Ixazomib Versus Placebo as Postinduction Maintenance Therapy in Newly Diagnosed Multiple Myeloma Patients: An Analysis by Age and Frailty Status of the TOURMALINE-MM4 Study.

BACKGROUND: The TOURMALINE-MM4 trial demonstrated a significant and clinically meaningful progression-free survival (PFS) benefit with ixazomib versus placebo as postinduction maintenance in nontransplant, newly-diagnosed multiple myeloma patients, with a manageable and well-tolerated toxicity profile. MATERIALS AND METHODS: In this subgroup analysis, efficacy and safety were assessed by age (< 65, 65-74, and ≥ 75 years) and frailty status (fit, intermediate-fit, and frail). RESULTS: In this analysis, PFS benefit with ixazomib versus placebo was seen across age subgroups, including patients aged < 65 years (hazard ratio [HR], 0.576; 95% confidence interval [CI], 0.299-1.108; P = .095), 65-74 years (HR, 0.615; 95% CI, 0.467-0.810; P < .001), and ≥ 75 years (HR, 0.740; 95% CI, 0.537-1.019; P = .064). PFS benefit was also seen across frailty subgroups, including fit (HR, 0.530; 95% CI, 0.387-0.727; P < .001), intermediate-fit (HR, 0.746; 95% CI, 0.526-1.058; P = .098), and frail (HR, 0.733; 95% CI, 0.481-1.117; P = .147) patients. With ixazomib versus placebo, rates of grade ≥ 3 treatment-emergent adverse events (TEAEs; 28-44% vs. 10-36%), serious TEAEs (15-29% vs. 3-29%), and discontinuation due to TEAEs (7-19% vs. 5-11%) were higher or similar across age and frailty subgroups, and generally somewhat higher in older age groups and intermediate-fit/frail patients in both arms. Treatment with ixazomib versus placebo did not adversely affect patient-reported quality-of-life scores across age and frailty status subgroups. CONCLUSION: Ixazomib is a feasible and effective maintenance option for prolonging PFS across this heterogeneous patient population.

Characteristics and outcomes of hospitalised adults with COVID-19 in a Global Health Research Network: a cohort study.

OBJECTIVE: To examine age, gender, and temporal differences in baseline characteristics and clinical outcomes of adult patients hospitalised with COVID-19. DESIGN: A cohort study using deidentified electronic medical records from a Global Research Network. SETTING/PARTICIPANTS: 67 456 adult patients hospitalised with COVID-19 from the USA; 7306 from Europe, Latin America and Asia-Pacific between February 2020 and January 2021. RESULTS: In the US cohort, compared with patients 18-34 years old, patients ≥65 had a greater risk of intensive care unit (ICU) admission (adjusted HR (aHR) 1.73, 95% CI 1.58 to 1.90), acute respiratory distress syndrome(ARDS)/respiratory failure (aHR 1.86, 95% CI 1.76 to 1.96), invasive mechanical ventilation (IMV, aHR 1.93, 95% CI, 1.73 to 2.15), and all-cause mortality (aHR 5.6, 95% CI 4.36 to 7.18). Men appeared to be at a greater risk for ICU admission (aHR 1.34, 95% CI 1.29 to 1.39), ARDS/respiratory failure (aHR 1.24, 95% CI1.21 to 1.27), IMV (aHR 1.38, 95% CI 1.32 to 1.45), and all-cause mortality (aHR 1.16, 95% CI 1.08 to 1.24) compared with women. Moreover, we observed a greater risk of adverse outcomes during the early pandemic (ie, February-April 2020) compared with later periods. In the ex-US cohort, the age and gender trends were similar; for the temporal trend, the highest proportion of patients with all-cause mortality were also in February-April 2020; however, the highest percentages of patients with IMV and ARDS/respiratory failure were in August-October 2020 followed by February-April 2020. CONCLUSIONS: This study provided valuable information on the temporal trends of characteristics and outcomes of hospitalised adult COVID-19 patients in both USA and ex-USA. It also described the population at a potentially greater risk for worse clinical outcomes by identifying the age and gender differences. Together, the information could inform the prevention and treatment strategies of COVID-19. Furthermore, it can be used to raise public awareness of COVID-19's impact on vulnerable populations.

Epidemiology and outcomes of gastroparesis, as documented in general practice records, in the United Kingdom.

OBJECTIVE: To generate real-world evidence for the epidemiology of gastroparesis in the UK, we evaluated the prevalence, incidence, patient characteristics and outcomes of gastroparesis in the Clinical Practice Research Datalink (CPRD) database. DESIGN: This was a retrospective, cross-sectional study. Prevalence and incidence of gastroparesis were evaluated in the CPRD database, with linkage to Hospital Episodes Statistics Admitted Patient Care and Office for National Statistics mortality data. Prevalence and incidence were age and sex standardised to mid-2017 UK population estimates. Descriptive analyses of demographics, aetiologies, pharmacological therapies and mortality were conducted. RESULTS: Standardised prevalence of gastroparesis, as documented in general practice records, was 13.8 (95% CI 12.6 to 15.1) per 100 000 persons in 2016, and standardised incidence of gastroparesis rose from 1.5 (95% CI 1.1 to 1.8) per 100 000 person-years in 2004 to 1.9 (95% CI 1.4 to 2.3) per 100 000 person-years in 2016. The most common disease aetiologies were idiopathic (39.4%) and diabetic gastroparesis (37.5%), with a similar distribution of type 1 and type 2 diabetes among the 90% who had type of diabetes documented. Patients with diabetic gastroparesis had a significantly higher risk of mortality than those with idiopathic gastroparesis after diagnosis (adjusted HR 1.9, 95% CI 1.2 to 3.0). Of those with gastroparesis, 31.6% were not offered any recognised pharmacological therapy after diagnosis. CONCLUSION: This is, to our knowledge, the first population-based study providing data on epidemiology and outcomes of gastroparesis in Europe. Further research is required to fully understand the factors influencing outcomes and survival of patients with gastroparesis.

Prevalence of Inflammatory Bowel Disease in Pediatric and Adult Populations: Recent Estimates From Large National Databases in the United States, 2007-2016.

BACKGROUND: The latest estimate of the prevalence of inflammatory bowel disease (IBD) in the United States was based on 2009 data, which indicates a need for an up-to-date re-estimation. The objectives of this study were to investigate the prevalence of all forms of IBD including ulcerative colitis (UC), Crohn's disease (CD), and IBD unspecified (IBDU). METHODS: Pediatric (age 2-17) and adult (age ≥18) IBD patients were identified from 2 large claims databases. For each year between 2007 and 2016, prevalence was calculated per 100,000 population and standardized based on the 2016 national Census. A fixed-effects meta-analytical model was used for overall prevalence. RESULTS: The pediatric prevalence of IBD overall increased by 133%, from 33.0/100,000 in 2007 to 77.0/100,000 in 2016. Among children, CD was twice as prevalent as UC (45.9 vs 21.6). Prevalence was higher in boys than girls for all forms of IBD, in contrast to the adult population where the prevalence was higher in women than men. We also found that the 10-17 age subgroup was the major contributor to the rising pediatric IBD prevalence. For adults, the prevalence of IBD overall increased by 123%, from 214.9 in 2007 to 478.4 in 2016. The prevalence rates of UC and CD were similar (181.1 vs 197.7) in 2016. CONCLUSIONS: Inflammatory bowel disease continues to affect a substantial proportion of the US population. In 2016, 1 in 209 adults and 1 in 1299 children aged 2-17 were affected by IBD. Prevalence of IBD has been increasing compared with previously published 2009 data.

Identifying Patients With Inflammatory Bowel Diseases in an Administrative Health Claims Database: Do Algorithms Generate Similar Findings?

Application of selective algorithms to administrative health claims databases allows detection of specific patients and disease or treatment outcomes. This study identified and applied different algorithms to a single data set to compare the numbers of patients with different inflammatory bowel disease classifications identified by each algorithm. A literature review was performed to identify algorithms developed to define inflammatory bowel disease patients, including ulcerative colitis, Crohn's disease, and inflammatory bowel disease unspecified in routinely collected administrative claims databases. Based on the study population, validation methods, and results, selected algorithms were applied to the Optum Clinformatics® Data Mart database from June 2000 to March 2017. The patient cohorts identified by each algorithm were compared. Three different algorithms were identified from literature review and selected for comparison (A, B, and C). Each identified different numbers of patients with any form of inflammatory bowel disease (323 833; 246 953, and 171 537 patients, respectively). The proportions of patients with ulcerative colitis, Crohn's disease, and inflammatory bowel disease unspecified were 32.0% to 47.5%, 38.6% to 43.8%, and 8.7% to 26.6% of the total population with inflammatory bowel disease, respectively, depending on the algorithm applied. Only 5.1% of patients with inflammatory bowel disease unspecified were identified by all 3 algorithms. Algorithm C identified the smallest cohort for each disease category except inflammatory bowel disease unspecified. This study is the first to compare numbers of inflammatory bowel disease patients identified by different algorithms from a single database. The differences between results highlight the need for validation of algorithms to accurately identify inflammatory bowel disease patients.

Risk factors for postoperative infection after gastrointestinal surgery among adult patients with inflammatory bowel disease: Findings from a large observational US cohort study.

BACKGROUND AND AIM: Postoperative infection (POI) is a major source of morbidity and prolongation of hospitalization in inflammatory bowel disease (IBD) patients. This large observational study was conducted to further describe risk factors and to quantify the proportion of POIs that are preventable. METHODS: We conducted a retrospective cohort analysis of the Optum US health insurance claims database. The study population included adults with ulcerative colitis (UC) or Crohn's disease (CD) who underwent lower gastrointestinal (GI) surgery of small intestine, colon, rectum, or anus during September 2014 to September 2016. Multiple logistic regression was used to identify and quantify risk factors and determine the proportion of infections that are preventable. RESULTS: A total of 3360 adult IBD patients with lower GI surgery were included in the study. Their mean age was 51 years, 52.5% were women, and 59.5% had CD. The 30-day POI incidence was 15.1% (95% confidence interval: 14.0-16.4%). We identified the following nonmodifiable or procedural risk factors: history of POI, open procedure, red blood cell transfusion within 6 months, preoperative hospital stay of at least 4 days, lower GI ostomy surgery, lower GI resection surgery, and a history of chronic obstructive pulmonary disease. Modifiable risk factors included corticosteroid use and anemia prior to surgery, but few infections were attributable to these modifiable factors. CONCLUSIONS: This large, observational, real-world evidence study from the US found that the majority of the observed risk factors were nonmodifiable or procedure-related. Corticosteroid use and anemia before surgery were identified as modifiable risk factors.

Incidence, prevalence, and natural history of primary sclerosing cholangitis in the United Kingdom.

Primary sclerosing cholangitis (PSC) is a rare obliterative fibrotic condition of the bile ducts. We assessed PSC epidemiology and natural history within the UK Clinical Practice Research Datalink (CPRD).Incidence and natural history of PSC were evaluated in a retrospective cohort study using linkage of CPRD, Hospital Episode Statistics, and Office for National Statistics data. Data from age, sex, and general practice-matched population controls provided a context for the incident PSC patients. Liver disease other than PSC was defined as autoimmune hepatitis, hepatitis, hepatomegaly, liver failure, cirrhosis, portal hypertension, cholangiocarcinoma, or hepatobiliary cancer.The age-standardized incidence of PSC was 0.68 (95% confidence interval [CI] 0.45-0.99) per 100,000 person-years and the age-standardized prevalence was 5.58 (95% CI 4.82-7.35) per 100,000 during 1998 to 2014. In all, 250 incident PSC patients met the inclusion criteria and each was matched with 5 controls (mean age 54 ±â€Š18 years, men 63.2%). A higher percentage of PSC patients had a history of inflammatory bowel disease (54% vs 2%) and liver disease other than PSC (22% vs 1%) than controls (standardized differenceweighted >0.1). During a median follow-up of 5 years, PSC patients were more likely to develop adverse health outcomes. The mortality rate per 1000 person-years was 3-fold higher in PSC than population controls (49.5 vs 16.1; incidence rate ratio 3.1, 95% CI 2.2-4.2).The incidence and prevalence of PSC observed in the UK CPRD were either comparable with or higher than previous studies. Compared with the general population, PSC patients had worse health outcomes including PSC disease progression, complications, and higher mortality.

Characteristics of patients potentially eligible for pharmacotherapy for weight loss in primary care practice in the United States.

OBJECTIVE: To describe the characteristics of real-world patients potentially eligible for adjunctive pharmacotherapy for weight loss. METHODS: Patients from the GE Centricity electronic medical record database were selected if they had body mass index (BMI) ≥30 or ≥27 to <30 kg m-2 with ≥1 obesity-associated comorbidity (hypertension, dyslipidemia, or type 2 diabetes) from 2002-2011; were aged ≥18 years and had ≥12 months of continuous enrollment before and after the date of first eligible BMI recorded (index date). Descriptive statistics and logistic regression were used for analysis. RESULTS: Of the 1,835,541 patients with overweight or obesity included, comorbidities were common (hypertension [55.4%], dyslipidemia [36.1%] and type 2 diabetes [13.4%]). The percentage of patients who received pharmacotherapy for weight loss was 0.7% within 12 months after the index date. Patients who received pharmacotherapy had higher BMI (median, 33.6 vs. 31.3 kg m-2), were younger (median, 42 vs. 52 years), primarily women (84.3 vs. 58.2%), commercially insured (70.1 vs. 50.4%) and had more frequent use of antidepressants (30.8 vs. 14.1%) and non-steroidal anti-inflammatory drugs (21.7 vs. 12.0%) than those who did not at baseline (all P values < 0.0001). CONCLUSIONS: Few eligible patients received pharmacotherapy for weight loss. Patients who received pharmacotherapy tended to be heavier, younger, female, commercially insured, and used more antidepressants and non-steroidal anti-inflammatory drugs.

Monitoring for proteinuria in patients with type 2 diabetes mellitus.

OBJECTIVE: The UK National Institute for Health and Care Excellence (NICE) guideline on diabetes recommends at least annual monitoring of patients with type 2 diabetes mellitus (T2DM) for proteinuria. To date, little has been published on the frequency of proteinuria monitoring in T2DM, and its association with risk factors for renal complications. We aimed to describe proteinuria monitoring in patients with T2DM. DESIGN: This study identified patients with T2DM aged 40 years or older with the first antidiabetic drug use in 2007-2012 (cohort entry) in the UK Clinical Practice Research Datalink. At least 1 year of registration before and after cohort entry was required. A test was considered undertaken if a medical or laboratory code indicated a urinary albumin or protein test. The percentage of patients with at least one test performed was obtained in 1 year after cohort entry and any time during follow-up. A Cox proportional hazards model was used to estimate the HRs of patients having the first screening test while adjusting for baseline covariates. RESULTS: 65 790 patients (mean age 63.0 years, men 57.5%, mean follow-up 41.0 months) were included, of whom 49 707 (75.6%) patients had at least one test in 1 year after antidiabetic drug initiation and 59 400 (90.3%) had at least one test any time during follow-up. Proteinuria monitoring decreased with time since initiation of antidiabetic drug therapy and with number of treatment changes and was independently associated with age, sex, smoking status, and year of antidiabetic drug initiation. 12.3% of patients with T2DM tested had a positive proteinuria test for the first screening performed in 1 year after initiation of antidiabetic drug therapy. CONCLUSIONS: The findings suggested suboptimal compliance with the NICE guideline on proteinuria monitoring in patients with T2DM and that level of monitoring appeared to depend on multiple clinical factors.

Increased risk of subsequent myocardial infarction in patients with type 2 diabetes: a retrospective cohort study using the U.K. General Practice Research Database.

OBJECTIVE: To compare the risk of subsequent myocardial infarction (MI) between patients with and without type 2 diabetes mellitus (T2DM) in a retrospective cohort study. RESEARCH DESIGN AND METHODS: Patients with their first MI recorded in the U.K. General Practice Research Database in 1997-2008 were classified as T2DM, diagnosed before or within 28 days after the date of the first recorded MI (i.e., the index date), or non-T2DM. Patients diagnosed within 28 days after the index date were assumed to have developed T2DM at baseline (i.e., before the index date). The primary outcome was the first subsequent MI. The secondary outcomes were all-cause death and a composite of all-cause death or subsequent MI. Cox proportional hazards models were fit to obtain hazard ratios (HRs) for all outcomes. RESULTS: A total of 7,411 T2DM (median age 72 years; men 63.4%) and 48,726 non-T2DM patients (median age 69 years; men 65.3%) were included. The crude incidences (per 1,000 patient-years) in T2DM vs. non-T2DM were 32.8 vs. 22.8 for subsequent MI, 83.7 vs. 52.1 for all-cause death, and 106.5 vs. 69.9 for the composite end point. The adjusted HRs for subsequent MI, all-cause death, and their combination were 1.41 (95% CI 1.27-1.56), 1.50 (1.41-1.60), and 1.42 (1.34-1.50), respectively, in women and 1.23 (1.14-1.34), 1.40 (1.33-1.47), and 1.33 (1.27-1.39) in men. CONCLUSIONS: Compared with non-T2DM, T2DM was associated with an increased risk for subsequent MI, all-cause death, and their composite end point. The risk tends to be higher in women than in men.

Comparing pioglitazone to insulin with respect to cancer, cardiovascular and bone fracture endpoints, using propensity score weights.

BACKGROUND: Diabetes is an important global disease, associated with significant morbidity and an increased risk of death due to chronic end-organ complications. The thiazolidinediones, used mainly as third-line agents in type 2 diabetes mellitus (T2DM), have been associated with some safety concerns, such as an increased risk of bladder cancer, an increased risk of bone fracture and heterogeneous effects on cardiovascular events. OBJECTIVE: This study aimed to evaluate safety data on pioglitazone for several outcomes and examine them in context with each other as well as with insulin, another third-line treatment for T2DM. METHODS: This retrospective cohort study extracted data from May 1, 2000 until June 30, 2010, from the i3 InVision Data Mart™ database. To adjust for the testing of multiple hypotheses, the Holm method was applied to endpoints representing potential harm from pioglitazone treatment, separately from those representing potential benefit from pioglitazone. The study population included patients with T2DM ≥ 45 years old who were new users of either pioglitazone or insulin. Key outcomes were incident cases of a composite of myocardial infarction (MI) or stroke requiring hospitalization; bone fracture requiring hospitalization; bladder cancer; and a composite of nine other selected cancers. Kaplan-Meier curves were generated and hazard ratios (HRs) for pioglitazone versus insulin were estimated from Cox proportional hazards models adjusted with inverse probability of treatment weights derived from propensity scores. RESULTS: A total of 56,536 patients (pioglitazone group 38,588; insulin group 17,948) qualified for the study. The mean follow-up was 2.2 years for pioglitazone and 1.9 years for insulin patients. Weighted survival analysis of the composite of MI and stroke, as well as the composite of nine cancers, yielded significant differences in favour of pioglitazone. For the composite of MI and stroke, the HR for pioglitazone versus insulin was 0.44 (95 % confidence interval [CI] 0.39-0.50, p < 0.0001). Modelling of the composite of nine selected cancers produced an HR of 0.78 (95 % CI 0.71-0.85, p < 0.0001). A non-statistically significant difference in favour of pioglitazone was observed in the incidence rate of bone fracture requiring hospitalization (HR 0.86, 95 % CI 0.74-1.01, p = 0.058). For bladder cancer, the overall incidence rates were relatively low and showed no significant difference between the two groups; the HR for pioglitazone versus insulin was 0.92 (95 % CI 0.63-1.33, p = 0.64). CONCLUSION: Compared with insulin, pioglitazone was associated with a significant reduction in the risk of MI and stroke requiring hospitalization, and a significant reduction in the risk of other selected cancers. While pioglitazone treatment may be linked with a lower risk of bladder cancer and bone fracture relative to insulin, these differences were not statistically significant.