The top 10 research priorities in diabetes and pregnancy according to women, support networks and healthcare professionals.

AIMS: To undertake a Priority Setting Partnership (PSP) to establish priorities for future research in diabetes and pregnancy, according to women with experience of pregnancy, and planning pregnancy, with any type of diabetes, their support networks and healthcare professionals. METHODS: The PSP used established James Lind Alliance (JLA) methodology working with women and their support networks and healthcare professionals UK-wide. Unanswered questions about the time before, during or after pregnancy with any type of diabetes were identified using an online survey and broad-level literature search. A second survey identified a shortlist of questions for final prioritisation at an online consensus development workshop. RESULTS: There were 466 responses (32% healthcare professionals) to the initial survey, with 1161 questions, which were aggregated into 60 unanswered questions. There were 614 responses (20% healthcare professionals) to the second survey and 18 questions shortlisted for ranking at the workshop. The top 10 questions were: diabetes technology, the best test for diabetes during pregnancy, diet and lifestyle interventions for diabetes management during pregnancy, emotional and well-being needs of women with diabetes pre- to post-pregnancy, safe full-term birth, post-natal care and support needs of women, diagnosis and management late in pregnancy, prevention of other types of diabetes in women with gestational diabetes, women's labour and birth experiences and choices and improving planning pregnancy. CONCLUSIONS: These research priorities provide guidance for research funders and researchers to target research in diabetes and pregnancy that will achieve greatest value and impact.

IL-7Rαlow memory CD8+ T cells are significantly elevated in patients with systemic lupus erythematosus.

OBJECTIVE: Human effector memory (EM) CD8(+) T cells include IL-7Rα(high) and IL-7Rα(low) cells with distinct cellular characteristics, including the expression of cytotoxic molecules. Both NK cells and the NK cell-associated molecule 2B4 that is expressed on CD8(+) T cells promote cytotoxicity. Here we analysed the expression of 2B4 on IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells and its contribution to cytotoxicity. We also analysed the frequency of IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells in patients with SLE or lupus and in healthy individuals given the potential role of cytotoxic CD8(+) T cells in the pathogenesis of lupus. METHODS: We used flow cytometry to measure the expression of 2B4 on IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells as well as the frequency of these cell populations in the peripheral blood of healthy individuals and patients with SLE. Also, 2B4-mediated cytotoxicity was quantitated in IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells using target cells with CD48 antigen. RESULTS: We found that IL-7Rα(high) EM CD8(+) T cells had higher levels of 2B4 expression compared with IL-7Rα(low) EM CD8(+) T cells. Triggering 2B4 enhanced the cytotoxic function of IL-7Rα(low) EM CD8(+) T cells against target cells. We also noticed that patients with SLE had an increased frequency of IL-7Rα(low) EM CD8(+) T cells that correlated with disease manifestation. CONCLUSION: Our findings show that SLE patients have increased IL-7Rα(low) EM CD8(+) T cells, possibly contributing to tissue damage through 2B4-mediated cytotoxicity.

Regulating human Th17 cells via differential expression of IL-1 receptor.

In humans, interleukin-1beta (IL-1beta) has been suggested as an essential cytokine for developing IL-17- or IL-17A-producing CD4(+) T helper 17 (Th17) cells. However, little is known about the relationship of IL-1 receptor expression and Th17 cell differentiation. We report here the presence of 2 distinct CD4(+) T-cell populations with and without expression of IL-1RI that correlates with the capacity to produce IL-17 in naive and memory CD4(+) T cells of human peripheral blood. IL-1RI(+) memory CD4(+) T cells had increased gene expression of IL17, RORC, and IRF4 even before T-cell receptor triggering, indicating that the effect of IL-1beta is programmed in these cells via IL-1RI. Although CD4(+) T cells from umbilical cord blood did not express IL-1RI, the cytokines IL-7, IL-15, and transforming growth factor-beta (TGF-beta) up-regulated IL-1RI expression on naive CD4(+) T cells, suggesting that IL-1RI(+) naive CD4(+) T cells develop in periphery. Furthermore, IL-17 production from the cytokine-treated naive CD4(+) T cells was induced by IL-1beta and this induction was blocked by IL-1R antagonist. These results indicate that human Th17 cell differentiation is regulated via differential expression of IL-1RI, which is controlled by IL-7 and IL-15.

Improving the fit of filtering facepiece respirators.

Aims To assess the effectiveness and acceptability of smartphone customised frame technology to improve the fit of disposable filtering facepiece class 3 (FFP3) respirators for dental staff who previously failed fit testing.Method In total, 20 volunteers who previously failed FFP3 fit testing were recruited to use smartphone technology (Bellus3D FaceApp) to have a 3D-printed bespoke face frame produced for them. They underwent qualitative fit testing with and without the frame with two freely available disposable FFP3 respirator designs (mask A: GVS F31000 Segre folded model; mask B: Valmy Spireor). The order of testing was random. Ease of use of the smartphone technology and the comfort of the frame were determined by questionnaire.Results Fit test passes increased from 5% without the frame to 70% and 95%, respectively, for masks A and B with the frame (p <0.01). Very few participants reported using the technology as difficult (n = 1/20) or the frame uncomfortable (n = 3/20) or difficult to wear (n = 0/20).Conclusion Customised frames produced using smartphone technology improved qualitative fit test pass rates for two commonly available FFP3 respirators. Using smartphone technology for frame design, wearing a frame and frame comfort levels were all acceptable to the majority of participants.

Mycobacterium szulgai pulmonary infection in a woman with anorexia nervosa.

A 40-year-old woman with severe anorexia nervosa was found to have a bilateral pulmonary infection with rare atypical mycobacterium Mycobacterium szulgai. Of note, she had no preexisting structural lung disease or history of tuberculosis, smoking, or HIV. Current data suggest that both impaired cell-mediated immunity and altered respiratory mechanics are risk factors for mycobacterial infection in patients with anorexia nervosa.

Association of cognitive distortions with problem and pathological gambling in adult male twins.

Treatment studies suggest that gambling-related irrational beliefs and attitudes (i.e., cognitive distortions (CDs)) contribute to the risk for problem gambling behavior. In a community sample of men, we investigated the associations among lifetime gambling-related CDs, psychiatric disorders other than pathological gambling , and problem gambling severity. Subjects were 1354 members of the Vietnam Era Twin Registry. Problem gambling and gambling-related CDs were derived from a 2002 interview using the National Opinion Research Center DSM-IV Screen for Gambling Problems (NODS). Exploratory factor analysis was performed with the 12 CD items to identify an underlying construct. Generalized linear models were computed to test for associations among CDs, psychiatric disorders other than pathological gambling, and gambling problem severity. Co-twin control analyses of monozygotic twin pairs discordant for problem gambling severity adjusted for genetic and shared environmental influences. Twelve CD items related to one underlying CD construct. After adjustment for lifetime psychiatric disorders, pathological gambling symptoms were positively associated with higher CD scores. Pathological gambling symptoms remained significantly associated with CD scores after controlling for genetic and shared environmental influence. These results provide empirical support for an association between gambling-related CDs and gambling problem severity, even after controlling for genetic and shared environmental influences and non-pathological gambling psychiatric disorders. Public health messages and therapeutic interventions that reinforce the randomness of gambling and draw attention to distorted thinking may prevent the development of problem gambling and improve treatment outcomes.

Factors associated with pathological gambling at 10-year follow-up in a national sample of middle-aged men.

BACKGROUND: The present analyses will expand on previous reports by considering the impact of eight psychiatric disorders and genetic vulnerability to problem (P) and pathological gambling gambling (PG). methods: Diagnoses of DSM-III-R life-time P and PG were derived in 1992 and past-year P and PG in 2002 from 1675 individual twins from the Vietnam Era Twin Registry. Logistic regression was used to predict past-year P and PG as a function of socio-demographics and life-time co-occurring psychiatric disorders including gambling problems measured in 1992. Co-twin analyses accounted for familial contributions to past-year gambling problems. RESULTS: High school or greater educational attainment was associated with less likelihood of current P and PG. With the exception of alcohol dependence and generalized anxiety/panic, all disorders studied remained associated significantly with an increase risk of past-year P and PG after adjusting for 1992 gambling symptoms. Past-year P and PG was associated significantly with the number of pathological gambling symptoms reported in 1992. After controlling for genetic and family environmental factors, one or more 1992 symptoms were associated with 2002 symptoms. CONCLUSIONS: Education and substance dependence, mood and antisocial personality disorders were associated with current gambling. A history of PG symptoms is the strongest predictor of past-year problem gambling.

Course of pathological gambling symptoms and reliability of the Lifetime Gambling History measure.

The DSM-IV describes pathological gambling as a chronic condition with an insidious course. However, several extant studies characterize pathological and problem gambling as fluctuating over time. The present analyses expand on previous reports by evaluating changes in pathological gambling symptoms across the lifetime. DSM-IV pathological gambling symptoms were assessed retrospectively to derive diagnoses and capture changes in symptoms over time using the Lifetime Gambling History (LGH) in a sample of 1343 middle aged males from the Vietnam Era Twin (VET) Registry. Two to four weeks after initial assessment, 196 participants were re-assessed to determine test-retest reliability of the LGH. A greater number of lifetime symptoms was associated with a higher number of changes in gambling patterns. Fluctuations in pathological gambling symptoms were common among individuals who reported two or more gambling phases, with decreases in symptoms reported as frequently as increases. Reliability data revealed high reliability in reports of pathological gambling symptom endorsement and age of symptom onset. Results are consistent with findings from community based studies that describe the course of problem gambling behaviors as changing over time. Evidence is also provided for the utility of the LGH in assessing lifetime pathological gambling symptoms.

Genetic and environmental contributions to pathological gambling symptoms in a 10-year follow-up.

Problem (P) and pathological gambling (PG) symptoms wax and wane. Past symptoms are a risk for future symptoms even after controlling for familial influences. To address the genetic architecture of lifetime PG and current PG symptoms, we tested for common and unique genetic factors to lifetime PG symptoms at baseline and past year PG symptoms at 10-year follow-up. Diagnostic and Statistical Manual of Mental Disorders (3rd ed., Rev.; DSM-III-R; American Psychiatric Association, 1987) lifetime criteria of one or more PG symptoms were derived in 1992 and past year PG symptoms in 2002 from 1675 individual twins from the Vietnam Era Twin Registry. Cholesky decomposition models were fit to baseline and past year PG symptoms. Under the best fitting model we observed that 49% of the risk for one or more baseline PG symptoms in 1992 was due to a genetic factor and 51% of the risk was due to a unique environmental factor. All of the genetic variance (57.5%) in risk to past year PG symptoms in 2002 was common with baseline PG symptoms. Unique environment accounted for the remaining variance in past year PG symptoms with 13% common to baseline and 30% specific to past year PG symptoms. The genetic contributions to lifetime and past year gambling symptoms 10 years later are similar. There is no evidence for genetic contributions unique to past year PG symptoms. However, most of the unique environmental influences to past year PG are not shared with lifetime PG. This may reflect the changed social-cultural environment between 1992 and 2002, characterized by increasing access to legalized gambling.

Characteristics of Clostridium difficile infection in patients hospitalized with myelodysplastic syndrome or acute myelogenous leukemia.

AIM: To evaluate factors associated with Clostridium difficile infection (CDI) and outcomes of CDI in the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) population. METHODS: After IRB approval, all MDS/AML patients hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center between August 2011 and December 2013 were identified. Medical charts were reviewed for demographics, clinical information, development of CDI, complications of CDI, and mortality. Patients with CDI, defined as having a positive stool PCR done for clinical suspicion of CDI, were compared to those without CDI in order to identify predictors of disease. A t-test was used for comparison of continuous variables and chi-square or Fisher's exact tests were used for categorical variables, as appropriate. RESULTS: Two hundred and twenty-three patients (60.1% male, mean age 61.3 years, 13% MDS, 87% AML) had 594 unique hospitalizations during the study period. Thirty-four patients (15.2%) were diagnosed with CDI. Factors significantly associated with CDI included lower albumin at time of hospitalization (P < 0.0001), prior diagnosis of CDI (P < 0.0001), receipt of cytarabine-based chemotherapy (P = 0.015), total days of neutropenia (P = 0.014), and total days of hospitalization (P = 0.005). Gender (P = 0.10), age (P = 0.77), proton-pump inhibitor use (P = 0.73), receipt of antibiotics (P = 0.66), and receipt of DNA hypomethylating agent-based chemotherapy (P = 0.92) were not significantly associated with CDI. CONCLUSION: CDI is common in the MDS/AML population. Factors significantly associated with CDI in this population include low albumin, prior CDI, use of cytarabine-based chemotherapy, and prolonged neutropenia. In this study, we have identified a subset of patients in which prophylaxis studies could be targeted.

Shared genetic contributions to pathological gambling and major depression in men.

CONTEXT: Although pathological gambling (PG) and major depression (MD) frequently co-occur, little is known regarding the relative contributions of environmental and genetic factors to the codevelopment of the disorders. OBJECTIVES: To estimate environmental and genetic contributions to PG and MD as defined in DSM-III-R and the lifetime co-occurrence of PG and MD. DESIGN: Survey data from the Vietnam Era Twin Registry were examined in biometric models. SETTING: Telephone interview. PARTICIPANTS: Of 10, 253 eligible participants, 7869 were successfully interviewed. MAIN OUTCOME MEASURES: Estimated genetic, shared environmental, and unique environmental contributions to PG and MD and their lifetime co-occurrence in bivariate models. RESULTS: Elevated odds ratios for MD were associated with those of PG (4.06; 95% confidence interval, 2.68-6.13), and the association remained significant following adjustment for sociodemographic and other psychiatric variables (odds ratio = 1.98; 95% confidence interval, 1.14-3.45). The best-fitting bivariate model indicated that 66% of the variance in PG and 41% of the variance in MD were owing to genetic factors, and 34% of the variance in PG and 59% of the variance in MD were owing to unique environmental factors. There was a substantial correlation between the genetic components of PG and MD (r(A) = 0.58), with 34% of the genetic variance for each disorder also contributing to that of the other. The best-fitting model estimated that 100% of the total overlap between PG and MD was genetic. CONCLUSIONS: The correlation between PG and MD in middle-aged men appears to be largely influenced by overlapping genetic factors. Future research is needed to determine the extent to which these findings extend to other groups (eg, women), identify specific genes, and generate improved prevention and treatment strategies.

Effect of genes, environment, and lifetime co-occurring disorders on health-related quality of life in problem and pathological gamblers.

BACKGROUND: Problem and pathological gambling are associated with many impairments in quality of life, including financial, family, legal, and social problems. Gambling disorders commonly co-occur with other psychiatric disorders, such as alcoholism and depression. Although these consequences and correlates have been reported, little is known about the health-related functional impairment associated with gambling. OBJECTIVE: To model differences in the health-related quality of life (HRQoL) among non-problem gamblers, problem gamblers, and pathological gamblers after controlling for lifetime co-occurring substance use disorders, psychiatric disorders, sociodemographics, and genetic and family environmental influences. DESIGN: Cohort and co-twin studies. SETTING: Nationally distributed community sample. PATIENTS: Male twin members of the Vietnam Era Twin Registry: 53 pathological gamblers, 270 subclinical problem gamblers, and 1346 non-problem gamblers (controls). INTERVENTIONS: We obtained HRQoL data, via the 8-Item Short-Form Health Survey, from all participants. Data from a subset of twin pairs discordant for gambling behavior was used to control for genetic and family environmental effects on HRQoL and problem gambling. Main Outcome Measure Health-related quality of life. RESULTS: Results from adjusted logistic regression analyses suggest little difference across groups in the physical domains of the health survey; however, for each mental health domain, pathological gamblers had lower HRQoL scores than problem gamblers (P<.05), who in turn had lower scores than non-problem gamblers (P<.05). After controlling for genes and family environment, no significant differences existed between the non-problem gambling twins and their problem or pathological gambling brothers, but adjusted co-twin analyses resulted in statistically significant differences in 4 of 8 subscales. CONCLUSIONS: Pathological and problem gambling are associated with significant decrements in HRQoL. This association is partly explained by genetic and family environmental effects and by lifetime co-occurring substance use disorders. Implications for clinicians, health care utilization, and public health issues are discussed.

Genetic studies of pathological gambling: a review of methodology and analyses of data from the Vietnam Era Twin Registry.

Twin studies represent an important and powerful approach to estimating the relative contributions of environmental and genetic factors to the expression of psychiatric illnesses. In this article, we first explain the rationale for using large populations of monozygotic and dizygotic twin pairs to estimate genetic and environmental contributions to a disorder and the statistical modeling associated with this approach. We then review results from studies of the Vietnam Era Twin Registry that use this methodology to examine the etiology of pathological gambling (PG) behaviors. The results provide strong evidence for genetic contributions to the development of PG in men and set the foundation for future studies aimed at identifying the manner in which specific genes and environmental factors individually and in conjunction contribute to PG.

Longitudinal driving performance in early-stage dementia of the Alzheimer type.

OBJECTIVES: To longitudinally assess on-road driving performance in healthy older adults and those with early-stage dementia of the Alzheimer type (DAT). DESIGN: A prospective longitudinal study. SETTING: Large urban medical center and surrounding area. PARTICIPANTS: A sample of 58 healthy controls, 21 participants with very mild DAT, and 29 participants with mild DAT participated. DAT was diagnosed using validated clinical diagnostic criteria and staged according to the Clinical Dementia Rating (CDR) Scale. MEASUREMENTS: Healthy controls and individuals with very mild DAT and mild DAT were administered a standardized on-road driving assessment over repeated times of testing. RESULTS: Subjects in the CDR=1 group (mild DAT) had a faster rate of receiving a rating of not safe on the driving test than subjects in the CDR=0 group (healthy controls; log rank test, P=.006), and the survival function of the CDR=0.5 group (very mild DAT) fell between those of the CDR=0 and CDR=1 groups. A Cox proportional hazards model indicated a significant difference in survival functions between the CDR=0 and CDR=1 groups after baseline age was controlled for (P<.001). Cox regression analysis also indicated that baseline age was a significant risk factor for a rating of "not safe" (P=.002). CONCLUSION: This study provides longitudinal evidence for a decline in driving performance over time, primarily in early-stage DAT, and supports the need not only for driving assessments, but also for reevaluation of individuals with very mild and mild DAT.

Identifying factors to improve oral cancer screening uptake: a qualitative study.

AIMS: To engage with high risk groups to identify knowledge and awareness of oral cancer signs and symptoms and the factors likely to contribute to improved screening uptake. METHODS: Focus group discussions were undertaken with 18 males; 40+ years of age; smokers and/or drinkers (15+ cigarettes per day and/or 15+ units of alcohol per week), irregular dental attenders living in economically deprived areas of Teesside. RESULTS: There was a striking reported lack of knowledge and awareness of oral cancer and its signs and symptoms among the participants. When oral/mouth cancer leaflets produced by Cancer Research UK were presented to the participants, they claimed that they would seek help on noticing such a condition. There was a preference to seek help from their general practitioner rather than their dentist due to perceptions that a dentist is 'inaccessible' on a physical and psychological level, costly, a 'tooth specialist' not a 'mouth specialist', and also not able to prescribe medication and make referrals to specialists. Interestingly, none of the 18 participants who were offered a free oral cancer examination at a dental practice took up this offer. CONCLUSIONS: The uptake of oral cancer screening may be improved by increasing knowledge of the existence and signs and symptoms of oral cancer. Other factors that may increase uptake are increased awareness of the role of dentists in diagnosing oral cancer, promotion of oral cancer screening by health professionals during routine health checks, and the use of a "health" screening setting as opposed to a "dental" setting for such checks.

Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus.

INTRODUCTION: Interleukin (IL)-17 is a proinflammatory cytokine that is produced largely by a unique CD4(+) T-helper (Th) subset called Th17 cells. The development of Th17 cells is suppressed by interferon (IFN)-gamma produced by Th1 cells, suggesting cross-regulation between Th17 and Th1 cells. Thus, this study analyzed the balance of CD4+ Th17 and Th1 cell responses in peripheral blood from patients with systemic lupus erythematosus (SLE) and healthy subjects. METHODS: Twenty-five adult patients with SLE and 26 healthy subjects matched for gender and age (+/- 2 years) were recruited. Peripheral blood mononuclear cells (PBMCs) from patients and healthy subjects were stimulated for 4 h ex vivo with phorbol myristate acetate (PMA) and ionomycin. The frequency of CD4(+) T cells producing IL-17 and/or IFN-gamma was measured by using flow cytometry. Expression of Th17-associated chemokine receptors CCR4 and CCR6 on CD4(+) T cells as well as plasma levels of Th17-polarizing cytokines were assessed. Disease activity was evaluated by the SLE disease activity index score (SLEDAI). Unpaired t test and Pearson correlation were used for statistical analyses. RESULTS: Patients with SLE had an increased frequency of CD4(+)IL-17(+) T cells compared with healthy subjects. However, the frequency of CD4(+)IFN-gamma(+) T cells was similar between the two groups, indicating an altered balance of Th17 and Th1 cell responses in SLE. Patients with SLE also had an increased frequency of CD4(+)CCR4(+)CCR6(+) T cells that are known to produce IL-17. The frequency of CD4(+)IL-17(+) T cells and CD4(+)CCR4(+)CCR6+ T cells correlated with disease activity. In measuring plasma levels of the Th17-polarizing cytokines, levels of IL-6 were higher in patients with SLE than in healthy subjects, although levels of IL-1beta, IL-21, IL-23, and transforming growth factor (TGF)-beta were not different between the two groups. CONCLUSIONS: We demonstrate an enhanced Th17 cell response that correlates with disease activity in patients with SLE, suggesting a role for IL-17 in the pathogenesis of lupus. Our data indicate that the mechanisms involved in balancing Th1 and Th17 regulation, as well as in producing IL-6, are aberrant in SLE, leading to an increased Th17 response. We suggest that CCR4 and CCR6 expression on CD4(+) T cells should be considered as markers of disease activity, and that IL-17 blocking may offer a therapeutic target in SLE.

A Latent Class Analysis of DSM-III-R Pathological Gambling Criteria in Middle-Aged Men: Association with Psychiatric Disorders.

PURPOSE: : This study was designed to empirically derive latent classes based on PG criteria and to assess the association between nongambling psychiatric disorders and specific classes. METHODS: : A total of 8138 community-based middle-aged men were surveyed, and 2720 were assessed for Diagnostic Interview Schedule, Version 3, Revised (DIS-III-R) pathologic gambling (PG). Latent class analysis (LCA) was applied to Diagnostic and Statistical Manual Version 3, Revised (DSM-III-R) criteria to identify gambling classes. χ and logistic regression models evaluated the association between gambling classes and lifetime psychiatric disorders. RESULTS: : The final model included 4 classes: class 0 (ie, 5418 individuals who never gambled 25 or more times per year) and classes 1-3 (identified by the LCA and comprising 2720 respondents assessed for PG). For the 9 individual criteria of PG, endorsement percentages ranged from 2%-6%, 4%-58%, and 53%-100% for classes 1-3, respectively. Nongambling psychiatric disorders were differentially associated with the 4 gambling classes, and psychopathology was more common in groups more frequently acknowledging PG criteria. CONCLUSIONS: : Empirical support is provided for distinct classes of gambling behaviors demonstrating differential associations with individual PG criteria and nongambling psychiatric disorders. The data-driven categorization of gambling behaviors provides direction for research on defining, preventing, and treating syndromal and subsyndromal PG.

Association between exposure to childhood and lifetime traumatic events and lifetime pathological gambling in a twin cohort.

The present study seeks to estimate the strength of the association between exposure to lifetime traumatic events and gambling problems while accounting for the potential contribution of psychiatric disorders, genetic factors, and family environmental influences. In 2002, structured diagnostic interviews were conducted with 1675 male twins to obtain data on exposure to traumatic events and pathological gambling. Multinomial regression tested for associations between each traumatic event and three levels of problem gambling (1-2 symptoms, at risk; 3-4 symptoms, problem gambling, and 5 or more symptoms, pathological gambling). Analyses of data from twin pairs discordant for gambling behavior controlled for genetic and family environmental factors. After adjustment for covariates, child abuse (relative risk [RR]=2.31), child neglect (RR=5.53), witnessing someone badly hurt or killed (RR=2.83), and physical attack (RR=3.39) were associated with pathological gambling. Genetic and family environmental factors significantly contributed to the association between exposure to traumatic events and one or more symptoms of problem gambling. Exposure to childhood and lifetime traumatic events are significantly associated with problem and pathological gambling. These associations are partially accounted for by psychiatric covariates and genetic and family environmental factors.

Impaired physical performance and the assessment of dementia of the Alzheimer type.

CONTEXT: Impaired physical performance may confound the clinical assessment of dementia of the Alzheimer type (DAT). OBJECTIVES: Determine whether: (1) Physical Performance Test (PPT) scores are associated with the Clinical Dementia Rating (CDR), (2) PPT scores are correlated with clinical measures of health, and (3) impaired physical performance affects the clinical assessment of DAT. DESIGN: A retrospective and cross-sectional study. SETTING: An Alzheimer's Disease Research Center. PARTICIPANTS: Ninety-nine research volunteers aged 85 years and older were assessed from September 1997 through July 1999; 45 had DAT (CDR = 0.5-2), and 54 were nondemented controls. MEASUREMENTS: Clinical health history, daily functioning, physical and neurologic status, CDR, sum of boxes, and total PPT score were obtained during clinical evaluation. Independently assessed psychometric measures of verbal and nonverbal episodic and semantic memory, visuospatial abilities, and psychometric speed yielded to a factor score representing general cognitive function. Our outcome measure was the CDR (ie, the clinical dementia rating, where higher scores indicate greater dementia severity). RESULTS: The majority (88%) of subjects in this sample of demented and nondemented older adults had some degree of physical impairment as measured by the PPT. Correlational analyses identified clinically important relationships (/taub/ > 0.30, p < 0.05) between impaired PPT performance, higher CDR rating, and poor general health, including difficulty ambulating. The correlation between PPT performance and dementia severity (taub = -0.36) decreased after controlling for cognitive ability (taub = -0.19). The correlation between the cognitive factor score and dementia severity when PPT performance was controlled (taub = -0.60) was similar to the unadjusted correlation of the factor score with dementia severity (taub = -0.64). CONCLUSIONS: The presence of some degree of physical impairment was common in our sample, and PPT scores correlated with both physical and cognitive impairment. Nevertheless, Alzheimer Disease Research Center clinicians appear able to successfully distinguish between physical and cognitive causes of functional impairment and assign a CDR rating that accurately reflects DAT severity in individuals with impaired physical performance.