Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies.

BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. RESULTS: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior. CONCLUSIONS: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. IMPACT: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.

Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD.

Background & Aims: Long-term studies of the prognosis of NAFLD are scarce. Here, we investigated the risk of major adverse liver outcomes (MALO) in a large cohort of patients with NAFLD. Methods: We conducted a cohort study with data from Swedish university hospitals. Patients (n = 1,260) with NAFLD without cirrhosis were diagnosed through biopsy or radiology, and had fibrosis estimated through vibration-controlled transient elastography, biopsy, or FIB-4 score between 1974 and 2020 and followed up through 2020. Each patient was matched on age, sex, and municipality with up to 10 reference individuals from the general population (n = 12,529). MALO were ascertained from Swedish national registers. The rate of events was estimated by Cox regression. Results: MALO occurred in 111 (8.8%, incidence rate = 5.9/1,000 person-years) patients with NAFLD and 197 (1.6%, incidence rate = 1.0/1,000 person-years) reference individuals during a median follow up of 13 years. The rate of MALO was higher in patients with NAFLD (hazard ratio = 6.6; 95% CI = 5.2-8.5). The risk of MALO was highly associated with the stage of fibrosis at diagnosis. In the biopsy subcohort (72% of total sample), there was no difference in risk between patients with and without non-alcoholic steatohepatitis. The 20-year cumulative incidences of MALO were 2% for the reference population, 3% for patients with F0, and 35% for F3. Prognostic information from biopsy was comparable to FIB-4 (C-indices around 0.73 vs. 0.72 at 10 years). Conclusions: This study provides updated information on the natural history of NAFLD, showing a high rate of progression to cirrhosis in F3 and a similar prognostic capacity of non-invasive tests to liver biopsy. Impact and implications: Several implications for clinical care and future research may be noted based on these results. First, the risk estimates for cirrhosis development are important when communicating risk to patients and deciding on clinical monitoring and treatment. Estimates can also be used in updated health-economic evaluations, and for regulatory agencies. Second, our results again highlight the low predictive information obtained from ascertaining NASHstatus by histology and call for more objective means by which to define NASH. Such methods may include artificial intelligence-supported digital pathology. We highlight that NASH is most likely the causal factor for fibrosis progression in NAFLD, but the subjective definition makes the prognostic value of a histological NASH diagnosis of limited value. Third, the finding that prognostic information from biopsy and the very simple Fibrosis-4 score were comparable is important as it may lead to fewer biopsies and further move the field towards non-invasive means by which to define fibrosis and, importantly, use non-invasive tests as outcomes in clinical trials. However, all modalities had modest discriminatory capacity and new risk stratification systems are needed in NAFLD. Repeated measures of non-invasive scores may be a potential solution.

Overall and subgroup prevalence of non-alcoholic fatty liver disease and prevalence of advanced fibrosis in the United States: An updated national estimate in National Health and Nutrition Examination Survey (NHANES) 2011-2018.

INTRODUCTION AND OBJECTIVES: Data on the prevalence of non-alcoholic fatty liver disease (NAFLD) in subgroups of the United States (US) population are limited. This study was conducted to estimate NAFLD prevalence overall and by subgroups, and prevalence of NAFLD with advanced fibrosis. MATERIALS AND METHODS: Using the National Health and Nutrition Examination Survey (NHANES) 2011-2018 data, a cross-sectional study was conducted. NAFLD was defined as having a US Fatty Liver Index (USFLI) ≥ 30 in the absence of other causes of liver disease, including excessive alcohol intake, chronic hepatitis B, and chronic hepatitis C. Likelihood for having advanced fibrosis was determined by the calculated NAFLD fibrosis score (NFS; high ≥ 0.676; low < -1.445) and fibrosis-4 index (FIB-4; high ≥ 2.67; low < 1.30). RESULTS: The weighted national prevalence of NAFLD in US adults was 26.7% (95% confidence interval: 25.3%-28.1%). Prevalence was higher among those aged ≥ 65 years, males, Mexican Americans, with BMI ≥ 35 kg/m2 (class 2 and 3 obesity) and with type 2 diabetes (T2D). Of those meeting the USFLI criterion for NAFLD, 18.1% and 3.7% were determined as having a high probability of advanced fibrosis based on NFS ≥ 0.676 and FIB-4 ≥ 2.67 cut-off values, respectively. CONCLUSIONS: This study supports an increased prevalence of NAFLD in specific subpopulations (aged ≥ 65 years, males, Mexican Americans, obese population, and patients with T2D). The observed difference in the prevalence of advanced fibrosis as estimated by NFS and FIB-4 highlights the challenge of choosing optimal cut-off values.

The Growing Economic and Clinical Burden of Nonalcoholic Steatohepatitis (NASH) in the United States.

Background: Nonalcoholic steatohepatitis (NASH) is a cause of chronic liver disease. Aim: Model the burden of NASH in the United States according to obesity. Methods: The discrete-time Markov model comprised adult NASH subjects moving through 9 health states and 3 absorbing death states (liver, cardiac, and other deaths) with 1-year cycles and a 20-year horizon. Given that reliable natural history data for NASH are not available, transition probabilities were estimated from the literature and population-based data. These rates were disaggregated to determine age-obesity group rates by applying estimated age-obesity patterns. The model considers 2019 prevalent NASH cases and new incident NASH cases (2020-2039), assuming that recent trends will continue. Annual per-patient costs by health state were based on published data. Costs were standardized to 2019 US dollars and inflated by 3% annually. Results: NASH cases in the United States are forecasted to increase by +82.6%, from 11.61 million (2020) to 19.53 million (2039). During the same period, cases of advanced liver disease increased +77.9%, from 1.51 million to 2.67 million, while its proportion remained stable (13.46%-13.05%). Similar patterns were observed in both obese and non-obese NASH. Among NASH, 18.71 million overall deaths, 6.72 million cardiac-specific deaths, and 1.71 million liver-specific deaths were observed by 2039. During this period, the projected cumulative direct healthcare costs were $1208.47 billion (obese NASH) and $453.88 billion (non-obese NASH). By 2039, the projected NASH attributable healthcare cost per patient increased from $3636 to $6968. Conclusions: There is a substantial and growing clinical and economic burden of NASH in the United States.

Continuity of Medication Use by US Adults With Diabetes, 2005-2019.

Importance: Consistent medication use is critical for diabetes management. Population surveillance of consistency of medication use may identify opportunities to improve diabetes care. Objective: To evaluate trends in longitudinal use of glucose-, blood pressure-, and lipid-lowering medications by adults with diabetes. Design, Setting, and Participants: This serial cross-sectional study assessed trends in longitudinal use of glucose-, blood pressure-, and lipid-lowering medications by adults with diagnosed diabetes participating in the Medical Expenditure Panel Survey (MEPS), which allows serial cross-sections and 2-year longitudinal follow-up, between the 2005 to 2006 panel and 2018 to 2019 panel. Population-weighted, nationally representative estimates for the US were reported. Included individuals were adult MEPS participants with diagnosed diabetes during both years (ie, during 2005 and 2006 or during 2018 and 2019) who participated in all survey rounds. Data were analyzed from August 2021 to November 2022. Main Outcomes and Measures: Longitudinal use over the 2 years was categorized as continued use (at least 1 fill per year), no use, inconsistent use, and new use by medication type (glucose-, blood pressure-, and lipid-lowering medications). New medications were defined as prescription fills for a medication type first prescribed and filled in year 2 of MEPS participation. Results: A total of 15 237 participants with diabetes (7222 individuals aged 45-64 years [47.4%]; 8258 [54.2%] female participants; 3851 Latino [25.3%]; 3619 non-Latino Black (23.8%), and 6487 non-Latino White [42.6%]) were included in the analytical sample. A mean of 19.5% (95% CI, 18.6%-20.3%), 17.1% (95% CI, 16.2%-18.1%), and 43.3% (95% CI, 42.2%-44.3%) of participants did not maintain continuity in use of glucose-, blood pressure-, or lipid-lowering medications, respectively, during both years of follow-up. The proportion of participants who continued use of glucose-lowering medication in both years trended down from 84.5% (95% CI, 81.8%-87.3%) in 2005 to 2006 to 77.4% (95% CI, 74.8%-80.1%) in 2018 to 2019; this decrease coincided with rate increases in inconsistent use (3.3% [95% CI, 1.9%-4.7%] in 2005-2006 to 7.1% [95% CI, 5.6%-8.6%] in 2018-2019) and no use (8.1% [95% CI, 6.0%-10.1%] in 2005-2006 to 12.9% [95% CI, 10.9%-14.9%] in 2018-2019). Inconsistent use of blood pressure-lowering medications trended upward from 3.9% (95% CI, 1.8%-6.0%) in 2005 to 2006 to 9.0% (95% CI, 7.0%-11.0%) in 2016 to 2017. Inconsistent use of lipid-lowering medication trended up to a high of 9.9% (95% CI, 7.0%-12.7%) in 2017 to 2018. Conclusions and Relevance: This study found that a mean of 19.5% of participants did not maintain continuity in use of glucose-lowering medication, with recent decreases, while a mean of 17.1% and 43.2% of participants did not maintain continuity of use of blood pressure- or lipid-lowering medications, respectively.

Trends and Variations in Emergency Department Use Associated With Diabetes in the US by Sociodemographic Factors, 2008-2017.

Importance: Little is known about emergency department (ED) use among people with diabetes and whether the pattern of ED use varies across geographic areas and population subgroups. Objective: To estimate recent national- and state-level trends in diabetes-related ED use overall and by race and ethnicity, rural or urban location, and insurance status. Design, Setting, and Participants: This cross-sectional study of adults visiting the ED with a diabetes-related diagnosis used serial data from the Nationwide Emergency Department Sample, a nationally representative database, and discharge records from 11 state emergency department databases for 2008, 2011, 2014, and 2016 to 2017. Data were analyzed from March 16 to November 9, 2020. Exposures: Reported race and ethnicity, rural or urban location, and insurance status. Data were stratified to generate state-specific estimates. Main Outcomes and Measures: Rates of ED use for all-cause visits among adults with diabetes (all-cause diabetes visits) and visits with primary diagnoses of diabetes-specific complications. Results: A larger portion of all-cause diabetes ED visits (n = 32 433 015) were by female (56.8%) and middle-aged (mean [SD] age, 58.4 [16.3] years) adults with diabetes. Nationally, all-cause diabetes ED visits per 10 000 adults increased 55.6% (95% CI, 50.6%-60.6%), from 257.6 (95% CI, 249.9-265.3) visits in 2008 to 400.8 (95% CI, 387.6-414.0) visits in 2017. All-cause diabetes ED visits increased more for urban (58.3%; 95% CI, 52.5%-64.1%) and uninsured subgroups (75.3% [95% CI, 59.8%-90.8%]) than for their counterparts. Diabetes-specific ED visits (weighted number of 1 911 795) nationally increased slightly among all subgroups. State-specific ED use rates show wide state-to-state variations in ED use by race and ethnicity, rural or urban location, and insurance. On average across states, diabetes-specific ED use among Black patients was approximately 3 times (rate ratio, 3.09 [95% CI, 2.91-3.30]) greater than among non-Hispanic White patients, and among Hispanic patients, it was 29% greater (rate ratio, 1.29 [95% CI, 1.19-1.40]) than among non-Hispanic White patients. The mean rate of ED use among rural patients was 34% greater (rate ratio, 1.34 [95% CI, 1.26-1.44]) than among urban patients. The mean rates of ED use among patients with Medicaid (rate ratio, 6.65 [95% CI, 6.49-6.82]) and Medicare (rate ratio, 4.37 [95% CI, 4.23-4.51]) were greater than among privately insured adults. Conclusions and Relevance: This study suggests that disparities in diabetes-related ED use associated with race and ethnicity, rural or urban location, and insurance status were persistent from 2008 to 2017 within and across states, as well as nationally. Further geographic and demographic-specific analyses are needed to understand the sources of inequity.

Trends and Demographic Disparities in Diabetes Hospital Admissions: Analyses of Serial Cross-Sectional National and State Data, 2008-2017.

OBJECTIVE: To analyze national and state-specific trends in diabetes-related hospital admissions and determine whether disparities in rates of admission exist between demographic groups and geographically dispersed states. RESEARCH DESIGN AND METHODS: We conducted serial cross-sectional analyses of the National Inpatient Sample (2008, 2011, 2014, and 2016) and State Inpatient Databases for Arizona, Florida, Kentucky, Iowa, Maryland, Nebraska, New Jersey, New York, North Carolina, Utah, and Vermont for 2008, 2011, 2014, and 2016/2017 among adult patients with type 1 and type 2 diabetes-related ICD codes (ICD-9 [250.XX] or ICD-10 [E10.XXX, E11.XXX, and E13.XXX]. We measured hospitalization rates for people with diabetes (all-cause hospitalizations) and for admissions with a primary diagnosis of diabetes or diabetes-related complications (diabetes-specific hospitalizations) per 10,000 people per year. RESULTS: Nationally, all-cause and diabetes-specific hospitalizations declined by 3.1% (95% CI -5.5, -0.7) and 19.1% (95% CI -21.6, -16.6), respectively, over 2008 to 2016. The analysis of individual states showed that diabetes-specific admissions in individuals ≥65 years old declined during this time (16.3-48.8% decrease) but increased among patients 18-29 years old (10.5-81.5% increase) and that rural diabetes-specific admissions decreased in just over half of the included states (15.2-69.2% decrease). There were no differences in changes in admission rates among different racial/ethnic groups. CONCLUSIONS: Overall, rates of diabetes-related hospitalizations decreased over 2008 to 2016/2017, but there were large state-level differences across subgroups of patients. The rise in diabetes hospitalizations among young adults is a cause for concern. These state- and subpopulation-level differences highlight the need for state-level policies and interventions to address disparities in diabetes health care use.

Gastric Antral Gastrointestinal Stromal Tumor Presenting With Severe Anemia.

Gastrointestinal stromal tumors are rare gastrointestinal tract growths associated with high rates of malignant transformation. Most cases are asymptomatic and can be identified by computed tomography scan. We present the case of a 50-year-old male with melena and fatigue. Endoscopy showed an ulcerated submucosal tumor diagnosed as a gastrointestinal stromal tumor after surgical resection; it did not present with metastasis and was successfully treated surgically without relapse.

Overexpression of the microtubule-binding protein CLIP-170 induces a +TIP network superstructure consistent with a biomolecular condensate.

Proper regulation of microtubule (MT) dynamics is critical for cellular processes including cell division and intracellular transport. Plus-end tracking proteins (+TIPs) dynamically track growing MTs and play a key role in MT regulation. +TIPs participate in a complex web of intra- and inter- molecular interactions known as the +TIP network. Hypotheses addressing the purpose of +TIP:+TIP interactions include relieving +TIP autoinhibition and localizing MT regulators to growing MT ends. In addition, we have proposed that the web of +TIP:+TIP interactions has a physical purpose: creating a dynamic scaffold that constrains the structural fluctuations of the fragile MT tip and thus acts as a polymerization chaperone. Here we examine the possibility that this proposed scaffold is a biomolecular condensate (i.e., liquid droplet). Many animal +TIP network proteins are multivalent and have intrinsically disordered regions, features commonly found in biomolecular condensates. Moreover, previous studies have shown that overexpression of the +TIP CLIP-170 induces large "patch" structures containing CLIP-170 and other +TIPs; we hypothesized that these structures might be biomolecular condensates. To test this hypothesis, we used video microscopy, immunofluorescence staining, and Fluorescence Recovery After Photobleaching (FRAP). Our data show that the CLIP-170-induced patches have hallmarks indicative of a biomolecular condensate, one that contains +TIP proteins and excludes other known condensate markers. Moreover, bioinformatic studies demonstrate that the presence of intrinsically disordered regions is conserved in key +TIPs, implying that these regions are functionally significant. Together, these results indicate that the CLIP-170 induced patches in cells are phase-separated liquid condensates and raise the possibility that the endogenous +TIP network might form a liquid droplet at MT ends or other +TIP locations.

Personal Protective Equipment and Donning and Doffing Techniques in the Cardiac Catheterization Laboratory During the COVID-19 Pandemic: Insights From an Internet Search for Protocols.

Background: Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic, a need for precise donning and doffing protocols for personal protective equipment (PPE) among healthcare infrastructures is paramount. Procedures involving the cardiac catheterization laboratory (CCL) are routinely non-aerosolizing but have the potential for rapid patient deterioration, creating the need for aerosolizing generating procedures. Multiple societal and governmental guidelines on the use of PPE during medical procedures are available on Internet websites; however, there is limited literature available in peer-reviewed formats in this context. This study aims to provide an overview of current PPE donning and doffing protocols specific to the catheterization laboratory. Methods: A series of internet searches regarding donning and doffing of PPE in the CCL including published articles and internet protocols were compiled and compared using Pubmed.gov, Google.com, www.twitter.com, and www.youtube.com. Results: Most institutions used N95 masks, shoe covers, at least one head covering, face shield or goggles, two pairs of gloves, and inner and outer gowns. Doffing variation was greater than donning. Doffing has the potential to contaminate the healthcare worker (HCW), and therefore, this step of PPE management requires further study. Common steps in temporal priority included cleaning of gloved hands, removal of outer (or only) gown, removal of outer gloves, repeat gloved hand cleaning, removal of facial PPE last, and a final non-gloved hand cleaning. Conclusions: This analysis provides a summary of commonly used practices that may be considered when designing CCL-specific PPE protocols. Analysis of consistent steps from the literature led the authors to formulate a suggested protocol for CCL HCWs when performing procedures on patients with confirmed or suspected/unknown COVID-19.

Trends in Receipt of American Diabetes Association Guideline-Recommended Care Among U.S. Adults With Diabetes: NHANES 2005-2018.

OBJECTIVE: To characterize national trends and characteristics of adults with diabetes receiving American Diabetes Association (ADA) guideline-recommended care. RESEARCH DESIGN AND METHODS: We performed serial cross-sectional analyses of 4,069 adults aged ≥20 years with diabetes who participated in the 2005-2018 National Health and Nutrition Examination Survey (NHANES). RESULTS: Overall, the proportion of U.S. adults with diabetes receiving ADA guideline-recommended care meeting all five criteria by self-report in the past year (having a primary doctor for diabetes and one or more visits for this doctor, HbA1c testing, an eye examination, a foot examination, and cholesterol testing) increased from 25.0% in 2005-2006 to 34.1% in 2017-2018 (P-trend = 0.004). For participants with age ≥65 years, it increased from 29.3% in 2005-2006 to 44.2% in 2017-2018 (P-trend = 0.001), whereas for participants with age 40-64 and 20-39 years, it did not change significantly during the same time period: 25.2% to 25.8% (P-trend = 0.457) and 9.9% to 26.0% (P-trend = 0.401), respectively. Those who were not receiving ADA guideline-recommended care were more likely to be younger, of lower socioeconomic status, uninsured, newly diagnosed with diabetes, not on diabetes medication, and free of hypercholesterolemia. CONCLUSIONS: Receipt of ADA guideline-recommended care increased only among adults with diabetes aged ≥65 years in the past decade. In 2017-2018, only one of three U.S. adults with diabetes reported receiving ADA guideline-recommended care, with even a lower receipt of care among those <65 years of age. Efforts are needed to improve health care delivery and equity in diabetes care. Insurance status is an important modifiable determinant of receiving ADA guideline-recommended care.

Reduced ovarian response to controlled ovarian stimulation is associated with increased oxidative stress in the follicular environment.

Serum estradiol (E2) level is routinely used to monitor the ovarian response during controlled ovarian hyperstimulation (COH) and the concentration of serum E2 may influence the oocyte quality and pregnancy outcome. However, the knowledge on the association between COH induced serum E2 level, oocyte quality and embryo development is limited. Therefore we investigated the association between serum E2 level, oxidative stress in the follicular fluid and granulosa cells (GCs) response to elucidate the association between E2 level and embryological outcome. In this study, patients (n = 30) undergoing ART were categorized as 'normal responders' (NR, n = 10), 'poor responders' (PR, n = 10) and hyper responders (HR, n = 10). The follicular fluid malondialdehyde (MDA) level was determined. The total RNA extracted from GCs was subjected to analyse the relative abundance of transcripts of stress response genes (P53, caspase 3,8-oxoguanine DNA glycosylase, OGG1 and heat shock protein 70; HSP70) and embryological outcome was noted. Follicular fluid MDA level was significantly higher in PR (p < 0.01) compared NR and HR whereas number of top-quality embryos were significantly lower in PR and HR compared to NR (p < 0.01). The relative expression of P53, HSP70, and OGG1 in GCs was significantly elevated in PR (p < 0.05-0.01). An inverse relationship was established between serum E2 level vs follicular MDA level (r = -0.45; p < 0.01) and follicular MDA level vs. number of top-quality embryos (r = -0.45; p < 0.01). Hence, patients with low serum E2 had elevated oxidative stress in their follicular environment and poor quality embryos implicating the risk of oxidative stress in patients with poor ovarian response.

Distance to glycemic goal at the time of treatment intensification in patients with type 2 diabetes mellitus failing metformin monotherapy in the United States.

Background: A substantial proportion of patients with type 2 diabetes mellitus (T2DM) do not reach their target HbA1c level on metformin. The objective of this retrospective observational cohort study is to better characterize the distance between HbA1c target and patient's actual HbA1c level (the distance to goal), using a target HbA1c of 7.0% (53 mmol/mol), in patients with T2DM who have started metformin monotherapy.Methods: We used data from the GE Centricity Electronic Medical Record database by IQVIA in 2016 in the United States (US) to identify adults with T2DM who started metformin monotherapy (MM) and received at least 90 days of treatment. Patients were categorized into three groups: those who achieved the goal of HbA1c <7.0%, those who did not achieve the goal of HbA1c <7.0% (i.e. failed MM) and received intensified treatment, and those who failed MM and did not receive intensified treatment. Distance to goal was computed for patients in each group.Results: We identified 20,704 patients in the US database who started MM; 1741 (8.4%) failed MM and received intensified treatment, while 4977 (24.0%) failed MM and did not receive intensified treatment. The mean post-MM HbA1c for those who failed MM and received intensified treatment was 8.7% (72 mmol/mol) (median 8.2%, 66 mmol/mol) and the mean distance to goal was 1.7% (median 1.2%). The mean post-MM HbA1c for those who failed MM and did not receive intensified treatment was 8.0% (64 mmol/mol) (median 7.5%, 58 mmol/mol) and the mean distance to goal was 1.0% (median 0.5%).Conclusion: A proportion of US T2DM patients do not achieve glycemic control (target HbA1c < 7.0%) despite 90 days of MM. Patients who failed MM and eventually received intensified treatment did so when their HbA1c distance to goal exceeded the level at which one add-on therapy alone might be sufficient to bring them to goal.

Dose distribution and up-titration patterns of metformin monotherapy in patients with type 2 diabetes.

AIMS: To assess the dose distribution among users of metformin monotherapy as well as the patterns of up-titration following initiation of therapy in people with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This was a retrospective cohort study of adults with T2DM in the United Kingdom (UK). Metformin dose distribution was assessed at 0, 6 and 12 months in people initiating metformin monotherapy (new users) and cross-sectionally in people with ongoing metformin monotherapy (prevalent users). Patterns and predictors of up-titration were also analysed in new users. Dose distributions and treatment patterns were assessed descriptively; predictors of up-titration were determined using multivariable logistic regressions. RESULTS: Totals of 6174 new users and 8733 prevalent users were included. New users initiated metformin at >0 mg to ≤500 mg (25%), >500 mg to ≤1000 mg (47%), >1000 mg to ≤1500 mg (17%) or >1500 mg to ≤2000 mg (12%) daily. This distribution did not vary over time. Prevalent users of metformin received doses of >0 mg to ≤500 mg (14%), >500 mg to ≤1000 mg (40%), >1000 mg to ≤1500 mg (15%), >1500 mg to ≤2000 mg (29%) or >2000 mg (1%) daily. Among new users of metformin, 6.7% and 10.8% had been up-titrated at 6 and 12 months, respectively, despite the majority having glycated haemoglobin >53 mmol/mol. Predictors of up-titration included younger age and higher HbA1c. CONCLUSIONS: A majority of T2DM patients taking metformin received a dose ≤1000 mg/day. Up-titration of metformin is infrequent in the first year postinitiation.

Factors associated with the discontinuation of dipeptidyl peptidase-4 inhibitors (DPP-4is) after initiation of insulin.

Objective: Type 2 diabetes (T2D) is a prevalent health problem. Oral agents, with the exception of metformin, are often discontinued with the initiation of insulin. The objective was to understand the proportion of patients discontinuing dipeptidyl peptidase-4 inhibitors (DPP-4is) and the reasons for the decision to discontinue.Methods: A retrospective study using a health claims database investigated discontinuation of DPP-4i in adult patients on a dual therapy of metformin and DPP-4i who initiated insulin (n = 3391). An online survey administered to 406 physicians in the US examined reasons for discontinuation. Physicians surveyed included endocrinologists (34.5%), general practitioners (32.5%), internal medicine specialists (30.5%), and diabetologists (2.5%), treating a monthly average of 154 patients.Results: Among patients treated with metformin and DPP-4is who were newly prescribed insulin, 33.3 and 57.3% discontinued DPP-4i therapy within 3 and 12 months, respectively. Patients who discontinued DPP-4i therapy had higher out-of-pocket costs and a greater proportion of renal and liver disease. Top 3 responses for discontinuation included adverse events/tolerability issues (58.9%), lack of efficacy/treatment goals not being met (55.4%) and additional cost of DPP-4i with insulin (48.5%). Top 3 responses for continuing DPP-4i included meeting treatment goals (70.7%), using a lower dose of insulin (65.3%) and good tolerability (48.0%). Physician characteristics, such as physician specialty, age, gender and location impacted to some extent the reasons for treatment decisions.Conclusions: A large proportion of patients discontinue DPP-4is in the real world when initiating insulin. The impact of physician characteristics in treatment decisions highlights the need for enhanced physician training and support as new clinical data emerges and therapy options are available.

Patient and prescriber characteristics among patients with type 2 diabetes mellitus continuing or discontinuing sulfonylureas following insulin initiation: data from a large commercial database.

OBJECTIVE: To describe patient and provider characteristics for patients with type 2 diabetes (T2DM) initiating basal insulin and describe basal insulin's impact on sulfonylurea (SU) discontinuation. METHODS: A retrospective cohort study was conducted using the HealthCore Integrated Research Database. Patients had ≥12 months of continuous coverage prior to initiating insulin, and were utilizing at least one anti-hyperglycemic drug at the time of insulin initiation. Predictors for SU discontinuation were evaluated utilizing Cox proportional hazards models. RESULTS: Among the 74,334 individuals aged ≥18 years with T2DM who initiated basal insulin from 2006-2015, 30% were taking metformin (MET) and SU when initiating insulin. Among the 22,418 MET/SU patients, 31% discontinued SU within 3 months of insulin initiation and, by 12 months, 55% had discontinued SU. Sulfonylurea discontinuation was similar among many patient and provider characteristics, while being modestly positively associated (p < .05; HRs <1.5) with female gender, more co-morbidities, cardiac revascularization, chronic liver disease, hospitalizations with a T2DM diagnosis, and hypoglycemia prior to insulin initiation. SU discontinuation was modestly inversely associated with receiving an insulin prescription from an endocrinologist (HR = 0.90, 95% CI = 0.85-0.95). CONCLUSIONS: Roughly half of commercially-insured T2DM patients discontinued SU within 1 year after insulin initiation, and SU discontinuation was not strongly associated with a range of patient and provider characteristics.

Quality of life analysis during transition from stationary to portable infusion pump in home parenteral nutrition patients: a Canadian experience.

BACKGROUND: Quality of life (QOL) of patients receiving home parenteral nutrition (HPN) may be impacted by device technology. Historically, our HPN patients used pole-mounted pumps which can hinder activities and affect QOL. METHODS: Patients receiving HPN with a pole-mounted pump completed Short Form 36 (SF-36®) and pump-specific questionnaires. Patients were then enrolled in a 2-month prospective crossover open study. Patients were randomized to use a pole-mounted pump or a portable pump. After 1 month, each arm crossed over. Measurements were repeated at 4 and 8 weeks. RESULTS: Participants included 5 males, 15 females; age 52.8 ± 3.3 (mean ± SEM) years; 50% had short bowel syndrome; received HPN for 83.3 ± 15.9 months; infused HPN over 11.2 ± 0.3 hours/day; 4.3 ± 0.4 days/week. Portable pump users scored 53.75 ± 5.64, 61.25 ± 6.14, and 40.31 ± 4.94 in SF-36v2 physical, social, and health vitality, respectively, while the stationary pump users scored 45.50 ± 4.82, 55.00 ± 5.97, and 35.31 ± 4.63, respectively (NS). They reported ease of movement between rooms (4.11 ± 0.21 vs 1.44 ± 0.20; P = .001); when traveling (5.00 ± 0.00 vs 3.00 ± 0.45; P < .02) (1 = very difficult, 5 = very easy); 5.0% were sleep disturbed with the portable compared to 42.1% with pole-mounted pump (P < .04). Overall, patients were significantly happier with the portable vs pole-mounted pump (4.53 ± 0.19 vs 2.68 ± 0.22; P < .001) (1 = very unhappy, 5 = very happy). CONCLUSION: Our HPN patients reported improved happiness and satisfaction regarding ease of use and function with a portable vs pole-mounted pump.

Mothers' "liquid gold": a quality improvement initiative to support early colostrum delivery via oral immune therapy (OIT) to premature and critically ill newborns.

Early breast milk, known as colostrum ("liquid gold") provides immune benefits to infants, offering potential risk reduction for nosocomial infection (NI) and necrotizing enterocolitis (NEC), a serious gastrointestinal emergency. Provision of colostrum is recognized as oral immune therapy (OIT) and is valuable to all NICU infants unable to feed orally. A quality improvement project was initiated by the multidisciplinary NICU Quality Care Council at London Health Sciences Centres-Victoria (LHSC-VH) to obtain mothers' colostrum for early OIT. The initiative was driven by the Canadian EPIQ (Evidence-based Practice for Improving Quality) group as a means of reducing the rates of NEC and NI, two major morbidities in the NICU. The overall aim was to facilitate the availability of OIT to preterm and critically ill neonates as soon as possible after birth.

Home parenteral nutrition in patients with systemic sclerosis: a retrospective review of 12 cases.

OBJECTIVE: To evaluate the effect of home total parenteral nutrition (HTPN) on the nutritional and functional status of patients with systemic sclerosis (SSc). METHODS: Retrospective review of SSc patients from the HTPN database at the University Health Network, Toronto, Canada, from 1998 to 2010. RESULTS: In total 12 subjects (9 females, 3 males) with SSc were identified. At initiation of HTPN, the age was 48.75 ± 3.94 years and the median body mass index was 16.8 kg/m(2) (range 12.3-21.3). This significantly increased to 18.3 kg/m(2) (17.0-21.7) at 6 months and to 19.7 kg/m(2) (17.0-24.6) at 12 months. The mean Karnofsky score at baseline was 58.00 ± 3.27, and the score at 12 months of 39.00 ± 13.29 did not change significantly. CONCLUSION: HTPN improved the nutritional status of these patients with SSc but it did not improve their functional status.

The Canadian Home Total Parenteral Nutrition (HTPN) Registry: vitamin K supplementation and bone mineral density.

BACKGROUND: Vitamin K supplementation improves bone health, and its absence might be associated with low bone mineral density (BMD). The authors aim to assess vitamin K supplementation practices in Canadian home parenteral nutrition (HPN) programs and their relationship with BMD. METHODS: This is a cross-sectional study of 189 patients from the Canadian HPN registry. RESULTS: All 189 patients studied received M.V.I.-12, which does not contain vitamin K. Of those, 41.3% were supplemented with 10 mg of intravenous vitamin K (VK+) weekly, whereas the others did not receive vitamin K except via lipid emulsion (VK-). Short bowel syndrome accounted for 69% of VK+ and 46% of VK- patients. On univariate analysis, VK+ patients had substantially lower body mass index (BMI) and received lower bisphosphonate infusion than did VK-patients. There were no statistically significant differences in HPN calcium or lipid content, liver function test results, age, sex, or reason for HPN between the 2 groups. Patients who were VK+ had higher lumbar spine T scores and hip T scores than did VK-patients. General linear modeling analysis, adjusted for BMI, age, PN magnesium, PN phosphate, PN calcium, and bisphosphonate as possible predictors of BMD, showed a trend toward better hip T scores (P = .063) for VK+ patients compared with VK- patients. CONCLUSION: In HPN patients supplemented with vitamin K, the trend toward a better hip BMD compared with no supplementation suggests a role for vitamin K in preserving BMD. This requires further study.