Polymorphisms in BACE2 may affect the age of onset Alzheimer's dementia in Down syndrome

It is known that Alzheimer's disease (AD) presents at an early age in people with Down syndrome (DS). The trisomy 21 in DS provides an opportunity to study the effect of duplicated genes in AD. APP and BACE2 are 2 genes located in chromosome 21 and related to AD. We looked into our cohort of 67 DS cases with dementia for the effect of BACE2 variants in age of onset of dementia. Of the 83 single-nucleotide polymorphisms (SNPs), 6 were associated with age of onset and another 8 SNPs were borderline associated. Our finding also replicated a previous study showing association of rs2252576 with AD.     

Full thickness squamous atypia of the glans penis on a background of Zoon's plasma cell balanitis

Erythroplasia of Queyrat (EQ) or squamous cell carcinoma in situ of the glans penis developed in a 79 year old uncircumsised gentleman who had a six year prior history of biopsy proven Zoon's plasma cell balanitis (ZB) affecting the same site on the glans. Prior to the development of clinically evident EQ, the glans had been treated with topical pimecrolimus 1% for one month. The glans was subsequently treated with topical 5-flourouracil 5% for two weeks which resulted in clinical clearance.
EQ is obviously an important differential for penile plaques because of the potential for progression to squamous cell carcinoma, while ZB is generally regarded as benign. The differentiation can only be reliably made histologically.
There are other case reports of both EQ ( 1 ) and carcinoma of the penis ( 2 ) arising in patients with ZB, raising the question as to whether ZB may actually reflect a reaction to underlying pre-existing pathology or even a premalignant state.
The addition of topical pimecrolimus shortly before EQ became clinically evident in this patient is concerning in the light of recent concern regarding the carcinogenicity of topical calcineurin inhibitors ( 3 ).
This case highlights the importance of close clinical follow up of persistent penile inflammatory lesions and prompt biopsy of clinically suspicious areas as second and potentially more serious pathology may occur concomitantly.     

‘Sussing that doctor out.’ Experiences and perspectives of people affected by hepatitis C regarding engagement with private general practitioners in South Australia: a qualitative study

Background

Australians with chronic hepatitis C (HCV) can access affordable Direct Acting Antiviral (DAA) treatments with high cure rates (>90%), via General Practitioners (GPs). Benefits from this treatment will be maximised if people with HCV readily disclose and engage with private GPs regarding HCV-related issues. Investigating the perceptions and experiences of people affected by HCV with GPs can allow for this pathway to care for HCV to be improved.

Methods

In 2013–2014, 22 purposively sampled participants from South Australia (SA) were interviewed. They a) had contracted or were at risk of hepatitis C (n?=?10), b) were key workers who had clients affected by HCV (n?=?6), and c) met both a) and b) criteria (n?=?6). The semi-structured interviews were recorded, transcribed and thematically analysed.

Results

People affected by HCV viewed GPs as a source of general healthcare but, due to negative experiences and perceptions, many developed a strategy of “sussing” out doctors before engaging with and disclosing to a GP regarding HCV-related issues. Participants were doubtful about the benefits of engagement and disclosure, and did not assume that they would be provided best-practice care in a non-discriminatory, non-judgemental way. They perceived risks to confidentiality and risks of changes to the care they received from GPs upon disclosure.

Conclusion

GPs may need to act in ways that counteract the perceived risks and persuade people affected by HCV of the benefits of seeking HCV-related care.

     

Disparities in Diabetes: The Nexus of Race,Poverty, and Place

Objectives. We sought to determine the role of neighborhood poverty and racial composition on race disparities in diabetes prevalence.Methods. We used data from the 1999–2004 National Health and Nutrition Examination Survey and 2000 US Census to estimate the impact of individual race and poverty and neighborhood racial composition and poverty concentration on the odds of having diabetes.Results. We found a race–poverty–place gradient for diabetes prevalence for Blacks and poor Whites. The odds of having diabetes were higher for Blacks than for Whites. Individual poverty increased the odds of having diabetes for both Whites and Blacks. Living in a poor neighborhood increased the odds of having diabetes for Blacks and poor Whites.Conclusions. To address race disparities in diabetes, policymakers should address problems created by concentrated poverty (e.g., lack of access to reasonably priced fruits and vegetables, recreational facilities, and health care services; high crime rates; and greater exposures to environmental toxins). Housing and development policies in urban areas should avoid creating high-poverty neighborhoods.In the United States, 25.6 million or 11.3% of adults aged 20 years and older had diabetes in 2010.1 Non-Hispanic Blacks had the highest prevalence at 12.6% compared with non-Hispanic Whites at 7.1%.1 Traditional explanations for the observed race disparity in diabetes prevalence include differences in health behaviors, socioeconomic factors, family history of diabetes, biological factors, and environmental factors.2–4 Little work has been conducted to understand how individual and environment-level factors operate together to produce disparities in diabetes prevalence.A relatively new line of research has begun to show that risk of diabetes is associated with neighborhood attributes that are also associated with race. Auchincloss et al. found that higher diabetes rates were related to lack of availability of neighborhood resources that support physical activity and healthy nutrition.5 Schootman et al. found that poor housing conditions were associated with diabetes prevalence.6 Black neighborhoods are more likely to be characterized by these risk factors (i.e., having food deserts, being less likely to have recreational facilities, and tending to have lower-quality housing than White neighborhoods).7–18 As such it stands to reason that failing to adjust national estimates of diabetes prevalence for these social conditions might influence perceptions of diabetes disparities. LaVeist et al. compared disparities in diabetes in an urban, racially integrated, low-income community with a national sample from the National Health Interview Survey.19,20 They found that when urban Whites and Blacks resided in the same low-income community, the race disparity in diabetes prevalence disappeared, largely because the prevalence rate for Whites increased substantially.19 Ludwig et al. used data from the Moving to Opportunity demonstration project and found a lower prevalence of diabetes among low-income adults who moved from high-poverty neighborhoods to low-poverty neighborhoods compared with low-income adults who moved from a high-poverty neighborhood to another high-poverty neighborhood.21 Findings from these studies suggest the need to further explore the role of place in race disparities in diabetes.We explored whether the nexus of race, poverty, and neighborhood racial composition and poverty concentration illuminates the race disparities in diabetes. Specifically, we examined (1) whether diabetes prevalence increases in predominantly Black neighborhoods compared with predominantly White neighborhoods, (2) whether diabetes prevalence is higher in poor neighborhoods than in nonpoor neighborhoods, and (3) whether the impact of neighborhood racial composition and poverty concentration on the risk of diabetes varies by race. We hypothesized that residential segregation and concentrated poverty (1) increase Black individuals’ exposure to environmental risks associated with poor health, (2) reduce their access to community amenities that promote good health and healthy behaviors, and (3) limit their access to social determinants that promote good health such as quality jobs, education, public safety, and social networks.7,22–24     

The cost-effectiveness of newer drugs as add-on therapy for children with focal epilepsies.

PURPOSE: Epilepsies in children are complex diseases. Guidelines are needed on the appropriate use of newer versus older anti-epileptic drugs (AEDs). This paper presents an individual patient-sampling model to assess the cost-effectiveness of using newer AEDs as add-on therapy in line with UK prescribing guidance. METHODS: Identification of the relevant parameters and treatment pathways for the model were achieved by a systematic review of the literature and discussions with clinical experts. Data were obtained from the literature and supplemented with data elicited from paediatric neurologists. The model considered paediatric patients over the period of childhood from the age of diagnosis to 18 years. RESULTS: The results suggest that the older and newer AEDs are similar in terms of drug retention rates and the average time in 'good' treatment outcomes. In terms of cost, the results indicate a consistent increase in cost (compared to older AEDs) when all of the newer AEDs are considered. The decision analysis results indicate that there are no important health benefits from the use of newer AEDs when used as add-on therapy. However, the analysis also reveals that the uncertainties in the model are greater than the differences between the drug strategies. CONCLUSIONS: To develop guidelines on the appropriate use of newer AEDs, better information is required from randomised controlled trials as there is insufficient data available in the public domain to accurately estimate the nature of the trade off between older versus newer AEDs.     

18F-FDG assessment of glucose disposal and production rates during fasting and insulin stimulation: a validation study.

The glucose analog (18)F-FDG is commonly used to quantify regional glucose uptake in vivo. The aim of this study was to test whether the analysis of plasma (18)F-FDG kinetics could be used to estimate endogenous glucose production (EGP) and the total rate of appearance (Ra), total rate of disappearance (Rd), and the metabolic clearance rate (MCR) of glucose. METHODS: Fourteen pigs were coinjected with (18)F-FDG and 6,6-(2)H-glucose ((2)H-G) during fasting (n = 6) and during physiologic (1.0 mU.kg(-1).min(-1), n = 4) and supraphysiologic (5.0 mU.kg(-1).min(-1), n = 4) euglycemic hyperinsulinemia. Arterial plasma was sampled for 180 min to quantify the parameters for the 2 tracers. RESULTS: Fasting Rd((2))(H-G) and Rd(FDG) were 12.3 +/- 2.1 and 13.3 +/- 1.3 micromol.kg(-1).min(-1) (difference not statistically significant [NS]). M values were more than doubled between the 2 clamp studies (P < 0.0001). Rd((2))(H-G) and Rd(FDG) were dose-dependently higher during the hyperinsulinemic state (19.8 +/- 3.7 vs. 18.9 +/- 1.1 and 31.4 +/- 4.1 vs. 31.9 +/- 2.3 in 1.0 and 5.0 mU.kg(-1).min(-1) studies, respectively; difference between tracers NS) than during the fasting state, with a parallel suppression of EGP((2))(H-G) and EGP(FDG). Parameters estimated by (18)F-FDG and (2)H-G were equivalent in all groups; their agreement was confirmed by Bland-Altman examination. Total Rd(FDG) correlated with Rd((2))(H-G) (r = 0.74; P = 0.003), M (r = 0.92; P = 0.001), MCR((2))(H-G) (r = 0.52; P = 0.037), and EGP((2))(H-G) (r = -0.71; P = 0.004). EGP(FDG) correlated with EGP((2))(H-G) (r = 0.62; P = 0.018), Rd((2))(H-G) (r = -0.78; P = 0.001), and MCR((2))(H-G) (r = -0.67; P = 0.008). The (18)F-FDG mean transit time correlated inversely with the M and Rd values and positively with EGP. CONCLUSION: The glucose analog (18)F-FDG can be used in the simultaneous estimation of whole-body glucose turnover and production and regional (18)F-FDG PET measurements under both fasting and insulin-stimulated conditions.     

Option Grids: Shared decision making made easier

Objective

To describe the exploratory use of short decision support tools for patients, called Option Grids. Option Grids are summary tables, using one side of paper to enable rapid comparisons of options, using questions that patients frequently ask (FAQs) and designed for face-to-face clinical encounters. To date, most evidence about ‘patient decision aids’ has been based on tools with high content levels, designed for patients to use independently, either before or after visits.

Methods

We studied the use of Option Grids in a quality improvement project, collecting field notes and conducting interviews with clinical teams.

Results

In the ‘Making Good Decisions in Collaboration’ (MAGIC) program, clinicians found that using Option Grids made it easier to explain the existence of options and reported a ‘handover’ effect, where patient involvement in decision making was enhanced.

Conclusion

Option Grids made options more visible and clinicians found it easier to undertake shared decision making when these tools were available. Used in a collaborative way, they enhance patients’ confidence and voice, increasing their involvement in collaborative dialogs.

Practice implications

Further work to confirm these preliminary findings is required, to measure processes and to assess whether these tools have similar impact in other clinical settings.     

Racial disparities in family-provider interactions for pediatric asthma care

Objective: Black and Latino children experience significantly worse asthma morbidity than their white peers for multifactorial reasons. This study investigated differences in family-provider interactions for pediatric asthma, based on race/ethnicity. Methods: This was a cross-sectional study of parent surveys of asthmatic children within the Population-Based Effectiveness in Asthma and Lung Diseases Network. Our study population comprised 647 parents with survey response data. Data on self-reported race/ethnicity of the child were collected from parents of the children with asthma. Outcomes studied were responses to the questions about family-provider interactions in the previous 12 months: (1) number of visits with asthma provider; (2) number of times provider reviewed asthma medications with patient/family; (3) review of a written asthma treatment plan with provider; and (4) preferences about making asthma decisions. Results: In multivariate adjusted analyses controlling for asthma control and other co-morbidities, black children had fewer visits in the previous 12 months for asthma than white children: OR 0.63 (95% CI 0.40, 0.99). Additionally, black children were less likely to have a written asthma treatment plan given/reviewed by a provider than their white peers, OR 0.44 (95% CI 0.26, 0.75). There were no significant differences by race in preferences about asthma decision-making nor in the frequency of asthma medication review. Conclusion: Black children with asthma have fewer visits with their providers and are less likely to have a written asthma treatment plan than white children. Asthma providers could focus on improving these specific family-provider interactions in minority children.     

Understanding and using time series analyses in addiction research

Time series analyses are statistical methods used to assess trends in repeated measurements taken at regular intervals and their associations with other trends or events, taking account of the temporal structure of such data. Addiction research often involves assessing associations between trends in target variables (e.g. population cigarette smoking prevalence) and predictor variables (e.g. average price of a cigarette), known as a multiple time series design, or interventions or events (e.g. introduction of an indoor smoking ban), known as an interrupted time series design. There are many analytical tools available, each with its own strengths and limitations. This paper provides addiction researchers with an overview of many of the methods available (GLM, GLMM, GLS, GAMM, ARIMA, ARIMAX, VAR, SVAR, VECM) and guidance on when and how they should be used, sample size det ermination, reporting and interpretation. The aim is to provide increased clarity for researchers proposing to undertake these analyses concerning what is likely to be acceptable for publication in journals such as Addiction. Given the large number of choices that need to be made when setting up time series models, the guidance emphasizes the importance of pre‐registering hypotheses and analysis plans before the analyses are undertaken.