SummaryBackgroundGlobal inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia.MethodsCancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0–14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995–99, 2000–04, and 2005–09), sex, and age at diagnosis (<1, 1–4, 5–9, and 10–14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML).FindingsWe analysed data from 89 828 children from 198 registries in 53 countries. During 1995–99, 5-year age-standardised net survival for all lymphoid leukaemias combined ranged from 10·6% (95% CI 3·1–18·2) in the Chinese registries to 86·8% (81·6–92·0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005–09, when age-standardised survival for lymphoid leukaemias ranged from 52·4% (95% CI 42·8–61·9) in Cali, Colombia, to 91·6% (89·5–93·6) in the German registries, and for AML ranged from 33·3% (18·9–47·7) in Bulgaria to 78·2% (72·0–84·3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000–04 and 2005–09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1–4 and 5–9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls.InterpretationGlobal inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood cancer survival.FundingCanadian Partnership Against Cancer, Cancer Focus Northern Ireland, Cancer In...

Several hospital-based studies suggest a circadian rhythm for stroke, with a peak of onset in the morning. To verify whether these results could be confirmed in a community-based study, we used data from the SEPIVAC, a community-based stroke register in Umbria, Italy. Cerebral infarctions (48%), primary intracerebral hemorrhages (54%), subarachnoid hemorrhages (53%) and ''not known'' strokes (51%) were all more common between 6 a.m. and noon, and this peak was still present when strokes recognized on awakening were evenly redistributed over the sleep period. Looking at the subgroups of cerebral infarction, lacunar syndromes were more common during sleep. Cerebral infarctions were more frequent during winter, and primary intracerebral hemorrhages during autumn.

The SEPIVAC study is a communitybased epidemiological survey of incidence and outcome of acute cerebrovascular disease in the Sixth Local Health Unit, Umbria, Italy (population 49 218). The study was carried out from 1 September 1986 to 31 August 1989. There were 375 patients who were registered with a first ever stroke, with a crude rate of 2-54 (95% confidence limits 2-29-2-81) per 1000 per year; the rate adjusted to the European population is 1 55 (CL 1-36-1-77). The age adjusted relative risk for males is 1-35 (CL 1-101-66). Up to 15% of the patients were not admitted to hospital during the acute phase of their disease. At least 286 (76-3%, CL 72-80 6) of the cases were due to cerebral ischaemia; in 56 of these (19-6%, CL 15-24-2) a clinical diagnosis of lacunar ischaemia was made. The 30 day case fatality rate was 20-3% (CL 16-2-24-3); between one and six months 7-5% (CL 5-10-6) of patients died.

The distribution of ovarian cancer histology varies widely worldwide. Type I epithelial, germ cell and sex cord-stromal tumours are generally associated with higher survival than type II tumours, so the proportion of these tumours may influence survival estimates for all ovarian cancers combined. The distribution of histological groups should be considered when comparing survival between countries and regions.

Damage to the myelin sheath and the neuroaxonal unit is a cardinal feature of multiple sclerosis; however, a detailed characterization of the interaction between myelin and axon damage in vivo remains challenging. We applied myelin water and multi-shell diffusion imaging to quantify the relative damage to myelin and axons (i) among different lesion types; (ii) in normal-appearing tissue; and (iii) across multiple sclerosis clinical subtypes and healthy controls. We also assessed the relation of focal myelin/axon damage with disability and serum neurofilament light chain as a global biological measure of neuroaxonal damage. Ninety-one multiple sclerosis patients (62 relapsing-remitting, 29 progressive) and 72 healthy controls were enrolled in the study. Differences in myelin water fraction and neurite density index were substantial when lesions were compared to healthy controls and normal-appearing MS tissue: both white matter and cortical lesions exhibited a decreased myelin water fraction and neurite density index compared with healthy (P &lt; 0.0001) and peri-plaque white matter (P &lt; 0.0001). Periventricular lesions showed decreased myelin water fraction and neurite density index compared with lesions in the juxtacortical region (P &lt; 0.0001 and P &lt; 0.05). Similarly, lesions with paramagnetic rims showed decreased myelin water fraction and neurite density index relative to lesions without a rim (P &lt; 0.0001). Also, in 75% of white matter lesions, the reduction in neurite density index was higher than the reduction in the myelin water fraction. Besides, normal-appearing white and grey matter revealed diffuse reduction of myelin water fraction and neurite density index in multiple sclerosis compared to healthy controls (P &lt; 0.01). Further, a more extensive reduction in myelin water fraction and neurite density index in normal-appearing cortex was observed in progressive versus relapsing-remitting participants. Neurite density index in white matter lesions correlated with disability in patients with clinical deficits (P &lt; 0.01, beta=-10.00); and neurite density index and myelin water fraction in white matter lesions were associated to serum neurofilament light chain in the entire patients cohort (P &lt; 0.01, beta=-3.60 and P &lt; 0.01, beta=0.13, respectively). These findings suggest that (i) myelin and axon pathology in multiple sclerosis is extensive in both lesions and normal-appearing tissue; (ii) particular types of lesions exhibit more damage to myelin and axons than others; (iii) progressive patients differ from relapsing-remitting because of more extensive axon/myelin damage in the cortex; and (iv) myelin and axon pathology in lesions is related to disability in patients with clinical deficits and global measures of neuroaxonal damage.