Atypical presentation of neuronal ceroid lipofuscinosis type 8 in a sibling pair and review of the eye findings and neurological features.

Purpose:To report atypical presentation of neuronal ceroid lipofuscinoses type 8 (CLN8) to the eye clinic and review clinical features of CLN8. Observations:Detailed eye exam by slit lamp exam, indirect ophthalmoscopy, fundus photography, optical coherence tomography, visual fields and electroretinogram (ERG). Molecular genetic testing using Next Generation Sequencing panel (NGS) and array Comparative Genomic Hybridization (aCGH).The siblings in this study presented to the eye clinic with retinitis pigmentosa and cystoid macular edema, and a history of seizures but no severe neurocognitive deficits or regression. Genetic testing identified a c.200C > T (p.A67V) variant in the CLN8 gene and a deletion encompassing the entire gene. Electron microscopy of lymphocytes revealed fingerprint inclusions in both siblings. Conclusions:and Importance: Pathogenic variants in CLN8 account for the retinitis pigmentosa and seizures in our patients however, currently, they do not have regression or neurocognitive decline. The presentation of NCL can be very diverse and it is important for ophthalmologists to consider this in the differential diagnosis of retinal disorders with seizures or other neurological features. Molecular genetic testing of multiple genes causing isolated and syndromic eye disorders using NGS panels and aCGH along with additional complementary testing may often be required to arrive at a definitive diagnosis

The relationship between early life urbanicity and depression in late adulthood: evidence from the Survey of Health, Ageing and Retirement in Europe

Objectives: We aimed to study the association of childhood urbanicity with depressive symptoms in late adulthood. Design, setting and participants: We used linear and logistic regressions to analyse data drawn from 20 400 respondents from the Survey of Health, Ageing and Retirement in Europe, a panel dataset incorporating a representative sample of the 50+ population in 13 European countries. Outcomes and analysis: Childhood urbanicity was determined using self-reports of the respondents’ circumstances at age 10, and late-adulthood depression using the EURO-D scale. We conditioned on circumstances early in life as well as later in life, most importantly late-adulthood urbanicity. We estimated the associations using linear regression models and limited dependent variable models. Results: A pooled regression of both men and women suggested that childhood urbanicity is associated non-monotonically with depression in late adulthood and is particularly apparent for those spending their childhoods in suburban settings. We found that individuals who spend the longest time in their childhood in a suburban home exhibit an average increase in probability of 3.4 (CI 1.1 to 5.7) percentage points in reporting four or more depressive symptoms. The association was robust to the inclusion of a host of household characteristics associated with childhood urbanicity and was independent of current urbanicity and current income. When broken down by gender, we found some evidence of associations between depressive outcomes and urban living for men, and stronger evidence of such associations with urban and suburban living for women who exhibit an increase of 5.6 (CI 2.2 to 9.0) percentage points in reporting four or more depressive symptoms. Conclusions: Our analysis reveals a relationship between childhood urbanicity and depression in late adulthood. The evidence presented on the nature of this relationship is not straightforward but is broadly suggestive of a link, differing by gender, between greater urbanicity and higher levels of depressive symptoms. The life-long nature of this association may potentially inform policy agendas aimed at improving urban and suburban living conditions

Centralising acute stroke care within clinical practice in the Netherlands: lower bounds of the causal impact

BACKGROUND Authors in previous studies demonstrated that centralising acute stroke care is associated with an increased chance of timely Intra-Venous Thrombolysis (IVT) and lower costs compared to care at community hospitals. In this study we estimated the lower bound of the causal impact of centralising IVT on health and cost outcomes within clinical practice in the Northern Netherlands. METHODS We used observational data from 267 and 780 patients in a centralised and decentralised system, respectively. The original dataset was linked to the hospital information systems. Literature on healthcare costs and Quality of Life (QoL) values up to 3 months post-stroke was searched to complete the input. We used Synthetic Control Methods (SCM) to counter selection bias. Differences in SCM outcomes included 95% Confidence Intervals (CI). To deal with unobserved heterogeneity we focused on recently developed methods to obtain the lower bounds of the causal impact. RESULTS Using SCM to assess centralising acute stroke 3 months post-stroke revealed healthcare savings of $US 1735 (CI, 505 to 2966) while gaining 0.03 (CI, − 0.01 to 0.73) QoL per patient. The corresponding lower bounds of the causal impact are$US 1581 and 0.01. The dominant effect remained stable in the deterministic sensitivity analyses with $US 1360 (CI, 476 to 2244) as the most conservative estimate. CONCLUSIONS In this study we showed that a centralised system for acute stroke care appeared both cost-saving and yielded better health outcomes. The results are highly relevant for policy makers, as this is the first study to address the issues of selection and unobserved heterogeneity in the evaluation of centralising acute stroke care, hence presenting causal estimates for budget decisions

Centralising acute stroke care within clinical practice in the Netherlands:lower bounds of the causal impact

Background: Authors in previous studies demonstrated that centralising acute stroke care is associated with an increased chance of timely Intra-Venous Thrombolysis (IVT) and lower costs compared to care at community hospitals. In this study we estimated the lower bound of the causal impact of centralising IVT on health and cost outcomes within clinical practice in the Northern Netherlands. Methods: We used observational data from 267 and 780 patients in a centralised and decentralised system, respectively. The original dataset was linked to the hospital information systems. Literature on healthcare costs and Quality of Life (QoL) values up to 3 months post-stroke was searched to complete the input. We used Synthetic Control Methods (SCM) to counter selection bias. Differences in SCM outcomes included 95% Confidence Intervals (CI). To deal with unobserved heterogeneity we focused on recently developed methods to obtain the lower bounds of the causal impact. Results: Using SCM to assess centralising acute stroke 3 months post-stroke revealed healthcare savings of $US 1735 (CI, 505 to 2966) while gaining 0.03 (CI, − 0.01 to 0.73) QoL per patient. The corresponding lower bounds of the causal impact are$US 1581 and 0.01. The dominant effect remained stable in the deterministic sensitivity analyses with $US 1360 (CI, 476 to 2244) as the most conservative estimate. Conclusions: In this study we showed that a centralised system for acute stroke care appeared both cost-saving and yielded better health outcomes. The results are highly relevant for policy makers, as this is the first study to address the issues of selection and unobserved heterogeneity in the evaluation of centralising acute stroke care, hence presenting causal estimates for budget decisions