Prevalence and prognostic significance of cardiac autonomic neuropathy in community-based people with type 2 diabetes: the Fremantle Diabetes Study Phase II.

BACKGROUND: There is a paucity of contemporary data on the prevalence and prognostic significance of cardiac autonomic neuropathy (CAN) from community-based cohorts with type 2 diabetes assessed using gold standard methods. The aim of this study was to assess these aspects of CAN in the longitudinal observational Fremantle Diabetes Study Phase II (FDS2). METHODS: FDS2 participants were screened at baseline using standardised cardiovascular reflex tests (CARTs) of heart rate variation during deep breathing, Valsalva manoeuvre and standing. CAN (no/possible/definite) was assessed from the number of abnormal CARTs. Multinomial regression identified independent associates of CAN status. Cox proportional hazards modelling determined independent baseline predictors of incident heart failure (HF) and ischaemic heart disease (IHD), and all-cause mortality. RESULTS: Of 1254 participants assessed for CAN, 86 (6.9%) were outside CART age reference ranges and valid CART data were unavailable for 338 (27.0%). Of the remaining 830 (mean age 62.3 years, 55.3% males, median diabetes duration 7.3 years), 51.0%, 33.7% and 15.3% had no, possible or definite CAN, respectively. Independent associates of definite CAN (longer diabetes duration, higher body mass index and resting pulse rate, antidepressant and antihypertensive therapies, albuminuria, distal sensory polyneuropathy, prior HF) were consistent with those reported previously. In Kaplan-Meier analysis, definite CAN was associated with a lower likelihood of incident IHD and HF versus no/possible CAN (P < 0.001) and there was a graded increase in all-cause mortality risk from no CAN to possible and definite CAN (P < 0.001). When CAN category was added to the most parsimonious models, it was not a significant independent predictor of IHD (P ≥ 0.851) or HF (P ≥ 0.342). Possible CAN (hazard ratio (95% CI) 1.47 (1.01, 2.14), P = 0.046) and definite CAN (2.42 (1.60, 3.67), P < 0.001) increased the risk of all-cause mortality versus no CAN. CONCLUSIONS: Routine screening for CAN in type 2 diabetes has limited clinical but some prognostic value.

Determinants of quality of life in family caregivers in MCI: a comparison with mild dementia.

OBJECTIVES: The aim of the current study was to investigate the health-related quality of life (HRQol) of the family caregiver in MCI, explore possible determinants and study possible differences with mild dementia. METHODS: This secondary data analysis included 145 persons with MCI and 154 persons with dementia and their family caregivers from two Dutch cohort studies. HRQoL was measured with the VAS of the EuroQol-5D-3L version. Regressions analyses were conducted to examine potential demographic and clinical determinants of the caregiver's HRQoL. RESULTS: The mean EQ5D-VAS in family caregivers of persons with MCI was 81.1 (SD 15.7), and did not significantly differ from family caregivers in mild dementia (81.9 (SD 13.0)). In MCI, patient measurements were not significantly associated with caregiver mean EQ5D-VAS. Concerning caregiver characteristics, being a spouse and a lower educational level were associated with a lower mean EQ5D-VAS (in a multiple linear regression model: unstandardized B -8.075, p = 0.013 and unstandardized B -6.162, p = 0.037 resp.). In mild dementia, the NPI item irritability showed an association with caregiver EQ5D-VAS in bivariate linear regression analyses. CONCLUSION: Results indicate that especially family caregiver characteristics seem to influence family caregiver HRQoL in MCI. Future research should include other potential determinants such as burden, coping strategies and relationship quality.

Trajectories of relationship quality in dementia: a longitudinal study in eight European countries.

OBJECTIVES: Relationship quality (RQ) between a person with dementia and a family carer may influence their health and quality of life. However, evidence regarding its course and influencing factors is limited. We aimed to explore RQ trajectories in dementia, and identify predictors of change. METHODS: We analysed longitudinal data from a cohort of 350 community-dwelling people with dementia and their informal carers, participating in the Actifcare study in eight European countries. The Positive Affect Index, rated separately by both people with dementia and their carers, assessed RQ. Other measures included the Neuropsychiatric Inventory Questionnaire (regarding persons with dementia), and the Relative Stress Scale, Sense of Coherence Scale and Lubben Social Network Scale (for carers). Trajectories and influencing factors were explored applying a latent growth model (LGM). RESULTS: RQ in the group of carers declined over 1 year, but RQ scores for the persons with dementia did not change. Higher stress in carers negatively influenced their baseline RQ ratings. Carer sense of coherence and being a spouse were associated with more positive baseline RQ carer assessments. Higher levels of neuropsychiatric symptoms were linked to decline in carers' RQ, whereas social support was associated with more positive RQ trajectories. CONCLUSION: This study provides a valuable insight into the course of RQ. LGM proved useful to explore the factors that influence RQ trajectories and variability within- and between-persons. Our findings emphasise the importance of carer-perceived social support and sense of coherence, and of reducing neuropsychiatric symptoms, in maintaining a good RQ.

Addressing relationship quality of people with dementia and their family carers: which profiles require most support?

Objective: The quality of the relationship between persons with dementia and family carers influences health and quality-of-life outcomes. Little is known regarding those at higher risk of experiencing a decline in relationship quality, who could potentially benefit the most from interventions. We aimed to identify these risk profiles and explore the underlying factors. Methods: We applied a latent profile analysis to relationship quality data from a 1-year follow-up of 350 dyads of persons with dementia and their informal carers from the Actifcare cohort in eight European countries. Assessments included sociodemographic, clinical, functional, psychosocial and quality-of-life measures. Relationship quality was assessed with the Positive Affect Index. A discriminant analysis explored factors influencing the risk profiles. Results: There were two relationship quality profiles among persons with dementia (gradually decreasing, 74.0%; low but improving, 26%) and two among carers (steadily poor, 57.7%; consistently positive, 42.3%). The 'gradually decreasing' profile (persons with dementia) was related to their levels of dependence and unmet needs, along with carers' social distress and negative feelings, lower baseline RQ and sense of coherence. The 'steadily poor' profile (carers) was influenced by their social distress and negative feelings, lower sense of coherence and perceived social support. These two predominant profiles showed significant decreases in quality-of-life over one year. Conclusions: Specific profiles of persons with dementia and their carers are at risk of worse relationship quality trajectories. By considering modifiable related factors (e.g., carers' stress), our findings can help develop tailored, effective interventions.

Rapid and nondestructive analysis of lipstick on different substrates using ATR-FTIR spectroscopy and chemometrics.

Lipstick can be an important piece of evidence in crimes like murders, rapes, and suicides. Due to its prevalence, it can be an important corroborative evidence in crime reconstruction. The analysis of such evidence can provide an evidentiary link between the suspect, the victim, object, or the crime scene. We report the use of nondestructive ATR-FTIR spectroscopy combined with chemometrics for the classification of 10 brands of lipsticks with nine samples each. Chemometric method of partial least square-discriminant analysis (PLS-DA) has been employed to interpret the data and classify the samples into their respective classes. The PLS-DA model provides an AUC figure above 0.99 in all brands except one; for which it is slightly less at 0.94. We have also tested the traces of these lipstick samples on different substrates treating them as unknowns in the already trained PLS-DA model. 100% of the samples on nine substrates viz. a cotton, nylon, plastic, dry tissue, denim (blue jeans), wet tissue, nitrile gloves, white paper, and polyester were correctly attributed to their source brand. In conclusion, the results suggest that ATR-FTIR combined with the chemometrics is a rapid, nondestructive, and accurate method for the discrimination and source attribution of lipstick. This study has potential for use in actual forensic casework conditions.

Interaction of caregiver-expressed emotions and neuropsychiatric symptoms in persons with dementia: a longitudinal cohort study.

OBJECTIVES: Neuropsychiatric symptoms (NPS) have a major impact in persons with dementia (PwD). The interaction between the caregiver and the person with dementia may be related to the emergence of NPS. The concept of expressed emotion (EE) is used to capture this dyadic interaction. The aim of the present study is to examine longitudinally the association between EE in caregivers and NPS in PwD living at home. DESIGN: A longitudinal cohort study with 2 years of follow-up. SETTING: PwD and their informal caregivers living at home in the south of the Netherlands. PARTICIPANTS: 112 dyads of PwD and their caregivers from the MAAstricht Study of BEhavior in Dementia. MAIN OUTCOME MEASURES: EE was measured at baseline with the Five-Minute Speech Sample and was used to classify caregivers in a low-EE or high-EE group. Associations between EE and neuropsychiatric subsyndromes (hyperactivity, mood and psychosis) measured with the Neuropsychiatric Inventory (NPI) were analysed over time. RESULTS: Seventy-six (67.9%) caregivers were classified in the low-EE group and 36 (32.1%) in the high-EE group. There was no difference between the EE groups in mean NPI scores over time. In the high-EE group, hyperactivity occurred more frequently than in the low-EE group at baseline (p=0.013) and at the other time points, but the mean difference was not always significant. There were no differences for the mood and psychosis subsyndromes. PwD with caregivers scoring high on the EE subcategory critical comments had an increased risk of institutionalisation (OR 6.07 (95% CI 1.14 to 32.14, p=0.034)) in comparison with caregivers scoring low on critical comments. CONCLUSIONS: High EE in informal caregivers is associated with hyperactivity symptoms in PwD. This association is likely to be bidirectional. Future studies investigating this association and possible interventions to reduce EE are needed.

What do family physicians know about interventional radiology? A survey of family physicians at a Large Canadian Annual Scientific Assembly.

PURPOSE: To quantify the level of background knowledge among family physicians with regard to interventional radiology (IR) procedures, duties, and clinical responsibilities and to develop recommendations on how to further educate family physicians in IR. MATERIALS AND METHODS: Paper surveys were administered to family physicians who attended the Ontario College of Family Physicians' Annual Scientific Assembly. Each survey consisted of 14 questions pertaining to IR procedures, clinical duties, collaboration, and education. RESULTS: A total of 213 of 229 (93%) attempted paper surveys were completed. Family physicians rated their knowledge of IR as poor (31%), adequate (53%), good (14%), or excellent (2%). A total of 98%, 71%, 47%, and 38% correctly identified that interventional radiologists performed image-guided biopsies, uterine artery embolization, radiofrequency ablation of tumors, and vascular angioplasties, respectively. Only 7% correctly identified that interventional radiologists are currently not recognized as distinct subspecialists by the Royal College of Physicians and Surgeons of Canada. Approximately 71% would refer patients directly to an interventional radiologist. A total of 96% believed that future education about IR would be "very" or "somewhat" helpful. Approximately 43% selected presentations given by interventional radiologists at family medicine conferences as their preferred method of future education. CONCLUSIONS: The data quantify and demonstrate the knowledge gap that exists among family physicians in Canada regarding IR procedures, duties, and responsibilities. Family physicians strongly support future education and collaboration with interventional radiologists. Eight results-based recommendations are made to further educate family physicians about IR and promote increased collaboration.

Prolonged stay at the paediatric intensive care unit associated with paediatric delirium.

The objective of this study was to investigate, under circumstances of routine care, the impact of paediatric delirium (PD) on length of stay in the paediatric intensive care unit (PICU) as well as on direct financial costs. A five-year prospective observational study (2002-2007) was carried out in a tertiary eight-bed PICU in the Netherlands. Critically ill children aged 1 to 18 years who were acutely, non-electively and consecutively admitted to the PICU and detected as having PD in routine care were compared to critically ill children aged 1 to 18 years without signs of PD. PD, population characteristics and severity of illness at admission were used as predictors for length of PICU stay. Differences in length of stay yielded short-term, direct medical costs associated with PD. Forty-nine children with and 98 children without PD were included. PD prolonged length of PICU stay with 2.39 days, independent of severity of illness, age, gender, mechanical ventilation and medical indication for admission (B = 0.38, P < 0.001). PD increased direct medical costs with 1.5%. The results suggest a negative prognostic influence of PD on duration of PICU stay in routine care, resulting in an increase of direct medical costs.

Depressive Symptoms in Mild Cognitive Impairment and the Risk of Dementia: A Systematic Review and Comparative Meta-Analysis of Clinical and Community-Based Studies.

BACKGROUND: Affective symptoms are considered a risk factor or prodromal symptom for dementia. Recent reviews indicate that depressive symptoms predict progression from mild cognitive impairment (MCI) to dementia, but results need to be further explored. OBJECTIVE: To investigate the effect of depressive symptoms on the development of dementia in people with MCI, and explore potential sources of between-study variability, including study setting by a systematic review and meta-analysis. METHODS: Databases were searched for prospective studies defining people with MCI at baseline, investigating dementia at follow-up and giving information about depressive symptoms. Two authors independently extracted data from the studies and rated the methodological quality. Meta-analyses were conducted using random-effect models to yield pooled risk ratios (RR). Meta-regression analyses tested differences between clinical and community-based studies and other sources of heterogeneity. RESULTS: Thirty-five studies, representing 14,158 individuals with MCI, were included in the meta-analysis. Depressive symptoms in MCI predicted dementia in 15 community-based studies (RR = 1.69, 95% CI 1.49-1.93, I2 = 0.0%), but not in 20 clinical studies (RR = 1.02, 95% CI 0.92-1.14, I2 = 73.0%). Further investigation of this effect showed that the mean age of community-based studies was significantly higher than of clinical studies but neither this nor other study characteristics explained variability in study outcomes. CONCLUSIONS: Depressive symptoms are associated with an increased risk of conversion from MCI to dementia in community-based studies. In contrast, evidence in clinical populations was insufficient with high heterogeneity.

Dopamine transporter-mediated cytotoxicity of 6-hydroxydopamine in vitro depends on expression of mutant alpha-synucleins related to Parkinson's disease.

6-Hydroxydopamine (6-OHDA) is widely used to produce animal models of Parkinson's disease (PD) by selectively destroying the nigro-striatal dopaminergic systems, but selective toxicity of 6-OHDA towards dopaminergic cells in vitro remains controversial. Mutant (A30P and A53T) alpha-synuclein isoforms cause increased vulnerability of cells towards various toxic insults and enhance dopamine transporter (DAT)-mediated toxicity of the selective dopaminergic neurotoxin and mitochondrial complex I inhibitor MPP(+) in vitro. Here we extend our recent studies on DAT-mediated toxicity to elucidate the mechanisms involved in selective dopaminergic toxicity of 6-OHDA. We studied the cytotoxicity as well as the toxic mechanisms of 6-OHDA in human embryonic kidney HEK-293 cells ectopically co-expressing mutant alpha-synucleins and the human DAT protein. 6-OHDA showed half-maximal toxic concentration (TC(50)) of 88 microM in HEK-hDAT cells without alpha-synuclein expression after 24 h, whereas the TC(50) values significantly decreased to 58 and 39 microM by expression of A30P and A53T alpha-synuclein, respectively. alpha-Synuclein expression did not affect 6-OHDA toxicity in HEK-293 cells not expressing the DAT. Analysis of intracellular parameters of cellular energy metabolism revealed that the co-expression of mutant alpha-synucleins in HEK-hDAT cells accelerates the reduction of intracellular net ATP levels and ATP/ADP ratios induced by 6-OHDA. Uptake function of the DAT was not altered by expression of alpha-synuclein isoforms. Our data suggest a mechanism of 6-OHDA-induced dopaminergic toxicity involving an interaction of mutant alpha-synucleins with the DAT molecule and subsequent acceleration of cellular energy depletion that might be relevant for the pathogenesis of PD.

Changes in characteristics and management of Asian and Anglo-Celts with type 2 diabetes over a 15-year period in an urban Australian community: The Fremantle Diabetes Study.

BACKGROUND: The aim of the present study was to determine temporal changes in characteristics and management of Asians with type 2 diabetes (T2D) compared with those of the majority Anglo-Celt (AC) patients in an urban Australian community. METHODS: Cross-sectional data from the observational Fremantle Diabetes Study (FDS) collected in 1993-96 (Phase I; FDS1) and 2008-11 (Phase II; FDS2) were analyzed for patients classified as Asian (n = 44 and 65 in FDS1 and FDS2, respectively) or AC (n = 796 and 793, respectively). Between-group differences in changes in key variables between FDS phases were analyzed by generalized linear modeling with adjustment for age and gender. RESULTS: Asians patients were significantly younger at diagnosis and recruitment and had a lower body mass index and smaller waist circumference than the AC participants in both FDS phases. They were also less likely to be treated for hypertension. Cardiovascular risk factors and their management and macrovascular complications were similar in the two groups over time. A greater propensity to retinopathy with Asian ethnicity in FDS1 (27.3% vs 13.5%; P = 0.23) was attenuated in FDS2 (23.7% vs 19.0%; P = 0.39). Asians had a significantly lower prevalence of peripheral sensory neuropathy in FDS2 (33.8% vs 63.3%; P < 0.001; adjusted P = 0.011 for between-group temporal change). CONCLUSIONS: There were persistent differences between the phenotypic features of Asian migrants with T2D versus AC patients in an Australian urban community over 15 years of follow-up, but management of diabetes and non-glycemic risk factors remained comparable. Ethnicity-specific differences in susceptibility to microvascular complications should be considered in clinical management.

Expression of mutant alpha-synucleins enhances dopamine transporter-mediated MPP+ toxicity in vitro.

Mutations in the alpha-synuclein gene (A30P and A53T) are reported to cause familial Parkinson's disease (PD), but it is not known how they result in selective dopaminergic cell death. Here we report on effects of mutant alpha-synucleins on dopamine transporter (DAT)-mediated toxicity of the selective dopaminergic neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) in vitro. We established human embryonic kidney HEK-293 cell lines stably co-expressing each alpha-synuclein isoform and the human DAT. We demonstrate that expression of all alpha-synuclein isoforms enhances toxicity of general complex I inhibition (rotenone), but only the expression of mutant alpha-synucleins induces significant increased DAT-dependent toxicity of very low concentrations of MPP+ compared to wild-type protein. Proteasomal inhibition by lactacystin does not alter MPP+-toxicity in all cell lines. Our data suggest a new mechanism of MPP+-induced dopaminergic toxicity by an interaction between mutant alpha-synucleins and the DAT, which is independent of the function of the proteasome.

The role of morbidity and mortality meetings in interventional radiology.

PURPOSE: To understand the current practice of interventional radiology (IR) morbidity and mortality (M&M) meetings among interventional radiologists in Europe, and to develop a set of results-based recommendations to increase the prevalence of IR M&M meetings. MATERIALS AND METHODS: Online electronic surveys were sent to members of the Cardiovascular and Interventional Radiology Society of Europe (CIRSE). Each survey consisted of 18 questions pertaining to IR M&M meetings. RESULTS: A total of 150 CIRSE members responded to the survey. Approximately 47% of respondents held IR M&M meetings in their departments. Among those who held IR M&M meetings, 42% held them monthly and 68% rated the quality of the meetings as good or excellent. Of those who did not have M&M meetings, 94% were interested in incorporating M&M meetings into their future practice. The most common reasons for not holding IR M&M meetings were lack of time (68%) and small IR practice groups (43%). A total of 85% were interested in learning more about IR M&M meetings. The preferred method of education about M&M meetings included annual radiology meetings (44%), peer-reviewed articles in radiology journals (31%), websites (26%), and newsletters (15%). CONCLUSIONS: The data demonstrate that although current practice of M&M meetings in European IR departments is limited, the majority of respondents believe that M&M meetings are beneficial to their practice. There is a need for guidelines or standards of practice to incorporate such meetings in IR departments to prevent medical errors, which may ultimately lead to enhanced patient safety and outcomes.

Comparison of Canadian medical graduates and international medical graduates in Canada: 1989-2007.

PURPOSE: To compare Canadian medical graduates (CMGs) and international medical graduates (IMGs) who completed postgraduate medical education in Canada from 1989 to 2007 by age, gender, specialty, and practice characteristics. METHOD: Data on all CMGs and IMGs who completed residencies or fellowships in Canada from 1989 to 2007 were extracted from the Canadian Post-M.D. Education Registry. Data from 1989-1993 and 2003-2007 were pooled for analysis. RESULTS: A total of 8,501 CMGs and 1,828 IMGs completed post-MD training at Canadian institutions between 1989 and 1993 inclusive; 7,734 CMGs and 1,879 IMGs completed such training between 2003 and 2007. From 1989-1993 to 2003-2007, the average age of CMGs increased from 29.8 to 31.1 years, and average age of IMGs increased from 36.1 to 37.0 years. From 1989-1993 to 2003-2007, the percentage of women increased from 41% (3,471/8,501) to 52% (4,016/7,734) and from 28% (509/1,828) to 42% (791/1,879) for CMGs and IMGs, respectively. The proportion of CMGs who trained in family medicine declined from 54% (4,568/8,501) to 38% (2,921/7,734) from 1989-1993 to 2003-2007. The percentage of IMGs who trained in family medicine increased from 19% (344/1,828) to 37% (699/1,879) during the same period. CONCLUSIONS: IMGs tended to be older, more likely to be men, and more likely to pursue family medicine than their CMG counterparts. These differences have implications in designing future health care policy and recruiting physicians from abroad. Other countries could look at their own physician demographics using this study's methods.

On the utility of diagnostic instruments for pediatric delirium in critical illness: an evaluation of the Pediatric Anesthesia Emergence Delirium Scale, the Delirium Rating Scale 88, and the Delirium Rating Scale-Revised R-98.

PURPOSE: Delirium is a poor-prognosis neuropsychiatric disorder. Pediatric delirium (PD) remains understudied, particularly at pediatric intensive care units (PICU). Although the Pediatric Anesthesia Emergence Delirium (PAED) scale, the Delirium Rating Scale (DRS-88), and the Delirium Rating Scale-Revised (DRS-R-98) are available, none have been validated for use in PICU settings. The aim of the present study was to investigate the use of the DRS/PAED instruments as diagnostic tools for PD in the PICU. METHODS: A prospective panel study was conducted, under circumstances of routine clinical care, investigating the diagnostic properties of the PAED, DRS-88, and DRS-R-98 in PICU patients at a tertiary university medical center. A total of 182 non-electively admitted, critically ill pediatric patients, aged 1-17 years, were included between November 2006 and February 2010. Sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated. Three psychometric properties were analyzed: (1) internal consistency (2) proportion of items not rateable, and (3) discriminative ability. RESULTS: The PAED could be completed in 144 (93.5%) patients, much more frequently than either the DRS-88 (66.9%) or the DRS-R-98 (46.8%). Compared with the clinical gold standard diagnosis of delirium, the PAED had a sensitivity of 91% and a specificity of 98% (AUC 0.99). The optimal PAED cutoff score as a screening instrument in this PICU setting was 8. Cronbach's alpha was 0.89; discriminative ability was high. CONCLUSIONS: The PAED is a valid instrument for PD in critically ill children, given its reliance on routinely rateable observational signs and symptoms.