Aims
To describe type 1 diabetes incidence in Scotland between 2006 and 2019.
Methods
Repeated annual cross‐sectional studies of type 1 diabetes incidence were conducted. Incident cases were ...identified from the Scottish Care Information—Diabetes Collaboration (SCI‐DC), a population‐based register of people with diagnosed diabetes derived from primary and secondary care data. Mid‐year population estimates for Scotland were used as the denominator to calculate annual incidence with stratification by age and sex. Joinpoint regression was used to investigate whether incidence changed during the study period. Age and sex‐specific type 1 diabetes incidence over the whole time period was estimated by quintile of the Scottish Index of Multiple Deprivation (SIMD), an area‐based measure, in which Q1 and Q5 denote the most and least deprived fifths of the population, respectively, with quasi‐Poisson regression used to compare incidence for Q5 compared to Q1.
Results
The median (IQR) age of the study population of 14,564 individuals with incident type 1 diabetes was 24.1 (12.3–42.4) years, 56% were men, 23% were in Q1 and 16% were in Q5. Incidence of T1DM was higher in men than women overall (at around 22 and 17 per 100,000, respectively) and in under 15 year olds (approximately 40 per 100,000 in both sexes) than other age groups and was similar across the study period in all strata. There was an inverse association between socio‐economic status and type 1 diabetes incidence for 15–29, 30–49 and 50+ year olds incidence rate ratio (IRR) for Q5 compared to Q1; IRR (95% CI) 0.52 (0.47–0.58), 0.68 (0.61–0.76) and 0.53(0.46–0.61), respectively but not for under 15 year olds 1.02 (0.92–1.12).
Conclusion
Incidence of type 1 diabetes varies by age, sex and socio‐economic status and has remained approximately stable from 2006 to 2019 in Scotland.
PURPOSE Despite frequent use of self-expanding stents (SES) in treating obstructive arterial lesions in Takayasu arteritis (TA), spontaneous delayed stent expansion (SDSE) in TA remains unstudied. ...This study aimed primarily to document and quantify SDSE and secondarily to determine factors that might be associated with this process. METHODS Consecutive TA patients with obstructive arterial lesions undergoing routine percutaneous intervention involving SES use (sized 1:1 with normal vessel diameter but dilated only to 4mm/5mm) were recruited prospectively. Final stent diameters obtained were measured at 1cm intervals along the length of the stent using fluoroscopic images and an indwelling marker catheter. At angiographic follow-up, stent diameters were measured again in identical fashion. Interval change in stent diameter at each point was averaged for each stent. In a small sub-study intravascular ultrasound was used at follow-up to obtain potential mechanistic insights. RESULTS Seventeen TA patients (age 33 ± 13 years, 15 female) had 22 arterial obstructive lesions (16 occlusions, 18 subclavian) treated with one SES each. Follow-up obtained in all patients after 8.7 ± 3.8 months (range 3-18 months) showed interval increase in mean stent diameter of 1.6 ± 0.5 mm, range 0.7-2.8 mm (P < 0.001); 36% of stents achieved 100% of the nominal diameter at follow-up, while 90% of stents achieved ≥90%. The degree of SDSE did not correlate with the segment of artery stented or with TA disease activity at baseline. Intravascular ultrasound in four lesions showed that SDSE was associated with positive medial-adventitial remodelling and that neointimal hyperplasia occurs concurrently, causing in-stent luminal narrowing. CONCLUSION SDSE, to diameters equal or close to nominal, occurs in all stenotic TA lesions treated with SES. The degree of SDSE does not correlate with the segment of artery stented or with TA disease activity at baseline. Preliminary results suggest that the mechanism by which SDSE is accommodated by the arterial wall is by positive medial-adventitial remodelling.
The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people ...hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.
Internal tandem duplications of the FLT3 gene (FLT3/ITD) portend poor outcome in both adult and pediatric AML and hematopoietic stem cell transplantation (HSCT) is often performed. Unfortunately, ...approximately 35% of patients will have disease recurrence despite HSCT and curative options are limited in that context. Sorafenib is an oral multi-target tyrosine kinase with demonstrable efficacy in this AML subtype. Moreover, retrospective studies in adults with FLT3/ITD+ AML suggest tolerability and potential clinical benefit of sorafenib when used in the post HSCT setting for treatment of early relapse or minimal residual disease (MRD) emergence. There is limited published data regarding sorafenib's tolerability and efficacy following HSCT in pediatric FLT3/ITD+ AML. We report here a retrospective review of our experience.
We conducted a retrospective study of pediatric FLT3/ITD+ patients treated with allogeneic HSCT followed by sorafenib in the first 18 months following HSCT. Between March 2008 and March 2012, 13 FLT3/ITD+ pediatric patients at 7 HSCT centers met criteria for study inclusion. Median age at time of treatment was 14 years (range 6-21 years) and 6/14 (46%) were male. 9 patients underwent matched family donor HSCT and 4 had a matched unrelated donor. Sorafenib was initiated early after HSCT (median: 66 days, range 44-170 days) as prophylaxis in 5 patients who were considered to have very high risk features including failure to achieve clinical remission (CR) following first course of chemotherapy (N=2), high allelic ratio FLT3/ITD at diagnosis (N=1) and MRD at time of HSCT (N=2). For the remainder, sorafenib was given after sign of relapse (MRD or morphologic) at a median of 90 days (range 45-480 days) following HSCT. 11/13 patients received single agent therapy; 2 patients with morphologic relapse received additional chemotherapy (N=1) or radiotherapy (N=1).
Among the entire group, post HSCT sorafenib therapy was initiated a median of 80 days following HSCT (range 44-480 days) at a median dose of 150 mg/m2/day (range 75-340 mg/m2/day) and continued for a median of 12 months (range 0.5-52 months). 9/13 patients (69%) experienced toxicity which was felt to be medically significant including thrombocytopenia (N=2), rash (N=3), anorexia (N=1), myelosuppression (N=3), infection (N=2) and life threatening cardiac dysfunction (N=1 in patient treated concomitantly with mitoxantrone). In 8/13 cases (61%) the toxicity resulted in reduction or temporary discontinuation of sorafenib yet all patients tolerated retrial of drug at the same or reduced dosing. One additional patient experienced dose limiting marrow hypoplasia at dosing of 340 mg/m2/day. Sorafenib did not appear to exacerbate GVHD. 8/13 (62%) patients had controlled GHVD at time of sorafenib initiation and only 2 patients had subsequent skin flare that was temporally associated with wean of immune suppression and did not preclude use of further sorafenib.
Overall, 10/13 (77%) patients remain alive and 7/13 (54%) are disease free. Of 7 patients in continued CR, the median survival is 3.6 years from HSCT (range 1.75-5.6 years); 6/7 are off sorafenib therapy for a median of 10.5 months (range 7-36 months) after receiving treatment for a median of 19 months (range 8-52 months). 6/13 patients (46%) experienced progressive or recurrent disease while on therapy, 3 of whom have died: 2 from rapid disease progression despite sorafenib initiation and 1 from wild-type FLT3 recurrence. 3 additional patients with recurrent disease are receiving salvage therapy, 1 of whom has achieved a 2nd CR. Of particular interest is the outcome of patients who received sorafenib for MRD in the peri transplant period. All 5 remain alive and disease-free a median of 3.6 years from HSCT (range 1.75-5.6 years) and have been off sorafenib for a median of 12 months (range 7-36 months). Conversely, of the 5 patients who started treatment for morphologic recurrence, only 1/5 (20%) remain in CR. Of 3 additional patients who received prophylactic treatment for high AR or poor induction response, 2/3 have recurred, 1 of whom is now in 2ndCR with higher dose sorafenib in combination with conventional chemotherapy.
Our study suggests that sorafenib is tolerable and may improve survival for pediatric patients who undergo HSCT for FLT3/ITD+ AML. Prospective study is necessary to further confirm tolerability and to determine the scope of clinical benefit for this high risk population.
Off Label Use: Sorafenib use in AML will be discussed.
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