolated Hyperparathyroidism (FIHP) and sporadic parathyroid carcinoma. We conducted CDC73 mutation analysis in an HPT-JT family and confirm carrier status of the proband's daughter. METHODS: The proband had primary hyperparathyroidism (parathyroid carcinoma) and uterine leiomyomata. Her father and daughter had hyperparathyroidism (parathyroid adenoma) but no other manifestations of HPT-JT. CDC73 mutation analysis (sequencing of all 17 exons) and whole-genome copy number variation (CNV) analysis was done on leukocyte DNA of the three affecteds as well as the proband's unaffected sister. RESULTS: A novel deletion of exons 4 to 10 of CDC73 was detected by CNV analysis in the three affecteds. A novel insertion in the 5'UTR (c.-4_-11insG) that co-segregated with the deletion was identified. By in vitro assay the 5'UTR insertion was shown to significantly impair the expression of the parafibromin protein. Screening for the mutated CDC73 confirmed carrier status in the proband's daughter and the biochemistry and ultrasonography led to pre-emptive surgery and resolution of the hyperparathyroidism. CONCLUSIONS: A novel gross deletion mutation in CDC73 was identified in a three-generation HPT-JT family emphasizing the importance of including screening for large deletions in the molecular diagnostic protocol.

Life course body mass index and risk and prognosis of amyotrophic lateral sclerosis: results from the ALS registry Swabia.

Weight loss appears as a strong predictor of survival of patients with amyotrophic lateral sclerosis, yet no data are currently available to describe the life course history of pre-diagnostic body mass index (BMI) in these patients. 393 ALS cases (mean age: 65.8 years, 57.3% men) and 791 controls matched by age and sex from a population-based case-control study of the ALS Registry Swabia were analyzed. Differences of BMI change in cases and controls over time were modeled using a multilevel additive model. In addition, survival in ALS cases by BMI change was modeled using an accelerated failure time model adjusted for prognostic factors. In ALS cases, BMI was consistently higher than in controls in the 20-70 years before the interview. Conditional logistic regression revealed an odds ratio of 1.05 (95% confidence interval (CI) 1.00-1.11, p = 0.041) per 1 kg/m2 higher BMI 35-45 years before interview. However, a sharp decrease was evident in the BMI of ALS cases about 10 years before disease onset. Moreover, weight loss was strongly associated with shorter survival in ALS patients. Illustrating this, patients with stable weight showed a median survival time of 22.1 (95%-CI 19.2-25.0) months, as compared to 13.4 (95%-CI 10.5-16.3) months for patients with weight loss of 2.5 kg/m2 over the last 3 months before the interview. Thus, alterations in body weight are present in ALS patients already decades before clinical manifestation of ALS, while weight loss precedes motor symptoms of several years and is associated with poor prognosis.

Sources of heterogeneity in studies of the BMI-mortality association.

BACKGROUND: To date, the amount of heterogeneity among studies of the body mass index-mortality association attributable to differences in the age distribution and length of follow-up has not been quantified. Therefore, we wanted to quantify the amount of heterogeneity attributable to age and follow-up in results of studies on the body mass index-mortality relation. METHODS: We used optima of the body mass index mortality association reported for 30 populations and performed meta-regression to estimate the amount of heterogeneity attributable to sex, ethnicity, mean age at baseline, percentage smokers, and length of follow-up. RESULTS: Ethnicity as single factor accounted for 36% (95% CI, 11-56%) of heterogeneity. Mean age and length of follow-up had an interactive effect and together accounted for 56% (95% CI, 24-74%) of the remaining heterogeneity. Sex did not significantly contribute to the heterogeneity, after controlling for ethnicity, age, and length of follow-up. CONCLUSIONS: A considerable amount of heterogeneity in studies of the body mass index-mortality association is attributable to ethnicity, age, and length of follow-up.

Epidemiologic research topics in Germany: a keyword network analysis of 2014 DGEpi conference presentations.

Knowledge of epidemiologic research topics as well as trends is useful for scientific societies, researchers and funding agencies. In recent years researchers recognized the usefulness of keyword network analysis for visualizing and analyzing scientific research topics. Therefore, we applied keyword network analysis to present an overview of current epidemiologic research topics in Germany. Accepted submissions to the 9th annual congress of the German Society for Epidemiology (DGEpi) in 2014 were used as data source. Submitters had to choose one of 19 subject areas, and were ask to provide a title, structured abstract, names of authors along with their affiliations, and a list of freely selectable keywords. Keywords had been provided for 262 (82 %) submissions, 1030 keywords in total. Overall the most common keywords were: "migration" (18 times), "prevention" (15 times), followed by "children", "cohort study", "physical activity", and "secondary data analysis" (11 times each). Some keywords showed a certain concentration under one specific subject area, e.g. "migration" with 8 of 18 in social epidemiology or "breast cancer" with 4 of 7 in cancer epidemiology. While others like "physical activity" were equally distributed over multiple subject areas (cardiovascular & metabolic diseases, ageing, methods, paediatrics, prevention & health service research). This keyword network analysis demonstrated the high diversity of epidemiologic research topics with a large number of distinct keywords as presented at the annual conference of the DGEpi.

Change in height, weight, and body mass index: longitudinal data from Austria.

OBJECTIVES: To quantify changes in height, weight and their compound effect on the body mass index (BMI) in a large cohort of Central-European men and women. METHODS: The Vorarlberg health monitoring and prevention program (VHM&PP) is a population-based risk factor surveillance program in Vorarlberg. Data of health examinations during January 1985 to June 2005 were available including 714,181 height and weight measurements in 185,192 persons (53.9% women). We estimated yearly percentage change of anthropometric parameters over the age range from 20 to 85 years within intervals of 5 years. RESULTS: We found that weight increased until the age of 70 years (from the age of 20 years: +24.8% in men and +27.6% in women), with the highest increase in men aged 20-25 years (1.07% per year). Height was shown to decrease starting from the age group 45-50 years. This decrease accelerated with age, and was more pronounced in women than in men. CONCLUSIONS: Weight is strongly related to aging. In older individuals height loss affects BMI and masks weight loss to some degree.

The relationship of weather with daily physical activity and the time spent out of home in older adults from Germany - the ActiFE study.

BACKGROUND: There is a need for a comprehensive evaluation of the associations between varieties of weather conditions on the time spent out-of-home (TOH) and on walking duration (WD) among older adults. We aim to investigate the extent to which various weather parameters (temperature, solar radiation, sunshine duration, humidity, windspeed, and rain) determine daily WD the TOH in older adults. METHODS: The ActiFE (Activity and Function in Older People in Ulm) study is a prospective study of participants aged 65 years or older who wore an accelerometer and kept a movement diary in up to three temporally separated waves from 2009 to 2018 for a duration up to seven days per wave (up to three weeks in summary). We used weather data from a weather station near the participants' homes. Age-adjusted and gender-stratified generalized mixed models were used to predict WD and TOH (with 95% confidence interval (CI)) within and between weather categories. Generalized additive models were computed for the single predictions at the weather quartile boundaries. Cubic splines (with 95% pointwise confidence bands (CB)) visualized the continuous course of the weather values. RESULTS: Higher temperatures, solar radiation and more hours of sunshine, led to an increase in WD and TOH, while higher precipitation, humidities and windspeeds led to a decrease. Women had in general higher WD and TOH times than men. CONCLUSIONS: Our data suggest that weather parameters have a considerable influence on PA and TOH. Future analyses and interpretation of PA data should therefore account for weather parameters.

A bibliometric analysis of orthogeriatric care: top 50 articles.

BACKGROUND: Population is ageing and orthogeriatric care is an emerging research topic. PURPOSE: This bibliometric review aims to provide an overview, to investigate the status and trends in research in the field of orthogeriatric care of the most influential literature. METHODS: From the Core Collection databases in the Thomson Reuters Web of Knowledge, the most influential original articles with reference to orthogeriatric care were identified in December 2020 using a multistep approach. A total of 50 articles were included and analysed in this bibliometric review. RESULTS: The 50 most cited articles were published between 1983 and 2017. The number of total citations per article ranged from 34 to 704 citations (mean citations per article: n = 93). Articles were published in 34 different journals between 1983 and 2017. In the majority of publications, geriatricians (62%) accounted for the first authorship, followed by others (20%) and (orthopaedic) surgeons (18%). Articles mostly originated from Europe (76%), followed by Asia-pacific (16%) and Northern America (8%). Key countries (UK, Sweden, and Spain) and key topic (hip fracture) are key drivers in the orthogeriatric research. The majority of articles reported about therapeutic studies (62%). CONCLUSION: This bibliometric review acknowledges recent research. Orthogeriatric care is an emerging research topic in which surgeons have a potential to contribute and other topics such as intraoperative procedures, fractures other than hip fractures or elective surgery are related topics with the potential for widening the field to research.

Association of clinical outcome assessments of mobility capacity and incident disability in community-dwelling older adults - a systematic review and meta-analysis.

The objective of the present review is to synthesize all available research on the association between mobility capacity and incident disability in non-disabled older adults. MEDLINE, EMBASE and CINAHL databases were searched without any limits or restrictions until February 2021. Published reports of longitudinal cohort studies that estimated a direct association between baseline mobility capacity, assessed with a standardized outcome assessment, and subsequent development of disability, including initially non-disabled older adults were included. The risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. Random-effect models were used to explore the objective. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The main outcome measures were the pooled relative risks (RR) per one conventional unit per mobility assessment for incident disability. A total of 40 reports (85,515 participants at baseline) were included. For usual and fast gait speed, the RR per -0.1 m/s was 1.23 (95% CI: 1.18-1.28; 26,638 participants) and 1.28 (95% CI: 1.19-1.38; 8161 participants), respectively. Each point decrease in Short Physical Performance Battery score increased the risk of incident disability by 30% (RR = 1.30, 95% CI: 1.23-1.38; 9183 participants). The RR of incident disability by each second increase in Timed Up and Go test and Chair Rise Test performance was 1.15 (95% CI: 1.09-1.21; 30,426 participants) and 1.07 (95% CI: 1.04-1.10; 9450 participants), respectively. The review concludes that among community-dwelling non-disabled older adults, poor mobility capacity is a potent modifiable risk factor for incident disability. Mobility impairment should be mandated as a quality indicator of health for older people.

Long-term low-level ambient air pollution exposure and risk of lung cancer - A pooled analysis of 7 European cohorts.

BACKGROUND/AIM: Ambient air pollution has been associated with lung cancer, but the shape of the exposure-response function - especially at low exposure levels - is not well described. The aim of this study was to address the relationship between long-term low-level air pollution exposure and lung cancer incidence. METHODS: The "Effects of Low-level Air Pollution: a Study in Europe" (ELAPSE) collaboration pools seven cohorts from across Europe. We developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates for nitrogen dioxide (NO2), fine particulate matter (PM2.5), black carbon (BC), and ozone (O3) to assign exposure to cohort participants' residential addresses in 100 m by 100 m grids. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). We fitted linear models, linear models in subsets, Shape-Constrained Health Impact Functions (SCHIF), and natural cubic spline models to assess the shape of the association between air pollution and lung cancer at concentrations below existing standards and guidelines. RESULTS: The analyses included 307,550 cohort participants. During a mean follow-up of 18.1 years, 3956 incident lung cancer cases occurred. Median (Q1, Q3) annual (2010) exposure levels of NO2, PM2.5, BC and O3 (warm season) were 24.2 µg/m3 (19.5, 29.7), 15.4 µg/m3 (12.8, 17.3), 1.6 10-5m-1 (1.3, 1.8), and 86.6 µg/m3 (78.5, 92.9), respectively. We observed a higher risk for lung cancer with higher exposure to PM2.5 (HR: 1.13, 95% CI: 1.05, 1.23 per 5 µg/m3). This association was robust to adjustment for other pollutants. The SCHIF, spline and subset analyses suggested a linear or supra-linear association with no evidence of a threshold. In subset analyses, risk estimates were clearly elevated for the subset of subjects with exposure below the EU limit value of 25 µg/m3. We did not observe associations between NO2, BC or O3 and lung cancer incidence. CONCLUSIONS: Long-term ambient PM2.5 exposure is associated with lung cancer incidence even at concentrations below current EU limit values and possibly WHO Air Quality Guidelines.

Growth Differentiation Factor-15 as a Potent Predictor of Long-Term Mortality among Subjects with Osteoarthritis.

BACKGROUND: Subjects with osteoarthritis (OA) are at increased risk for cardiovascular (CV) and all-cause mortality. Whether biomarkers improve outcome prediction in these patients remains to be elucidated. We investigated the association between growth differentiation factor 15 (GDF-15), a novel stress-responsive cytokine, and long-term all-cause mortality among OA patients. METHODS: Within the Ulm Osteoarthritis Study, GDF-15 has been measured in the serum of 636 subjects, who underwent hip or knee arthroplasty between 1995 and 1996 (median age 65 years). RESULTS: During a median follow-up of 19.7 years, a total of 402 deaths occurred. GDF-15 was inversely associated with walking distance. Compared to the bottom quartile (Q), subjects within the top quartile of GDF-15 demonstrated a 2.69-fold increased risk of dying (hazard ratio (HR) (95% confidence interval (CI)) 2.69 (1.82-3.96) adjusted for age, sex, BMI, smoking status, localization of OA, diabetes, maximum walking distance, total cholesterol, and cystatin C. Further adjustment for NT-proBNP, troponin I, and hs-C-reactive protein did not change the results appreciably (HR (95%CI) 1.56 (1.07-2.28); 1.75 (1.21-2.55); 2.32 (1.55-3.47) for Q2, Q3, and Q4 respectively, p for trend < 0.001). CONCLUSIONS: In subjects with OA, GDF-15 represents a potent predictor of decreased survival over >20 years, independently of conventional CV risk factors, renal, cardiac, and inflammatory biomarkers as well as walking disability, previously associated with increased mortality and lower extremity OA.

Relationship between cardiac biomarker concentrations and long-term mortality in subjects with osteoarthritis.

Osteoarthritis (OA) is associated with adverse cardio-metabolic features. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponins T and I (hs-cTnT and hs-cTnI) are well-characterized cardiac markers and provide prognostic information. The objective was to assess the association of cardiac biomarker concentrations with long-term mortality in subjects with OA. In a cohort of 679 OA subjects, undergoing hip or knee replacement during 1995/1996, cardiac biomarkers were measured and subjects were followed over 20 years. During a median follow-up of 18.4 years, 332 (48.9%) subjects died. Median of hs-cTnT, hs-cTnI, and NT-proBNP at baseline was 3.2 ng/L, 3.9 ng/L, and 96.8 ng/L. The top quartile of NT-proBNP was associated with increased risk of mortality (Hazard Ratio (HR) 1.79, 95% confidence interval (CI) 1.17-2.73) after adjustment for covariates including troponins (hs-cTnT HR 1.30 (95% CI 0.90-1.89), hs-cTnI HR 1.32 (95% CI 0.87-2.00) for top category). When biomarker associations were evaluated as continuous variables, only NT-proBNP (HR per log-unit increment 1.34, 95% CI 1.16-1.54) and hs-cTnI (HR 1.38, 95% CI 1.11-1.72) showed robust results. Elevated cardiac biomarker concentrations predicted an increased risk of long-term mortality and strongest for NT-proBNP and hs-cTnI. These results might help to identify subjects at risk and target preventive efforts early.

Regional variation of care dependency after hip fracture in Germany: A retrospective cohort study using health insurance claims data.

OBJECTIVE: To investigate variation of care dependency after hip fracture across German regions based on the assessment by the German statutory long-term care insurance. DATA SOURCES/STUDY SETTING: Patient-level statutory health and long-term care insurance claims data from 2009-2011 and official statistical data from Germany. STUDY DESIGN: We performed a retrospective cohort study. Investigated multinomial outcome categories were increase in care dependency (new onset or a higher care dependency than pre-fracture), no change as reference and death as competing risk in the quarterly period following hip fracture (follow-up 3 months). Regional variation was operationalized with the variance of regional-level random intercepts based on generalized linear mixed models. We adjusted for patient and regional characteristics. PRINCIPAL FINDINGS: The study included 122,887 hip fracture patients in 95 German postal code regions. Crude outcomes were 30.87% increase in care dependency and 14.35% death. Results indicated modest variation on regional level. Male sex, increasing age, increasing comorbidity, pertrochanteric and subtrochanteric fracture site compared to femoral neck, time from hospital admission to surgery of 3 or more days, as well as increasing inpatient length of stay, non-participation in rehabilitation and regions with lower hospital density were positively associated with an increase in care dependency. CONCLUSIONS: Several characteristics on patient and regional level associated with the outcome were identified. Variation in the increase in care dependency after hip fracture appeared to be attributable primarily to patient characteristics. Variation on regional level was only modest.

Metabolic factors and hip fracture risk in a large Austrian cohort study.

To explore the association of incident hip fractures with metabolic syndrome (MetS) and its single components, we designed a prospective cohort study of hip fracture incidence among 117,053 participants of a population-based health surveillance program in Vorarlberg, the westernmost Austrian province. Incident hip fractures were recorded between 5 and 10 years after inclusion at baseline from 2003 to 2009. Applying Cox proportional hazard models for each MetS component and for a composite z-score for MetS, hazards for fracture were estimated in quintiles, as continuous z-score variables, and as pathological cut off values. Mean age was 50.1 ± 15.6 years at baseline, 5-10 years after which 947 incident hip fractures occurred. An association of a higher composite MetS score with decreased hip fracture risk was observed in women (HR 0.80, 95%-CI 0.88-0.96, p < 0.01) which disappeared upon adjustment for BMI. BMI was inversely associated with hip fracture risk in women and men (HR for the highest compared with the lowest quintile: 0.83 (95%-CI: 0.63-1.10, p trend < 0.05) and 0.55 (95%-CI: 0.38-0.79, p trend < 0.001), respectively). Only in women, hip fracture risk was reduced at high cholesterol levels (HR for the highest relative to the lowest quintile: 0.64, 95%-CI: 0.48-0.84, p trend < 0.05) and in hypercholesterolemic patients (HR 0.82, 95%-CI: 0.67-0.99, p < 0.05), but elevated in hyperglycemic patients (HR 1.33, 95%-CI: 1.05-1.70, p < 0.05). Hypertriglyceridemia was associated with increased male hip fracture risk (HR 1.33, 95%-CI: 1.03-1.72, p < 0.05). The inverse association between the MetS and hip fracture risk is mainly driven by one single component, namely BMI.

Correction to: Lazy Sundays: role of day of the week and reactivity on objectively measured physical activity in older people.

[This corrects the article DOI: 10.1186/s11556-019-0226-1.].

Comparison of wait times across the breast cancer treatment pathway among screened women undergoing organized breast assessment versus usual care.

OBJECTIVE: The benefit of organized breast assessment on wait times to treatment among asymptomatic women is unknown. The Ontario Breast Screening Program (OBSP) offers screening and organized assessment through Breast Assessment Centres (BAC). This study compares wait times across the treatment pathway among screened women diagnosed with breast cancer through BAC and usual care (UC). METHODS: A retrospective design identified two concurrent cohorts of postmenopausal women aged 50-69 within the OBSP diagnosed with screen-detected invasive breast cancer and assessed in BAC (n = 2010) and UC (n = 1844) between 2002 and 2010. Demographic characteristics were obtained from the OBSP. Medical chart abstraction provided prognostic and treatment data. Multinomial logistic regression examined associations of assessment type with wait times from abnormal mammogram to surgery, chemotherapy or radiotherapy. RESULTS: Compared with through UC, postmenopausal women diagnosed through BAC were significantly less likely to have longer wait times (days) from an abnormal mammogram to definitive surgery (> 89 vs. ≤ 47; OR = 0.63; 95% CI = 0.52-0.77), from final surgery to radiotherapy (> 88 vs. ≤ 55; OR = 0.71; 95% CI = 0.54-0.93) and from final chemotherapy to radiotherapy (> 41 vs. ≤ 28; OR = 0.52; 95% CI = 0.36-0.76). Conversely, women assessed through BAC compared with through UC were more likely to experience longer wait times from final surgery to chemotherapy (> 64 vs. ≤ 40; OR = 1.49; 95% CI = 1.04-2.14). CONCLUSION: Shorter wait times to most treatments for postmenopausal women diagnosed in BAC further supports that women with an abnormal mammogram should be managed through organized assessment. Continued evaluation of factors influencing wait times to treatment is essential for quality improvement and patient outcomes.