Patients' and physicians' beliefs and attitudes towards integrating personalized risk estimates into patient education about left ventricular assist device therapy.

BACKGROUND: Personalized risk (PR) estimates may enhance clinical decision making and risk communication by providing individualized estimates of patient outcomes. We explored stakeholder attitudes toward the utility, acceptability, usefulness and best-practices for integrating PR estimates into patient education and decision making about Left Ventricular Assist Device (LVAD). METHODS AND RESULTS: As part of a 5-year multi-institutional AHRQ project, we conducted 40 interviews with stakeholders (physicians, nurse coordinators, patients, and caregivers), analyzed using Thematic Content Analysis. All stakeholder groups voiced positive views towards integrating PR in decision making. Patients, caregivers and coordinators emphasized that PR can help to better understand a patient's condition and risks, prepare mentally and logistically for likely outcomes, and meaningfully engage in decision making. Physicians felt it can improve their decision making by enhancing insight into outcomes, enhance tailored pre-emptive care, increase confidence in decisions, and reduce bias and subjectivity. All stakeholder groups also raised concerns about accuracy, representativeness and relevance of algorithms; predictive uncertainty; utility in relation to physician's expertise; potential negative reactions among patients; and overreliance. CONCLUSION: Stakeholders are optimistic about integrating PR into clinical decision making, but acceptability depends on prospectively demonstrating accuracy, relevance and evidence that benefits of PR outweigh potential negative impacts on decision making quality.

Performance of a Risk Analytic Tool (Index of Tissue Oxygen Delivery "IDO2") in Pediatric Cardiac Intensive Care Unit of a Developing Country.

Objective: To determine the performance of a commercially available risk analytic tool (IDO2) to estimate the risk for SVO2 < 40% in patients admitted in cardiac intensive care unit (CICU). Methods: Medical and T3 records of all patients (aged 1 day to 12 years, weight >2 kg) who received care in the CICU between October 1st, 2019 and October 1st, 2020, had SvO2 lab(s) drawn during CICU course and whose data was transmitted to T3, were included. The average IDO2 Index was computed in the 30-min period immediately prior to each SvO2 measurement and used as a predictor score for SvO2 < 40%. Results: A total of 69 CICU admissions from 65 patients, median age 9.3 months (interquartile range 20.8) were identified. Surgical and medical patients were 61 (88%) and 8 (12%) respectively; 4 (5.7%) patients had single ventricle physiology. Tetralogy of Fallot n = 23 (33.3%) and ventricular septal defects 17 (24.6%) were major cardiac diagnosis. Sixty-one (89.9%) of the admissions were successfully discharged from the hospital. Of the 187-total included SvO2 labs, 17 (9%) were <40%. The AUC of estimating SvO2 < 40% IDO2 was 0.87 [confidence interval (CI): 0.79-0.94]. Average IDO2 above 75 had the highest absolute risk (42.11, CI: 20.25-66.50) and highest RR (4.63, CI: 2.31-9.28, p-value < 0.0001) of SvO2 < 40%. Conclusion: IDO2 performed well in estimating low SvO2 (<40%) in pediatric patients presenting to a CICU in a low resource setting. Future work is needed to determine the effect of this risk analytic tool on clinical outcomes in such a setting.

Genetic clinicians' confidence in BOADICEA comprehensive breast cancer risk estimates and counselees' psychosocial outcomes: A prospective study.

Counseling for familial breast cancer focuses on communicating the gene test result (GENE) to counselees, but risk prediction models have become more complex by including non-genetic risk factors (NGRF) and polygenic risk scores (PRS). We examined genetic clinicians' confidence in counseling and counselees' psychosocial outcomes, using the BOADICEA risk prediction tool with different categories of risk factors as input. A prospective observational study in Dutch, French and German genetic clinics was performed including 22 clinicians, and 406 of 460 (88.3%) eligible cancer-unaffected women at high breast cancer risk assessed at pre-test and 350 (76.1%) at post-test. We performed multilevel analyses accounting for the clinician, and counselees' characteristics. Overall, risk estimates category by GENE versus GENE+ NGRF, or GENE+NGRF+PRS differed in 11% and 25% of counselees, respectively. In multilevel analyses, clinicians felt less confident in counseling when the full model provided lower breast cancer risks than GENE (i.e., in 8% of cases). Older counselees expressed higher breast cancer risk perception and worries about the hereditary predisposition when the full model provided higher breast cancer risks than GENE only. Genetic clinicians appear confident with breast cancer risk comprehensive models, which seem only to affect perceptions of older counselees.

Risk Estimates of Agricultural Injuries and Fatalities in Central India.

The purpose of the study was to describe the nature, magnitude, causes, and economic impact, and also to evaluate risk estimates of agricultural incidents occurring during 2012-2013 in Madhya Pradesh, India. The study was carried out in 360 villages in 9 districts of Madhya Pradesh namely Datia, Shivpuri, Balaghat, Barwani, Indore, Jhabua, Narshigpur, Satna, and Bhopal. A total of 92 793 agricultural workers participated in a survey of agricultural incidents. Of 21 agricultural incidents, 14% were fatal and 86% non-fatal in nature. The agricultural incident rates were 0.23/1000 agricultural worker per year and 0.2/1000 agricultural machines per year. The annual monetary loss due to deaths in agricultural incidents in Madhya Pradesh was estimated to be Rs. 16 935.4 lakhs. The economic loss due to agricultural incidents is more severe that resulted in significant loss to the workers due to absence from work. Hence, it is important to map down the cause and taking preventive measures to reduce the losses.

Omega-3 Fatty Acids in Erythrocyte Membranes as Predictors of Lower Cardiovascular Risk in Adults without Previous Cardiovascular Events.

Background: This study investigated the association of omega-3 polyunsaturated fatty acids (n-3 PUFA) within erythrocyte membranes and cardiovascular risk assessed by three different estimates. Methods: Inclusion criteria were individuals of both sexes, 30 to 74 years, with at least one cardiovascular risk factor, and no previous cardiovascular events (n = 356). Exclusion criteria were individuals with acute or chronic severe diseases, infectious diseases, pregnant, and/or lactating women. Plasma biomarkers (lipids, glucose, and C-reactive protein) were analyzed, and nineteen erythrocyte membrane fatty acids (FA) were identified. The cardiovascular risk was estimated by Framingham (FRS), Reynolds (RRS), and ACC/AHA-2013 Risk Scores. Three patterns of FA were identified (Factor 1, poor in n-3 PUFA), (Factor 2, poor in PUFA), and (Factor 3, rich in n-3 PUFA). Results: Total cholesterol was inversely correlated with erythrocyte membranes C18:3 n-3 (r = -0.155; p = 0.004), C22:6 n-3 (r = -0.112; p = 0.041), and total n-3 (r = -0.211; p < 0.001). Total n-3 PUFA was associated with lower cardiovascular risk by FRS (OR = 0.811; 95% CI= 0.675-0.976). Regarding RRS, Factor 3 was associated with 25.3% lower odds to have moderate and high cardiovascular risk (OR = 0.747; 95% CI = 0.589-0.948). The ACC/AHA-2013 risk score was not associated with isolated and pooled FA. Conclusions:n-3 PUFA in erythrocyte membranes are independent predictors of low-risk classification estimated by FRS and RRS, which could be explained by cholesterol-lowering effects of n-3 PUFA.

Value of Coronary Calcium Scoring in Symptomatic and Asymptomatic Coronary Artery Disease Patients.

AIM AND OBJECTIVE: The study aimed to estimate the relationship between Coronary Calcium Scoring (CCS) and the presence of different degrees of obstructive coronary artery disease (CAD) to avoid unnecessary examinations and hence unnecessary radiation exposure and contrast injection. BACKGROUND: Coronary Calcium Scoring (CCS) is a test that uses x-ray equipment to produce pictures of the coronary arteries to determine the degree of its narrowing by the build-up of calcified plaques. Despite the lack of definitive data linking ionizing radiation with cancer, the American Heart Association supports widely that practitioners of Computed tomography Coronary Angiography (CTCA) should keep "patient radiation doses as low as reasonably achievable but consistent with obtaining the desired medical information". METHODS: Data obtained from 275 CTCA examinations were reviewed. Radiation effective doses were estimated for both CCS and CTCA, and measures to keep them as low as possible were presented. CCS and Framingham risk estimates were compared to obtain the final results of CTCA to detect sensitivity and specificity of each one in detecting obstructive lesions. RESULTS: CCS is a strong discriminator for obstructive CAD with high sensitivity and specificity and correlates well with the degree of obstruction even more than Framingham risk estimate, which has high sensitivity and low specificity. CONCLUSION: CCS helps to reduce the effective radiation dose if properly evaluated to skip unnecessary CTCA if obstructive lesions are unlikely, and this as a test does not use contrast material, thus harmful effect on the kidney will be avoided as most of the coronary atherosclerotic patients have renal problems.

Vitamin D Receptor Polymorphisms and Cancer.

Increasing scientific evidence supports the link between vitamin D and cancer risk. The active metabolite 1,25(OH)2D exerts its activity by binding to the vitamin D receptor (VDR), an intracellular receptor that mediates transcriptional activation and repression of target genes. The binding of 1,25(OH)2D to VDR is able to regulate hundreds of different genes. VDR is active in virtually all tissues including the colon, breast, lung, ovary, bone, kidney, parathyroid gland, pancreatic b-cells, monocytes, T lymphocytes, melanocytes, keratinocytes, and also cancer cells.The relevance of VDR gene restriction fragment length polymorphisms for various types of cancer has been investigated by a great number of studies.We have carried out a systematic review of the literature to analyze the relevance of more VDR polymorphisms (Fok1, Bsm1, Taq1, Apa1, and Cdx2) for individual malignancies considering ethnicity as a key factor for heterogeneity.Up to December 2018, we identified 176 independent studies with data to assess the risk of breast, prostate, colorectal, skin (melanoma and non-melanoma skin cancer), lung, ovarian, kidney, bladder, gallbladder, esophageal, thyroid, head and neck, liver and pancreatic cancer, oral squamous cell carcinoma, non-Hodgkin lymphoma, multiple myeloma and sarcoma.Significant associations with VDR polymorphisms have been reported for prostate (Fok1, Bsm1, Taq1, Apa1, Cdx2), breast (Fok1, Bsm1, Taq1, Apa1, CdX2), colorectal (Fok1, Bsm1, Taq1, Apa1), and skin cancer (Fok1, Bsm1, Taq1). Very few studies reported risk estimates for the other cancer sites.Conflicting data have been reported for most malignancies, and at present, it is still not possible to make any definitive statements about the importance of the VDR genotype for cancer risk. It seems probable that other factors such as ethnicity, phenotype, 25(OH)D plasma levels, and UV radiation exposure play a role as confounding factors and introduce heterogeneity.To conclude, there is some indication that VDR polymorphisms may modulate the risk of some cancer sites and in future studies VDR genetic variation should be integrated also with assessment of vitamin D status and stratified by ethnicity.

Health impacts of long-term ozone exposure in China over 2013-2017.

Increasing ozone concentrations are becoming a severe problem for air pollution in China and have an adverse impact on human health. Here we evaluate premature deaths attributable to long-term exposure to ambient ozone in China between 2013 and 2017 with an air quality model at 5 km resolution and the latest estimates of the relative risk to health. We use a modified inverse distance weighting method to bias-correct the key model-simulated ozone metrics. We find that on a 5-year average basis there are 186,000 (95% Confidence Interval: 129,000-237,000) respiratory deaths and 125,000 (42,000-204,000) cardiovascular deaths attributable to ozone exposure. Sichuan exhibits the largest per capita respiratory mortality (0.31‰) among all provinces. We find that there are 73,000 (51,000-93,000) premature respiratory deaths in urban areas, accounting for 39% of total deaths. Between 2013 and 2017 the population-weighted annual average maximum daily 8-h average ozone (AMDA8) and premature respiratory deaths increased by 14% and 31%, respectively, at a national level. Changes in precursor emissions explain most of these increases, with differences in meteorology accounting for 21% and 16% respectively. Interannual variations in population-weighted ozone and premature respiratory deaths at a provincial level are much larger than those at a national level, particularly in northern, central and eastern China. These findings emphasize that ozone should be an important focus of future air quality policies in China, and tighter controls of precursor emissions are urgently needed.

Frequency of Breast Cancer Thoughts and Lifetime Risk Estimates: A Multi-Institutional Survey of Women Undergoing Screening Mammography.

PURPOSE: The aim of this study was to quantify women's personal estimates of breast cancer risk and frequency of breast cancer thoughts. METHODS: Women from five medical centers were surveyed before their screening mammographic examinations. Participants were queried on their baseline anxiety and demographics, then asked how many times in the past month they had thought about developing breast cancer. Participants were then notified of the 12% lifetime average breast cancer risk and asked to estimate their personal risk both subjectively and objectively. Comparisons were made between responses and the demographic variables. RESULTS: There were 2,747 completed surveys for analysis. Women reported 2.5 ± 6.6 thoughts of cancer on average in the prior month. More frequent thoughts were associated with personal or family history of breast cancer, greater anxiety, and genetic testing (P < .001 for all). Among women without cancer risk factors (n = 1,412), there were 1.4 cancer thoughts per month, which was associated with baseline anxiety (P < .001). The median lifetime breast cancer risk was 12% among all women, with 37.4% high risk (>20%) estimates. Demographic variables associated with increased risk estimates were previous cancer diagnosis, higher education, genetic testing, white race, increased age, and greater anxiety (P < .01 for all). Among women with no risk factors, the median estimated risk was 10%, with 16.7% providing estimates greater than 20%, associated with baseline anxiety and white race (P < .001 for both). CONCLUSIONS: Increased breast cancer thoughts and personal cancer estimates are associated with specific patient demographics. Improved understanding of patient perspectives could improve shared decision-making discussions and thus patient care.

Questioning Estimates of Natural Pandemic Risk.

The central argument in this article is that the probability of very large natural pandemics is more uncertain than either previous analyses or the historical record suggest. In public health and health security analyses, global catastrophic biological risks (GCBRs) have the potential to cause "sudden, extraordinary, widespread disaster," with "tens to hundreds of millions of fatalities." Recent analyses focusing on extreme events presume that the most extreme natural events are less likely than artificial sources of GCBRs and should receive proportionately less attention. These earlier analyses relied on an informal Bayesian analysis of naturally occurring GCBRs in the historical record and conclude that the near absence of such events demonstrates that they are rare. This ignores key uncertainties about both selection biases inherent in historical data and underlying causes of the nonstationary risk. The uncertainty is addressed here by first reconsidering the assumptions in earlier Bayesian analyses, then outlining a more complete analysis accounting for several previously omitted factors. Finally, relationships are suggested between available evidence and the uncertain question at hand, allowing more rigorous future estimates.

Evolving Epidemiology of Japanese Encephalitis: Implications for Vaccination.

PURPOSE OF REVIEW: We examine the present global burden of Japanese encephalitis (JE) in endemic populations, summarize published cases in travelers since 2009, examine current guidelines for vaccination for international travelers, and consider challenges in prevention of this vector-borne disease. RECENT FINDINGS: We identified 11 JE cases in travelers that were published in peer-reviewed literature since 2009. JE incidence in endemic countries appears to be declining but the number of JE cases reported to the World Health Organization (WHO) varied from estimates derived from other published reports based on serosurveys or sentinel surveillance. Current JE vaccines appear to be safe and are not associated with delayed hypersensitivity in contrast to the older mouse brain vaccine. Given differences between WHO-reported cases and local surveillance data, future research on true incidence is needed. Regular assessment will inform JE risk in travelers. National and international guidelines on JE vaccination varied; we suggest areas for improvement.

Risk communication in genetic counseling: Exploring uptake and perception of recurrence numbers, and their impact on patient outcomes.

Providing recurrence numbers is often considered a fundamental component of genetic counseling. We sought to fill knowledge gaps regarding how often patients actively seek recurrence numbers, and how they impact patient outcomes. We conducted a retrospective chart review at a clinic where patients routinely complete the Genetic Counseling Outcomes Scale (GCOS, measuring empowerment) pre (T1)/post (T2) appointment. Using analysis of covariance, we evaluated the effect on T2 GCOS score of: (1) receiving recurrence numbers and (2) patient perception of recurrence numbers. Recurrence numbers were a primary indication for 134/300 patients (45%). After counseling about etiology and risk-reducing strategies, 116 patients (39%) opted to receive recurrence numbers, with most (n = 64, 55%) perceiving the number to be lower than expected. There was no difference in T2 GCOS scores between those who: (1) received recurrence numbers vs those who did not, or (2) perceived the number to be lower than expected vs those with other perceptions. However, a subset of patients who did not receive recurrence numbers had larger increases in GCOS scores. Our data provide impetus to question the assumption that recurrence numbers should be routinely provided in genetic counseling, and show that in naturalistic practice, optimal patient outcomes are not contingent on receipt of recurrence numbers.

Environmental risk factors associated with low birth weight: The case study of the Haifa Bay Area in Israel.

BACKGROUND: Low birth weight (LBW) is known to be associated with infant mortality and postnatal health complications. Previous studies revealed strong relationships between LBW rate and several socio-demographic factors, including ethnicity, maternal age, and family income. However, studies of association between LBW rate and environmental risk factors remain infrequent. STUDY METHODS: We retrieved a geo-referenced data set, containing 7216 individual records of children born in 2015 in the Haifa Bay Area in Israel. Using this dataset, we analysed factors affecting LBW prevalence by applying two alternative techniques: analysis of LBW rates in small census area (SCAs) and more recently developed double kernel density (DKD) relative risk (RR) estimates. RESULTS: In the SCA models, LBW rate was found to be associated with proximity to petrochemical industries (B=-0.26, 95%CI=-0.30, -0.22), road density (B=0.05, 95%CI=0.02, 0.08), distance to the seashore (B=0.17, 95%CI=0.14, 0.22), PM2.5 (B=0.06, 95%CI=0.04, 0.09) and NOx (B=0.10, 95%CI=0.06, 0.13) exposure estimates. Although similar factors emerged in the DKD models as well, in most cases, the effects of these factors in the latter models were found to be stronger: proximity to petrochemical industries (B=-0.48, 95%CI= -0.51, -0.30), road density (B=0.05, 95%CI=0.02, 0.08), distance to the seashore (B=0.24, 95%CI=0.21, 0.27), PM2.5 (B=0.08, 95%CI=0.05, 0.10) and NOx (B=0.20, 95%CI=0.17, 0.23) exposure estimates. In addition, elevation above the sea level was found to be statistically significant in spatial dependence models estimated for both DKD and SCA rates (P < 0.01). CONCLUSION: The analysis revealed an excess LBW rate in residential areas located close to petrochemical industries and a protective effect of seashore proximity and elevation above the sea level on the LBW rate. We attribute the latter finding to the moderating effect of elevated seashore locations on outdoor temperatures during the hot summer season.

Dynamic Risk Estimates of Outcome in Chinese Patients with Well-Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation.

BACKGROUND: This study was conducted to compare the staging systems for the prediction of long-term disease status in patients with well-differentiated thyroid carcinoma (WDTC), and to find out the earliest postoperative period predictor of long-term persistence/recurrence of disease. METHODS: Patients with WDTC (n = 356; Mage = 41.5 ± 12.7 years) followed for at least five years (12.3 ± 5.0 years) after thyroidectomy and 131I remnant ablation at a tertiary regional hospital in Taiwan were retrospectively studied. Each patient was risk stratified using the American Joint Cancer Committee (stage I-IV) and American Thyroid Association (low, intermediate, and high risk) staging systems after operation and first 131I remnant ablation and using response to initial therapy reclassification (RTR; excellent, indeterminate, biochemical incomplete, and structural incomplete response) system, which is determined 6-24 months after the first 131I ablation. The clinical outcome was defined as no evidence of disease (NED; suppressed thyroglobulin [Tg] <0.5 ng/mL, stimulated Tg <1 ng/mL, and no structural detectable disease), biochemical persistent disease (BPD; suppressed Tg ≥0.5 ng/mL or stimulated Tg ≥1 ng/mL in the absence of structural disease), structural persistent disease (SPD; locoregional or distant metastases with any Tg level), or recurrent disease (RD; biochemical or structural disease identified after a period of NED). RESULTS: At the time of final follow-up, 78.4% (n = 279) of the patients had NED, 9.3% (n = 33) had BPD, 10.1% (n = 36) had SPD, and 2.2% (n = 8) developed RD. All three systems could predict the increasing trend of SPD and the decreasing trend of NED with advancing stage of disease. However, the ATA risk estimates could be significantly refined by the RTR system, especially for the ATA high-risk group, in which 29.2% developed SPD/RD during follow-up. The RTR system reduced the likelihood of finding SPD/RD to 3.7% in those demonstrating an excellent response to therapy, and increased the likelihood to 78.6% in those demonstrating a structural incomplete response. Among the earliest postoperative factors, only the Tg level at the first 131I ablation could predict long-term persistence/recurrence. CONCLUSIONS: The results highly support incorporating the RTR system to modify the initial risk estimate during follow-up among Chinese patients with WDTC.

The Impact of Disease and Drugs on Hip Fracture Risk.

We report the risks of a comprehensive range of disease and drug categories on hip fracture occurrence using a strict population-based cohort design. Participants included the source population of a Swedish county, aged ≥50 years (n = 117,494) including all incident hip fractures during 1 year (n = 477). The outcome was hospitalization for hip fracture (ICD-10 codes S72.0-S72.2) during 1 year (2009-2010). Exposures included: prevalence of (1) inpatient diseases [International Classification of Diseases (ICD) codes A00-T98 in the National Patient Register 1987-2010] and (2) prescribed drugs dispensed in 2010 or the year prior to fracture. We present age- and sex-standardized risk ratios (RRs), risk differences (RDs) and population attributable risks (PARs) of disease and drug categories in relation to hip fracture risk. All disease categories were associated with increased risk of hip fracture. Largest risk ratios and differences were for mental and behavioral disorders, diseases of the blood and previous fracture (RRs between 2.44 and 3.00; RDs (per 1000 person-years) between 5.0 and 6.9). For specific drugs, strongest associations were seen for antiparkinson (RR 2.32 [95 % CI 1.48-1.65]; RD 5.2 [1.1-9.4]) and antidepressive drugs (RR 1.90 [1.55-2.32]; RD 3.1 [2.0-4.3]). Being prescribed ≥10 drugs during 1 year incurred an increased risk of hip fracture, whereas prescription of cardiovascular drugs or ≤5 drugs did not appear to increase risk. Diseases inferring the greatest PARs included: cardiovascular diseases PAR 22 % (95 % CI 14-29) and previous injuries (PAR 21 % [95 % CI 16-25]; for specific drugs, antidepressants posed the greatest risk (PAR 16 % [95 % CI 12.0-19.3]).

The need for transparency and reproducibility in documenting values for regulatory decision making and evaluating causality: The example of formaldehyde.

Reproducibility and transparency in scientific reporting is paramount to advancing science and providing the foundation required for sound regulation. Recent examples demonstrate that pivotal scientific findings cannot be replicated, due to poor documentation or methodological bias, sparking debate across scientific and regulatory communities. However, there is general agreement that improvements in communicating and documenting research and risk assessment methods are needed. In the case of formaldehyde, the peer-review conducted by a National Academy of Sciences (NAS) Committee questioned the approaches used by the Integrated Risk Information System (IRIS) in developing draft unit risk values. Using the original data from the key study (Beane Freeman et al., 2009) and documentation provided in the draft IRIS profile, we attempted to duplicate the reported inhalation unit risk values and address the NAS Committee's questions regarding application of the appropriate dose-response model. Overall, documentation of the methods lacked sufficient detail to allow for replication of the unit risk estimates, specifically for Hodgkin lymphoma and leukemias, the key systemic endpoints selected by IRIS. The lack of apparent exposure-response relationships for selected endpoints raises the question whether quantitative analyses are appropriate for these endpoints, and if so, how results are to be interpreted.

Dietary patterns and the risk of CVD and all-cause mortality in older British men.

Dietary patterns are a major risk factor for cardiovascular morbidity and mortality; however, few studies have examined this relationship in older adults. We examined prospective associations between dietary patterns and the risk of CVD and all-cause mortality in 3226 older British men, aged 60-79 years and free from CVD at baseline, from the British Regional Heart Study. Baseline FFQ data were used to generate thirty-four food groups. Principal component analysis identified dietary patterns that were categorised into quartiles, with higher quartiles representing higher adherence to the dietary pattern. Cox proportional hazards examined associations between dietary patterns and risk of all-cause mortality and cardiovascular outcomes. We identified three interpretable dietary patterns: 'high fat/low fibre' (high in red meat, meat products, white bread, fried potato, eggs), 'prudent' (high in poultry, fish, fruits, vegetables, legumes, pasta, rice, wholemeal bread, eggs, olive oil) and 'high sugar' (high in biscuits, puddings, chocolates, sweets, sweet spreads, breakfast cereals). During 11 years of follow-up, 899 deaths, 316 CVD-related deaths, 569 CVD events and 301 CHD events occurred. The 'high-fat/low-fibre' dietary pattern was associated with an increased risk of all-cause mortality only, after adjustment for confounders (highest v. lowest quartile; hazard ratio 1·44; 95 % CI 1·13, 1·84). Adherence to a 'high-sugar' diet was associated with a borderline significant trend for an increased risk of CVD and CHD events. The 'prudent' diet did not show a significant trend with cardiovascular outcomes or mortality. Avoiding 'high-fat/low-fibre' and 'high-sugar' dietary components may reduce the risk of cardiovascular events and all-cause mortality in older adults.

Patients' perceptions of mortality risk for localized prostate cancer vary markedly depending on their treatment strategy.

Treatment choice for localized prostate cancer (PCa) is a controversial issue, and mortality risk is probably the most decisive factor in this regard. The study aimed to compare prostate-cancer-specific mortality risk estimates for different treatment options assigned by patients managed with active surveillance (AS), radical prostatectomy (RP) and patients who had discontinued AS (DAS). Patients initially managed with AS or RP (N = 370) were matched according to length of therapy. All patients completed mailed questionnaires assessing their mortality risk estimates (in %) and prostate-cancer-specific anxiety. Differences in risk estimates among the three treatment groups were analyzed using ANOVA, relationships of clinical and psychosocial variables with risk estimates using standard multiple regression. In all treatment groups, the prostate- cancer-specific mortality risk was overestimated. This applied whether it was the patient's own treatment or the alternative treatment option. RP patients assigned a mortality risk to AS that was almost three times higher than that assigned to RP (50.9 ± 25.0 vs. 17.8 ± 19.7, d = 1.48; p < 0.001). Anxiety was significantly associated with risk estimates for AS (p = 0.008) and RP (p = 0.001). Compared with clinical data that suggest that the prostate-cancer-specific mortality risk for AS is low and does not significantly differ from that for RP, patients strongly overestimated the mortality risk. This was most markedly so in RP patients, who drastically overestimated the benefits of RP compared to the risk of AS. This overestimation could increase overtreatment and should therefore be corrected by better patient education.

Prevalence and clinical significance of neutropenia discovered in routine complete blood cell counts: a longitudinal study.

BACKGROUND: Neutropenia, defined as an absolute blood neutrophil count (ANC) <1.5 G L(-1) , may accompany a variety of diseases. However, the clinical significance of neutropenia detected in a routine complete blood cell count is poorly understood. METHODS: Using a primary care resource, comprising more than 370 000 individuals, we assessed the association with a number of previously recognized conditions as well as all-cause mortality in the 4 years following the identification of neutropenia. By matching laboratory data with Danish nationwide health registers, risk estimates were assessed. RESULTS: Neutropenia was observed in approximately 1% of all individuals and was associated dose dependently with viral infections, haematological malignancies (but not autoimmune disorders or solid cancers) and mortality. Neutropenia was particularly associated with HIV, acute leukaemias and myelodysplastic syndromes. Odds ratios [95% confidence interval (CI)] for viral infections were 2.32 (1.84-2.91), 2.80 (2.20-3.57) and 4.77 (3.22-7.07) for subnormal (≥1.5-1.8 G L(-1) ), mild (≥1.0-1.5 G L(-1) ) and moderate-severe (≥0.0-1.0 G L(-1) ) neutropenic individuals, respectively (all P < 0.001). Likewise, odds ratios (95% CI) for haematological malignancies were 3.23 (2.35-4.45), 8.69 (6.58-11.47) and 46.03 (33.98-62.35 ), for the same neutropenia levels, respectively (all P < 0.001). Thus, the lower the ANC, the greater the likelihood of these diseases. The relative risk estimates observed for severe neutropenia corresponded to absolute risks of haematological malignancies and mortality from any cause of 40% and >50%, respectively. CONCLUSIONS: Neutropenia is an ominous sign necessitating careful follow-up. The risk estimates presented here support focusing attention to viral diseases and haematological malignancies when neutropenia is observed.

A Retrospective Evaluation of the Benefit of Referring Pediatric Cancer Patients to an External Proton Therapy Center.

BACKGROUND: Pediatric cancer patients requiring radiation therapy (RT) have been routinely assessed and referred to proton therapy (PT) at an external institution. The benefit of the delivered PT compared to the state-of-the-art intensity modulated x-ray RT (XT) at the home institution was evaluated. PROCEDURE: Twenty-four consecutive children referred for PT during 2010-2013 for craniospinal (CSI, n = 10), localized intracranial (IC, n = 7), head/neck (HN, n = 4) or parameningeal (PM, n = 3) lesions were included. The median age was 8 years (2-16 years). XT plans were generated for each patient, blinded to the PT delivered. Dosimetry, estimated growth hormone deficiency (GHD), and neurocognitive dysfunction (NCD) risks were compared for PT and XT (Wilcoxon). RESULTS: PT started (median) 5 weeks (± 1.3 weeks, 95% CI) after referral. For CSI patients, PT was clearly superior to XT plans with median dose reductions for the heart, lungs and thyroid of 17, 2.5 and 18 Gy, respectively (P = 0.005). The median estimated NCD and GHD risks were 1-3 (max 16) and 2 (max 61) percentage points, respectively, lower for PT compared to XT. The median of the mean doses to the brain, cochleae and pituitary gland was lower with PT than XT for the IC, H/N and PM patients (P < 0.039). For a single IC patient, the dose to hippocampi and optic chiasm was higher for PT compared to XT. CONCLUSIONS: PT clearly benefitted the patients studied, except for IC disease where differences between PT and XT were modest, and comparative PT and XT treatment planning is warranted prior to referral.