Incidence, prevalence and survival in patients with Langerhans cell histiocytosis: A national registry study from England, 2013-2019.

This analysis is the largest population-based study to date to provide contemporary and comprehensive epidemiological estimates of all third edition of the International Classification of Diseases for Oncology (ICD-O-3) coded Langerhans cell histiocytosis (LCH) from England. People of all ages were identified from the National Cancer Registration Dataset using ICD-O-3 morphologies 9751-9754 for neoplasms diagnosed in 2013-2019. A total of 658 patients were identified, of whom 324 (49%) were children aged <15 years. The age-standardised incidence rate was 4.46 (95% confidence interval [CI] 3.99-4.98) per million children and 1.06 (95% CI 0.94-1.18) per million adults aged ≥15 years. Prevalence of LCH was 9.95 (95% CI 9.14-10.81) per million persons at the end of 2019. The 1-year overall survival (OS) was 99% (95% CI 97%-100%) for children and 90% (95% CI 87%-93%) for adults. Those aged ≥60 years had poorer OS than those aged <15 years (hazard ratio [HR] 22.12, 95% CI 7.10-68.94; p < 0.001). People in deprived areas had lower OS than those in the least deprived areas (HR 5.36, 95% CI 1.16-24.87; p = 0.03). There will inevitably be other environmental factors and associations yet to be identified, and the continued standardised data collection will allow further evaluation of data over time. This will be increasingly important with developments in LCH management following the large collaborative international trials such as LCH IV.

Incidence and survival of haemophagocytic lymphohistiocytosis: A population-based cohort study from England.

BACKGROUND: Haemophagocytic lymphohistiocytosis (HLH) is a rare hyper-inflammatory condition with poor outcomes. OBJECTIVES: Few population-based estimates of the incidence and survival in adults exist. We aimed to provide these data for England. METHODS: We used population-based linked data from primary care, secondary care, cancer registries and mortality databases in England to identify people diagnosed with HLH between 1 January 2000 and 31 December 2016. We calculated annual incidence rates by age and sex, modelled change in incidence over time with Poisson regression, calculated overall 1-year survival using Kaplan-Meier methods and estimated adjusted hazard ratios (HRs) of death using a Cox proportional hazards model. RESULTS: We identified 214 patients with HLH. The reported age and sex-adjusted incidence increased twofold over the period, from around one to around two per million. Incidence was highest in those below 1 year (14.6 per million) and ≥75 years (2.2 per million), and lowest in those aged 15-44 years (0.8 per million). One-year survival varied by age and sex from 77% (95% confidence interval [CI] 63%-86%) in those <15 years to 30% (95% CI 14%-49%) in those ≥75. In patients with haematological cancer, the adjusted HR for death was 2.60 (95% CI 1.45-4.66) compared to patients with no malignant or rheumatological disease. CONCLUSION: The incidence of HLH diagnosis in England has increased between 2000 and 2016 and occurs in all ages with varying underlying diseases. One-year survival varies substantially, being particularly poor in those aged over 75 years and those with haematological malignancy.

A validation study of the identification of haemophagocytic lymphohistiocytosis in England using population-based health data.

We assessed the validity of coded healthcare data to identify cases of haemophagocytic lymphohistiocytosis (HLH). Hospital Episode Statistics (HES) identified 127 cases within five hospital Trusts 2013-2018 using ICD-10 codes D76.1, D76.2 and D76.3. Hospital records were reviewed to validate diagnoses. Out of 74 patients, 73 were coded D76.1 or D76.2 (positive predictive value 89·0% [95% Confidence Interval {CI} 80·2-94·9%]) with confirmed/probable HLH. For cases considered not HLH, 44/53 were coded D76.3 (negative predictive value 97·8% [95% CI 88·2-99·9%]). D76.1 or D76.2 had 68% sensitivity in detecting HLH compared to an established active case-finding HLH register in Sheffield. Office for National Statistics (ONS) mortality data (2003-2018) identified 698 patients coded D76.1, D76.2 and D76.3 on death certificates. Five hundred and forty-one were coded D76.1 or D76.2 of whom 524 (96·9%) had HLH in the free-text cause of death. Of 157 coded D76.3, 66 (42·0%) had HLH in free text. D76.1 and D76.2 codes reliably identify HLH cases, and provide a lower bound on incidence. Non-concordance between D76.3 and HLH excludes D76.3 as an ascertainment source from HES. Our results suggest electronic healthcare data in England can enable population-wide registration and analysis of HLH for future research.

Incidence, prevalence and mortality of autoimmune hepatitis in England 1997-2015. A population-based cohort study.

BACKGROUND & AIMS: There are few population-based studies of the incidence and mortality of autoimmune hepatitis. The burden of the disease and how it has changed over time have not been fully explored. We conducted a population-based cohort study on the incidence and mortality of autoimmune hepatitis in England, 1997-2015. METHODS: From the Clinical Practice Research Datalink we included 882 patients diagnosed with autoimmune hepatitis in England, 1997-2015. The patients were followed through 2015, and we calculated the sex- and age-standardized incidence and prevalence of autoimmune hepatitis. We examined variation in incidence by sex, age, calendar year, geographical region and socioeconomic status, and incidence rate ratios were calculated with Poisson regression. We calculated all-cause and cause-specific mortality. RESULTS: The overall standardized incidence rate of autoimmune hepatitis was 2.08 (95% confidence interval 1.94-2.22) per 100,000 population per year, higher in women, higher in older age and independent of region and socioeconomic status. From 1997 to 2015 the incidence doubled from 1.27 (95% confidence interval 0.51-2.02) to 2.56 (95% confidence interval 1.79-3.33) per 100,000 population per year. The 10-year cumulative all-cause mortality was 31.9% (95% confidence interval 27.6-36.5), and the 10-year cumulative liver-related mortality, including hepatocellular carcinoma was ~10.5%. CONCLUSIONS: This population-based study showed that the incidence of autoimmune hepatitis doubled over an eighteen-year period. The incidence was particularly high in older women and was similar across all regions of England and independent of socioeconomic status. Patients with autoimmune hepatitis had a high mortality.

Mortality After Extrahepatic Gastrointestinal and Abdominal Wall Surgery in Patients With Alcoholic Liver Disease: A Systematic Review and Meta-Analysis.

AIMS: This meta-analysis aimed to define the perioperative risk of mortality in patients with alcoholic liver disease (ALD) undergoing extrahepatic gastrointestinal surgery. METHODS: Systematic searches of Embase, Medline and CENTRAL were undertaken to identify studies reporting about patients with ALD undergoing extrahepatic gastrointestinal surgery published since database inception to January 2019. Studies were only considered if they reported on mortality as an outcome. Pooled analysis of mortality was stratified as benign and malignant surgery and specific operative procedures where feasible. RESULTS: Of the 2899 studies identified, only five studies met inclusion criteria, representing cholecystectomy (one study), umbilical hernia repair surgery (one study) and oesophagectomy (three studies). The total number of patients with ALD in these studies was 172. Therefore, any study on liver disease patients undergoing extrahepatic surgery that crucially included a subset with alcohol aetiology was included as a secondary analysis even though they failed to stratify mortality by underlying aetiology. The total number of studies that met this expanded inclusion criteria was 62, reporting on 37,703 patients with liver disease of which 1735 (4.5%) had a definite diagnosis of ALD. Meta-analysis of proportions of in-hospital mortality in patients with ALD undergoing upper gastrointestinal cancer surgery (oesophagectomy) was 23% [95% confidence interval (CI) 14-35%, I2 = 0%]. In-hospital mortality following oesophagectomy in liver disease patients of all aetiologies was lower, 14% (95% CI 9-21%, I2 = 41.1%). CONCLUSION: Postoperative in-hospital mortality is high in patients with liver disease and ALD in particular. However, the currently available evidence on ALD is limited and precludes definitive conclusions on postoperative mortality risk.

The risk of venous thromboembolism after surgery for esophagogastric malignancy and the impact of chemotherapy: a population-based cohort study.

To define the incidence of postoperative venous thromboembolism (VTE) and effects of chemotherapy in a population undergoing surgery for esophagogastric cancer. This population-based cohort study used linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data from England to identify subjects undergoing esophageal or gastric cancer surgery between 1997 and 2014. Exposures included age, comorbidity, smoking, body mass index, and chemotherapy. Crude rates and adjusted hazard ratios (HRs) were calculated for rate of first postoperative VTE using Cox regression models. The cumulative incidence of VTE at 1 and 6 months was estimated accounting for the competing risk of death from any cause. Of the 2,452 patients identified, 1,012 underwent gastrectomy (41.3%) and 1,440 esophagectomy (58.7%). Risk of VTE was highest in the first month, with absolute VTE rates of 114 per 1,000 person-years (95% CI 59.32-219.10) following gastrectomy and 172.73 per 1,000 person-years (95% CI 111.44-267.74) following esophagectomy. Neoadjuvant and adjuvant chemotherapy was associated with a six-fold increased risk of VTE following gastrectomy, HR 6.19 (95% CI 2.49-15.38). Cumulative incidence estimates of VTE at 6 months following gastrectomy in patients receiving no chemotherapy was 1.90% and esophagectomy 2.21%. However, in those receiving both neoadjuvant and adjuvant chemotherapy, cumulative incidence following gastrectomy was 10.47% and esophagectomy, 3.9%. VTE rates are especially high in the first month following surgery for esophageal and gastric cancer. The cumulative incidence of VTE at 6 months is highest in patients treated with chemotherapy. In this category of patients, targeted VTE prophylaxis may prove beneficial during chemotherapy treatment.

Early Life Incidence of Gastrointestinal and Respiratory Infections in Children With Gastroschisis: A Cohort Study.

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.

Limited risks of major congenital anomalies in children of mothers with IBD and effects of medications.

BACKGROUND & AIMS: Concerns persist about the risk of major congenital anomalies in children of women with inflammatory bowel disease (IBD), and whether medication use affects risk. We assessed these risks, and variations in use of medications by women with IBD before, during, and after pregnancy. METHODS: We accessed data on children born to women 15-45 y old from 1990 through 2010, using a mother-child linked dataset from an electronic database of primary care records containing medical diagnoses, events, and drug prescriptions from across the United Kingdom. We identified pregnant women with IBD, and all prescriptions for 5-aminosalicylates azathioprine/6-mercaptopurine, and corticosteroids were extracted from their primary care records. We calculated risks of major congenital anomaly in children of mothers with and without IBD, and in children exposed or not exposed to 5-aminosalicylates, azathioprine/6-mercaptopurine, or corticosteroids during their first trimester of fetal development. Logistic regression with a generalized estimating equation was used to provide risk estimates adjusted for confounders. We calculated proportions of women taking medications before, during, and after pregnancy and assessed whether cessation was associated with subsequent disease flares. RESULTS: Risks of a major congenital anomaly in 1703 children of mothers with IBD and 384,811 children of mothers without IBD were 2.7% and 2.8%, respectively. This corresponded to an adjusted odds ratio of 0.98 (95% confidence interval [CI], 0.73-1.31). In children of women with IBD, the adjusted odds ratios of a major congenital anomaly associated with drug use were 0.82 (95% CI, 0.42-1.61) for 5-aminosalicylates 0.48 (95% CI, 0.15-1.50) for corticosteroids, and 1.27 (95% CI, 0.48-3.39) for azathioprine/6-mercaptopurine. No increases in heart, limb, or genital anomalies were found in children of women with IBD; 31.2% of women discontinued 5-aminosalicylates and 24.6% discontinued azathioprine/6-mercaptopurine in early pregnancy. The risk of flares later in pregnancy was not related to cessation of medication. CONCLUSIONS: We found no evidence that IBD during pregnancy or medical therapy for IBD during pregnancy increases the risk of a major congenital anomaly in children. Patients should receive appropriate guidance on use of medication before and during pregnancy.

Women with celiac disease present with fertility problems no more often than women in the general population.

BACKGROUND & AIMS: Studies have associated infertility with celiac disease. However, these included small numbers of women attending infertility specialist services and subsequently screened for celiac disease, and therefore may not have been representative of the general population. We performed a large population-based study of infertility and celiac disease in women from the United Kingdom. METHODS: We identified 2,426,225 women with prospective UK primary care records between 1990 and 2013 during their child-bearing years from The Health Improvement Network database. We estimated age-specific rates of new clinically recorded fertility problems among women with and without diagnosed celiac disease. Rates were stratified by whether celiac disease was diagnosed before the fertility problem or afterward and compared with rates in women without celiac disease using Poisson regression, adjusting for sociodemographics, comorbidities, and calendar time. RESULTS: Age-specific rates of new clinically recorded fertility problems in 6506 women with celiac disease were similar to the rates in women without celiac disease (incidence rate ratio, 1.12; 95% confidence interval, 0.88-1.42 among women age 25-29 years). Rates of infertility among women without celiac disease were similar to those of women with celiac disease before and after diagnosis. However, rates were 41% higher among women diagnosed with celiac disease when they were 25-29 years old, compared with women in the same age group without celiac disease (incidence rate ratio, 1.41; 95% confidence interval, 1.03-1.92). CONCLUSIONS: Women with celiac disease do not have a greater likelihood of clinically recorded fertility problems than women without celiac disease, either before or after diagnosis, except for higher reports of fertility problems between 25-39 years if diagnosed with CD. These findings should assure most women with celiac disease that they do not have an increased risk for fertility problems.

Pregnancy complications and adverse birth outcomes among women with celiac disease: a population-based study from England.

OBJECTIVES: Evidence-based information about adverse birth outcomes and pregnancy complications is crucial when counseling women with celiac disease (CD); however, limited population-based data on such risks exist. We estimated these for pregnant women with CD diagnosed before and after delivery. METHODS: We included all singleton pregnancies between 1997 and 2012 using linked primary care data from the Clinical Practice Research Datalink and secondary care Hospital Episode Statistics data. Risks of pregnancy complications (antepartum and postpartum hemorrhage, pre-eclampsia, and mode of delivery) and adverse birth outcomes (preterm birth, stillbirth, and low birth weight) were compared between pregnancies of women with and without CD using logistic/multinomial regression. Risks were stratified on the basis of whether women were diagnosed or yet undiagnosed before delivery. RESULTS: Of 363,930 pregnancies resulting in a live birth or stillbirth, 892 (0.25%) were among women with CD. Diagnosed CD was not associated with an increased risk of pregnancy complications or adverse birth outcomes compared with women without CD. However, the risk of postpartum hemorrhage and assisted delivery was slightly higher among pregnant women with diagnosed CD (adjusted odds ratio (aOR)=1.34). We found no increased risk of any pregnancy complication among those with undiagnosed CD. We only observed a 1% absolute excess risk of preterm birth and low birth weight among undiagnosed CD mothers corresponding to aOR=1.24 (95% confidence interval (CI)=0.82-1.87) and aOR=1.36 (95% CI=0.83-2.24), respectively. CONCLUSIONS: Whether diagnosed or undiagnosed during pregnancy, CD is not associated with a major increased risk of pregnancy complications and adverse birth outcomes. These findings are reassuring to both women and clinicians.

Bleeds and resource use in hemophilia B: retrospective observational study.

OBJECTIVES: To describe people with hemophilia B (PWHB) in the US who experience bleeds despite factor replacement therapy and to quantify the associated burden from the third-party payer perspective. STUDY DESIGN: Observational study of adult male PWHB treated with factor IX replacement therapy identified from the PharMetrics Plus claims data from 2010 to 2019. METHODS: Patients with medically recorded bleeds (MRBs) were identified using diagnostic codes. Rates and rate ratios of inpatient admissions, emergency department (ED) visits, and outpatient visits among PWHB with and without MRBs were estimated. The presence of comorbidities was identified using diagnostic codes, and the analysis was stratified by age group. RESULTS: There were 345 PWHB with MRBs and 252 without MRBs. More than half of PWHB with MRBs (56.8%) had 1 or more comorbidity vs 39.3% of PWHB without MRBs. The prevalence of anxiety and depression was high in PWHB, regardless of bleed status and age group, whereas the prevalence of other comorbidities increased with age group. The rate of all-cause inpatient admissions for PWHB with MRBs was 14.8 per 100 person-years (95% CI, 12.8-17.1), 2.5 times higher than for PWHB without MRBs. The rate of all-cause ED visits for PWHB with MRBs was 67.6 per 100 person-years (95% CI, 63.2-72.3), 2.7 times higher than for those without MRBs. CONCLUSIONS: This study reports significant resource use and clinical burden among PWHB who seek medical care. PWHB with MRBs had considerable all-cause resource use compared with PWHB without MRBs. The prevalence of mental illness was consistently high across all age groups.

Treatment patterns and healthcare resource utilization in patients with metastatic hormone-sensitive prostate cancer and nonmetastatic castration-resistant prostate cancer in China: a real-world observational study.

AIM: This study assessed the treatment patterns, healthcare resource utilization (HRU), costs, and annual prevalence and incidence of metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC) in China. METHODS: A retrospective study was conducted using electronic medical records (EMR) of patients with prostate cancer from three tertiary-care hospitals in China between January 2014 and March 2021. Descriptive statistics were used to analyze study outcomes. RESULTS: In total, 1086 patients with mHSPC and 679 patients with nmCRPC were included. From 2015 to 2020, the annual percentage of prevalent and incident cases of mHSPC decreased from 22.4% to 20.0% and 11.1% to 6.9%, respectively; for nmCRPC, these increased from 3.8% to 13.6% and 3.3% to 8.4%. Androgen-deprivation therapy and first-generation antiandrogens (bicalutamide or flutamide) were the most frequently prescribed prostate cancer-related medications at baseline and follow-up in patients with mHSPC. Bicalutamide was the most frequently prescribed prostate cancer-related medication during follow-up in patients with nmCRPC. For mHSPC, inpatient admission costs were the highest, with the median (interquartile range) costs per person-month being USD 403.00 (USD 85.50-1226.20), whereas outpatient visit costs were the highest for nmCRPC (USD 372.60 [USD 139.50-818.50]). LIMITATIONS: EMR-based study design did not capture treatment patterns, HRU and associated costs, and healthcare encounters that occurred outside of participating hospitals, which could have led to underestimation of the true disease burden. CONCLUSIONS: A contrasting trend of a decline in the prevalence and incidence of mHSPC and an increase in these for nmCRPC was observed between 2015 and 2020 in China. Androgen-deprivation therapy and first-generation antiandrogens were the most frequently prescribed prostate cancer-related medications. Healthcare resource utilization was driven by inpatient costs in mHSPC and outpatient costs in nmCRPC.

Smoking is a Risk Factor for Autoimmune Hepatitis: An English Registry-Based Case-Control Study.

Purpose: Smoking is a risk factor for some autoimmune diseases, but its association with autoimmune hepatitis remains unknown. We conducted a population-based matched case-control study to examine the association between tobacco smoking and the risk of autoimmune hepatitis in England. Patients and Methods: From the Clinical Practice Research Datalink and linked Hospital Episode Statistics, 2005-2017, we included 987 cases diagnosed with autoimmune hepatitis after age 18 years and up to 10 frequency-matched population controls per case. We used multiple logistic regression to estimate the odds ratio of autoimmune hepatitis in ever-smokers vs never-smokers, adjusting for sex, age, general practice, calendar time of registration with the general practice, and socioeconomic status. Results: The autoimmune hepatitis cases were more likely to be ever-smokers than the controls (44% vs 37%). The ever-smokers had an increased risk of autoimmune hepatitis compared with the never-smokers (adjusted odds ratio = 1.20, 95% confidence interval 1.03-1.39). Conclusion: Smoking was associated with an increased risk of autoimmune hepatitis.

Patient characteristics, treatment patterns, healthcare resource utilization, and costs among patients diagnosed with neurofibromatosis type 1 with and without plexiform neurofibromas in Japan.

OBJECTIVES: The 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. METHODS: Cohorts 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). RESULTS: A 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. CONCLUSIONS: NF1 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.

Carprofen-imprinted monolith prepared by reversible addition-fragmentation chain transfer polymerization in room temperature ionic liquids.

To obtain fast separation, ionic liquids were used as porogens first in combination with reversible addition-fragmentation chain transfer (RAFT) polymerization to prepare a new type of molecularly imprinted polymer (MIP) monolith. The imprinted monolithic column was synthesized using a mixture of carprofen (template), 4-vinylpyridine, ethylene glycol dimethacrylate, [BMIM]BF4, and chain transfer agent (CTA). Some polymerization factors, such as template-monomer molar ratio, the degree of crosslinking, the composition of the porogen, and the content of CTA, on the column efficiency and imprinting effect of the resulting MIP monolith were systematically investigated. Affinity screening of structurally similar compounds with the template can be achieved in 200 s on the MIP monolith due to high column efficiency (up to 12,070 plates/m) and good column permeability. Recognition mechanism of the imprinted monolith was also investigated.

Preparation and characterization of an imprinted monolith by atom transfer radical polymerization assisted by crowding agents.

A method based on reverse atom transfer radical polymerization (R-ATRP) and molecular crowding has been used for design and synthesis of monolithic molecularly imprinted polymers (MIPs) capable of recognizing ibuprofen (IBU). 4-Vinylpyridine (4-VP) was used as the functional monomer, and ethylene glycol dimethacrylate (EDMA) was the crosslinking monomer. Azobisisobutyronitrile (AIBN)-CuCl(2)-N,N,N',N",N"-pentamethyldiethylenetriamine (PMDETA) was used as the initiating system. Compared with conventional radical polymerization-based IBU-MIPs, the imprinting effects of the obtained IBU-MIPs was enhanced, suggesting the merit of combination of reverse ATRP and molecular crowding. In addition, it was found that the polymerization time of the molecularly imprinted monolithic column, the amount of template, the degree of crosslinking, and the composition of mobile phase greatly affected retention of the template and the performance of molecular recognition.

1-year survival in haemophagocytic lymphohistiocytosis: a nationwide cohort study from England 2003-2018.

Haemophagocytic lymphohistiocytosis (HLH) is a lethal syndrome of excessive immune activation. We undertook a nationwide study in England of all cases of HLH diagnosed between 2003 and 2018, using linked electronic health data from hospital admissions and death certification. We modelled interactions between demographics and comorbidities and estimated one-year survival by calendar year, age group, gender and comorbidity (haematological malignancy, auto-immune, other malignancy) using Cox regression. There were 1628 people with HLH identified. Overall, crude one-year survival was 50% (95% Confidence interval 48-53%) which varied substantially with age (0-4: 61%; 5-14: 76%; 15-54: 61%; > 55: 24% p < 0.01), sex (males, 46%, worse than females, 55% p < 0.01) and associated comorbidity (auto-immune, 69%, haematological malignancy 28%, any other malignancy, 37% p < 0.01). Those aged < 54 years had a threefold increased risk of death at 1-year amongst HLH associated with malignancy compared to auto-immune. However, predicted 1-year survival decreased markedly with age in those with auto-immune (age 0-14, 84%; 15-54, 73%; > 55, 27%) such that among those > 55 years, survival was as poor as for patients with haematological malignancy. One-year survival following a diagnosis of HLH varies considerably by age, gender and associated comorbidity. Survival was better in those with auto-immune diseases among the young and middle age groups compared to those with an underlying malignancy, whereas in older age groups survival was uniformly poor regardless of the underlying disease process.

Liver blood marker testing in UK primary care: a UK wide cohort study, 2004-2016.

OBJECTIVE: We aimed to determine (1) the temporal trends of liver enzyme testing in UK general practice and (2) how these vary among different subgroups at risk of chronic liver disease (CLD). DESIGN: Retrospective cohort study. SETTING: UK primary care database (Clinical Practice Research Datalink (CPRD)), 2004-2016. PARTICIPANTS: Patients aged 18 years or over, registered in the CPRD from 1 January 2004 to 31 December 2016. OUTCOME MEASURES: The frequency of testing recorded within the study period in general practice was calculated for: alanine aminotransferase (ALT); aspartate aminotransferase (AST); gamma glutamyl transferase (GGT); alkaline phosphatase (ALP); bilirubin and platelets. Analyses were conducted in subgroups of patients at high risk of developing liver disease. RESULTS: The study cohort included 2 912 066 individuals with median follow-up of 3.2 years. The proportion of patients with at least one measurement for ALT, ALP, bilirubin or platelet test gradually increased over the course of the study period and fell for AST and GGT. By 2016, the proportion of the population receiving one of more tests in that year was: platelet count 28.0%, ALP 26.2%, bilirubin 25.6%, ALT 23.7%, GGT 5.1% and AST 2.2%. Those patients with risk factors for CLD had higher proportions receiving liver marker assessments than those without risk factors. CONCLUSIONS: The striking finding that AST is now only measured in a fraction of the population has significant implications for routine guidance which frequently expects it. A more nuanced approach where non-invasive markers are targeted towards individuals with risk factors for CLD may be a solution.

Risk of venous thromboembolism among women receiving ospemifene: a comparative observational study.

Introduction: The primary aim of this study was to compare the incidence of venous thromboembolism (VTE) among women initiating ospemifene vs other selective estrogen receptor modulator (SERM) therapies for estrogen-deficiency conditions or breast cancer prevention, and vs women with untreated vulvar and vaginal atrophy (VVA). The secondary objective examined numerous additional safety outcomes. Methods: This was a retrospective cohort study using the IBM Watson MarketScan claims database. Women receiving ospemifene, another SERM, or with a new diagnosis of VVA with no treatment from 1 May 2013 to 2 October 2018 were followed through the claims for incident adverse outcomes. The primary outcome was the first occurrence of VTE following cohort entry; secondary outcomes included cerebrovascular events and other adverse events potentially associated with SERM use. Cox models compared the risk of VTE between ospemifene and comparators, using a variety of approaches to control for confounding. Results: The incidence of VTE during the first continuous treatment episode was 3.39 (95% confidence interval [CI]: 1.55-6.43) events per 1,000 person-years (PY) for ospemifene (N = 8977), 11.30 (95% CI: 8.81-14.28) events per 1,000 PY for comparator SERM (N = 12,621), and 10.92 (95% CI: 10.49-11.37) events per 1,000 PY for untreated VVA (N = 242,488). Cox models indicated no increase in risk of VTE for ospemifene vs other SERMs (hazard ratio [HR]: 0.40, 95% CI: 0.19-0.82), and vs untreated VVA (HR: 0.47, 95% CI: 0.24-0.91). Conclusion: This real-world safety analysis found no increase in risk of VTE or other adverse events with use of ospemifene in postmenopausal women. Plain Language Summary: Introduction: This study assessed the risk of venous thromboembolism (VTE) among women treated with ospemifene or another selective estrogen receptor modulator (SERM) therapy and women with untreated vulvar and vaginal atrophy (VVA). Numerous additional safety outcomes were examined.Methods: This study was conducted in the IBM Watson MarketScan claims database. Women receiving ospemifene, another SERM, or with a new diagnosis of VVA with no treatment from 1 May 2013 to 2 October 2018 were followed through the claims for adverse outcomes, including VTE, cerebrovascular events (such as stroke), and other outcomes that might occur with use of a SERM. The analyses compared the risk of VTE between ospemifene and the other two groups, using methods that accounted for differences in patient characteristics between the groups. Because few women over 72 years old used ospemifene, the main analyses examined women aged 54-72 years.Results: The analyses included 8,977 ospemifene users, 12,621 other SERM users, and 242,488 women with untreated VVA. Among women aged 54-72 years, only 9 experienced a VTE during ospemifene treatment, while 55 other SERM users and 1,788 women with untreated VVA had a VTE. The analyses that accounted for differences between the groups confirmed that the risk of VTE was no higher in ospemifene users than in either comparison group.Conclusion: This real-world safety analysis found no increase in risk of VTE or other adverse events with use of ospemifene in postmenopausal women.