Final long-term results of a phase I/II study of dose-escalated intensity-modulated radiotherapy for locally advanced laryngo-hypopharyngeal cancers.

OBJECTIVES: We previously described dose-escalated intensity-modulated radiotherapy (IMRT) in squamous cell cancer of the larynx/hypopharynx (SCCL/H) to offer improved locoregional control with a low incidence of toxicity at 2 years. We now present outcome and safety data at 5 years. MATERIALS AND METHODS: A sequential cohort Phase I/II trial design was used. Patients with SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. RESULTS: Between 09/2002 and 01/2008, 60 patients (29 DL1, 31 DL2) with stage III (41% DL1, 52% DL2) and stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 5.7 (1.0-10.2) years and for DL2 was 6.0 (0.3-8.4) years. Five-year local control rates (95% confidence interval) for DL1 and DL2, respectively, were 68% (50.6-85.4%) and 75% (58.9-91.1%), locoregional progression-free survival rates were 54% (35.6-72.4%) and 62.6% (44.8-80.4%), and overall survival was 61.9% (44.1-79.7) and 67.6 (51.1-84.1%). Five-year laryngeal preservation rates were 66.7% (37.4-87.9%) and 71.4% (44.4-85.8%), respectively. Cumulative toxicities reported were: one patient in DL1 and 2 in DL2 developed benign pharyngeal strictures. No other G3/4 toxicities were reported. CONCLUSIONS: Dose-escalated IMRT at DL2 achieves higher 5-year local control, larynx preservation and survival rates with acceptable late toxicity. Recruitment into a Cancer Research UK Phase III study (ART-DECO), with DL2 as the experimental arm, is ongoing.

Laboratory testing for and diagnosis of nutritional deficiencies in pregnancy before and after bariatric surgery.

OBJECTIVE: Bariatric surgery can reduce the risk of obesity-related complications of pregnancy, but may cause essential nutrient deficiencies. To assess adherence to laboratory testing guidelines, we examined frequency of testing for and diagnosis of deficiency during preconception and pregnancy using claims data in women with a delivery and bariatric surgery. METHODS: Retrospective analysis of claims from seven Blue Cross/Blue Shield plans between 2002 and 2008. We included women with a delivery and bariatric surgery within the study period. We used common procedural terminology (CPT) and ICD-9 codes to define laboratory testing and deficiencies for iron, folate, vitamin B12, vitamin D, and thiamine. Using Student's t-test and chi-square testing, we compared frequency of laboratory tests and diagnoses during 12 months preconception and 280 days of pregnancy between women with pregnancy before versus after surgery. We used multivariate logistic regression to evaluate for predictors of laboratory testing. RESULTS: We identified 456 women with pregnancy after bariatric surgery and 338 before surgery. The frequency of testing for any deficiency was low (9%-51%), but higher in those with pregnancy after surgery (p<0.003). The most common deficiency was vitamin B12 (12%-13%) with pregnancy after surgery (p<0.006). Anemia and number of health provider visits were independent predictors of laboratory testing. CONCLUSION: Women with pregnancy after bariatric surgery were tested for and diagnosed with micronutrient deficiencies more frequently than those with pregnancy before surgery. However, most laboratory testing occurred in less than half the women and was triggered by anemia. Increased testing may help identify nutrient deficiencies and prevent consequences for maternal and child health.

Change in claims-based diabetes medications is a diabetes improvement indicator.

BACKGROUND: Because laboratory test results are less available to researchers than claims data, a claims-based indicator of diabetes improvement would be valuable. OBJECTIVES: To determine whether a decrease in medication use for diabetes parallels clinical improvement in glycemic control. STUDY DESIGN: This was a retrospective cohort study using up to 3.5 years of pharmacy and laboratory data from 1 private insurer. Data included 104 patients with diabetes who underwent bariatric surgery and had at least 1 glycated hemoglobin (A1C) test before and after surgery. METHODS: We assigned each A1C test to a 90-day interval before or after surgery. Medication availability was noted for the midpoint of the interval (on insulin, on oral medications, count of medications). Each subject could contribute 1 presurgery and up to 3 postsurgery observations. We recorded the changes in A1C test results and medication use from the presurgery to the postsurgery period. Using the A1C test as the reference standard, positive and negative predictive values of medication-based indicators were calculated. RESULTS: After bariatric surgery, A1C test values decreased by more than 1% and the count of unique medications decreased by 0.6. All 3 medication-based indicators had high positive predictive values (0.85) and low negative predictive values (0.20), and count of medications had better performance than the other indicators. CONCLUSIONS: Without clinical information, a decrease in use of medications can serve as a proxy for clinical improvement. Validation of results in other settings is needed.

Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study.

IMPORTANCE: Acute pancreatitis has significant morbidity and mortality. Previous studies have raised the possibility that glucagonlike peptide 1 (GLP-1)-based therapies, including a GLP-1 mimetic (exenatide) and a dipeptidyl peptidase 4 inhibitor (sitagliptin phosphate), may increase the risk of acute pancreatitis. OBJECTIVE: To test whether GLP-1-based therapies such as exenatide and sitagliptin are associated with an increased risk of acute pancreatitis. We used conditional logistic regression to analyze the data. DESIGN: Population-based case-control study. SETTING: A large administrative database in the United States from February 1, 2005, through December 31, 2008. PARTICIPANTS: Adults with type 2 diabetes mellitus aged 18 to 64 years. We identified 1269 hospitalized cases with acute pancreatitis using a validated algorithm and 1269 control subjects matched for age category, sex, enrollment pattern, and diabetes complications. MAIN OUTCOME MEASURE: Hospitalization for acute pancreatitis. RESULTS: The mean age of included individuals was 52 years, and 57.45% were male. Cases were significantly more likely than controls to have hypertriglyceridemia (12.92% vs 8.35%), alcohol use (3.23% vs 0.24%), gallstones (9.06% vs 1.34), tobacco abuse (16.39% vs 5.52%), obesity (19.62% vs 9.77%), biliary and pancreatic cancer (2.84% vs 0%), cystic fibrosis (0.79% vs 0%), and any neoplasm (29.94% vs 18.05%). After adjusting for available confounders and metformin hydrochloride use, current use of GLP-1-based therapies within 30 days (adjusted odds ratio, 2.24 [95% CI, 1.36-3.68]) and recent use past 30 days and less than 2 years (2.01 [1.37-3.18]) were associated with significantly increased odds of acute pancreatitis relative to the odds in nonusers. CONCLUSIONS AND RELEVANCE: In this administrative database study of US adults with type 2 diabetes mellitus, treatment with the GLP-1-based therapies sitagliptin and exenatide was associated with increased odds of hospitalization for acute pancreatitis.

Impact of bariatric surgery on health care costs of obese persons: a 6-year follow-up of surgical and comparison cohorts using health plan data.

IMPORTANCE: Bariatric surgery is a well-documented treatment for obesity, but there are uncertainties about the degree to which such surgery is associated with health care cost reductions that are sustained over time. OBJECTIVE: To provide a comprehensive, multiyear analysis of health care costs by type of procedure within a large cohort of privately insured persons who underwent bariatric surgery compared with a matched nonsurgical cohort. DESIGN: Longitudinal analysis of 2002-2008 claims data comparing a bariatric surgery cohort with a matched nonsurgical cohort. SETTING: Seven BlueCross BlueShield health insurance plans with a total enrollment of more than 18 million persons. PARTICIPANTS: A total of 29 820 plan members who underwent bariatric surgery between January 1, 2002, and December 31, 2008, and a 1:1 matched comparison group of persons not undergoing surgery but with diagnoses closely associated with obesity. MAIN OUTCOME MEASURES: Standardized costs (overall and by type of care) and adjusted ratios of the surgical group's costs relative to those of the comparison group. RESULTS: Total costs were greater in the bariatric surgery group during the second and third years following surgery but were similar in the later years. However, the bariatric group's prescription and office visit costs were lower and their inpatient costs were higher. Those undergoing laparoscopic surgery had lower costs in the first few years after surgery, but these differences did not persist. CONCLUSIONS AND RELEVANCE: Bariatric surgery does not reduce overall health care costs in the long term. Also, there is no evidence that any one type of surgery is more likely to reduce long-term health care costs. To assess the value of bariatric surgery, future studies should focus on the potential benefit of improved health and well-being of persons undergoing the procedure rather than on cost savings.

Clinical outcomes after bariatric surgery: a five-year matched cohort analysis in seven US states.

BACKGROUND: Bariatric surgery is the most effective weight loss treatment, yet few studies have reported on short- and long-term outcomes postsurgery. METHODS: Using claims data from seven Blue Cross/Blue Shield health plans serving seven states, we conducted a non-concurrent, matched cohort study. We followed 22,693 persons who underwent bariatric surgery during 2003-2007 and were enrolled at least 6 months before and after surgery. Using logistic regression, we compared serious and less serious adverse clinical outcomes, hospitalizations, planned procedures, and obesity-related co-morbidities between groups for up to 5 years. RESULTS: Relative to controls, surgery patients were more likely to experience a serious [odds ratio (OR) 1.9; 95% confidence interval (CI) 1.8-2.0] or less serious (OR 2.5, CI 2.4-2.7) adverse clinical outcome or hospitalization (OR 1.3, CI 1.3-1.4) at 1 year postsurgery. The risk remained elevated until 4 years postsurgery for serious events and 5 years for less serious outcomes and hospitalizations. Some complication rates were lower for patients undergoing laparoscopic surgery. Planned procedures, such as skin reduction, peaked in postsurgery year 2 but remained elevated through year 5. Surgery patients had a 55% decreased risk of obesity-related co-morbidities, such as type 2 diabetes, in the first year postsurgery, which remained low throughout the study (year 5: OR 0.4, CI 0.4-0.5). CONCLUSIONS: While bariatric surgery is associated with a higher risk of adverse clinical outcomes compared to controls, it also substantially decreased obesity-related co-morbidities during the 5-year follow-up.

Prompt reduction in use of medications for comorbid conditions after bariatric surgery.

BACKGROUND: Bariatric surgery leads to weight loss, but it is unclear whether surgery reduces conditions associated with obesity. We explored this by assessing the change in use of medications to treat diabetes mellitus, hypertension, and hyperlipidemia in the year following surgery. METHODS: This is a cohort study using administrative data from 2002 to 2005 from seven Blue Cross/Blue Shield Plans. We compared the mean number of medications at the time of surgery and in the subsequent year. Medication usage by surgical patients was also compared to usage by matched enrollees without surgery but with a propensity score suggesting obesity. With Poisson and logistic regression, we tested for statistical differences in usage, accounting for repeated measures and controlling for age, sex, and diabetes. We also evaluated medications expected to be less influenced by surgery (antidepressants, thyroid replacement, and antihistamines). RESULTS: Our cohort included 6,235 enrollees with bariatric surgery. Their mean age was 44 years with 82% women; 34% had diabetes. Medication use declined significantly by 3 months. By 12 months after surgery, medication use for diabetes, hypertension, and hyperlipidemia had declined by 76%, 51%, and 59%, respectively. In contrast, thyroid hormone, antihistamine, and antidepressant use decreased by only 6%, 15%, and 9%, respectively. Enrollees without surgery had a modest increase in medications for diabetes, hypertension, and hyperlipidemia of 4%, 8%, and 20%, respectively. CONCLUSIONS: Medication use for three serious obesity-associated conditions decreased promptly following surgery. The clinical and economic benefits of reduced medication requirements should be considered when making decisions about the effects of bariatric surgery.