Diagnostic Subcategories Research Articles

Correlation of thyroid nodule fine‐needle aspiration cytology with corresponding histology at Mayo Clinic, 2001–2007: An institutional experience of 1,945 cases

Following the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference, the thyroid fine-needle aspiration biopsy (FNAB) practice at Mayo Clinic, Rochester, Minnesota, conducted retrospective analyses correlating cytologic and histologic evaluations of thyroid nodules. Cytologic and histologic reports were retrieved for patients with thyroid nodules who underwent thyroid FNAB between January 2001 and December 2007, with subsequent surgical thyroid resection. Cases were classified by major cytologic and histologic diagnosis and specific diagnostic subcategories. Of 1,945 FNAB cytologic results, 180 (9.3%) were nondiagnostic; 512 (26.3%) were negative for malignancy; 27 (1.4%) were atypical; 729 (37.5%) were suspicious for malignancy; and 497 (25.6%) were positive for malignancy. Histology was benign in 1,179 (60.6%) and malignant in 766 (39.4%). For thyroid malignancy as the disease outcome, at cytologic thresholds of atypical, suspicious, and positive, overall sensitivity of thyroid FNAB was 94.5%, 94.1%, and 65.0%, respectively, and specificity was 46.0%, 48.3%, and 98.5%, respectively. Positive predictive value for all malignancies was 97.0%, and negative predictive value was 92.0%. When separated by specific malignant outcomes, diagnoses of papillary carcinoma, medullary carcinoma, and lymphoma had specificity of suspicious FNAB diagnoses ranging from 90.5% to 99.6%; positive predictive value ranged from 87.5% to 91.4%. For follicular or Hürthle carcinoma, suspicious FNAB diagnoses had a specificity of 52.5% and a positive predictive value of 5.9%. Sensitivity of indeterminate FNAB diagnoses ranged from 72.7% to 95.3%. For follicular or Hürthle pattern malignancies, indeterminate cytologic diagnoses should be interpreted with caution by the clinician considering surgical management. Diagn. Cytopathol. 2012;40:E27-E32. © 2010 Wiley Periodicals, Inc.

New Fluency, Cognition Diagnosis Codes

New Fluency, Cognition Diagnosis Codes

Externalising and emotional categories, diagnostic groups and clinical profiles

BackgroundIt has been proposed that gains would be made in the validity of the psychiatric classification system if many of the present 'neurotic' or personality disorders were subsumed into two over-arching groups, externalising and emotional disorders. If diagnostic sub-categories from the first digit coding structures within ICD-10 do, in fact, share clinical phenomenology that align with the major externalising/emotional distinction, this further supports the proposal and contributes to face validity. The aim of the study was to examine the distribution of particular psychopathology within and between two proposed over-arching groupings - externalising and emotional disorders - in a clinical sample.MethodThe distributions of HoNOS derived information in relation to the proposed clusters of emotional disorders and extrinsic disorders are examined.ResultsStatistically significant differences in profiles between the emotional and the externalising groupings are consistent with the proposed classification development. The HoNOS (Health of Nation Outcome Scale) measures of self harm, depression, aggression, occupational/leisure problems and drug and alcohol consumption are the five most significant discriminators between the two groups.DiscussionThe details of the profile differences within the two over arching groups suggest that further examination is required. Useful work could include examination in credibly large and unselected patient populations of the factor structure demonstrated in non patient samples. Prospective comprehensive trials of the contributions the proposed classification could make to clinical decision making would also help illuminate this area.

Prevalence of cervical intraepithelial neoplasia grades II/III and cervical cancer in patients with cytological diagnosis of atypical squamous cells when high-grade intraepithelial lesions (ASC-H) cannot be ruled out

The latest update of the Bethesda System divided the category of atypical squamous cells of undetermined significance (ASCUS) into ASC-US (undetermined significance) and ASC-H (high-grade intraepithelial lesion cannot be ruled out). The aims here were to measure the prevalence of pre-invasive lesions (cervical intraepithelial neoplasia, CIN II/III) and cervical cancer among patients referred to Instituto Fernandes Figueira (IFF) with ASC-H cytology, and compare them with ASC-US cases. Cross-sectional study with retrospective data collection, at the IFF Cervical Pathology outpatient clinic. ASCUS cases referred to IFF from November 1997 to September 2007 were reviewed according to the 2001 Bethesda System to reach cytological consensus. The resulting ASC-H and ASC-US cases, along with new cases, were analyzed relative to the outcome of interest. The histological diagnosis (or cytocolposcopic follow-up in cases without such diagnosis) was taken as the gold standard. The prevalence of CIN II/III in cases with ASC-H cytology was 19.29% (95% confidence interval, CI, 9.05-29.55%) and the risk of these lesions was greater among patients with ASC-H than with ASC-US cytology (prevalence ratio, PR, 10.42; 95% CI, 2.39-45.47; P = 0.0000764). Pre-invasive lesions were more frequently found in patients under 50 years of age with ASC-H cytology (PR, 2.67; 95% CI, 0.38-18.83); P = 0.2786998). There were no uterine cervical cancer cases. The prevalence of CIN II/III in patients with ASC-H cytology was significantly higher than with ASC-US, and division into ASC diagnostic subcategories had good capacity for discriminating the presence of pre-invasive lesions.

Understanding the Reliability of Diagnostic Variables in a Chinese Medicine Examination

The question of the objectivity of the clinical examination has been raised in relation to Western and non-Western medical systems. Western practitioners are often skeptical about Traditional Chinese Medicine (TCM), on the basis that its diagnostic variables and subcategories of disease appear subjective and not repeatable. We conducted a study investigating the reproducibility of individual diagnostic observations within three of the four diagnostic methods used in a TCM examination: inspection, palpation, and auscultation. Three TCM practitioners participated in the study, and examined 45 adults who had mild-to-moderate hypercholesterolemia but were otherwise healthy. Results indicated that while there are certain features of the TCM system that are highly objective and repeatable, such as detection of the presence of shen, character of breath sounds, and pulse speed, there are other features that are subjective and unreliable, such as color under the eyes and tongue body color. This poses a challenge for TCM practitioners to improve their clinical practice and demonstrates to Western medical practitioners that TCM does in part rest on a rigorous and objective empirical basis.

11C]PiB in patients with amnestic and non-amnestic MCI

The ability to quantify amyloid deposition using in vivo neuroimaging labeling compounds, such as the Pittsburgh Compound B [11C]PiB for amyloid holds the promise of confirming the diagnosis of Alzheimer's disease (AD) prior to autopsy. The use of [11C]PiB to identify pre-clinical AD (i.e., in patients with Mild Cognitive Impairment; MCI) may prove beneficial as this would allow interventions to be targeted earlier when the response to intervention is potentially greater. To date, however, few studies have compared diagnostic subcategories of MCI using [11C]PiB. Twenty two older individuals (range 61-93 years) diagnosed with MCI enrolled in the Michigan Alzheimer's Disease Research Center underwent [11C]PiB positron emission tomogrophy (PET) scan. Patients were divided into [11C]PiB “positive” or [11C]PiB “negative” groups: [11C]PiB positive individuals demonstrated frontal cortical binding in excess of subcortical white matter binding. In addition, all individuals were administered a battery of neuropsychological tests that included measures from the NACC Uniform Data Set. Fourteen of the 22 patients were positive for abnormal [11C]PiB binding. Of those 14, 13 of the patients had MCI amnestic type (8 memory alone, 5 memory plus additional cognitive impairment). Of the 8 who were negative for [11C]PiB, only 3 presented as MCI amnestic type, with 5 diagnosed as MCI nonamnestic (χ2=7.9, p<.005). The [11C]PiB positive group demonstrated poorer performance on measures of visual memory (immediate memory p<0.04, delayed recall p<0.03) and verbal recognition (p<0.05). No differences were found in other cognitive domains, though a trend was evident for more executive functioning impairment in the [11C]PiB negative group (p<.09). Amyloid deposition in patients with diagnosed MCI is more prevalent in patients who present with memory deficits. As previous research has suggested that patients with MCI amnestic type are at a higher risk of developing Alzheimer's disease (AD), the use of [11C]PiB scans may help in the identification of those individuals who are at greatest risk for AD. Supported by NIH-NIA P50 AG08671 and the Michigan Alzheimer's Disease Research Center.

The Clinical Utility of Microarray-Based Gene Expression Profiling in the Diagnosis and Sub-Classification of Leukemia: Final Report on 3252 Cases from the International MILE Study Group

During the years of 2005 to 2008, the MILE (Microarray Innovations in LEukemia) study research program was performed in 11 laboratories across three continents: 7 from the European Leukemia Network (ELN, WP13), 3 from the US and 1 in Singapore. The first stage was designed as biomarker discovery phase to generate whole-genome gene expression profiles (GEP) from recognized categories of clinically relevant leukemias and myelodysplastic syndromes (MDS). These were C1: mature B-ALL with t(8;14), C2: pro-B-ALL with t(11q23)/MLL, C3: c-ALL/pre-B-ALL with t(9;22), C4: T-ALL, C5: ALL with t(12;21), C6: ALL with t(1;19), C7: ALL with hyperdiploid karyotype, C8: c-ALL/pre-B-ALL without specific genetic abnormalities, C9: AML with t(8;21), C10: AML with t(15;17), C11: AML with inv(16)/t(16;16), C12: AML with t(11q23)/MLL, C13: AML with normal karyotype or other abnormalities, C14: AML with complex aberrant karyotype, C15: CLL, C16: CML, C17: MDS, and C18: non-leukemic and healthy bone marrow samples as controls and were compared to conventional diagnostic assays (“Gold Standard”). Data from the completed MILE Stage I included 2143 retrospectively collected adult and pediatric samples tested with HG-U133 Plus 2.0 microarrays (Affymetrix). In total only 47 analyses (2.1%) failed technical quality criteria. Cross-validation accuracy (average of three 30-fold cross-validations) of the final 2096 MILE Stage I samples was 92.1% concordant with the center-specific “Gold Standard” diagnosis (average call rate 99.4%). In nine classes the sensitivity was ≥94.3%: C2, C3, C4, C5, C9, C10, C11, C15, and C16. Lower sensitivities were observed for C7, C8, C14, and C17; which can largely be explained by the biological heterogeneity and non-standardized “Gold Standard” definitions for these entities. Yet, it is notable that all these classes showed specificities above 98.1%. In order to assess the clinical utility of microarray-based diagnostics a prospective Stage II was subsequently performed using a customized microarray representing 1480 probe sets. Overall, 1156 high quality GEP have been generated in MILE Stage II and represent an independent and blinded test set for the algorithms developed. A focused classification scheme aimed at accurately addressing only acute leukemias resulted in a 95.5% median sensitivity and a 99.5% median specificity for the 14 classes included in the classifier (C1 – C14, n=696). Lower accuracies were observed for the interface of C7–C8 in ALL, as well as C12 and C14 in AML. Interestingly, during the process of discrepant results analyses, it was observed that for 7.5% (n=52) of acute leukemias microarray results were correctly diagnosing samples as compared to the initial “Gold Standard” diagnoses entered into the study database, either because of erroneous entries into case report forms (24%) or subsequent re-testing of left-over material following the suggested diagnosis from the microarray (76%). In addition, predicted accuracies for CLL, CML and MDS in Stage II were 99.2%, 95.2%, and 81.5%, respectively. In conclusion, the MILE research study confirms in a final cohort of 3252 patients that microarrays accurately classify acute and chronic leukemia samples into known diagnostic and prognostic sub-categories. This final report underlines that the standardized method of gene expression profiling with low technical failure rate and simplified standard operating procedures may improve current “Gold Standards” as an adjunct to conventional diagnostic algorithms and potentially offers a reliable diagnostic/prognostic tool for many patients who don't have access to a state-of-the-art “Gold Standard” workup. Our gene expression database, intended to be submitted to the public domain, will further contribute to research that aims to elucidate the molecular understanding of leukemias.

High Prevalence of Elderly Anemia Is Seen in a Large Inner City Outpatient Population and Is Predictive of Decreased Overall Survival across All Ethnic Groups

Recent work has hinted at the prognostic importance of anemia in the elderly and has tried to identify causes. In an effort to further explore this important clinical problem, we decided to determine the prevalence, etiology and prognostic implications of anemia in a large inner city cohort of elderly outpatients. A total of 40,417 individuals ≥65 years of age seen at Montefiore medical system outpatient clinics from January 1st 1997 to May 1st 2008 who underwent a complete blood count within 3 months of the visit were included in the cohort. Using gender specific WHO criteria, we determined 35.3% of men (out of 15,629) and 28.8% of women (out of 24,788) were anemic at the time of their first clinic visit. A follow up of their blood counts showed that ultimately 70.7% of men and 65.4% of women subsequently developed anemia, thus demonstrating a very high incidence in this population. Among anemic patients, 14.2% had microcytosis and 11.2% had macrocytosis. Of all microcytic anemic patients, 57.3% had both ferritin and iron saturation performed and 19.1% of those tested met criteria for iron deficiency anemia. Of all macrocytic anemic patients, 51.7% had folate and 53.2% had B12 levels checked. However, of those tested only 0.6% and 6.8% had folate and B12 deficiency respectively. This percentage of abnormal findings was similar to non-anemics (0.3% and 5.5% respectively). Evaluation for further etiologies of anemia revealed that 10.0% had thrombocytopenia, 13.5% had leukopenia, and 2.0% had neutropenia, raising the possibility of bone marrow failure and myelodysplastic syndrome (MDS) in these patients. Of the 3,471 anemic patients with other cytopenias, only 6.1% had a bone marrow examination (n=213). Subsequent diagnosis of MDS was made in a minority of these patients. A search for other chronic diseases among the anemic group revealed an elevated creatinine in 11.2%, a subsequently elevated TSH in 17.5%, transaminitis in 28.0% and hypoalbuminemia in 21.9%. Of anemic patients who had an ESR and an ANA assay performed, 69.7% and 23.1% had abnormal results respectively. Overall, a possible etiology based on the above laboratory findings was only identified in 61.9% of anemic patients. Of the small number of anemic patients who had every one of the above tests performed (n=662), 12.1% did not have any abnormal results.To determine the functional importance of these findings, Kaplan-Meier curves and multivariate Cox regression analyses were performed to compare survival and mortality in this cohort. Anemic patients had reduced overall survival regardless of ethnicity (Figure 1). Interestingly, among the elderly, minorities appeared to have better survival than Caucasian whites regardless of anemia status. This is likely secondary to selection bias in this age group as minorities have higher mortality rates below age 65. Adjusting for age and gender, the overall hazard ratio (HR) comparing anemic patients with nonanemic patients was 2.15 (p<0.001). Repeating for each ethnicity subgroup resulted in adjusted HRs of 1.93 (p<0.001) in whites, 2.00 (p<0.001) in blacks, and 2.44 (p<0.001) in Hispanics. Multivariate analyses of various lab parameters demonstrated that an elevated RDW (>16.6%) was the strongest predictor of decreased survival in anemic patients with an age/gender/Hb-adjusted HR of 1.73 (p<0.001). (Figure 2) Thrombocytopenia (HR= 1.37, p<0.001), leukocytosis (HR=1.37, p<0.001), neutropenia (HR=1.23, p=0.032) and macrocytosis (HR=1.24, p<0.001) were additional poor prognostic factors, raising the possibility of MDS as an adverse diagnostic subcategory of anemia in the elderly.In conclusion, we determined that anemia is very common among the elderly in the outpatient setting, and the majority of non-anemic patients ≥65 years of age ultimately develop this condition. Folate/B12 screening has minimal diagnostic utility in anemic patients. Anemia is associated with decreased survival in all racial groups, with larger effects in African Americans and Hispanics. An elevated RDW and the presence of other cytopenias are highly predictive of mortality in anemic patients even after controlling for age, gender and hemoglobin. [Display omitted] [Display omitted]

Brain morphometry volume in autistic spectrum disorder: a magnetic resonance imaging study of adults

Several prior reports have found that some young children with autism spectrum disorder [ASD; including autism and Asperger's syndrome and pervasive developmental disorder - not otherwise specified (PDD-NOS)] have a significant increase in head size and brain weight. However, the findings from older children and adults with ASD are inconsistent. This may reflect the relatively small sample sizes that were studied, clinical heterogeneity, or age-related brain differences. Hence, we measured head size (intracranial volume), and the bulk volume of ventricular and peripheral cerebrospinal fluid (CSF), lobar brain, and cerebellum in 114 people with ASD and 60 controls aged between 18 and 58 years. The ASD sample included 80 people with Asperger's syndrome, 28 with autism and six with PDD-NOS. There was no significant between-group difference in head and/or lobar brain matter volume. However, compared with controls, each ASD subgroup had a significantly smaller cerebellar volume, and a significantly larger volume of peripheral CSF. Within ASD adults, the bulk volume of cerebellum is reduced irrespective of diagnostic subcategory. Also the significant increase in peripheral CSF may reflect differences in cortical maturation and/or ageing.

An International Multi-Center Study To Define the Application of Microarray-Based Gene Expression Profiling in the Diagnosis and Sub-Classification of Leukemia (MILE Study): Analysis of Completed Stage I with 2030 Patients Achieved a 95.4% Accuracy.

In 2005, the MILE (Microarray Innovations in LEukemia) study research program was initiated with 11 centers: 7 from the European Leukemia Network (ELN, WP13), 3 from the US, and 1 in Singapore. The first stage was designed to assess the ability of GEP to classify leukemias into 17 recognized categories as compared to conventional diagnostic assays (“Gold Standards”). These include: mature B-ALL with t(8;14), pro-B-ALL with t(11q23)/MLL, c-ALL/pre-B-ALL with t(9;22), T-ALL, ALL with t(12;21), ALL with t(1;19), ALL with hyperdiploid karyotype, c-ALL/pre-B-ALL without specific genetic abnormalities, i.e. t(9;22), AML with t(8;21), AML with t(15;17), AML with inv(16)/t(16;16), AML with t(11q23)/MLL, AML with normal karyotype, AML with complex karyotype, CML, CLL, and MDS, as well as non-leukemic and healthy bone marrow samples as controls. We now report the data from the completed MILE Stage I, which included 2030 adult and pediatric samples utilizing HG U133 Plus 2.0 (Affymetrix). 102 (5%) were removed from the study for protocol violations, most often for an incomplete “Gold Standard”. All microarrays were also assessed for their technical performance (e.g. micorarray scaling factor, signal to noise ratio, etc.). In total only 36 samples (1.9%) failed these technical quality criteria. Cross validation accuracy (average of three 30-fold cross validations) of the remaining 1892 MILE Stage I samples is 95.4% concordant with the “Gold Standard” diagnosis. In ten classes the concordance was ≥97% i.e. for pro-B-ALL with t(11q23)/MLL, T-ALL, AML with t(8;21), AML with inv(16)/t(16;16), AML with normal karyotype, CLL, CML and MDS, as well as for the healthy or non-leukemia samples. The following classes showed lower sensitivities (range 74%-91%): mature B-ALL with t(8;14), c-ALL/pre-B-ALL with t(9;22), ALL with t(1;19), ALL with hyperdiploid karyotype, c-ALL/pre-B-ALL without specific abnormalities, AML with t(11q23)/MLL, and AML with complex karyotype. This can largely be explained by biological heterogeneity and weak “gold standard” definitions. It is notable that all these classes showed specificities above 98.4%. The second stage now prospectively process additional 1000 samples on a custom designed microarray using 1,449 probe sets only. So far 755 samples have been analyzed and will represent an independent and blinded test set for the algorithms developed in stage I. In conclusion, the MILE research study confirms that standardized microarray-based GEP may accurately classify leukemia samples into known diagnostic and prognostic sub-categories with a low technical failure rate and a very high accuracy.

Examination of a Large Patient Population for the Presence of Symptoms and Signs of Temporomandibular Disorders

Temporomandibular Disorder (TMD) is a term generally applied to a condition or conditions characterized by pain and/or dysfunction of the masticatory apparatus. Its characterization has been difficult because of the large number of symptoms and signs attributed to this disorder and to variation in the number and types manifested in any particular patient. For this study, data on 4,528 patients, presenting over a period of 25 years to a single examiner for TMD treatment, was made available for retrospective analysis and determination of whether the TMD care-seeking patient can be profiled, particularly pain difficulties. All patients in this database filled out a questionnaire and were examined for the prevalence of a range of symptoms and clinical examination findings (signs) commonly attributed to TMD. There was no attempt in this study to assign patients to TMD diagnostic subcategories. The data collected were analyzed to determine which of these symptoms and signs were sufficiently “characteristic of the TMD condition” that they might be used in diagnosis, research and treatment, especially in patients needing relief from pain and discomfort. All 4,528 patients reported symptoms and all but 190 of them also showed signs upon examination. Symptoms most commonly reported on the questionnaire included (i) pain (96.1%), (ii) headache (79.3%), (iii) temporomandibular joint discomfort or dysfunction (75.0%) and (iv) ear discomfort or dysfunction (82.4%). In the 4,338 patients who showed signs, the most prevalent was tenderness to palpation of the pterygoid muscles (85.1%), followed by tenderness to palpation of the temporomandibular joints (62.4%). Pain symptoms and signs were often accompanied by compromised mandibular movements, TMJ sounds and dental changes, such as incisal edge wear and excessive overbite. Clearly prevalence of pain disclosed by the symptoms and signs examinations was high. Patients showed variable prevalence and nonprevalence of eight categories of painful symptoms and seven categories of painful signs. Despite the variability, these might be developed in the future into TMD scores or indices for studying and unraveling the TMD conundrum.

Changes in the incidence of occupational disability as a result of back and neck pain in the Netherlands

BackgroundBack pain (including neck pain) is one of the most prevalent health problems for which physicians are consulted. Back pain can decrease the quality of life considerably during a great part of the lives of those who suffer from it. At the same time it has an enormous economic impact, mainly through sickness absence and long-term disability. The objective of this paper is to compare the incidence of occupational disability as a result of back and neck pain in 1980–1985 to 1999–2000 and to explain the findings.MethodsA descriptive study was performed at population level of changes in incidence of occupational disability as a result of back and neck pain. Statistics from the National Institute of Social Insurance in the Netherlands are used to calculate age and gender specific incidence rates for back pain diagnoses based on the ICD-classification. Incidence rate ratios stratified according to gender and adjusted for age were calculated to indicate changes over time.ResultsThe incidence of occupational disability as a result of back pain decreased significantly by 37% (95% CI 37%–38%) in men and with 21% (95% CI 20%–24%) in women, after adjustment for age. For overall occupational disability as a result of all diagnoses this was 18% (95% CI 18%–19%) and 34% (95% CI 33%–35%) respectively. Changes were not homogeneous over diagnostic subcategories and age groups. Spondylosis decreased most in men by 59% (95% CI 57%–61%). The incidence of non-specific back pain and neck pain increased most by 196% (95% CI 164%–215%). Post-laminectomy syndrome increased over all age categories both for men (85%, 95% CI 61%–113%) and women (113%, 95% CI 65%–179%).ConclusionThe decrease in occupational disability as a result of back pain was larger than the decrease in occupational disability over all diagnoses. However, time trends were not homogeneous over age-, nor over sex- nor back pain categories. Most of this decrease was due to general changes such as legal and economic changes. One of several additional explanations for a decrease is the changed view on management of back pain.

Sleep Complaints and Psychiatric Symptoms in Children Evaluated at a Pediatric Mental Health Clinic

To examine the association of sleep problems with psychiatric symptoms in children evaluated at a university-based outpatient child psychiatry clinic. Parents of 174 children attending psychiatric services completed a 47-item Childhood Sleep Questionnaire and the Behavioral Assessment System for Children. Psychiatric diagnosis was obtained through retrospective chart review. Sleep characteristics were compared among 4 diagnostic subcategories: attention-deficit/hyperactivity disorder (ADHD) alone (n=29), ADHD with comorbid mood and anxiety disorders (ADHD+; n=50), mood and anxiety disorders alone (n=67), and other psychiatric disorders (n= 28). Data from sleep habits survey of 174 community children without reported psychiatric history served as controls. Children with psychiatric disorders had a significantly higher prevalence of sleep complaints compared with nonpsychiatric controls. Children with ADHD had frequent nocturnal awakenings, bad dreams, and bedtime struggles. In addition, the presence of leg jerks during sleep was particularly frequent in patients with ADHD compared with any other psychiatric disorder. More frequent nighttime awakenings were present in children with mood and anxiety disorders. Sleep duration and sleep latency strongly correlated with aggression, hyperactivity, and depression. Restless sleep scores highly correlated with all psychiatric symptoms. Sleep problems are highly prevalent among children with psychiatric disorders. Children with ADHD and comorbid anxiety or mood disorders are more likely to report sleep disturbances. Restless sleep, long sleep latency, short sleep duration, and frequent nocturnal awakenings correlate with the severity of psychiatric symptoms.

Suicide Research Based on Danish Registers

In the last 5 years there has been a series of remarkable studies on suicide from Denmark based on their longitudinal case registers. These registers include the Danish Psychiatric Central Register, which since 1969 has recorded data on all psychiatric inpatients; the Integrated Data base for Labor Market Research, which contains sociodemographic data on all Danes, as well as market conditions; the Danish Civil Registration System, which contains a unique personal identifier which allows linkage to first degree relatives, the Cause of Death Register, and the Danish Twin Register (Qin et al., 2003; Tomassini et al., 2003). Although there had been descriptive data of over 50,000 suicides published in the mid-19th century in France by Lisle (1856), until the publication of this Danish work there had been nothing to match the sophisticated analyses on such large numbers of persons. For example, Qin et al. (2003) reported on 21,169 persons who died by suicide between 1981 and 1997 and 423,128 live comparison subjects. They used the population attributable risks (PAR) statistic, which allows for the delineation of the proportion of a condition that could be eliminated if certain risk factors could also be eliminated, thereby placing risk factors in perspective rather than simply acknowledging that any specific individual factor may be of statistical significance. By so doing they extended earlier work of Mortensen et al. (2000), and demonstrated that suicide risk was overwhelmingly associated with mental illness requiring hospitalization, which had a PAR of 40.3%. This was in contrast to the next significant factors being 25.8% for single marital status, 10.2% for being an aged pensioner, and 8.8% for having the lowest quartile income, factors which are hardly amenable to any intervention. These factors were in contrast to the PAR of 2.8% for unemployment, which, although still statistically significant and of importance in its own right, is probably of little practical relevance in terms of any broad community programs designed to prevent suicide. Mortensen et al. (2000) previously commented on the significance of such analyses, and they noted that “Reports of high relative risk and attributable risk associated with unemployment and other socioeconomic factors may be confounded and overestimated owing to the lack of adjustment for the association with mental disorders.” The PAR statistic allows for such adjustment, and it is only by having access to such large data bases and using newer statistical techniques that this perspective can be fully appreciated. In other studies examining those with mood disorders, Hoyer et al. (2004) reported that suicide was the cause of death for 6% of 53,466 patients who were admitted for an affective disorder between 1973 and 1993, and Kessing (2004) analyzed data more recent than the 10th version of the International Classification of Diseases (ICD) in Denmark in 1994 to demonstrate that there was an increasing gradation of suicide risk for those who had mild, moderate, and severe depression. This demonstrated the utility of the ICD diagnostic subcategories based on a dimensional view of depression, and confirmed clinical beliefs about the prognosis and suicide risk of those with increasing degrees of depression. A further demonstration of the powerful statistical capabilities of these registers is provided by a study examining the effect of children in modifying suicide risk in adults. It has generally been considered that the presence of children is a protective factor, and Qin and Mortensen (2003) have confirmed this in research on 18,611 suicides between 1981 and 1997. Indeed, the numbers allowed detailed analyses which demonstrated that parents with children who died or who had been hospitalized for psychiatric illness had a greater risk of suicide, and the risk was even higher if the death of the child was by suicide. Similar clinically useful findings confirming the value of family ties as a protection against suicide have emerged from the twin study of Tomassini et al. (2003), who followed 21,653 individual twins who were alive in 1943 for

Children's Communication Checklist (CCC) scores in 11-year-old children with communication impairments.

The pragmatic skills of children with communication disorders and their assessment are currently an issue for speech and language therapy and educational placement. To explore whether different subgroups of children with communication disorders score differently on the Children's Communication Checklist (CCC) and to study how they compare with published normative data. A sample of 161 eleven-year-old children with a history of communication disorders was assessed using the CCC. The main use of this questionnaire was to establish whether pragmatic impairments were part of a child's communication difficulty. Although the checklist was originally designed for research purposes, normative data for this scale have been recently published as well as group data from a number of different clinical groups. Whilst the present CCC data have been previously reported descriptively for a wider sample, they have not been examined in terms of subgroups or compared directly with normative information and similarly diagnosed individuals from other studies. Of the children assessed, 52 (33%) scored in the normal range (within 1 SD) on the pragmatic scale, 40 (26%) fell between 1 and 2 SD below the normative mean, and 64 (41%) scored below 2 SD of the mean of typically developing children (aged 6-16 years). Thus, the majority (67%) scored out of the normal range for pragmatic skill at 11 years of age. The cohort was separated into four diagnostic subcategories: those with a definite diagnosis of autistic spectrum disorder (n=15); those with typical specific language impairment (n=82); generally impaired (n=37); and those with a clinical history of primary pragmatic language impairment (independent of CCC score, n=27). Findings show that those generally impaired and with specific language impairment were less impaired than the other groups on the CCC pragmatic scale. There was a significant trend for those with autistic spectrum disorders to score lowest through pragmatic language impairment, generally impairment to specific language impairment. It is argued that a cut-off of 140 may prove more useful at this age than the 132 level previously published for 8 year olds. Results suggest that the CCC can be used as a clinical tool, but in conjunction with other reliable measures.

Primary anaplastic lymphoma kinase-negative anaplastic large cell lymphoma of the brain in a patient with acquired immunodeficiency syndrome.

Abstract Anaplastic large cell lymphoma is a unique diagnostic subcategory of the T-cell lymphomas in the current World Health Organization classification. Representing approximately 3% of adult and 10% to 30% of childhood non-Hodgkin lymphomas, anaplastic large cell lymphoma classically consists of CD30+ large lymphoid cells with abundant cytoplasm and pleomorphic, often horseshoe-shaped or kidney-shaped nuclei. Among the reported nodal and extranodal sites of occurrence, the gastrointestinal tract and central nervous system have rarely been noted. We report a case of primary anaplastic lymphoma kinase–negative anaplastic large cell lymphoma in the brain of a 46-year-old patient with acquired immunodeficiency syndrome. T-cell lineage was confirmed by T-cell receptor γ chain gene rearrangements using polymerase chain reaction, and extra copies of the anaplastic lymphoma kinase gene of chromosome 2 were demonstrated by fluorescence in situ hybridization analysis. To our knowledge, primary anaplastic large ...

Is all chronic pain the same? A 25-year follow-up study

Many apparently distinctive clinical syndromes of pain and dysfunction show considerable overlap in both population and clinical settings. If the explanation is that they all share a common underlying mechanism, then we hypothesize that any one syndrome will be unlikely to retain its distinctiveness over time. Consultation data from general practice records for 10,073 women, collected between 1968 and 1978, was linked with information on pain complaints obtained from a subsequent postal survey carried out in 1994. Illness episodes were identified from the general practice records and grouped into diagnostic subcategories. Associations between these and future pain complaints were explored, adjusting for age, smoking, body mass index and social class in a series of nested case–control analyses. Overall, the strongest independent associations of current pain were with episodes of musculoskeletal illness and mental disorders recorded 15–25 years earlier; these associations were more marked for widespread pain (odds ratios 1.8 and 1.7, respectively) than for non-widespread pain (ORs 1.3 and 1.2, respectively). In analyses of specific illness subcategories, the strongest links for head and neck pain were with earlier migraine. Back pain was most strongly associated with earlier back complaints, and abdominal pain with earlier intestinal-related problems. By contrast, chest pain was most strongly linked with earlier psychological illness. Earlier soft tissue illness episodes showed no distinctive patterns of associations over time with subsequent regional pain complaints. This analysis provides some support for shared mechanisms of chronicity across regional pain complaints, particularly in relation to the earlier occurrence of mental illness and the development of widespread pain. However, there is strong evidence that regional pain complaints also track distinctively over time. This argues against chronic functional and pain syndromes all being the same problem with a common mechanism of persistence, and in favor of unique regional influences on chronicity as well.

Geographic and temporal analysis of folate-sensitive fetal malformations.

To identify potential geographic and temporal clustering of folate-sensitive fetal malformations as a prelude to a targeted preconception curriculum in folic acid supplementation. Our comprehensive prenatal anomaly database was queried to select fetal malformations presumed to be sensitive to preconception folate insufficiency. Evidence of geographic clustering was evaluated by distribution of individual cases using zip codes of maternal residence. Potential temporal clustering of anomalies was sought by tabulating the frequency of each anomaly category during 5 consecutive 2-year intervals between 1992 and 2001. Over a 10-year period, approximately 2000 fetal anomalies were identified, of which 400 (20%) were considered potentially folate sensitive. We found geographic clustering of ventral wall defects as well as obstructive uropathy by zip code analysis. Significant increases in the frequencies of cardiac defects (P <.001) and obstructive uropathy (P <.001) were noted during the epoch of this study. A moderate increase in anomaly frequency was also seen in the diagnostic subcategory of gastroschisis, in which 15 of 27 total gastroschisis cases occurred in 2000-2001. Geographic clustering and temporal trends in anomaly rates were noted in certain folate-sensitive malformation categories. Identification of specific, high-incidence regions may provide an opportunity for targeted interventions designed to supplement the national folic acid campaign.

Assesssing the prevalance and exploring the aetiology of intellectual disability in the early twentieth century: the experience of policy and practice in New South Wales

From the beginning of the twentieth century to the failure of the passage of the New South Wales Mental Defectives Bill in 1930, several investigations were conducted in an attempt to assess the prevalence of intellectual disability in the Australian community. During this period, 7252 people were admitted to state mental hospitals in New South Wales with a diagnosis of congenital or infantile mental deficiency, including the diagnostic subcategories of epileptic insanity and general paralysis of the insane. Using primary source material including annual reports of the New South Wales Lunacy Department, New South Wales Inspector General of the Insane Correspondence Files, and aggregated diagnostic data from patient case notes, this article will discuss attempts to assess the prevalence of intellectual disability in Australia and more specifically in New South Wales during the period and attempts to attribute causation. Epilepsy and syphilis will be discussed in terms of causation and correlation as specific co-morbid conditions associated with intellectual disability.

Mental health insurance claims among spouses of frequent business travellers

Objectives: Following up on two earlier publications showing increased psychological stress and psychosocial effects of travel on the business travellers this study investigated the health of spouses of business travellers....