Limitations of the Mini-Mental State Examination for screening dementia in a community with low socioeconomic status

The Mini-Mental State Examination (MMSE) is the most widely used instrument for the screening of cognitive impairment worldwide, but its ability to produce valid estimates of dementia in populations of low socioeconomic status and minimal literacy skills has not been adequately established. The authors investigated the psychometric properties of the MMSE in a community-based sample of older Brazilians. Cross-sectional one-phase population-based study of all residents of pre-defined areas of the city of Sao Paulo, aged 65 years or over. The Brazilian version of the MMSE was compared with DSM-IV diagnosis of dementia assessed with a harmonized one-phase procedure developed by the 10/66 Dementia Research Group. Analyses were performed with 1,933 participants of the SPAH study. Receiver operating characteristic analysis showed that the MMSE cut-point of 14/15 was associated with 78.7% sensitivity and 77.8% specificity for the diagnosis of dementia amongst participants with no formal education, and the cut-point 17/18 with 91.9% sensitivity and 89.5% specificity for those with at least 1 year of formal education (areas under the curves 0.87 and 0.94, respectively; P = 0.03). Even with these best fitting cut-points, the MMSE estimate of the prevalence of dementia was four times higher than determined by the DSM-IV criteria. Education, age, sex and income influenced MMSE scores, independently of dementia caseness. The MMSE is an adequate tool for screening dementia in older adults with minimum literacy skills, but misclassification is unacceptably high for older adults who are illiterate, which has serious consequences for research and clinical practice in low and middle income countries, where the proportion of illiteracy among older adults is high.

Histopathology of mast cells and cytokines during healing of human mucosal leishmaniasis

Mast cells (MCs) are associated with chronic inflammatory diseases. However, there is no study evaluating the importance of MCs in the mucosal leishmaniasis (ML). The aim of this study was to quantify the most important cytokines associated with mucosal leishmaniasis, before and after disease treatment, correlating with the healing. A cohort of 12 patients with ML was evaluated, and biopsies were taken before and after the treatment. A quantitative estimation of MCs and some cytokines was analysed by density of the labelled cells through immunohistochemistry. The MCs count in the tissue from patients with ML before treatment showed a mean of 29.3 +/- 37.9 cells/mm(2). The MCs count in patients with ML after healing decreased to 14.8 +/- 23.9 cells/mm(2). There was an inverse relation of MCs with IFN-gamma and IL-4 expression (r(2) = 29.4 and r(2) = 22.3 with P < 0.05). The expression of IL-10 and TNF-alpha was not related with MCs count. MCs decrease after treatment associated with decrease of IL-4 and IFN-gamma. The explanations of cytokine correlation are discussed in the article.

Histologic Study of Acute Vocal Fold Wound Healing After Corticosteroid Injection in a Rabbit Model

Objectives: Injectable corticosteroids have been used in phonosurgery to prevent scarring of the vocal fold because of their effects of wound healing, and to ensure better voice quality. We histologically evaluated the effects of dexamethasone sodium phosphate infiltration on acute vocal fold wound healing in rabbits 3 and 7 days after surgically induced injury by quantification of the inflammatory reaction and collagen deposition. Methods: A standardized surgical incision was made in the vocal folds of 12 rabbits, and 0.1 mL dexamethasone sodium phosphate (4 mg/mL) was injected into the left vocal fold. The right vocal fold was not injected and served as the control. The larynges were collected 3 and 7 days after surgery. For histologic analysis, the vocal folds were stained with hematoxylin-eosin for quantification of the inflammatory response and with picrosirius red for qunatification of collagen depostion. Results: There was no quantitative difference in the inflammatory response between vocal folds injected with the corticosteroid and control vocal folds. However, the rate of collage deposition was significantly lower in the corticosteroid-treated group at 3 and 7 days after injury (p = 0.002). Conclusions: The present results suggest that dexamethasone reduces collagen depostion during acute vocal fold wound healing.

Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative

Context: There is limited information on the prevalence and correlates of bipolar spectrum disorder in international population-based studies using common methods. Objectives: To describe the prevalence, impact, patterns of comorbidity, and patterns of service utilization for bipolar spectrum disorder (BPS) in the World Health Organization World Mental Health Survey Initiative. Design, Setting, and Participants: Crosssectional, face-to-face, household surveys of 61 392 community adults in 11 countries in the Americas, Europe, and Asia assessed with the World Mental Health version of the World Health Organization Composite International Diagnostic Interview, version 3.0, a fully structured, lay-administered psychiatric diagnostic interview. Main Outcome Measures: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) disorders, severity, and treatment. Results: The aggregate lifetime prevalences were 0.6% for bipolar type I disorder (BP-I), 0.4% for BP-II, 1.4% for subthreshold BP, and 2.4% for BPS. Twelve-month prevalences were 0.4% for BP-I, 0.3% for BP-II, 0.8% for subthreshold BP, and 1.5% for BPS. Severity of both manic and depressive symptoms as well as suicidal behavior increased monotonically from subthreshold BP to BP-I. By contrast, role impairment was similar across BP subtypes. Symptom severity was greater for depressive episodes than manic episodes, with approximately 74.0% of respondents with depression and 50.9% of respondents with mania reporting severe role impairment. Three-quarters of those with BPS met criteria for at least 1 other disorder, with anxiety disorders (particularly panic attacks) being the most common comorbid condition. Less than half of those with lifetime BPS received mental health treatment, particularly in low-income countries, where only 25.2% reported contact with the mental health system. Conclusions: Despite cross-site variation in the prevalence rates of BPS, the severity, impact, and patterns of comorbidity were remarkably similar internationally. The uniform increases in clinical correlates, suicidal behavior, and comorbidity across each diagnostic category provide evidence for the validity of the concept of BPS. Treatment needs for BPS are often unmet, particularly in low-income countries.

Development of Lifetime Comorbidity in the World Health Organization World Mental Health Surveys

Context: Although numerous studies have examined the role of latent variables in the structure of comorbidity among mental disorders, none has examined their role in the development of comorbidity. Objective: To study the role of latent variables in the development of comorbidity among 18 lifetime DSM-IV disorders in the World Health Organization World Mental Health Surveys. Design: Nationally or regionally representative community surveys. Setting: Fourteen countries. Participants: A total of 21 229 survey respondents. Main Outcome Measures: First onset of 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders assessed retrospectively in the World Health Organization Composite International Diagnostic Interview. Results: Separate internalizing (anxiety and mood disorders) and externalizing (behavior and substance disorders) factors were found in exploratory factor analysis of lifetime disorders. Consistently significant positive time-lagged associations were found in survival analyses for virtually all temporally primary lifetime disorders predicting subsequent onset of other disorders. Within-domain (ie, internalizing or externalizing) associations were generally stronger than between-domain associations. Most time-lagged associations were explained by a model that assumed the existence of mediating latent internalizing and externalizing variables. Specific phobia and obsessive-compulsive disorder (internalizing) and hyperactivity and oppositional defiant disorders (externalizing) were the most important predictors. A small number of residual associations remained significant after controlling the latent variables. Conclusions: The good fit of the latent variable model suggests that common causal pathways account for most of the comorbidity among the disorders considered herein. These common pathways should be the focus of future research on the development of comorbidity, although several important pairwise associations that cannot be accounted for by latent variables also exist that warrant further focused study.

Twelve-Month Prevalence of and Risk Factors for Suicide Attempts in the World Health Organization World Mental Health Surveys

Objective: Although suicide is a leading cause of death worldwide, clinicians and researchers lack a data-driven method to assess the risk of suicide attempts. This study reports the results of an analysis of a large cross-national epidemiologic survey database that estimates the 12-month prevalence of suicidal behaviors, identifies risk factors for suicide attempts, and combines these factors to create a risk index for 12-month suicide attempts separately for developed and developing countries. Method: Data come from the World Health Organization (WHO) World Mental Health (WMH) Surveys (conducted 2001-2007), in which 108,705 adults from 21 countries were interviewed using the WHO Composite International Diagnostic Interview. The survey assessed suicidal behaviors and potential risk factors across multiple domains, including socio-demographic characteristics, parent psychopathology, childhood adversities, DSM-IV disorders, and history of suicidal behavior. Results: Twelve-month prevalence estimates of suicide ideation, plans, and attempts are 2.0%, 0.6%, and 0.3%, respectively, for developed countries and 2.1%, 0.7%, and 0.4%, respectively, for developing countries. Risk factors for suicidal behaviors in both developed and developing countries include female sex, younger age, lower education and income, unmarried status, unemployment, parent psychopathology, childhood adversities, and presence of diverse 12-month DSM-IV mental disorders. Combining risk factors from multiple domains produced risk indices that accurately predicted 12-month suicide attempts in both developed and developing countries (area under the receiver operating characteristic curve = 0.74-0.80). Conclusions: Suicidal behaviors occur at similar rates in both developed and developing countries. Risk indices assessing multiple domains can predict suicide attempts with fairly good accuracy and may be useful in aiding clinicians in the prediction of these behaviors. J Clin Psychiatry 2010;71(12):1617-1628 (C) Copyright 2010 Physicians Postgraduate Press, Inc.

Cytogenetic molecular delineation of a terminal 18q deletion suggesting neo-telomere formation

Deletion of the long arm of chromosome 18 is one of the most common segmental aneusomies compatible with life and usually involves a deletion of the terminal chromosomal region. However, the mechanisms implicated in the stabilization of terminal deletions are not well understood. In this study, we analyzed a girl with moderate mental retardation who had a cytogenetically visible terminal 18q deletion. In order to characterize the breakpoint in the terminal 18q region, we used fluorescence In situ hybridization (FISH) with bacterial artificial chromosomes (BACs) and pan-telomeric probes and also the array technique based on comparative genomic hybridization (array-CGH). FISH with pan-telomeric probes revealed no signal in the terminal region of the deleted chromosome, indicating the absence of normal telomere repeat (TTAGGG)n sequences in 18q. We suggest that neo-telomere formation by chromosome healing was involved in the repair and stabilization of this terminal deletion. (C) 2010 Elsevier Masson SAS. All rights reserved.

Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys

Background Although significant associations of childhood adversities with adult mental disorders are widely documented, most studies focus on single childhood adversities predicting single disorders. Aims To examine joint associations of 12 childhood adversities with first onset of 20 DSM-IV disorders in World Mental Health (WMH) Surveys in 21 countries. Method Nationally or regionally representative surveys of 51 945 adults assessed childhood adversities and lifetime DSM-IV disorders with the WHO Composite International Diagnostic Interview (CIDI). Results Childhood adversities were highly prevalent and interrelated. Childhood adversities associated with maladaptive family functioning (e.g. parental mental illness, child abuse, neglect) were the strongest predictors of disorders. Co-occurring childhood adversities associated with maladaptive family functioning had significant subadditive predictive associations and little specificity across disorders. Childhood adversities account for 29.8% of all disorders across countries. Conclusions Childhood adversities have strong associations with all classes of disorders at all life-course stages in all groups of WMH countries. Long-term associations imply the existence of as-yet undetermined mediators.

Biomechanical evaluation on tendon reinsertion by comparing trans-osseous suture and suture anchor at different stages of healing: Experimental study on rabbits

Background: Through an experimental biomechanical study on rabbits, tendon reinsertion by means of trans-osseous suture on a spongy bone bed and suture anchor were evaluated comparatively at different phases of healing. Methods: Twenty-four New Zealand White rabbits were used: 2 as pilots, 4 as the control group, and 18 as the experimental group. These 18 animals underwent sectioning and reinsertion of the Achilles tendon bilaterally, using the technique of trans-osseous suture on 1 side and suture anchor on the other. All the pelvic limbs that underwent the procedure were then immobilized for 3 weeks. The experimental group was divided into 3 groups that were sacrificed, respectively, 3, 6, and 12 weeks later. The tendon-bone complex was subjected to biomechanical tests to evaluate the parameters of maximum strength, stiffness, and yield strength. Results: There was no statistically significant difference between the suture anchor group and the trans-osseous suture group, in relation to yield strength (3 weeks, P = .222; 6 weeks, P = .465; and 12 weeks, P = .200) or maximum strength (3 weeks, P = .222; 6 weeks, P = .076; and 12 weeks, P = .078). In relation to stiffness, the suture anchor group showed a statistically significant difference only at 3 weeks of healing ( P = .032) over the trans-osseous suture group. Conclusion: The technique of suturing with an anchor was shown to be similar to the technique of trans-osseous suture for the studied parameters. Level of evidence: Basic Science Study, In-Vitro Biomechanics Study. (C) 2010 Journal of Shoulder and Elbow Surgery Board of Trustees.

Associations of serious mental illness with earnings: results from the WHO World Mental Health surveys

Background Burden-of-illness data, which are often used in setting healthcare policy-spending priorities, are unavailable for mental disorders in most countries. Aims To examine one central aspect of illness burden, the association of serious mental illness with earnings, in the World Health Organization (WHO) World Mental Health (WMH) Surveys. Method The WMH Surveys were carried out in 10 high-income and 9 low- and middle-income countries. The associations of personal earnings with serious mental illness were estimated. Results Respondents with serious mental illness earned on average a third less than median earnings, with no significant between-country differences (chi(2)(9)=5.5-8.1, P=0.5-0.79). These losses are equivalent to 0.3-0.8% of total national earnings. Reduced earnings among those with earnings and the increased probability of not earning are both important components of these associations: Conclusions These results add to a growing body of evidence that mental disorders have high societal costs. Decisions about healthcare resource allocation should take these costs into consideration.

Screening for serious mental illness in the general population with the K6 screening scale: results from the WHO World Mental Health (WMH) survey initiative

Data are reported on the background and performance of the K6 screening scale for serious mental illness (SMI) in the World Health Organization (WHO) World Mental Health (WMH) surveys. The K6 is a six-item scale developed to provide a brief valid screen for Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) SMI based on the criteria in the US ADAMHA Reorganization Act. Although methodological studies have documented good K6 validity in a number of countries, optimal scoring rules have never been proposed. Such rules are presented here based on analysis of K6 data in nationally or regionally representative WMH surveys in 14 countries (combined N = 41,770 respondents). Twelve-month prevalence of DSM-IV SMI was assessed with the fully-structured WHO Composite International Diagnostic Interview. Nested logistic regression analysis was used to generate estimates of the predicted probability of SMI for each respondent from K6 scores, taking into consideration the possibility of variable concordance as a function of respondent age, gender, education, and country. Concordance, assessed by calculating the area under the receiver operating characteristic curve, was generally substantial (median 0.83; range 0.76-0.89; inter-quartile range 0.81-0.85). Based on this result, optimal scaling rules are presented for use by investigators working with the K6 scale in the countries studied. Copyright (c) 2010 John Wiley & Sons, Ltd.

AGE DIFFERENCES IN THE PREVALENCE AND CO-MORBIDITY OF DSM-IV MAJOR DEPRESSIVE EPISODES: RESULTS FROM THE WHO WORLD MENTAL HEALTH SURVEY INITIATIVE

Background: Although depression appears to decrease in late life, this could be due to misattribution of depressive symptoms to physical disorders that increase in late we. Methods: We investigated this issue by studying age differences in co-morbidity of DSM-IV major depressive episodes (MDE) with chronic physical conditions in the WHO World Mental Health (WMH) surveys, a series of community epidemiological surveys of respondents in 10 developed countries (n = 52,485) and 8 developing countries (n = 37,265). MDE and other mental disorders were assessed with the Composite International Diagnostic Interview (CIDI). Organic exclusion rules were not used to avoid inappropriate exclusion of cases with physical co-morbidity. Physical conditions were assessed with a standard chronic conditions checklist. Results: Twelve-month DSM-IV/CIDI MDE was significantly less prevalent among respondents ages 65+ than younger respondents in developed but not developing countries. Prevalence of co-morbid mental disorders generally either decreased or remained stable with age, while co-morbidity of MDE with mental disorders generally increased with age. Prevalence of physical conditions, in comparison, generally increased with age, while co-morbidity of MDE with physical conditions generally decreased with age. Depression treatment was lowest among the elderly in developed and developing countries. Conclusions: The weakening associations between MDE and physical conditions with increasing age argue against the suggestion that the low estimated prevalence of MDE among the elderly is due to increased confounding with physical disorders. Future study is needed to investigate processes that might lead to a decreasing impact of physical illness on depression among the elderly. Depression and Anxiety 27:351-364, 2010. (C) 2009 Wiley-Liss, Inc.

Using a combination of MLPA kits to detect chromosomal imbalances in patients with multiple congenital anomalies and mental retardation is a valuable choice for developing countries

Conventional karyotyping detects anomalies in 3-15% of patients with multiple congenital anomalies and mental retardation (MCA/MR). Whole-genome array screening (WGAS) has been consistently suggested as the first choice diagnostic test for this group of patients, but it is very costly for large-scale use in developing countries. We evaluated the use of a combination of Multiplex Ligation-dependent Probe Amplification (MLPA) kits to increase the detection rate of chromosomal abnormalities in MCA/MR patients. We screened 261 MCA/MR patients with two subtelomeric and one microdeletion kits. This would theoretically detect up to 70% of all submicroscopic abnormalities. Additionally we scored the de Vries score for 209 patients in an effort to find a suitable cut-off for MLPA screening. Our results reveal that chromosomal abnormalities were present in 87 (33.3%) patients, but only 57 (21.8%) were considered causative. Karyotyping detected 15 abnormalities (6.9%), while MLPA identified 54 (20.7%). Our combined MLPA screening raised the total detection number of pathogenic imbalances more than three times when compared to conventional karyotyping. We also show that using the de Vries score as a cutoff for this screening would only be suitable under financial restrictions. A decision analytic model was constructed with three possible strategies: karyotype, karyotype + MLPA and karyotype + WGAS. Karyotype + MLPA strategy detected anomalies in 19.8% of cases which account for 76.45% of the expected yield for karyotype + WGAS. Incremental Cost Effectiveness Ratio (ICER) of MLPA is three times lower than that of WGAS, which means that, for the same costs, we have three additional diagnoses with MLPA but only one with WGAS. We list all causative alterations found, including rare findings, such as reciprocal duplications of regions deleted in Sotos and Williams-Beuren syndromes. We also describe imbalances that were considered polymorphisms or rare variants, such as the new SNP that confounded the analysis of the 22q13.3 deletion syndrome. (C) 2011 Elsevier Masson SAS. All rights reserved.

Phototherapy Promotes Healing of Chronic Diabetic Leg Ulcers That Failed to Respond to Other Therapies

Objective: We tested the hypothesis that combined 660 and 890 nm LED phototherapy will promote healing of diabetic ulcers that failed to respond to other forms of treatment. Research Design and Methods: A double-blind randomized placebo controlled design was used to study 23 diabetic leg ulcers in two groups of 14 patients. Group one ulcers were cleaned, dressed with 1% silver sulfadiazine cream and treated with ""placebo"" phototherapy (<1.0 J cm(-2)) twice per week, using a Dynatron Solaris 705 (R) device. Group two ulcers were treated similarly but received 3 J cm(-2) dose. Results: At each of 15,30,45,60,75, and 90 days of healing, mean ulcer granulation and healing rates were significantly higher for group two than the ""placebo"" group (P < 0.02). While ""placebo"" treated ulcers worsened during the initial 30 days, group two ulcers healed rapidly; achieving 56% more granulation and 79.2% faster healing by day 30, and maintaining similarly higher rates of granulation and healing over the ""placebo"" group all through. By day 90, 58.3% of group two ulcers had healed fully and 75% had achieved 90-100% healing. In contrast, only one ""placebo"" treated ulcer healed fully by day 90; no other ulcer attained >90% healing. Conclusion: Combined 660 and 890 nm light promotes rapid granulation and healing of diabetic ulcers that failed to respond to other forms of treatment. Lasers Surg. Med. 41:433-441, 2009. (C) 2009 Wiley-Liss, Inc.

Low-Intensity Pulsed Ultrasound Accelerates Healing in Rat Calcaneus Tendon Injuries

STUDY DESIGN: Controlled laboratory study. OBJECTIVE: To evaluate the effect of low-intensity therapeutic ultrasound on the murine calcaneus tendon healing process. BACKGROUND: Therapeutic ultrasound promotes formation and maturation of scar tissue. METHODS: Calcaneus tendon tenotomy and tenorrhaphy was performed on 28 Wistar rats. After the procedure, the animals were randomly divided into 2 groups. The animals in the experimental group received a 5-minute ultrasound application, once a day, at a frequency of 1 MHz, a spatial average temporal average intensity of 0.1 W/cm(2), and a spatial average intensity of 0.52 W/cm(2) at a 16-Hz frequency pulse mode (duty cycle, 20%). Data for the injured side were normalized in relation to the data from the contralateral healthy calcaneus tendon (relative values). The animals in the control group received sham treatment. After a 28-day treatment period, the animals were sacrificed and their tendons surgically removed and subjected to mechanical stress testing. The parameters analyzed were cross-sectional area (mm(2)), ultimate load (N), tensile strength (MPa), and energy absorption (mJ). RESULTS: A significant difference between groups was found for the relative values of ultimate load and tensile strength. The mean +/- SD ultimate load of the control group was -3.5% +/- 32.2% compared to 33.3% +/- 26.8% for the experimental group (P = .005). The mean tensile strength of the control group was -47.7% +/- 19.5% compared to -28.1% +/- 24.1% for the experimental group (P = .019). No significant difference was found in cross-sectional area and energy absorption. CONCLUSION: Low-intensity pulsed ultrasound produced by a conventional therapeutic ultrasound unit can positively influence the calcaneus tendon healing process in rats. J Ort hop Sports Phys Ther 2011;41(7):526-531, Epub 2 February 2011. doi:10.2519/jospt.2011.3468