Background In 2016 the WHO declared HIV self-testing and self-sampling an effective and safe test option that can reduce testing barriers. HIV self-tests and self-sampling kits (HIVST/HIVSS) are... Show moreBackground In 2016 the WHO declared HIV self-testing and self-sampling an effective and safe test option that can reduce testing barriers. HIV self-tests and self-sampling kits (HIVST/HIVSS) are available for purchase at Dutch community pharmacies since 2019. We investigated the availability and accessibility of HIVST/HIVSS in community pharmacies, and factors associated with test availability. Methods An online survey among all Dutch community pharmacies (n=1,987) was conducted between April and June 2021. Availability of HIVST/HIVSS and experiences of pharmacists with the test offer were analyzed with descriptive statistics. The association of pharmacy and pharmacists’ characteristics with HIVST/HIVSS availability was explored by logistic regression analysis. Results In total, 465 pharmacists completed the questionnaire. Of the responding pharmacists, 6.2% (n=29) offered HIVST/HIVSS. The majority (82.8%) sold between 0 and 20 tests per year. In total, pharmacies sold an estimated 370 HIVST/HIVSS per year. Pharmacies having HIVST/HIVSS available were less often located in moderately-urbanized to rural neighborhoods (OR 0.35, 95%CI 0.16–0.77 versus highly-urbanized), and were less often located in moderateto-low SES neighborhoods (OR 0.40, 95%CI 0.18–0.88 versus high-SES). Reasons for not offering HIVST/HIVSS by pharmacists were no or little demand (69.3%), and not being familiar with these tests (17.4%). 52% of the pharmacists provided information about testing to test buyers. Reported options to improve the test offer were giving advice about (performing) the test to test buyers (72.4%), placing tests visible on the counter (51.7%), and advertisement (37.9%). Conclusion HIVST/HIVSS have a limited practical availability in Dutch community pharmacies since their introduction in 2019, especially in lower-urbanized and lower-SES areas. Further research is needed to explore how to expand access to HIVST/HIVSS through community pharmacies in the Netherlands, and how to tailor it to the needs of pharmacy clients Show less
Background Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo... Show moreBackground Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients.MethodsThis nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and <= 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as <= 90 degrees arterial and <= 270 degrees venous involvement without occlusion. Patients receive 8cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36Gy in 15 fractions) during the second cycle, followed by surgery and 4cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3years and 1.5years follow-up.DiscussionThe PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer.Trial registrationPrimary registry and trial identifying number: EudraCT: 2017-002036-17.Date of registration: March 6, 2018.Secondary identifying numbers: The Netherlands National Trial Register - NL7094, NL61961.078.17, MEC-2018-004. Show less
BackgroundPancreatic 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... Show moreBackgroundPancreatic 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/designPACAP-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.DiscussionThe 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 registrationClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018. Show less
Kouwe, E. van der; Andriesse, D.; Bos, H.; Giuffrida, C.; Heiser, G. 2018
Properly benchmarking a system is a difficult and intricate task. Unfortunately, even a seemingly innocuous benchmarking mistake can compromise the guarantees provided by a given systems security... Show moreProperly benchmarking a system is a difficult and intricate task. Unfortunately, even a seemingly innocuous benchmarking mistake can compromise the guarantees provided by a given systems security defense and also put its reproducibility and comparability at risk. This threat is particularly insidious as it is generally not a result of malice and can easily go undetected by both authors and reviewers. Moreover, as modern defenses often trade off security for performance in an attempt to find an ideal design point in the performance-security space, the damage caused by benchmarking mistakes is increasingly worrisome. To analyze the magnitude of the phenomenon, we identify a set of 22 "benchmarking crimes" that threaten the validity of systems security evaluations and perform a survey of 50 defense papers published in top venues. To ensure the validity of our results, we perform the complete survey twice, with two independent readers. We find only a very small number of disagreements between readers, showing that our assessment of benchmarking crimes is highly reproducible. We show that benchmarking crimes are widespread even in papers published at tier-1 venues. We find that tier-1 papers commit an average of five benchmarking crimes and we find only a single paper in our sample that committed no benchmarking crimes. Moreover, we find that the scale of the problem is constant over time, suggesting that the community is not yet addressing it despite the problem being now more relevant than ever. This threatens the scientific process, which relies on reproducibility and comparability to ensure that published research advances the state of the art. We hope to raise awareness of these issues and provide recommendations to improve benchmarking quality and safeguard the scientific process in our community. Show less
