Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): a multicenter stepped-wedge cluster randomized controlled trial.

BACKGROUND: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. METHODS/DESIGN: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. DISCUSSION: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.

Etiology of diarrhea in a rural community in western Thailand: importance of enteric viruses and enterovirulent Escherichia coli.

The etiology of gastroenteritis was determined in children and adults with diarrhea seen at a district hospital and three government health clinics in Suan Phung, western Thailand, in 1991. Enteric viruses (rotavirus and astrovirus) were identified in 40%, shigellae in 18%, attaching and effacing Escherichia coli in 13%, Campylobacter jejuni in 9%, and enterotoxigenic E. coli in 7% of children < 5 years old with diarrhea seen at the hospital. Enteric viruses were detected in 15% (24/156) of patients with diarrhea > or = 5 years old and were the only enteric pathogens identified in 12 patients ages 7-79 years (2 astrovirus, 10 rotavirus infections). Attaching and effacing E. coli, rotavirus, and astrovirus were potential causes of diarrhea in children and adults in this population.

The changing epidemiology of invasive group A streptococcal infections and the emergence of streptococcal toxic shock-like syndrome. A retrospective population-based study.

OBJECTIVE: To determine disease incidence and changes in the epidemiology of invasive group A streptococcal infections in a community in Arizona. DESIGN AND SETTING: We retrospectively surveyed microbiology records from all 10 hospitals in Pima County, Arizona, to identify patients who had Streptococcus pyogenes isolated from blood, sterile body fluid, or tissue biopsy specimens between April 1985 and March 1990. Demographic and clinical information was abstracted from the medical records of these patients. PATIENTS: A total of 128 patients with a median age of 53.5 years (range, 6 months to 96 years). OUTCOME MEASURES: Racial/ethnic differences in disease incidence; mortality and changes in the clinical spectrum of disease over the study period. RESULTS: The annual age-adjusted incidence was 4.3 per 100,000 but was 46.0 per 100,000 among Native Americans. Advanced age, age less than 5 years, hypotension, and multi-organ system involvement were significantly associated with increased mortality. From 1985 to 1990, the proportion of infections with hypotension, rash, desquamation, renal impairment, and gastrointestinal involvement increased significantly (chi 2 for trend P < or = .02 for each feature). A toxic shock-like syndrome occurred in 8% of infections since 1988, compared with none of the infections between 1985 and 1987 (P = .04). Patients with the syndrome were younger than patients with other invasive infections (median age 15 vs 54 years, P = .02), and were less likely to have underlying medical conditions (P = .008). CONCLUSIONS: Significant changes occurred in the spectrum of invasive group A streptococcal infections in Pima County, Arizona, between 1985 and 1990. Native Americans were at increased risk of acquiring these infections. Patients with the streptococcal toxic shock-like syndrome had epidemiologic features that distinguished them from patients with other invasive infections, including younger age and less underlying illness.

Enterococcal bacteremia: to treat or not to treat, a reappraisal.

The treatment of enterococcal bacteremia not associated with endocarditis has been controversial. We retrospectively reviewed 81 episodes of enterococcal bacteremia and categorized them as to their clinical significance, using a strict case definition. Of the 81 episodes, 41 met our criteria for clinical significance. Mortality was 51% among the 41 patients with clinically significant bacteremia and 50% among the 40 patients with bacteremia of uncertain clinical significance. Despite these equivalent overall mortality figures, antibiotic therapy specific for Enterococcus species was associated with reduced in-hospital mortality among patients with clinically significant infections (relative risk [RR] = 0.46, 95% confidence interval [CI] = 0.27-0.77); mortality was also reduced in the first 7 days after the detection of bacteremia, when death was relatively likely to be directly due to the bacteremic episode (RR = 0.17, CI = 0.04-0.74). The association between appropriate antibiotic therapy and reduced mortality remained statistically significant when adjustments were made for a number of other factors related to mortality, including age, underlying conditions, prior use of antibiotics, nosocomial acquisition, polymicrobial etiology, prior surgery, and source of infection. Thus enterococcal isolates from the blood, even when of doubtful clinical significance, are poor prognostic markers associated with high mortality. However, when the clinical significance of bacteremia is defined by strict criteria, specific therapy against Enterococcus species is associated with improved outcome.