Lu Ban

ObjectivesThe objectives of this study were to retrospectively investigate the patient characteristics, treatment patterns, healthcare resource utilization (HCRU), and healthcare costs related to management of neurofibromatosis type 1 (NF1) in Japan.MethodsCohorts of NF1 patients with or without plexiform neurofibromas (PN) were identified from the Medical Data Vision database in 2008-2019. Baseline characteristics, NF1 medications, HCRU, and associated costs were assessed using descriptive statistics. All-cause HCRU and costs following the first confirmed NF1 diagnosis date were analyzed per patient per year (PPPY) in Japanese Yen (JPY) and United States Dollar (USD).ResultsA total of 4394 NF1 patients without PN and 370 NF1 patients with PN were identified. The mean age was 35.0 and 36.9 years, respectively. The proportion of patients with PN treated with medications was higher than that in patients without PN (except for antirheumatic/immunologic agents). Analgesics/non-steroidal anti-inflammatory drugs were the most frequently prescribed NF1 medications (44.3% and 56.0% in patients without and with PN, respectively), followed by inpatient prescriptions of opioids/opioid-like agents (17.8% and 27.6%, respectively). Inpatient admissions accounted for the highest costs in both cohorts with the average cost PPPY being JPY 2,133,277 (USD 19,861) for patients without PN and JPY 1,052,868 (USD 9802) for patients with PN.ConclusionsNF1 is treated primarily with supportive care with analgesics/non-steroidal anti-inflammatory drugs being the most frequently prescribed NF1 medications in Japan. Findings underscored the unmet need and substantial economic burden among patients with NF1 and highlighted the need for new treatment options for patients with this disease.

Background Haemophagocytic lymphohistiocytosis (HLH) is rare, results in high mortality and is increasingly being diagnosed. Little is known about what is driving the apparent rise in the incidence of this disease. Methods Using national linked electronic health data from hospital admissions and death certification cases of HLH that were diagnosed in England between 1/1/2003 and 31/12/2018 were identified using a previously validated approach. We calculated incidence rates of diagnosed HLH per million population using mid-year population estimates by calendar year, age group, sex and associated comorbidity (haematological malignancy, inflammatory rheumatological or bowel diseases (IBD)) associated with the diagnosis of HLH. We modelled trends in incidence and the interactions between calendar year, age and associated comorbidity using Poisson regression. Findings There were 1674 people with HLH diagnosed in England between 2003 and 2018. The incidence rate quadrupled (Incidence Rate Ratio (IRR) 2018 compared to 2003: 3.88 95% Confidence Interval (CI) 2.91 to 5.28), increasing 11% annually (adjusted IRR 1.11 95% CI 1.09 to 1.12). There was a rising trend in all age groups except those aged less than 5 years. There was a transition across the age groups with greater increases in those aged 5 to 14 years of HLH associated with rheumatological disease/IBD compared to HLH associated with haematological malignancy, with similar increases in HLH associated with both co-morbidities for those 15-54, and greater increases in associated haematological malignancies for those 55 years and older. Interpretation The incidence of HLH in England has quadrupled between 2003 and 2018, increasing 11% annually. Substantial variation in the incidence occurred by age group and by HLH associated comorbidities with inflammatory rheumatological diseases or IBD associated HLH increasing more among the young and middle age groups, whereas in older age groups the largest increase was seen with haematological malignancy-associated HLH. Evidence before this study There is a paucity of population-based data on the epidemiology of HLH worldwide. The available evidence relies mostly upon a collection of cases series published in The Lancet in 2014 which described 2197 cases of HLH in adults reported in the literature to that point. Almost all of these were from tertiary referral specialist centres and/or described in small case series. The incidence of HLH has only been described in a few reports – and mainly this has focused on children with primary HLH. No previous studies have been large enough to examine trends in incidence by age, sex, underlying risk factors and calendar time. Added value of this study This study quantifies the incidence of diagnosed HLH for the first time in a nationwide manner for all age groups. It reports on 1674 patients with HLH from England and shows that there is substantial variation in the incidence by age group, associated disease and calendar time. The results imply reasons for the increase in HLH could be related to the increasing occurrence of haematological cancer, inflammatory rheumatological or bowel diseases and the treatments given for these conditions. This study has been carried out in partnership with the National Congenital Anomalies and Rare Diseases Registration Service and the methodology described can in future be applied to many rare diseases that as yet lack a way of quantifying crucial epidemiological metrics. Implications of all the available evidence The incidence of HLH is rising rapidly in people older than 5 years of age. This could be due to an increase in the biologic, immunomodulation or immunosuppressive therapy being used in people with haematological cancer and inflammatory rheumatological and bowel diseases. Further work should focus on how to minimise the risk of HLH occurring, or to improve treatment of this often fatal disease among those who need treatment for an associated comorbidity.

Background and Aims: Cystic fibrosis (CF) is a multi-system genetic disorder affecting >72,000 people worldwide. Most people with CF experience gastrointestinal symptoms and some will develop complications such as distal intestinal obstruction syndrome. However the mechanisms of symptoms and complications are not understood. We evaluated gut function and transit of CF using magnetic resonance imaging (MRI). Our hypotheses were: oro-caecal transit time (OCTT) is longer in CF, with lower small bowel water content (SBWC). Methods: Twelve people with CF at a tertiary centre and 12 age and sex-matched controls underwent serial MRIs over 1 day, with meals at set times. The primary endpoint was OCTT, assessed by the appearance of a food bolus in the caecum. Other measures included SBWC, colonic volume, gastric half-emptying time and gastrointestinal symptoms. Results: OCTT was longer in CF (controls 210 minutes [173, 315] vs. CF 330 minutes [270, >360], p=0.04). There was no difference in gastric half-emptying times (controls 80 minutes [66, 88] vs. CF 97 [71, 128], p=0.3). Corrected SBWC was higher in CF (controls 34 L.min/m ² [28, 41] vs. CF 63 L.min/m ² [36, 80], p=0.021), with minimal second post-prandial decrease suggesting impaired ileal emptying. Corrected colonic volumes were higher in CF (controls 123 L.min/m ² [89, 146] vs. CF 186 L.min/m ² [166, 209], p=0.012). There were no differences in gastrointestinal symptoms. Conclusions: Significant differences in gut function and transit exist between CF and controls. Our methodology provides a platform for studying gastrointestinal function in CF and has identified new potential mechanisms of dysfunction. ClinicalTrials.gov NCT03566550

Objectives: Survival in infants with gastroschisis is increasing although little is known about early childhood morbidity. In the context of a hypothesized link between the gastrointestinal (GI) tract and immune function, this study explores rates of GI and respiratory infections in children with gastroschisis.Methods: We conducted a population‐based retrospective cohort study using data from the Health Improvement Network, a large database of UK primary care medical records. We identified children born from 1990 to 2013, and extracted follow‐up data to their fifth birthday. We calculate incidence rates (IR) of GI and respiratory tract infections, overall and stratified by age, sex, socioeconomic status, and gestational age at birth, and compared these between children with and without gastroschisis by calculating adjusted incidence rate ratios (aIRR).Results: Children with gastroschisis had a 65% higher IR of GI infection compared to children without (aIRR 1.65, 95% confidence interval [CI] 1.37–1.99, P < 0.001). Children with gastroschisis had a 27% higher IR of all respiratory tract infections (aIRR 1.27, 95% CI 1.12–1.44, P < 0.001) and more than 2‐fold increase in lower respiratory tract infections compared to children without the condition (aIRR 2.15, 95% CI 1.69–2.74, P < 0.001).Conclusions: Children born with gastroschisis have a significantly higher incidence of GI and respiratory tract infections compared to children without gastroschisis. This association requires further investigations but could be related to the neonatal care they receive such as delayed enteral feeding or frequent antibiotic courses altering the gut microbiome and developing immune system.

Introduction: Research has suggested that delivery is associated with an increased risk of stroke in women; however, there is a lack of contemporary estimates on the incidence of stroke in and after pregnancy compared with the baseline risk in women of childbearing age in Sweden. Patients and methods: All women aged 15–49 years with live births/stillbirths in 1992–2011 were identified from the Swedish Medical Birth Registry linked with the National Patient Registry. First stroke during the study period was identified. Incidence rates per 100,000 person-years and adjusted incidence rate ratios (IRRs) were calculated for antepartum, peripartum and early and late postpartum periods, compared with all other available follow-up time (time before pregnancy and after postpartum) using Poisson regression adjusted for maternal age, education attainment and calendar time. Results: Of 1,124,541 women, 3094 had a first incident stroke (331 occurred during pregnancy or first 12 weeks postpartum), about half having ischaemic stroke. The incidence was 15.0 per 100,000 person-years (95% confidence interval 14.5–15.6) in non-pregnant time. The incidence was lower antepartum (7.3/100,000 person-years, 6.0–8.9; adjusted IRR = 0.7, 0.5–0.8) but higher peripartum (314.4/100,000 person-years, 247.5–399.5; adjusted IRR = 27.3, 21.4–34.9) and early postpartum (64.0/100,000 person-years, 54.1–75.7; adjusted IRR = 5.5, 4.6–6.6). The increased risk in peripartum was more evident for intracerebral haemorrhage than other types of stroke. Conclusion: Overall risk of stroke was low in women of childbearing age, but stroke risk peaks in the peripartum and early postpartum periods. Future work should address factors that contribute to this increased risk in order to develop approaches to attenuate risk.

Though the risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA) has been established in Western population, little is known about the risk in Chinese people with RA. Our objective was to estimate the risk of CVD in Chinese people with RA using hospital medical records data. The inpatients medical record database 2005–2015 of Sichuan provincial people’s hospital was examined. All individuals with a primary diagnosis of RA were included as cases, and those of osteoarthritis (OA) were included as controls, which consisted of the unmatched dataset. Then, RA cases and OA controls were matched by sex and age at 1:1 ratio, forming the matched dataset. The morbidity of CVD (including ischemia heart disease (IHD), congestive heart failure (CHF), et al), stroke and arthrosclerosis were extracted from the database, so as the demographic data and comorbidities related to CVD. Multiple logistic regression analysis was used to estimate the risk of CVD in RA adjusted for demographics and comorbidities using the unmatched dataset. Sensitivity analysis was conducted 1) considering interaction terms between RA and comorbidities, and 2) using multivariable conditional logistic regression for the matched dataset. The unmatched dataset comprised of 1824RA cases and 1995 OA controls and the matched dataset comprised of 1022 pairs of sex and age matched RA and OA patients. RA exhibited increased odds of prevalent CVD compared with OA, and the adjusted ORs (95%CIs) for CVD, stroke, IHD, CHF, and atherosclerosis were1.86(1.42–2.43), 1.11(0.71–1.74), 1.47(0.97–2.24), 2.09(1.03–4.22), and 2.49 (1.97–3.13), respectively, and was 2.26 (1.29–3.96)for IHD further adjusted for interaction term. The matched dataset analysis found similar results. Chinese people with RA were approximated 2 times more likely to have CVD, IHD, CHF and atherosclerosis compared with those with OA. The findings justified the need of further longitudinal study to establish the causal-relationship between RA and CVD and to estimate the precise risk in this population.

Background: Pregnant women may have an increased risk of stroke compared with nonpregnant women of similar age, but the magnitude and the timing of such risk are unclear. We examined the risk of a first stroke event in women of childbearing age and compared the risk during pregnancy and in the early postpartum period with the background risk outside these periods. Methods and Results: We conducted an open cohort study of 2 046 048 women aged 15 to 49 years between April 1, 1997, and March 31, 2014, using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care records in England. Risk of first stroke was assessed by calculating the incidence rate of stroke in antepartum, peripartum (2 days before until 1 day after delivery), and early (first 6 weeks) and late (second 6 weeks) postpartum periods compared with nonpregnant time using a Poisson regression model with adjustment for maternal age, socioeconomic group, and calendar time. A total of 2511 women had a first stroke. The incidence rate of stroke was 25.0 per 100 000 person‐years (95% CI 24.0–26.0) in nonpregnant time. The rate was lower antepartum (10.7 per 100 000 person‐years, 95% CI 7.6–15.1) but 9‐fold higher peripartum (161.1 per 100 000 person‐years, 95% CI 80.6–322.1) and 3‐fold higher early postpartum (47.1 per 100 000 person‐years, 95% CI 31.3–70.9). Rates of ischemic and hemorrhagic stroke both increased peripartum and early postpartum. Conclusions: Although the absolute risk of first stroke is low in women of childbearing age, healthcare professionals should be aware of a considerable increase in relative risk during the peripartum and early postpartum periods.