Objective

To characterise the relationship between simvastatin and risk of acute pancreatitis (AP).

Design

We conducted a retrospective cohort study (2006-2012) on data from an integrated healthcare system in southern California. Exposure to simvastatin was calculated from time of initial dispensation until 60 days following prescription termination. AP cases were defined by ICD-9 CM 577.0 and serum lipase≥3 times normal. Patients were censored at death, last follow-up, and onset of AP or end-of-study. Incidence rate of pancreatitis among simvastatin users was compared with the adult reference population. Robust Poisson regression was used to generate risk ratio (RR) estimates for simvastatin use adjusted for age, gender, race/ethnicity, gallstone-related disorders, hypertriglyceridaemia, smoking and alcohol dependence. Analysis was repeated for atorvastatin.

Results

Among 3,967,859 adult patients (median duration of follow-up of 3.4 years), 6399 developed an initial episode of AP. A total of 707,236 patients received simvastatin during the study period. Patients that received simvastatin were more likely to have gallstone-related disorders, alcohol dependence or hypertriglyceridaemia compared with the reference population. Nevertheless, risk of AP was significantly reduced with simvastatin use, crude incidence rate ratio 0.626 (95% CL 0.588, 0.668), p<0.0001. In multivariate analysis, simvastatin was independently associated with reduced risk of pancreatitis, adjusted RR 0.29 (95% CL 0.27, 0.31) after adjusting for age, gender, race/ethnicity, gallstone disorders, alcohol dependence, smoking and hypertriglyceridaemia. Similar results were noted with atorvastatin, adjusted RR 0.33(0.29, 0.38).

Conclusions

Use of simvastatin was independently associated with reduced risk of AP in this integrated healthcare setting. Similar findings for atorvastatin suggest a possible class effect.

Background

Although advanced pancreatic ductal adenocarcinoma (PDAC) is characterized by progressive weight loss and nutritional deterioration, the effect of cancer cachexia and body mass index (BMI) at diagnosis on survival remains unclear.

Methods

We retrospectively evaluated a prospectively collected internal cancer registry of PDAC cases from 2006-2014 at the Kaiser Permanente Medical Center. Cancer cachexia was defined as weight loss greater than 5% over the 6 months prior to diagnosis. Multivariate cox proportional hazards regression was used to assess the influence of cachexia on survival. To evaluate effect measure modification of this relationship, we performed additional analyses stratified by race, BMI class, stage, receipt of surgery and receipt of chemotherapy. We tested for heterogeneity by fitting models with an interaction term for cachexia and the modifying variable.

Results

Of the 977 patients, 611 (63%) were identified with cachexia. Cachexia in PDAC patients was prevalent across all stages of disease and BMI classes. Patients with cachexia had lower survival (median 4.3 months, IQR 1.7-10.0) compared to those without cachexia (median 5.2 months, IQR 2.0-10.6), log-rank P=0.03. In this analysis BMI at diagnosis was not associated with survival. In the multivariate Cox regression, cachexia was independently associated with decreased overall survival (HR 1.24, CI: 1.06-1.45, P=0.01). However, the effect of cachexia on survival outcomes was modified by receipt of chemotherapy. Cachectic patients who did not receive chemotherapy had a 40% increase in risk of death compared to non-cachectic patients (HR 1.40, CI: 1.12-1.75), while those receiving chemotherapy were unaffected by cachexia (HR 1.04, CI: 0.82-1.32, P_interaction=0.01).

Conclusions

In the largest cohort of pancreatic cancer patients examined to date, cachexia and not obesity is independently associated with worse survival in PDA and its effect is negated by systemic chemotherapy.

Gastric carcinoma (GC) disproportionately affects Asian Americans. We examined whether history of upper gastrointestinal (GI) endoscopy was associated with lower stage at GC diagnosis among Asian Americans and whether origin of providers influenced referral for endoscopy. We employed Surveillance Epidemiology and End Results-Medicare data on Asian Americans diagnosed with GC in 2004-2013 (n = 1,554). Stage distribution, GI conditions at diagnosis, and history of endoscopy were compared between Asian ethnic groups. Multivariate logistic regression adjusting for age, sex, poverty level, tumor location, and histology was used to examine the association of ethnicity and endoscopic history with stage I disease at diagnosis of GC. Koreans were more likely to be diagnosed with stage I, T1a GC and have prior history of endoscopy, compared with other Asian ethnicities (24% vs. 8% for stage I, T1a; 40% vs. 15% for endoscopy). Patients with primary care providers of concordant ethnic origin were more likely to have history of endoscopy. Asian American patients with GC with history of endoscopy were more likely to be diagnosed with GC at stage I disease (adjusted OR, 3.07; 95% confidence interval, 2.34-4.02). Compared with other Asian Americans, Koreans were diagnosed with GC at earlier stages owing to common history of endoscopy, which was more often undergone by patients with primary care providers of concordant ethnic origin. Overall, upper GI endoscopy was associated with early detection of GC in Asian Americans. Novelty and Impact. It is well-established that Asian Americans in the United States are disproportionately affected by gastric cancer. In our study we found that Asian American patients treated by physicians of similar ethnic background are more likely to undergo upper GI endoscopy in the United States, leading to early detection of gastric cancer and longer survival. Given this, targeted endoscopic screening in Asian Americans should be considered for early detection of GC.

Introduction

Coronavirus disease 2019 rapidly shifted health care toward telehealth. We assessed satisfaction with and preferences for telehealth among patients with irritable bowel syndrome (IBS).

Methods

We conducted a cross-sectional survey in an integrated healthcare system in Southern California with members aged 18-90 years with an International Classification of Diseases 9 and 10 codes for IBS from office-based encounters between June 1, 2018, and June 1, 2020. Eligible patients were emailed a survey assessing telehealth satisfaction overall and by patient-related factors, IBS characteristics, health and technologic literacy, utilization, and coronavirus disease 2019 perceptions. We identified perceived telehealth benefits and challenges. Multivariable logistic regression identified predictors of telehealth dissatisfaction.

Results

Of 44,789 surveys sent, 5,832 (13.0%) patients responded and 1,632 (3.6%) had Rome IV IBS. Among 1,314 (22.5%) patients with IBS and prior telehealth use (mean age 52.6 years [17.4]; 84.9% female; and 59.4% non-Hispanic White, 29.0% Hispanic, and 5.6% non-Hispanic Black), 898 (68.3%) were satisfied, 130 (9.9%) were dissatisfied, and 286 (21.8%) felt neutral. In addition, 78.6% would use telehealth again. Independent predictors of telehealth dissatisfaction include social media use of once a week or less (adjusted odds ratio [OR] = 2.1; 1.3-3.5), duration of IBS for <1 year (adjusted OR = 8.2; 1.9-35.8), and willingness to travel 60 plus minutes for face-to-face visits (adjusted OR = 2.6; 1.4-3.7). Patients' main concern with telehealth was a lack of physical examination.

Discussion

Most of the patients with IBS are satisfied with telehealth. Shorter duration of IBS diagnosis, comfort with technology, and increased willingness to travel were associated with telehealth dissatisfaction. These predictors may help identify a target population for a focused IBS-telehealth program.

Objectives

Acute pancreatitis has a highly variable course. Currently there is no widely accepted method to measure disease activity in patients hospitalized for acute pancreatitis. We aimed to develop a clinical activity index that incorporates routine clinical parameters to assist in the measurement, study, and management of acute pancreatitis.

Methods

We used the UCLA/RAND appropriateness method to identify items for inclusion in the disease activity instrument. We conducted a systematic literature review followed by two sets of iterative modified Delphi meetings including a panel of international experts between November 2014 and November 2015. The final instrument was then applied to patient data obtained from five separate study cohorts across Southern California to assess profiles of disease activity.

Results

From a list of 35 items comprising 6 domains, we identified 5 parameters for inclusion in the final weighted clinical activity scoring system: organ failure, systemic inflammatory response syndrome, abdominal pain, requirement for opiates and ability to tolerate oral intake. We applied the weighted scoring system across the 5 study cohorts comprising 3,123 patients. We identified several distinct patterns of disease activity: (i) overall there was an elevated score at baseline relative to discharge across all study cohorts, (ii) there were distinct patterns of disease activity related to duration of illness as well as (iii) early and persistent elevation of disease activity among patients with severe acute pancreatitis defined as persistent organ failure.

Conclusions

We present the development and initial validation of a clinical activity score for real-time assessment of disease activity in patients with acute pancreatitis.

Background & aims

Observational studies of predominantly white populations have found new-onset diabetes to be associated with increased risk of pancreatic cancer. We sought to determine whether this relationship applies to other races or ethnicities and to identify metabolic profiles associated with increased risk of pancreatic cancer.

Methods

We conducted a population-based cohort study of Asian, black, Hispanic and white patients from Kaiser Permanente Southern California from 2006 through 2016 (n = 1,499,627). Patients with diabetes were identified based on glucose and hemoglobin A1c (HbA1c) measurements. We used Cox regression to assess the relationship between diabetes status and duration and pancreatic cancer. For patients with recent diagnoses of diabetes (1 year or less) we compared longitudinal changes in glucose, HbA1c, and weight, from time of diabetes diagnosis through 3 years prior to the diagnosis, in patients with vs without pancreatic cancer.

Results

We identified 2,002 incident cases of pancreatic cancer from nearly 7.5 million person-years of follow-up. Compared to patients without diabetes, individuals who received a recent diagnosis of diabetes had an almost 7-fold increase in risk of pancreatic cancer (relative risk, 6.91; 95% CI, 5.76-8.30). Among patients with a recent diagnosis of diabetes, those who developed pancreatic cancer had more rapid increases in levels of glucose (Δslope: cases, 37.47 mg/dL vs non-cases, 27.68 mg/dL) and HbA1c (Δslope: cases, 1.39% vs non-cases, 0.86%) in the month preceding the diagnosis of diabetes, and subtle weight loss in the prior years (slope: cases -0.18 kg/interval vs non-cases 0.33 kg/interval). These longitudinal changes in markers of metabolism were stronger for specific race and ethnic groups.

Conclusions

In a study of a large ethnically diverse population, we found risk of pancreatic cancer to be increased among patients with a diagnosis of diabetes in the past year among different races and ethnicities. Weight loss and rapid development of poor glycemic control were associated with increased risk of pancreatic cancer in multiple races.

Background and objective

Early detection methods for pancreatic cancer are lacking. We aimed to develop a prediction model for pancreatic cancer based on changes in health captured by healthcare claims data.

Methods

We conducted a case-control study on 29,646 Medicare-enrolled patients aged 68 years and above with pancreatic ductal adenocarcinoma (PDAC) reported to the Surveillance Epidemiology an End Results (SEER) tumor registries program in 2004-2011 and 88,938 age and sex-matched controls. We developed a prediction model using multivariable logistic regression on Medicare claims for 16 risk factors and pre-diagnostic symptoms of PDAC present within 15 months prior to PDAC diagnosis. Claims within 3 months of PDAC diagnosis were excluded in sensitivity analyses. We evaluated the discriminatory power of the model with the area under the receiver operating curve (AUC) and performed cross-validation by bootstrapping.

Results

The prediction model on all cases and controls reached AUC of 0.68. Excluding the final 3 months of claims lowered the AUC to 0.58. Among new-onset diabetes patients, the prediction model reached AUC of 0.73, which decreased to 0.63 when claims from the final 3 months were excluded. Performance measures of the prediction models was confirmed by internal validation using the bootstrap method.

Conclusion

Models based on healthcare claims for clinical risk factors, symptoms and signs of pancreatic cancer are limited in classifying those who go on to diagnosis of pancreatic cancer and those who do not, especially when excluding claims that immediately precede the diagnosis of PDAC.

Objectives

It has been suggested that statins exert potential anti-tumor effects. The relationship between statin use and outcomes in pancreatic cancer is controversial. We hypothesized that statin use at baseline would impact survival among patients with early-stage pancreatic cancer and that the effect might vary by individual statin agent.

Methods

We conducted a retrospective cohort study on data from an integrated healthcare system. We included patients with pancreatic cancer stage I-IIb who underwent resection for curative intent between January 2005 and January 2011. Baseline statin use was characterized as any prior use as well as active use of either simvastatin or lovastatin. Intensity of exposure was calculated as average daily dose prior to surgery. Overall and disease-free survival was assessed from surgery until the end of study (April 2014). We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the impact of baseline statin use on survival, adjusting for age, sex, Charlson comorbidity score, resection margin, disease stage, and receipt of adjuvant chemotherapy.

Results

Among 226 patients, 71 (31.4%) had prior simvastatin use and 27 (11.9%) had prior lovastatin use at baseline. Prior simvastatin but not lovastatin use was associated with improved survival (median 28.5 months (95% confidence limit (CL) 20.8, 38.4) for simvastatin vs. 12.9 months (9.6, 15.5) for lovastatin vs. 16.5 months (14.1, 18.9) for non-statin users; log-rank P=0.0035). In Cox regression, active simvastatin use was independently associated with reduced risk for mortality (adjusted hazard ratio (HR) 0.56 (95% CL 0.38, 0.83), P=0.004) and risk for recurrence (adjusted HR 0.61 (0.41, 0.89), P=0.01). Survival improved significantly among patients who received moderate-high-intensity (median 42.1 months (24.0,52.7)) doses compared with those who received low-intensity doses of simvastatin (median 14.1 months (8.6, 23.8), log-rank P=0.03).

Conclusions

The effects of statins varied by agent and dose. Active use of moderate-high-dose simvastatin at baseline was associated with improved overall and disease-free survival among patients undergoing resection for pancreatic cancer.

Objectives

The aim of this study was to evaluate the effect of serum triglycerides on the development of multiple or persistent organ failure in patients with acute pancreatitis.

Methods

A retrospective cohort study was conducted among patients hospitalized for acute pancreatitis between 2006 and 2013. Triglyceride levels measured before and within 72 hours of admission were compared. In addition, the effect of triglyceride levels on the development of multiple or persistent organ failure during hospitalization for acute pancreatitis was assessed.

Results

Among 2519 patients, 267 patients (10.6%) developed organ failure, of which 75 patients developed multiple system organ failure and 82 patients developed persistent organ failure. Triglyceride levels in patients who developed organ failure were initially much higher than in patients who did not develop organ failure, but by 72 hours into admission, approached levels of patients who did not develop organ failure. Approximately 8% of patients had triglyceride levels greater than 500 mg/dL, the majority of which had similarly high levels before admission.

Conclusions

Increased triglyceride levels were associated with the development of multiple or persistent organ failure among patients hospitalized with acute pancreatitis. Patients with high triglyceride levels at the time of admission were likely to have high triglyceride levels before admission.

An international symposium entitled "Acute pancreatitis: progress and challenges" was held on November 5, 2014 at the Hapuna Beach Hotel, Big Island, Hawaii, as part of the 45th Anniversary Meeting of the American Pancreatic Association and the Japanese Pancreas Society. The course was organized and directed by Drs. Stephen Pandol, Tooru Shimosegawa, Robert Sutton, Bechien Wu, and Santhi Swaroop Vege. The symposium objectives were to: (1) highlight current issues in management of acute pancreatitis, (2) discuss promising treatments, (3) consider development of quality indicators and improved measures of disease activity, and (4) present a framework for international collaboration for development of new therapies. This article represents a compilation and adaptation of brief summaries prepared by speakers at the symposium with the purpose of broadly disseminating information and initiatives.