Clinical use and efficacy of biphasic insulin lispro 50/50 in people with insulin treated diabetes-A nationwide evaluation of clinical practice

© 2015 Informa UK Ltd. Objectives: This study aims to investigate the metabolic effects of biphasic insulin lispro 50/50 in routine clinical practice. A total of 229 patients who were 18 years old with diabetes, newly treated with biphasic insulin lispro 50/50, were sourced from six secondary care services in England. Methods: Detailed clinical parameters were compared at baseline, and 3 and 6 months post-initiation. Responders was defined as those with HbA1c 1% (11mmol/mol) at 6 months. Results: HbA1c showed significant reduction:-0.93% (-10mmol/mol) and-1.2% (-13mmol/mol) at 3 and 6 months respectively, while no significant change was noted for all the other parameters. When analyzed according to frequencies of injections/day, the greatest reduction was observed with the three times a day regimen (-1.0% [-11.0mmol/mol] and-1.3% [-14.6mmol/mol] at 3 and 6 months respectively). HbA1c reduction was greatest in the group who previously received a basal-bolus insulin regimen: (-0.8% [-9.0mmol/mol] and-1.5% [-16.2mmol/mol] at 3 and 6 months respectively). Reduction in weight was observed at 3 months (-1.8kg±4.3) only for those who were previously on a basal-bolus insulin regimen. Insulin doses increased following conversion to biphasic insulin lispro 50/50, irrespective of the types of insulin used prior to biphasic insulin lispro 50/50, but this was not associated with weight gain. The independent predictors of response to biphasic insulin lispro 50/50 were baseline HbA1c, Caucasian, presence of nephropathy, prior use of basal-bolus insulin and prior use of other premixed combination. Conclusion: Biphasic insulin lispro 50/50 is therefore an effective therapeutic option for achieving glycemic control in patients with suboptimal HbA1c levels, especially among those who were previously on a basal-bolus insulin regimen and those who received it three times daily, with a neutral effect on weight parameters. Limitations: This was a retrospective study of routine clinical practice and is therefore limited by allocation bias and some missing data. Information on rates of hypoglycemia and quality of life are not available

Additive subdistribution hazards regression for competing risks data in case-cohort studies

In survival data analysis, a competing risk is an event whose occurrence precludes or alters the chance of the occurrence of the primary event of interest. In large cohort studies with long-term follow-up, there are often competing risks. Further, if the event of interest is rare in such large studies, the case-cohort study design is widely used to reduce the cost and achieve the same efficiency as a cohort study. The conventional additive hazards modeling for competing risks data in case-cohort studies involves the cause-specific hazard function, under which direct assessment of covariate effects on the cumulative incidence function, or the subdistribution, is not possible. In this paper, we consider an additive hazard model for the subdistribution of a competing risk in case-cohort studies. We propose estimating equations based on inverse probability weighting methods for the estimation of the model parameters. Consistency and asymptotic normality of the proposed estimators are established. The performance of the proposed methods in finite samples is examined through simulation studies and the proposed approach is applied to a case-cohort dataset from the Sister Study

Premenopausal gynecologic surgery and survival among black and white women with breast cancer

Purpose: In the United States, hysterectomies and oophorectomies are frequently performed before menopause for benign conditions. The procedures are associated with reduced breast cancer-specific mortality among White women. The relationship between premenopausal gynecologic surgery and mortality in Black women with breast cancer is unknown. Methods: This investigation used incident invasive cases of breast cancer from Phases 1 and 2 of the Carolina Breast Cancer Study a population-based study that recruited Black and White women in North Carolina between 1993 and 2001. Premenopausal gynecologic surgery was operationalized in three categories: no surgery; hysterectomy with bilateral oophorectomy; hysterectomy with conservation of ≥ 1 ovary. Mortality was ascertained using the National Death Index, last updated in 2016. Multivariable-adjusted Cox Proportional Hazard Models were used to estimate the effect of premenopausal surgery on breast cancer-specific and all-cause mortality Results: Hysterectomy with bilateral oophorectomy was associated with reduced breast cancer-specific mortality (HR 0.68; 95% CI 0.49, 0.96). White and Black women had a similar reduction in breast cancer-specific mortality. (HR among white: 0.66; 95% CI 0.43, 1.02), (HR among Black: 0.67; 95% CI 0.37, 1.21). Conclusions: There was a similar reduction in breast cancer-specific mortality following premenopausal, pre-diagnosis hysterectomy with bilateral oophorectomy across both Black and White women

Two-Point Functions and Boundary States in Boundary Logarithmic Conformal Field Theories

Our main aim in this thesis is to address the results and prospects of boundary logarithmic conformal field theories: theories with boundaries that contain the above Jordan cell structure. We have investigated c_{p,q} boundary theory in search of logarithmic theories and have found logarithmic solutions of two-point functions in the context of the Coulomb gas picture. Other two-point functions have also been studied in the free boson construction of BCFT with SU(2)_k symmetry. In addition, we have analyzed and obtained the boundary Ishibashi state for a rank-2 Jordan cell structure [hep-th/0103064]. We have also examined the (generalised) Ishibashi state construction and the symplectic fermion construction at c=-2 for boundary states in the context of the c=-2 triplet model. The differences between two constructions are interpreted, resolved and extended beyond each case.Comment: Ph.D. Thesis (University of Oxford), 96 pages, the layout is modified from the origina

Long-term patterns of excess mortality among endometrial cancer survivors

Background: We investigated excess mortality after endometrial cancer using conditional relative survival estimates and standardized mortality ratios (SMR). Methods: Women diagnosed with endometrial cancer during 2000-2017 (N ¼ 183,153) were identified in the Surveillance Epidemiology and End Results database. SMRs were calculated as observed deaths among endometrial cancer survivors over expected deaths among demographically similar women in the general U.S. population. Five-year relative survival was estimated at diagnosis and each additional year survived up to 12 years post-diagnosis, conditional on survival up to that year. Results: For the full cohort, 5-year relative survival was 87.7%, 96.2%, and 97.1% at 1, 5, and 10 years post-diagnosis, respectively. Conditional 5-year relative survival first exceeded 95%, reflecting minimal excess mortality compared with the general population, at 4 years post-diagnosis overall. However, in subgroup analyses, conditional relative survival remained lower for Black women (vs. White) and for those with regional/distant stage disease (vs. localized) throughout the study period. The overall SMR for all-cause mortality decreased from 5.90 [95% confidence interval (CI), 5.81-5.99] in the first year after diagnosis to 1.16 (95% CI, 1.13-1.19) at 10þ years; SMRs were consistently higher for non-White women and for those with higher stage or grade disease. Conclusions: Overall, endometrial cancer survivors had only a small survival deficit beyond 4 years post-diagnosis. However, excess mortality was greater in magnitude and persisted longer into survivorship for Black women and for those with more advanced disease. Impact: Strategies to mitigate disparities in mortality after endometrial cancer will be needed as the number of survivors continues to increase

Disparities in mortality from noncancer causes among adolescents and young adults with cancer

Background: Few studies have examined noncancer outcomes among patients diagnosed with cancer as adolescents and young adults (AYA). We examined risk of mortality from noncancer causes after an AYA cancer diagnosis and investigated disparities according to race/ethnicity and other characteristics. Methods: Patients with a first primary cancer at ages 15 to 39 years diagnosed during 1987 to 2015 were identified in the Surveillance, Epidemiology, and End Results database (N = 242,940 women, 158,347 men). Survival months were accrued from diagnosis until death or December 2015. Multivariable-adjusted HRs were used to examine disparities in mortality from all noncancer causes, cardiovascular diseases (CVD), and infectious diseases (ID) according to race/ethnicity, geographic region, and county-level characteristics. Results: For all cancer types combined, the 10-year cumulative incidence of noncancer-related death after AYA cancer was 2% and 5% among women and men, respectively. With adjustment for cancer type, all noncancer mortality was increased among non-Hispanic Black AYAs [HR vs. nonHispanic White: HRWomen = 2.31; 95% confidence interval (CI): 2.16-2.47; HRMen = 2.17; 95% CI: 2.05-2.30] and those in the South (HR vs. Northeast: HRWomen = 1.18; 95% CI: 1.07-1.29; HRMen = 1.42; 95% CI: 1.31-1.55) or in rural counties (HR vs. metro: HRWomen = 1.74; 95% CI: 1.47-2.07; HRMen = 1.57; 95% CI: 1.33-1.86). Mortality from CVD and ID was also elevated among non-Hispanic Black AYAs. Conclusions: Results of this study suggest that noncancer mortality after AYA cancer is highest among survivors who are non-Hispanic Black or live in the South or in rural counties. Impact: Our analyses highlight disparities among AYAs with cancer and identify subgroups that may be targeted for increased medical surveillance or behavioral interventions

Cardiovascular disease diagnoses among older women with endometrial cancer

Background: Endometrial cancer (EC) shares risk factors (e.g. obesity) with cardiovascular disease (CVD), yet little research has investigated CVD diagnoses among EC survivors. We aimed to describe the burden of CVD diagnoses among older women with EC compared to women without a cancer history. Methods: Women aged 66+ years with an EC diagnosis during 2004–2017 (N = 44,386) and matched women without cancer (N = 221,219) were identified in the SEER-Medicare linked data. An index date was defined as the cancer diagnosis date of the EC case in that matched set. ICD-9/10 diagnosis codes were used to define CVD outcomes in the Medicare claims. Prevalent CVD was identified using diagnosis codes in the year before the index date. Hazard ratios (HRs) for incident CVD diagnoses after the index date were estimated using multivariable Cox proportional hazards regression. Women with a prevalent CVD were excluded from incidence analyses for that outcome. Results: Compared to women without cancer, women with EC had a higher prevalence of CVD diagnoses at the index date. In analyses beginning follow-up at 1 year post-index date, EC survivors had an increased risk of incident CVD diagnoses including ischemic heart diseases (HR = 1.73; 95% CI: 1.69–1.78), pulmonary heart disease (HR = 1.95; 95% CI: 1.88–2.02), and diseases of the veins and lymphatics (HR = 2.71; 95% CI: 95% CI: 2.64–2.78). Risk of CVD diagnoses among women with EC was also elevated within the first year post-index date. Conclusions: Management of pre-existing CVD and monitoring for incident CVD may be critical during EC treatment and throughout long-term survivorship

Trends in surgical treatment of early-stage breast cancer reveal decreasing mastectomy use between 2003 and 2016 by age, race, and rurality

Purpose: To examine trends in the surgical treatment of breast cancer by age, rurality, and among Black women in a populous, racially diverse, state in the Southeastern United States of America. Methods: We identified women diagnosed with localized or regional breast cancer between 2003 and 2016 in the North Carolina Central Cancer Registry (n = 86,776). Using Joinpoint regression we evaluated the average annual percentage change in proportion of women treated with mastectomy versus breast-conserving surgery overall, by age group, among Black women, and for women residing in rural areas. Results: Overall, the rate of mastectomy usage in the population declined 2.5% per year between 2003 and 2016 (95% CI − 3.2, − 1.7). Over this same time interval, breast-conserving surgery increased by 1.6% per year (95% CI 0.9, 2.2). These temporal trends in surgery were also observed among Black women and rural residing women. Trends in surgery type varied by age group: mastectomy declined over time among women > 50 years, but not among women aged 18–49 at diagnosis. Discussion: In contrast to national studies that reported increasing use of mastectomy, we found declining mastectomy rates in the early 2000s in a Southern US state with a racially and geographically diverse population. These decreasing trends were consistent among key subgroups affected by cancer inequities, including Black and White rural women

Adjuvant radiation therapy and health-related quality of life among older women with early-stage endometrial cancer: an analysis using the SEER-MHOS linkage

Purpose: Radiation therapy (RT) has been associated with decreased health-related quality of life (HRQOL) in clinical trials of early-stage endometrial cancer (EC), but few studies have examined the association in real-world settings. We assessed HRQOL associated with adjuvant RT for older women with early-stage EC within a large U.S. population-based registry resource. Methods: The Surveillance Epidemiology and End Results and the Medicare Health Outcomes Survey linkage (1998–2017) was used to identify women with early-stage EC aged ≥ 65 years at survey who received surgery and were diagnosed ≥ 1-year prior (n = 1,140). HRQOL was evaluated with the 36-item Short-Form Health Survey (SF-36) until 2006 and the Veterans RAND 12-Item Health Survey (VR-12) post 2006. Ordinary least squares regression was used to estimate mean difference (MD) in T scores and 95% confidence intervals (CIs) comparing treatment groups (surgery alone, adjuvant external beam radiation therapy [EBRT], or adjuvant vaginal brachytherapy [VBT]) after accounting for confounders using propensity score weighting. Results: Overall, RT was not associated with physical health (MD = 0.97; 95% CI = − 1.13, 3.07) or mental health (MD = − 0.78; 95% CI = − 2.60, 1.05) relative to surgery alone. In analyses by RT type, adjuvant VBT was associated with better general health on the SF-36/VR-12 subscale (MD = 3.59; 95% CI = 0.56, 6.62) relative to surgery alone. No statistically significant associations were observed for adjuvant VBT and physical or mental health, or for adjuvant EBRT and any HRQOL domain. Conclusion: Older women with early-stage EC treated with adjuvant RT did not report worse physical and mental HRQOL scores compared to those treated with surgery alone, though relevant symptoms should be evaluated further to fully understand the disease and treatment specific aspects of the HRQOL

Patient characteristics and health system factors associated with adjuvant radiation therapy receipt in older women with early-stage endometrial cancer

Introduction: Among women with early-stage endometrial cancer (EC), age, stage, grade, and histology are used to determine fitness for adjuvant radiation therapy (RT) administration. We examined non-cancer factors associated with adjuvant RT receipt in older women with early-stage EC. Materials & methods: Using data from the Surveillance Epidemiology and End Results cancer registry program linked with Medicare claims, we identified 25,654 women (aged ≥66 years) diagnosed with first primary stage I-II EC during 2004–2017 who underwent a hysterectomy. Diagnosis and procedure codes were used to identify adjuvant RT claims filed for the seven-month period post-hysterectomy. Multivariable log-binomial regression was used to estimate adjuvant RT prevalence associated with patient characteristics and health system factors after adjustment for age, frailty, and endometrial factors. Results: Adjuvant RT was less commonly administered to Asian American and Pacific Islander patients than non-Hispanic White patients (Prevalence ratio [PR], 0.84; 95% confidence interval [CI], 0.73 to 0.97). Compared to women treated in the Northeast region, women treated other regions of the US were less likely to undergo adjuvant RT (PR, 0.75; 95% CI, 0.71 to 0.79). Residing in rural or high neighborhood-poverty counties was associated with lower adjuvant RT administration. Higher comorbidity score was not associated with reduced prevalence of adjuvant RT receipt; however, women with high probability of predicted probability of frailty were less likely to undergo adjuvant RT (PR, 0.67; 95% CI, 0.55 to 0.81) compared to women with low probability of frailty. Women who received lymph node assessment were more likely to undergo adjuvant RT compared to women who did not (PR, 1.43; 95% CI, 1.34 to 1.51). Women treated by a gynecologic oncologist were more likely to undergo adjuvant RT compared to women treated by a non-gynecologic oncologist (PR 1.09; 95% CI, 1.04 to 1.14). Adjuvant RT was more commonly administered to women treated in larger academic hospitals. Discussion: Findings suggest that various non-cancer factors affect the delivery of adjuvant RT to older women with early-stage EC in real-world oncology practice. Advancing our understanding of factors associated with adjuvant RT administration may help expand equitable access to RT