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Background: Regional variations in healthcare outcomes in England have been historically reported. This study analyses the variations in long term colorectal cancer survival across different regions in England. Methods: Relative survival analysis of population data obtained from all cancer registries in England between 2010 and 2014. Results: Totally, 167,501 patients were studied. Regions in the southern England had better outcomes with Southwest and Oxford registries having 63.5 and 62.7% 5 year relative survival. In contrast, Trent and Northwest cancer registries had 58.1% relative survival (p< 0.01). The regions in the north fared below the national average. The survival outcomes reflected socio-economic deprivation status, the best performing regions in the south having low levels of deprivation (5.3 and 6.5% having maximum deprivation in Southwest and Oxford, respectively). The regions with worst long term cancer outcomes had high levels of deprivation with 25% and 17% having high levels of deprivation in Northwest and Trent regions. Conclusion: There are significant variations in long term colorectal cancer survival between different regions in England, southern England had better relative survival when compared with the northern regions. Disparities in socio-economic depravation status in different regions may be associated with worse colorectal cancer outcomes.

OBJECTIVE--Insulin resistance (1R) is associated with diabetes. IR is higher during puberty in both sexes, with some studies showing the increase to be independent of changes in adiposity. Few longitudinal [...]

OBJECTIVE--Recent evidence suggests that, in children, traditional markers of metabolic disturbance are related only weakly to physical activity. We therefore sought to establish the corresponding relationships with newer metabolic markers. [...]

Secular trends in childhood obesity suggest that many children are gaining excess fat, thereby contributing to an emerging epidemic of type 2 diabetes in young people (1,2). However, it is [...]

IMPORTANCE: Mutations of the glucocerebrosidase gene, GBA1 (OMIM 606463), are the most important risk factor for Parkinson disease (PD). In vitro and in vivo studies have reported that ambroxol increases β-glucocerebrosidase (GCase) enzyme activity and reduces α-synuclein levels. These observations support a potential role for ambroxol therapy in modifying a relevant pathogenetic pathway in PD. OBJECTIVE: To assess safety, tolerability, cerebrospinal fluid (CSF) penetration, and target engagement of ambroxol therapy with GCase in patients with PD with and without GBA1 mutations. INTERVENTIONS: An escalating dose of oral ambroxol to 1.26 g per day. DESIGN, SETTING, AND PARTICIPANTS: This single-center open-label noncontrolled clinical trial was conducted between January 11, 2017, and April 25, 2018, at the Leonard Wolfson Experimental Neuroscience Centre, a dedicated clinical research facility and part of the University College London Queen Square Institute of Neurology in London, United Kingdom. Participants were recruited from established databases at the Royal Free London Hospital and National Hospital for Neurology and Neurosurgery in London. Twenty-four patients with moderate PD were evaluated for eligibility, and 23 entered the study. Of those, 18 patients completed the study; 1 patient was excluded (failed lumbar puncture), and 4 patients withdrew (predominantly lumbar puncture–related complications). All data analyses were performed from November 1 to December 14, 2018. MAIN OUTCOMES AND MEASURES: Primary outcomes at 186 days were the detection of ambroxol in the CSF and a change in CSF GCase activity. RESULTS: Of the 18 participants (15 men [83.3%]; mean [SD] age, 60.2 [9.7] years) who completed the study, 17 (8 with GBA1 mutations and 9 without GBA1 mutations) were included in the primary analysis. Between days 0 and 186, a 156-ng/mL increase in the level of ambroxol in CSF (lower 95% confidence limit, 129 ng/mL; P < .001) was observed. The CSF GCase activity decreased by 19% (0.059 nmol/mL per hour; 95% CI, –0.115 to –0.002; P = .04). The ambroxol therapy was well tolerated, with no serious adverse events. An increase of 50 pg/mL (13%) in the CSF α-synuclein concentration (95% CI, 14-87; P = .01) and an increase of 88 ng/mol (35%) in the CSF GCase protein levels (95% CI, 40-137; P = .002) were observed. Mean (SD) scores on part 3 of the Movement Disorders Society Unified Parkinson Disease Rating Scale decreased (ie, improved) by 6.8 (7.1) points (95% CI, –10.4 to –3.1; P = .001). These changes were observed in patients with and without GBA1 mutations. CONCLUSIONS AND RELEVANCE: The study results suggest that ambroxol therapy was safe and well tolerated; CSF penetration and target engagement of ambroxol were achieved, and CSF α-synuclein levels were increased. Placebo-controlled clinical trials are needed to examine whether ambroxol therapy is associated with changes in the natural progression of PD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02941822; EudraCT identifier: 2015-002571-24

Background:Anti-Müllerian hormone (AMH) is produced by Sertoli cells of the testes and granulosa cells of the ovary. There are limited prospective longitudinal data assessing AMH concentrations throughout childhood in both sexes.

•Only half of included studies reported adherence during the intervention.•As few as 4% reported adherence and drop-out at any follow up.•Little consensus exists on definition of adherence or determination of drop-out.•TESTEX is a tool designed for appraising methodological quality of exercise studies.•Clear, transparent measurement and reporting of adherence and drop-out is required.