Defining Catastrophic Costs and Comparing Their Importance for Adverse Tuberculosis Outcome with Multi-Drug Resistance: A Prospective Cohort Study,Peru

Background

Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TB-affected households) may worsen poverty and health. Extreme TB-associated costs have been termed “catastrophic” but are poorly defined. We studied TB-affected households'' hidden costs and their association with adverse TB outcome to create a clinically relevant definition of catastrophic costs.

Methods and Findings

From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2–4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related costs. Costs were expressed as a proportion of the household''s annual income. In poorer households, costs were lower but constituted a higher proportion of the household''s annual income: 27% (95% CI = 20%–43%) in the least-poor houses versus 48% (95% CI = 36%–50%) in the poorest. Adverse TB outcome was defined as death, treatment abandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a defined treatment outcome had an adverse outcome. Total costs ≥20% of household annual income was defined as catastrophic because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95% CI = 43%–61%] versus 38% [95% CI = 34%–41%], p<0.003). Adverse outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95% CI = 4.7–15], p<0.001), previous TB (OR = 2.1 [95% CI = 1.3–3.5], p = 0.005), days too unwell to work pre-treatment (OR = 1.01 [95% CI = 1.00–1.01], p = 0.02), and catastrophic costs (OR = 1.7 [95% CI = 1.1–2.6], p = 0.01). The adjusted population attributable fraction of adverse outcomes explained by catastrophic costs was 18% (95% CI = 6.9%–28%), similar to that of MDR TB (20% [95% CI = 14%–25%]). Sensitivity analyses demonstrated that existing catastrophic costs thresholds (≥10% or ≥15% of household annual income) were not associated with adverse outcome in our setting. Study limitations included not measuring certain “dis-saving” variables (including selling household items) and gathering only 6 mo of costs-specific follow-up data for MDR TB patients.

Conclusions

Despite free TB care, having TB disease was expensive for impoverished TB patients in Peru. Incurring higher relative costs was associated with adverse TB outcome. The population attributable fraction indicated that catastrophic costs and MDR TB were associated with similar proportions of adverse outcomes. Thus TB is a socioeconomic as well as infectious problem, and TB control interventions should address both the economic and clinical aspects of this disease. Please see later in the article for the Editors'' Summary     

A Prospective Cohort Study to Examine the Association between Dietary Patterns and Depressive Symptoms in Older Chinese People in Hong Kong

Introduction

Dietary patterns are culturally specific and there is limited data on the association of dietary patterns with late-life depression in Chinese. This study examined the associations between dietary patterns and baseline and subsequent depressive symptoms in community-dwelling Chinese older people in Hong Kong.

Methods

Participants aged ≥65 year participating in a cohort study examining the risk factors for osteoporosis completed a validated food frequency questionnaire at baseline between 2001 and 2003. Factor analysis was used to identify three dietary patterns: “vegetables-fruits” pattern, “snacks-drinks-milk products” pattern, and “meat-fish” pattern. Depressive symptoms were measured at baseline and 4-year using the validated Geriatric Depression Scale. Multiple logistic regression was used for cross-sectional analysis (n = 2,902) to assess the associations between dietary patterns and the presence of depressive symptoms, and for longitudinal analysis (n = 2,211) on their associations with 4-year depressive symptoms, with adjustment for socio-demographic and lifestyle factors.

Results

The highest quartile of “vegetables-fruits” pattern score was associated with reduced likelihood of depressive symptoms [Adjusted OR = 0.55 (95% CI: 0.36–0.83), p_trend = 0.017] compared to the lowest quartile at baseline. Similar inverse trend was observed for the highest quartile of “snacks-drinks-milk products” pattern score [Adjusted OR = 0.41 (95% CI: 0.26–0.65), p_trend<0.001] compared to the lowest quartile. There was no association of “meat-fish” pattern with the presence of depressive symptoms at baseline. None of the dietary patterns were associated with subsequent depressive symptoms at 4-year.

Conclusion

Higher “vegetables-fruits” and “snacks-drinks-milk products” pattern scores were associated with reduced likelihood of baseline depressive symptoms in Chinese older people in Hong Kong. The longitudinal analyses failed to show any causal relationship between dietary patterns and depressive symptoms in this population.     

Beneficial Effect of Isoniazid Preventive Therapy and Antiretroviral Therapy on the Incidence of Tuberculosis in People Living with HIV in Ethiopia

Background

IPT with or without concomitant administration of ART is a proven intervention to prevent tuberculosis among PLHIV. However, there are few data on the routine implementation of this intervention and its effectiveness in settings with limited resources.

Objectives

To measure the level of uptake and effectiveness of IPT in reducing tuberculosis incidence in a cohort of PLHIV enrolled into HIV care between 2007 and 2010 in five hospitals in southern Ethiopia.

Methods

A retrospective cohort analysis of electronic patient database was done. The independent effects of no intervention, “IPT-only,” “IPT-before-ART,” “IPT-and-ART started simultaneously,” “ART-only,” and “IPT-after-ART” on TB incidence were measured. Cox-proportional hazards regression was used to assess association of treatment categories with TB incidence.

Results

Of 7,097 patients, 867 were excluded because they were transferred-in; a further 823 (12%) were excluded from the study because they were either identified to have TB through screening (292 patients) or were on TB treatment (531). Among the remaining 5,407 patients observed, IPT had been initiated for 39% of eligible patients. Children, male sex, advanced disease, and those in Pre-ART were less likely to be initiated on IPT. The overall TB incidence was 2.6 per 100 person-years. As compared to those with no intervention, use of “IPT-only” (aHR = 0.36, 95% CI = 0.19–0.66) and “ART-only” (aHR = 0.32, 95% CI = 0.24–0.43) were associated with significant reduction in TB incidence rate. Combining ART and IPT had a more profound effect. Starting IPT-before-ART (aHR = 0.18, 95% CI = 0.08–0.42) or simultaneously with ART (aHR = 0.20, 95% CI = 0.10–0.42) provided further reduction of TB at ∼80%.

Conclusions

IPT was found to be effective in reducing TB incidence, independently and with concomitant ART, under programme conditions in resource-limited settings. The level of IPT provision and effectiveness in reducing TB was encouraging in the study setting. Scaling up and strengthening IPT service in addition to ART can have beneficial effect in reducing TB burden among PLHIV in settings with high TB/HIV burden.     

Social and Emotional Values of Sounds Influence Human (Homo sapiens) and Non-Human Primate (Cercopithecus campbelli) Auditory Laterality

The last decades evidenced auditory laterality in vertebrates, offering new important insights for the understanding of the origin of human language. Factors such as the social (e.g. specificity, familiarity) and emotional value of sounds have been proved to influence hemispheric specialization. However, little is known about the crossed effect of these two factors in animals. In addition, human-animal comparative studies, using the same methodology, are rare. In our study, we adapted the head turn paradigm, a widely used non invasive method, on 8–9-year-old schoolgirls and on adult female Campbell''s monkeys, by focusing on head and/or eye orientations in response to sound playbacks. We broadcast communicative signals (monkeys: calls, humans: speech) emitted by familiar individuals presenting distinct degrees of social value (female monkeys: conspecific group members vs heterospecific neighbours, human girls: from the same vs different classroom) and emotional value (monkeys: contact vs threat calls; humans: friendly vs aggressive intonation). We evidenced a crossed-categorical effect of social and emotional values in both species since only “negative” voices from same class/group members elicited a significant auditory laterality (Wilcoxon tests: monkeys, T = 0 p = 0.03; girls: T = 4.5 p = 0.03). Moreover, we found differences between species as a left and right hemisphere preference was found respectively in humans and monkeys. Furthermore while monkeys almost exclusively responded by turning their head, girls sometimes also just moved their eyes. This study supports theories defending differential roles played by the two hemispheres in primates'' auditory laterality and evidenced that more systematic species comparisons are needed before raising evolutionary scenario. Moreover, the choice of sound stimuli and behavioural measures in such studies should be the focus of careful attention.     

Association between Melanocytic Nevi and Risk of Breast Diseases: The French E3N Prospective Cohort

Background

While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk.

Methods and Findings

We prospectively analyzed data from E3N, a cohort of French women aged 40–65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990–15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with “very many” nevi had a significantly higher breast cancer risk (HR = 1.13, 95% CI = 1.01–1.27 versus “none”; p _trend = 0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI = 3,674–4,649) per 100,000 women with “very many” nevi. The association was restricted to premenopausal women (HR = 1.40, p _trend = 0.01), even after full adjustment (HR = 1.34, p _trend = 0.03; p _homogeneity = 0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose–response relationships between number of nevi and history of biopsy-confirmed BBD (n = 5,169; p _trend<0.0001) and family history of breast cancer in first-degree relatives (n = 7,472; p _trend = 0.0003). The main limitations of our study include self-report of number of nevi using a qualitative scale, and self-reported history of biopsied BBD.

Conclusions

Our findings suggest associations between number of nevi and the risk of premenopausal breast cancer, BBD, and family history of breast cancer. More research is warranted to elucidate these relationships and to understand their underlying mechanisms. Please see later in the article for the Editors'' Summary     

The Relationship between Water,Sanitation and Schistosomiasis: A Systematic Review and Meta-analysis

Background

Access to “safe” water and “adequate” sanitation are emphasized as important measures for schistosomiasis control. Indeed, the schistosomes'' lifecycles suggest that their transmission may be reduced through safe water and adequate sanitation. However, the evidence has not previously been compiled in a systematic review.

Methodology

We carried out a systematic review and meta-analysis of studies reporting schistosome infection rates in people who do or do not have access to safe water and adequate sanitation. PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to 31 December 2013, without restrictions on year of publication or language. Studies'' titles and abstracts were screened by two independent assessors. Papers deemed of interest were read in full and appropriate studies included in the meta-analysis. Publication bias was assessed through the visual inspection of funnel plots and through Egger''s test. Heterogeneity of datasets within the meta-analysis was quantified using Higgins'' I².

Principal Findings

Safe water supplies were associated with significantly lower odds of schistosomiasis (odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.47–0.61). Adequate sanitation was associated with lower odds of Schistosoma mansoni, (OR = 0.59, 95% CI: 0.47–0.73) and Schistosoma haematobium (OR = 0.69, 95% CI: 0.57–0.84). Included studies were mainly cross-sectional and quality was largely poor.

Conclusions/Significance

Our systematic review and meta-analysis suggests that increasing access to safe water and adequate sanitation are important measures to reduce the odds of schistosome infection. However, most of the studies were observational and quality was poor. Hence, there is a pressing need for adequately powered cluster randomized trials comparing schistosome infection risk with access to safe water and adequate sanitation, more studies which rigorously define water and sanitation, and new research on the relationships between water, sanitation, hygiene, human behavior, and schistosome transmission.     

Common SNPs in FTO Gene Are Associated with Obesity Related Anthropometric Traits in an Island Population from the Eastern Adriatic Coast of Croatia

Background

Multiple studies have provided compelling evidence that the FTO gene variants are associated with obesity measures. The objective of the study was to investigate whether FTO variants are associated with a broad range of obesity related anthropometric traits in an island population.

Methodology/Principal Findings

We examined genetic association between 29 FTO SNPs and a comprehensive set of anthropometric traits in 843 unrelated individuals from an island population in the eastern Adriatic coast of Croatia. The traits include 11 anthropometrics (height, weight, waist circumference, hip circumference, bicondilar upper arm width, upper arm circumference, and biceps, triceps, subscapular, suprailiac and abdominal skin-fold thicknesses) and two derived measures (BMI and WHR). Using single locus score tests, 15 common SNPs were found to be significantly associated with “body fatness” measures such as weight, BMI, hip and waist circumferences with P-values ranging from 0.0004 to 0.01. Similar but less significant associations were also observed between these markers and bicondilar upper arm width and upper arm circumference. Most of these significant findings could be explained by a mediating effect of “body fatness”. However, one unique association signal between upper arm width and rs16952517 (P-value = 0.00156) could not be explained by this mediating effect. In addition, using a principle component analysis and conditional association tests adjusted for “body fatness”, two novel association signals were identified between upper arm circumference and rs11075986 (P-value = 0.00211) and rs16945088 (P-value = 0.00203).

Conclusions/Significance

The current study confirmed the association of common variants of FTO gene with “body fatness” measures in an isolated island population. We also observed evidence of pleiotropic effects of FTO gene on fat-free mass, such as frame size and muscle mass assessed by bicondilar upper arm width and upper arm circumference respectively and these pleiotropic effects might be influenced by variants that are different from the ones associated with “body fatness”.     

Does Stress Increase the Risk of Atopic Dermatitis in Adolescents? Results of the Korea Youth Risk Behavior Web-Based Survey (KYRBWS-VI)

This study investigated the relationship between level of stress in middle and high school students aged 12–18 and risk of atopic dermatitis. Data from the Sixth Korea Youth Risk Behavior Web-based Survey (KYRBWS-VI), a cross-sectional study among 74,980 students in 800 middle schools and high schools with a response rate of 97.7%, were analyzed. Ordinal logistic regression analyses were conducted to determine the relationship between stress and atopic dermatitis with severity. A total of 5,550 boys and 6,964 girls reported having been diagnosed with atopic dermatitis. Younger students were more likely to have atopic dermatitis. Interestingly, the educational level of parents was found to be associated with having atopic dermatitis and having more severe condition. In particular, girls with mothers with at least college education had a 41% higher risk of having atopic dermatitis and severe atopic condition (odds ratio (OR)) = 1.41, 95% CI, 1.22–1.63; P<0.0001) compared with those with mothers who had attended middle school at most. Similar trend was shown among both boys and girls for their father''s education level. The stress level was found to be significantly associated with the risk of atopic dermatitis. Compared to boys with who reported “no stress”, boys with “very high” stress had 46% higher the risk of having more severe atopic dermatitis (OR = 1.46, 95% CI, 1.20–1.78; P<0.0001), 44% higher (OR = 1.44, 95% CI, 1.19–1.73; P<0.0001) with “high” stress, and 21% higher (OR = 1.21, 95% CI, 1.00–1.45; P = 0.05) with “moderate” stress. In contrast, we found no statistically significant relationship between stress and atopic dermatitis in girls. This study suggests that stress and parents'' education level were associated with atopic dermatitis. Specifically, degree of stress is positively correlated with likelihood of being diagnosed with this condition and increasing the severity.     

Economic Impact of Maternal Death on Households in Rural China: A Prospective Cohort Study

Objective

To assess the economic impact of maternal death on rural Chinese households during the year after maternal death.

Methods

A prospective cohort study matched 183 households who had suffered a maternal death to 346 households that experienced childbirth without maternal death in rural areas of three provinces in China. Surveys were conducted at baseline (1–3 months after maternal death or childbirth) and one year after baseline using the quantitative questionnaire. We investigated household income, expenditure, accumulated debts, and self-reported household economic status. Difference-in-Difference (DID), linear regression, and logistic regression analyses were used to compare the economic status between households with and without maternal death.

Findings

The households with maternal death had a higher risk of self-reported “household economy became worse” during the follow-up period (adjusted OR = 6.04, p<0.001). During the follow-up period, at the household level, DID estimator of income and expenditure showed that households with maternal death had a significant relative reduction of US$ 869 and US$ 650, compared to those households that experienced childbirth with no adverse event (p<0.001). Converted to proportions of change, an average of 32.0% reduction of annual income and 24.9% reduction of annual expenditure were observed in households with a maternal death. The mean increase of accumulated debts in households with a maternal death was 3.2 times as high as that in households without maternal death (p = 0.024). Expenditure pattern of households with maternal death changed, with lower consumption on food (p = 0.037), clothes and commodity (p = 0.003), traffic and communication (p = 0.022) and higher consumption on cigarette or alcohol (p = 0.014).

Conclusion

Compared with childbirth, maternal death had adverse impact on household economy, including higher risk of self-reported “household economy became worse”, decreased income and expenditure, increased debts and changed expenditure pattern.     

The Phylogeographical Pattern and Conservation of the Chinese Cobra (Naja atra) across Its Range Based on Mitochondrial Control Region Sequences

The vulnerable Chinese cobra (Naja atra) ranges from southeastern China south of the Yangtze River to northern Vietnam and Laos. Large mountain ranges and water bodies may influence the pattern of genetic diversity of this species. We sequenced the mitochondrial DNA control region (1029 bp) using 285 individuals collected from 23 localities across the species'' range and obtained 18 sequences unique to Taiwan from GenBank for phylogenetic and population analysis. Two distinct clades were identified, one including haplotypes from the two westernmost localities (Hekou and Miyi) and the other including haplotypes from all sampling sites except Miyi. A strong population structure was found (Φst = 0.76, P<0.0001) with high haplotype diversity (h = 1.00) and low nucleotide diversity (π = 0.0049). The Luoxiao and Nanling Mountains act as historical geographical barriers limiting gene exchange. In the haplotype network there were two “star” clusters. Haplotypes from populations east of the Luoxiao Mountains were represented within one cluster and haplotypes from populations west of the mountain range within the other, with haplotypes from populations south of the Nanling Mountains in between. Lineage sorting between mainland and island populations is incomplete. It remains unknown as to how much adaptive differentiation there is between population groups or within each group. We caution against long-distance transfers within any group, especially when environmental differences are apparent.     

Contribution of Psychosocial Factors to the Association between Socioeconomic Position and Takeaway Food Consumption

Objective

To examine whether psychosocial factors mediate (explain) the association between socioeconomic position and takeaway food consumption.

Design

A cross-sectional postal survey conducted in 2009.

Setting

Participants reported their usual consumption of 22 takeaway food items, and these were grouped into a “healthy” and “less healthy” index based on each items'' nutritional properties. Principal Components Analysis was used to derive three psychosocial scales that measured beliefs about the relationship between diet and health (α = 0.73), and perceptions about the value (α = 0.79) and pleasure (α = 0.61) of takeaway food. A nutrition knowledge index was also used. Socioeconomic position was measured by highest attained education level.

Subjects

Randomly selected adults (n = 1,500) aged between 25–64 years in Brisbane, Australia (response rate  =  63.7%, N = 903).

Results

Compared with those with a bachelor degree or higher, participants with a diploma level of education were more likely to consume “healthy” takeaway food (p = 0.023) whereas the least educated (high school only) were more likely to consume “less healthy” choices (p = 0.002). The least educated were less likely to believe in a relationship between diet and health (p<0.001), and more likely to have lower nutritional knowledge compared with their highly educated counterparts (p<0.001). Education differences in beliefs about the relationship between diet and health partly and significantly mediated the association between education and “healthy” takeaway food consumption. Diet- and health-related beliefs and nutritional knowledge partly and significantly mediated the education differences in “less healthy” takeaway food consumption.

Conclusions

Interventions that target beliefs about the relationship between diet and health, and nutritional knowledge may reduce socioeconomic differences in takeaway food consumption, particularly for “less healthy” options.     

Comparison and Relative Utility of Inequality Measurements: As Applied to Scotland’s Child Dental Health

This study compared and assessed the utility of tests of inequality on a series of very large population caries datasets. National cross-sectional caries datasets for Scotland’s 5-year-olds in 1993/94 (n = 5,078); 1995/96 (n = 6,240); 1997/98 (n = 6,584); 1999/00 (n = 6,781); 2002/03 (n = 9,747); 2003/04 (n = 10,956); 2005/06 (n = 10,945) and 2007/08 (n = 12,067) were obtained. Outcomes were based on the d₃mft metric (i.e. the number of decayed, missing and filled teeth). An area-based deprivation category (DepCat) measured the subjects’ socioeconomic status (SES). Simple absolute and relative inequality, Odds Ratios and the Significant Caries Index (SIC) as advocated by the World Health Organization were calculated. The measures of complex inequality applied to data were: the Slope Index of Inequality (absolute) and a variety of relative inequality tests i.e. Gini coefficient; Relative Index of Inequality; concentration curve; Koolman & Doorslaer’s transformed Concentration Index; Receiver Operator Curve and Population Attributable Risk (PAR). Additional tests used were plots of SIC deciles (SIC¹⁰) and a Scottish Caries Inequality Metric (SCIM¹⁰). Over the period, mean d₃mft improved from 3.1(95%CI 3.0–3.2) to 1.9(95%CI 1.8–1.9) and d₃mft = 0% from 41.1(95%CI 39.8–42.3) to 58.3(95%CI 57.8–59.7). Absolute simple and complex inequality decreased. Relative simple and complex inequality remained comparatively stable. Our results support the use of the SII and RII to measure complex absolute and relative SES inequalities alongside additional tests of complex relative inequality such as PAR and Koolman and Doorslaer’s transformed CI. The latter two have clear interpretations which may influence policy makers. Specialised dental metrics (i.e. SIC, SIC¹⁰ and SCIM¹⁰) permit the exploration of other important inequalities not determined by SES, and could be applied to many other types of disease where ranking of morbidity is possible e.g. obesity. More generally, the approaches described may be applied to study patterns of health inequality affecting worldwide populations.     

Self-Management Behavior in Patients with Type 2 Diabetes: A Cross-Sectional Survey in Western Urban China

Purpose

To investigate the current status of diabetic self-management behavior and the factors influencing this behavior in Chengdu, a typical city in western China.

Methods

We performed stratified sampling in 6 urban districts of Chengdu. We used questionnaires concerning self-management knowledge, self-management beliefs, self-management efficacy, social support, and self-management behavior to investigate patients with T2DM from August to November 2011. All of the data were analyzed using the SPSS 17.0 statistical package.

Results

We enrolled a total of 364 patients in the present study. The median score of self-management behavior was 111.00, the interquartile range was 100.00–119.00, and the index score was 77.77. Self-management was described as “good” in 46%, “fair” in 45%, and “poor” in 6% of patients. A multiple-factor analysis identified age (OR, 0.43; 95% CI, 0.20–0.91; P = 0.026), education in “foot care” (OR, 0.42; 95% CI, 0.18–0.99; P = 0.048), self-management knowledge (OR, 0.86; 95% CI, 0.80–0.92; P<0.001), self-management belief (OR, 0.92; 95% CI, 0.87–0.97; P = 0.002), self-efficacy (OR, 0.93; 95% CI, 0.90–0.96; P<0.001), and social support (OR, 0.62; 95% CI, 0.41–0.94; P = 0.023) as positive factors. Negative factors included diabetes duration (5–9 years: OR, 14.82; 95% CI, 1.64–133.73; P = 0.016; and ≥10 years: OR, 10.28; 95% CI, 1.06–99.79; P = 0.045) and hospitalization experience (OR, 2.96; 95% CI, 1.64–5.36; P<0.001).

Conclusion

We observed good self-management behavior in patients with T2DM in Chengdu. When self-management education is provided, age, education, knowledge, belief, self-efficacy, and social support should be considered to offer more appropriate intervention and to improve patients'' behavior.     

Memory Concerns,Memory Performance and Risk of Dementia in Patients with Mild Cognitive Impairment

Background

Concerns about worsening memory (“memory concerns”; MC) and impairment in memory performance are both predictors of Alzheimer''s dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI).

Methods

We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models.

Results

Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33–4.89), lower memory performance (HR = 0.63, 95%CI: 0.56–0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18–3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment.

Conclusions

Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients'' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI.     

Increased Gray Matter Diffusion Anisotropy in Patients with Persistent Post-Concussive Symptoms following Mild Traumatic Brain Injury

A significant percentage of individuals diagnosed with mild traumatic brain injury (mTBI) experience persistent post-concussive symptoms (PPCS). Little is known about the pathology of these symptoms and there is often no radiological evidence based on conventional clinical imaging. We aimed to utilize methods to evaluate microstructural tissue changes and to determine whether or not a link with PPCS was present. A novel analysis method was developed to identify abnormalities in high-resolution diffusion tensor imaging (DTI) when the location of brain injury is heterogeneous across subjects. A normative atlas with 145 brain regions of interest (ROI) was built from 47 normal controls. Comparing each subject’s diffusion measures to the atlas generated subject-specific profiles of injury. Abnormal ROIs were defined by absolute z-score values above a given threshold. The method was applied to 11 PPCS patients following mTBI and 11 matched controls. Z-score information for each individual was summarized with two location-independent measures: “load” (number of abnormal regions) and “severity” (largest absolute z-score). Group differences were then computed using Wilcoxon rank sum tests. Results showed statistically significantly higher load (p = 0.018) and severity (p = 0.006) for fractional anisotropy (FA) in patients compared with controls. Subject-specific profiles of injury evinced abnormally high FA regions in gray matter (30 occurrences over 11 patients), and abnormally low FA in white matter (3 occurrences over 11 subjects). Subject-specific profiles provide important information regarding the pathology associated with PPCS. Increased gray matter (GM) anisotropy is a novel in-vivo finding, which is consistent with an animal model of brain trauma that associates increased FA in GM with pathologies such as gliosis. In addition, the individualized analysis shows promise for enhancing the clinical care of PPCS patients as it could play a role in the diagnosis of brain injury not revealed using conventional imaging.     

Parapapillary Atrophy: Histological Gamma Zone and Delta Zone

Background

To examine histomorphometrically the parapapillary region in human eyes.

Methodology/Principal Findings

The histomorphometric study included 65 human globes (axial length:21–37 mm). On anterior-posterior histological sections, we measured the distance Bruch''s membrane end (BME)-optic nerve margin (“Gamma zone”), BME-retinal pigment epithelium (RPE) (“Beta zone”), BME-beginning of non-occluded choriocapillaris, and BME-beginning of photoreceptor layer. “Delta zone” was defined as part of gamma zone in which blood vessels of at least 50 µm diameter were not present over a length of >300 µm. Beta zone (mean length:0.35±0.52 mm) was significantly (P = 0.01) larger in the glaucoma group than in the non-glaucomatous group. It was not significantly (P = 0.28) associated with axial length. Beta zone was significantly (P = 0.004) larger than the region with occluded choriocapillaris. Gamma zone (mean length:0.63±1.25 mm) was associated with axial length (P<0.001;r² = 0.73) with an increase starting at an axial length of 26.5 mm. It was not significantly (P = 0.24) associated with glaucomatous optic neuropathy. Delta zone (present only in eyes with axial length of ≥27 mm) was associated with axial length (P = 0.001) and scleral flange length (P<0.001) but not with glaucoma (P = 0.73).

Conclusions/Significance

Parapapillary gamma zone (peripapillary sclera without overlying choroid, Bruch''s membrane and deep retinal layers) was related with axial globe elongation and was independent of glaucoma. Delta zone (no blood vessels >50 µm diameter within gamma zone) was present only in highly axially elongated globes and was not related with glaucoma. Beta zone (Bruch''s membrane without RPE) was correlated with glaucoma but not with globe elongation. Since the region with occluded choriocapillaris was smaller than beta zone, complete loss of RPE may have occurred before complete choriocapillaris closure.     

"Timed Up & Go": A Screening Tool for Predicting 30-Day Morbidity in Onco-Geriatric Surgical Patients? A Multicenter Cohort Study

ObjectiveTo determine the predictive value of the “Timed Up & Go” (TUG), a validated assessment tool, on a prospective cohort study and to compare these findings to the ASA classification, an instrument commonly used for quantifying patients’ physical status and anesthetic risk.BackgroundIn the onco-geriatric surgical population it is important to identify patients at increased risk of adverse post-operative outcome to minimize the risk of over- and under-treatment and improve outcome in this population.Methods280 patients ≥70 years undergoing elective surgery for solid tumors were prospectively recruited. Primary endpoint was 30-day morbidity. Pre-operatively TUG was administered and ASA-classification was registered. Data were analyzed using multivariable logistic regression analyses to estimate odds ratios (OR) and 95% confidence intervals (95%-CI). Absolute risks and area under the receiver operating characteristic curves (AUC’s) were calculated.Results180 (64.3%) patients (median age: 76) underwent major surgery. 55 (20.1%) patients experienced major complications. 50.0% of patients with high TUG and 25.6% of patients with ASA≥3 experienced major complications (absolute risks). TUG and ASA were independent predictors of the occurrence of major complications (TUG:OR 3.43; 95%-CI = 1.14–10.35. ASA1 vs. 2:OR 5.91; 95%-CI = 0.93–37.77. ASA1 vs. 3&4:OR 12.77; 95%-CI = 1.84–88.74). AUC_TUG was 0.64 (95%-CI = 0.55–0.73, p = 0.001) and AUC_ASA was 0.59 (95%-CI = 0.51–0.67, p = 0.04).ConclusionsTwice as many onco-geriatric patients at risk of post-operative complications, who might benefit from pre-operative interventions, are identified using TUG than when using ASA.     

Traumatic Fibromyositis: A Critical Review of an Enigmatic Concept

Traumatic fibromyositis is not an inflammation; there is no fever, leukocytosis or increased sedimentation rate; electrical characteristics and serum enzyme levels are within normal limits, and there are no observable pathologic alterations, although they have been carefully searched for. Recent attempts to express the effects of muscular sprain or strain as a biochemical disturbance expressed in an unusual pattern of lactate dehydrogenase isoenzymes appear not only to be technically flawed but inconsistent with results of conventional enzyme studies on other muscle and interstitial inflammations. In the author''s view, “traumatic” fibromyositis is no more than a verbal construct arrived at by adding an adjectival modifier to the old terms for idiopathic rheumatic disorders. An examination of the evolution of the concept of traumatic fibromyositis shows that it lacks validity as a clinical diagnosis and ought to be abandoned.