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Current guidelines recommend colonoscopy within 24 h for acute lower gastrointestinal bleeding; however, the evidence in support for colonic diverticular hemorrhage (CDH) indications remains insufficient.To investigate the effectiveness of early colonoscopy on the length of hospital stay for CDH patients.We conducted a single-center retrospective cohort study. Patients who underwent colonoscopy within 24 h of presentation (early group) were compared with those who underwent colonoscopy beyond 24 h of presentation (elective group). The primary outcome was the length of hospital stay, and secondary outcomes were the identification of stigmata of recent hemorrhage (SRH), rebleeding, red blood cell transfusion more than 4 units, and interventional radiology and abdominal surgery after colonoscopy.We identified 574 CDH cases. Patients were divided into the early (Early colonoscopy within 24 h, on arrival for CDH, could not improve the length of hospital stay.

Background: The cardiorenal effects of sodium-glucose cotransporter 2 inhibition (empagliflozin 25 mg QD) combined with angiotensin-converting enzyme inhibition (ramipril 10 mg QD) were assessed in this mechanistic study in patients with type 1 diabetes with potential renal hyperfiltration. Methods: Thirty patients (out of 31 randomized) completed this double-blind, placebo-controlled, crossover trial. Recruitment was stopped early because of an unexpectedly low proportion of patients with hyperfiltration. Measurements were obtained after each of the 6 treatment phases over 19 weeks: (1) baseline without treatment, (2) 4-week run-in with ramipril treatment alone, (3) 4-week combined empagliflozin-ramipril treatment, (4) a 4-week washout, (5) 4-week combined placebo-ramipril treatment, and (6) 1-week follow-up. The primary end point was glomerular filtration rate (GFR) after combination treatment with empagliflozin-ramipril compared with placebo-ramipril. GFR was corrected for ramipril treatment alone before randomization. At the end of study phase, the following outcomes were measured under clamped euglycemia (4 to 6 mmol/L): inulin (GFR) and para-aminohippurate (effective renal plasma flow) clearances, tubular sodium handling, ambulatory blood pressure, arterial stiffness, heart rate variability, noninvasive cardiac output monitoring, plasma and urine biochemistry, markers of the renin-angiotensin-aldosterone system, and oxidative stress. Results: Combination treatment with empagliflozin-ramipril resulted in an 8 mL/min/1.73 m 2 lower GFR compared with placebo-ramipril treatment ( P =0.0061) without significant changes to effective renal plasma flow. GFR decrease was accompanied by a 21.3 mL/min lower absolute proximal fluid reabsorption rate ( P =0.0092), a 3.1 mmol/min lower absolute proximal sodium reabsorption rate ( P =0.0056), and a 194 ng/mmol creatinine lower urinary 8-isoprostane level ( P =0.0084) relative to placebo-ramipril combination treatment. Sodium-glucose cotransporter 2 inhibitor/angiotensin-converting enzyme inhibitor combination treatment resulted in additive blood pressure–lowering effects (clinic systolic blood pressure lower by 4 mm Hg [ P =0.0112]; diastolic blood pressure lower by 3 mm Hg [ P =0.0032]) in conjunction with a 94.5 dynes × sex/cm 5 lower total peripheral resistance ( P =0.0368). There were no significant changes observed to ambulatory blood pressure, arterial stiffness, heart rate variability, or cardiac output with the addition of empagliflozin. Conclusions: Adding sodium-glucose cotransporter 2 inhibitor treatment to angiotensin-converting enzyme inhibitor resulted in an expected GFR dip, suppression of oxidative stress markers, additive declines in blood pressure and total peripheral resistance. These changes are consistent with a protective physiologic profile characterized by the lowering of intraglomerular pressure and related cardiorenal risk when adding a sodium-glucose cotransporter 2 inhibitor to conservative therapy. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02632747.

Background The role of computed tomography (CT) in the initial diagnosis of pancreatic cancer (PC) is well-known. CT reports made by radiologists are important as not all patients with PC are examined by specialists; however, some cases are not identified based on CT reports. Diagnosis via imaging of PC is sometimes difficult, and the diagnostic rate of PC and other pancreatic diseases can vary across radiologists. This study examined the diagnostic rate of PC in initial CT reports and the details of cases with diagnostic difficulties. Methods Clinical data of 198 patients with histologically diagnosed PC were retrospectively collected between January 2018 and April 2022. Out of these contrast-enhanced CT was performed in 192 cases (124 men and 68 women) and these cases were examined. Results In the reports, PC was not reported as the main diagnosis in 18 patients (9.4%; 11 men and 7 women; mean age, 69.7 years). Among these 18 cases, intrapancreatic mass lesions were detected in 3 (1.6%), indirect findings such as bile duct/pancreatic duct stenosis or dilation were detected in 5 (2.6%), and no PC-related findings were found in 10 (5.2%). The specialists suspected PC in 15 of these 18 cases based on initial CT reports. Seventeen cases were confirmed by endoscopic ultrasound-fine needle aspiration (EUS-FNA) and one by biopsy after upper gastrointestinal endoscopy. Conclusions To improve accuracy of the diagnosis of the PC, it is important that specialists provide feedback to diagnostic radiologists regarding the findings they did not report. Additionally, non-specialists should be aware of the importance to seek the advice of specialists when such indirect findings or any kind of pancreatic mass are present. EUS-FNA should be performed by specialists when there is clinical information which indicates pancreatic disease of any kind.

Endoscopic papillary balloon dilation (EPBD)—a low-risk procedure for bleeding—has been suggested as an alternative to endoscopic sphincterotomy (EST) for papillary dilatation in patients undergoing choledocholithotomy and at a high risk of bleeding. Several guidelines recommend dual antiplatelet therapy (DAPT) be reduced to single antiplatelet therapy (SAPT) when EST is performed. However, there is no evidence that EPBD increases the risk of bleeding in patients receiving DAPT. Thus, we aimed to address this problem. We included 31 patients who underwent EPBD for CBD stones and received DAPT or SAPT prior to EPBD (9 in the DAPT group and 22 in the SAPT group) treated at our hospital from May 2014 to August 2022. The DAPT group included patients who underwent EPBD without antiplatelet therapy withdrawal or with a shorter withdrawal period than those recommended by the guidelines. In the DAPT group, one of the two antiplatelet agents used was thienopyridine. No bleeding was observed after EPBD in this study. We did not find any significant between-group differences in the change in hemoglobin levels and post-ERCP pancreatitis. Thus, we propose that EPBD does not increase the bleedingrisk in patients with DAPT.

Endoscopic resection, particularly endoscopic submucosal dissection (ESD), for colorectal cancers enables a precise pathological diagnosis and safe R0 resection. The recurrence rate after ESD is generally extremely low, with annual surveillance colonoscopy recommended. However, surveillance may not be considered for super-elderly patients owing to their condition. This is a case report of an 85-year-old man in whom curative resection was achieved for an intramucosal adenocarcinoma with ESD. The patient presented with a hypoechoic mass located in his lower right abdomen, diagnosed via surveillance abdominal ultrasound. He had undergone curative ESD for intramucosal cecal cancer 2 years prior. Colonoscopy revealed a type 2 epithelial tumor at the proximal aspect of the ESD scar. Ileocolic resection with lymph node dissection was performed. An epithelial tumor and well-differentiated adenocarcinoma but not a submucosal tumor was detected in the mucosal layer. The lesion was diagnosed not as a local recurrence after ESD but as a newly emerged original advanced cancer. After ESD for colorectal cancer, a newly developed advanced cancer may occur at the site of the ESD scar in a shorter term than usual. Surveillance colonoscopy after ESD is necessary even for super-elderly patients.

The goal of this mechanistic trial was to determine the kidney and cardiovascular effects of combined treatment with an SGLT2i (empagliflozin 25mg QD) and an ACEi (ramipril 10mg QD) for 4 weeks in patients at risk of renal hyperfiltration. In this randomized, double-blind, placebo-controlled, cross-over trial, measurements were obtained following each of the 4 treatment phases: 1) no treatment, 2) 4-week ramipril treatment alone, 3) 4-week empagliflozin-ramipril combination treatment, and 4) 4-week placebo-ramipril combination treatment. The primary endpoint was GFR after empagliflozin-ramipril treatment compared to placebo-ramipril. At the end of each study phase the following measurements were performed under clamped euglycemia (4-6 mmol/L) : inulin (GFR) and paraaminohippurate (effective renal plasma flow, ERPF) clearances, tubular sodium handling, ambulatory blood pressure, arterial stiffness, heart rate variability, non-invasive cardiac output monitoring, plasma and urine biochemistry. Empagliflozin-ramipril treatment resulted in an 8ml/min/1.73m2 lower GFR (p=0.0061) , lower absolute proximal fluid reabsorption rate (p=0.0092) , lower absolute proximal sodium reabsorption rate (p=0.0056) , and lower urinary 8-isoprostane (p=0.0084) relative to placebo-ramipril treatment. Empagliflozin-ramipril treatment resulted in additive blood pressure lowering effects (SBP p=0.0112; DBP p=0.0032) and a lower total peripheral resistance (p=0.0368) . There were no other significant changes observed with the addition of empagliflozin. SGLT2i-ACEi combination treatment resulted in an expected GFR “dip”, suppression of oxidative stress markers, and additive declines in blood pressure and total peripheral resistance in this mechanistic study. These changes are consistent with a protective physiological profile characterized by the lowering of intraglomerular pressure and related cardiorenal risk when adding an SGLT2i to conservative therapy. Disclosure Y. Lytvyn: None. K. Kimura: Employee; 3Boehringer Ingelheim Canada Ltd./Ltée. N. Peter: Employee; Boehringer Ingelheim Pharma GmbH & Co.KG. V.S. Lai: Advisory Panel; Baxter. J. Tse: None. L. Cham: None. B.A. Perkins: Advisory Panel; Abbott Diabetes, Insulet Corporation, Sanofi. Board Member; Novo Nordisk. Research Support; BMO Bank of Montreal, Novo Nordisk. Other Relationship; Abbott Diabetes, Insulet Corporation, Medtronic, Novo Nordisk. N. Soleymanlou: Employee; Boehringer Ingelheim Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc. D. Cherney: Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk, Mitsubishi Tanabe Pharma Corporation, Sanofi. Funding Boehringer Ingelheim and CIHR, Diabetes Canada and the Heart and Stroke Richard Lewar Centre of Excellence and the Heart and Stroke Foundation of Canada

Background Upper gastrointestinal (GI) bleeding is the most important presentation of an aorto-duodenal fistula (ADF). Early diagnosis is difficult, and the disease is associated with high mortality. The present study aimed to examine the clinical and the endoscopic characteristics of ADF in eight patients who presented to our hospital. We also sought to clarify the diagnostic approach towards the disease. Methods The present study examined the clinical and the endoscopic/computed tomography (CT) characteristics of ADF in eight patients who were definitively diagnosed with this condition in a 12-year period at our hospital. Results The patients comprised of five men and three women, with a mean age of 69.8 years. Upper gastrointestinal bleeding was the chief complaint for all the patients. Out of these, two patients presented with shock. The patients’ mean haemoglobin at presentation was 7.09 g/dL, and the mean number of blood transfusions was 7.5. All patients had undergone intervention to manage an aortic pathology in the past. As the first investigation, an upper GI endoscopy in 5 and a CT scan in 3 patients were performed. In cases where CT scan was performed first, no definitive diagnosis was obtained, and the diagnosis was confirmed by performing an upper GI endoscopy. In cases where endoscopy was performed first, definitive diagnosis was made in only one case, and the other cases were confirmed by the CT scan. In some cases, tip attachments, converting to long endoscopes, and marking clips were found useful. Conclusions In patients who have undergone intervention to manage an aortic pathology and have episodes of upper gastrointestinal bleeding, ADF cannot be definitively diagnosed with only one investigation. In addition, when performing upper GI endoscopy in cases where an ADF is suspected, tip attachment, converting to a long endoscope, and using marking clips can be helpful.

To prevent the increase of resistant bacteria, it is important to minimize the use of antimicrobial agents. Studies have found that administration for ≤3 days after successful endoscopic retrograde cholangiopancreatography (ERCP) is appropriate. Therefore, the present study aimed to verify if administration of antimicrobial agents can be further shortened to ≤2 days after ERCP. We divided 390 patients with mild and moderate cholangitis who underwent technically successful ERCP from January 2018 to June 2020 and had positive blood or bile cultures into two groups: antibiotic therapy within two days of ERCP (short-course therapy, SCT; n = 59, 15.1%), and for >3 days (long-course therapy, LCT; n = 331, 84.9%). The increased severity after admission and other outcomes were compared between the two groups, and the risk factors for increased severity were verified. There were no between-group differences in patient characteristics. Total length of hospital stay was shorter in SCT than in LCT, and other outcomes in SCT were not significantly different from those in LCT. Being 80 or older was a risk factor for increased severity; however, SCT was not associated with increased severity. Antimicrobial therapy for ≤2 days after successful ERCP is adequate in patients with mild and moderate acute cholangitis.

Pancreatic pseudocyst and portal vein thrombosis are common conditions resulting from acute and chronic pancreatitis. However, pancreatic pseudocyst-portal vein fistula (PPVF) is a rare and life-threatening complication. In PPVF patients, drainage or operative therapy is necessary under certain conditions, including communication between the pseudocyst and pancreatic duct, pancreatic duct stricture, pancreatic duct stone, and infection that is difficult to control with antibiotics. We describe the case of a 78-year-old woman who presented with an infected pancreatic pseudocyst invading the portal venous system with obstruction due to thromboembolization. Conservative therapy with antibiotics was insufficient. We, therefore, performed endoscopic ultrasound-guided cyst-drainage (EUS-CD). During EUS-CD, PPVF and pseudocyst-pancreatic duct fistula were confirmed by contrast medium injection. Despite the presence of the pseudocyst-pancreatic duct fistula, the pancreatic duct was not visualized in the pancreatic head, suggesting stricture in the main pancreatic duct. We, therefore, performed endoscopic retrograde pancreatography, which revealed pancreatic stone in the main pancreatic duct. Then, we added a 7-Fr pancreatic stent. She was discharged after 89 days of hospitalization. We reviewed the literature on the management of PPVF formation, and EUS-CD is considered to be a good treatment option for PPVF patients without portal vein patency.

Background: Acute esophageal mucosal lesions (AEMLs) cause circumferential mucosal damage in the lower esophagus in patients with deteriorating general health. However, its etiology remains unclear. AEML is often diagnosed and treated as severe reflux esophagitis (sRE), particularly that of Los Angeles classification grade D (sRE-D). This study aimed to determine whether it is appropriate to classify these two diseases according to the characteristics of the proximal mucosa of erosion as previously reported, and to clarify the clinical features of AEML in comparison with sRE-D.Methods: Patients were classified into AEML and sRE-D groups, based on previous reports. Patient background, presence of shock, medical history, medications, comorbidities, death during hospitalization, blood sampling data, endoscopic findings, and presence of stenosis after treatment were evaluated.Results: There were significantly more cases with comorbidities in the AEML group than in the sRE-D group, particularly comorbidities involving infectious diseases. In addition, abnormalities in blood test results were significantly more frequent in the AEML group than in the sRE-D group. This suggests that the onset of AEML may be due to peripheral circulatory disturbance caused by worsening general condition.Conclusions: AEML and sRE-D showed distinctly different features and it was considered reasonable to distinguish them. AEML, unlike sRE-D, may be caused by microcirculatory disturbances related to comorbidities rather than gastric acid reflux. However, it is under-recognized and should be considered in the setting of upper gastrointestinal bleeding in patients with deteriorating general condition.

Background Bleeding can be a serious adverse event of endoscopic sphincterotomy (EST). However, the risk of EST bleeding between direct oral anticoagulant (DOAC) users and those who received no antithrombotic agents has not been clarified. This study analyzed the risk factors for bleeding after EST in patients on DOAC and evaluated the Japan Gastroenterological Endoscopy Society (JGES) guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Methods We retrospectively analyzed 524 patients treated with EST who received DOAC or no antithrombotic drug from May 2016 to August 2019. We investigated the risk factors for bleeding. DOAC was typically discontinued for ≤ 1-day based on the JGES guideline. Although DOAC therapy recommenced the next morning after EST in principle, the duration of DOAC cessation and heparin replacement were determined by the attending physician based on each patient’s status. Results The number of patients on DOAC (DOAC group) and those not on antithrombotic drug (no-drug group) was 42 (8.0%) and 482 (92.0%), respectively. DOAC was discontinued for ≤ 1-day in 17 (40.0%) patients and for > 1-day in 25 (60.0%). Of the 524 patients, 21 (4.0%) had EST bleeding. The bleeding rate was higher in the DOAC group (14.0%) (p = 0.004). Multivariate analysis showed that bleeding occurred more frequently in patients on DOAC (odds ratio [OR] 3.95, 95% confidence interval [CI] 1.37–11.4, p = 0.011), patients with low platelet counts (p = 0.001), and elderly patients (> 80 years old) (OR 3.36, 95%CI 1.17–9.65, p = 0.024). Conclusions DOAC treatment, low platelet count, and old age (> 80 years old) are risk factors for EST bleeding. Although the bleeding incidence increased in patients on DOAC who received antithrombotic therapy according to the JGES guidelines, successful hemostasis was achieved with endoscopy in all cases, and no thrombotic events occurred after cessation of DOAC. Thus, the JGES guidelines are acceptable.

Objectives Considering that pathogens resistant to initial antibiotic therapies for cholangitis can affect mortality rates, appropriate initial empiric antibiotic therapy is important. However, evidence regarding the influence of pathogens resistant to initial antibiotics in patients with cholangitis who have undergone early endoscopic retrograde cholangiopancreatography (ERCP) is limited, and the conditions in several cases can improve with early ERCP even when pathogens resistant to initial antibiotics are detected on time. Therefore, this study aimed to assess the influence of pathogens resistant to initial antibiotics on the course of cholangitis in patients undergoing early ERCP. Materials and methods Patients (n=266) with positive blood or bile culture results treated with early ERCP were divided into those with cultures that were resistant to the initial antibiotics (antibiotic-resistant group; n=66; 24.8%) and those with cultures that were sensitive to the initial antibiotics (antibiotic-sensitive group; n=200; 75.2%). The duration of hospitalization, in-hospital mortality rates due to cholangitis, rates of increased disease severity, and complications during hospitalization were studied. Results Enterococcus, Enterobacter, Citrobacter, and Pseudomonas species showed high resistance to several antibiotics. No significant between-group differences were found in the duration of hospitalization, in-hospital mortality rates due to cholangitis, and rates of increased disease severity. However, the rate of post-ERCP cholecystitis was significantly higher in the antibiotic-resistant group than in the antibiotic-sensitive group (p=0.0245). Conclusions Even if the initial antibiotics were ineffective, the rate of fatal outcomes did not increase among patients with cholangitis who had undergone early ERCP. However, when initial antibiotics were ineffective, the frequency of post-ERCP cholecystitis increased even after early bile duct decompression.

A 72-year-old man who had been on continuous ambulatory peritoneal dialysis treatment for 10 years underwent cardiopulmonary bypass for aortic valve replacement due to aortic valve stenosis. After surgery, he experienced pancreatitis, and rupture of a splenic artery aneurysm. He went into cardiopulmonary arrest but was successfully treated by transcatheter arterial embolization (TAE) with cardiopulmonary resuscitation. At three weeks after TAE, CT showed heterogeneous enhancement and the accumulation of pancreatic fluid in the pancreatic tail. At 4 months after TAE, he had sepsis and CT showed greater fluid collection with emphysema in comparison to 3 months previously. We diagnosed infected walled-off necrosis (WON). Conservative therapy with antibiotics was not sufficiently effective; thus, we performed endoscopic ultrasound-guided drainage (EUS-D). Contrast imaging revealed WON with colonic fistula. The WON remarkably decreased in size on CT after EUS-D. We experienced a rare case of ischemic acute pancreatitis (AP) caused by cardiopulmonary bypass complicated with infected WON with a colonic fistula. Ischemic AP more frequently shows a severe course with a fatal outcome in comparison to AP of other causes. However, in our case, ischemic AP with infected WON was successfully treated by EUS-D despite the presence of a WON with a colonic fistula.

We herein report the definitive diagnosis of rectovaginal endometriosis in two cases. Case 1 involved a 46-year-old woman with abdominal pain and hematochezia. The diagnosis after the first and second examinations using lower gastrointestinal (GI) endoscopy was unclear. Differential diagnoses included mucosa-associated lymphoid tissue and colorectal cancer. The third lower GI endoscopy with a targeted biopsy, performed during menstruation, confirmed rectovaginal endometriosis. Case 2 involved a 38-year-old woman with hematochezia. Lower GI endoscopy during menstruation revealed rectovaginal endometriosis. When rectovaginal or bowel endometriosis is suspected, lower GI endoscopy and a targeted biopsy during menstruation can prevent unnecessary surgery.

Background: An aorto-duodenal fistula presents with upper gastrointestinal bleeding and hematemesis. Early diagnosis is difficult, and the disease is associated with high mortality. Sometimes, a small amount of bleeding, known as herald bleed, occurs repeatedly and may be judged as upper gastrointestinal bleeding, prompting emergency upper endoscopy. Diagnostic methods and surgical treatment during herald bleeding are important for saving lives. However, most fistulas form in the horizontal duodenum, and active bleeding is rarely found in patients with herald bleeding. Moreover, an aorto-duodenal fistula is rarely diagnosed based on upper endoscopy alone. Methods: The present study examined the clinical and endoscopic characteristics of aorto-duodenal fistula in eight patients who underwent upper endoscopy before diagnosis at our hospital. It also sought to clarify how aorto-duodenal fistula can be appropriately diagnosed. Results: All patients had a history of aortic treatment, and many could not be diagnosed by computed tomography scan or upper endoscopy alone. Regarding the endoscopic findings, patients were seen to have stent/vascular prosthesis exposure, which is diagnostic of aorto-duodenal fistula as well as pulsatile lesions and massive fresh bleeding of obscure origin in the duodenum. Conclusions: If the diagnosis is unclear, clinicians may need to observe the horizontal duodenum using a fitted tip attachment or long scope. Since vital signs may fluctuate during endoscopy, a series of tests should be performed immediately. Proactive placement of marking clips in likely areas of the fistula may facilitate diagnosis via computed tomography. The present results demonstrate that proper diagnosis and prompt surgical treatment save lives in patients with aorto-duodenal fistula.

Background Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalizations for heart failure in patients with or without diabetes. More evidence is needed regarding their effects across the broad spectrum of heart failure, including those with reduced ejection fraction (HFrEF). Methods We randomly assigned, in double-blind fashion, 3730 patients with class II-IV heart failure and left ventricular ejection fraction ≤40% to receive empagliflozin (10 mg once daily) or placebo, in addition to standard therapy for HFrEF. The primary outcome was a composite of cardiovascular death and hospitalization for worsening heart failure. Results Over a median of 16 months, the primary outcome occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio 0.75; 95% CI: 0.65-0.86; P Conclusions Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure, regardless of the presence or absence of diabetes.

SummaryThe therapeutic management of venous thromboembolism (VTE) is rapidly evolving. Following the positive results of pivotal large-scale randomised trials, the non-vitamin K antagonist oral anticoagulants (NOACs) represent an important alternative to standard anticoagulation. In phase III studies, dabigatran was as effective as, and significantly safer than warfarin. Additional information on real-world data of dabigatran is now warranted. RE-COVERY DVT/PE is a multi-centre, international, observational (i. e. non-interventional) study enrolling patients with acute DVT and/or PE within 30 days after objective diagnosis. The study is designed with two phases. Phase 1 has a cross-sectional design, enrolling approximately 6000 patients independently of treatment choice, with the aim of providing a contemporary picture of the management of VTE worldwide. Phase 2 has a prospective cohort design, with follow-up of one year, enrolling 8000 patients treated with dabigatran or vitamin K antagonists (VKAs) with the aim of comparing their safety, defined by the occurrence of major bleeding, and effectiveness, defined by the occurrence of symptomatic recurrent VTE. RE-COVERY DVT/PE will complement both the results of other observational studies in this field and the results of phase III studies with dabigatran, in particular by assessing its clinical benefit in various patient subgroups treated in routine clinical practice.

Results of pharmacometric analyses influence high-level decisions such as clinical trial design, drug approval, and labeling. Key challenges for timely delivery of pharmacometric analyses are the data assembly process and tracking and documenting the modeling process and results. Since clinical efficacy and safety data typically reside in the biostatistics computing area, an integrated computing platform for pharmacometric and biostatistical analyses would be ideal. A case study is presented integrating a pharmacometric modeling platform into an existing statistical computing environment (SCE). The feasibility and specific configurations of running common PK/PD programs such as NONMEM and R inside of the SCE are provided. The case study provides an example of an integrated repository that facilitates efficient data assembly for pharmacometrics analyses. The proposed platform encourages a good pharmacometrics working practice to maintain transparency, traceability, and reproducibility of PK/PD models and associated data in supporting drug development and regulatory decisions.

Results of pharmacometric analyses influence high-level decisions such as clinical trial design, drug approval, and labeling. Key challenges for timely delivery of pharmacometric analyses are the data assembly process and tracking and documenting the modeling process and results. Since clinical efficacy and safety data typically reside in the biostatistics computing area, an integrated computing platform for pharmacometric and biostatistical analyses would be ideal. A case study is presented integrating a pharmacometric modeling platform into an existing statistical computing environment (SCE). The feasibility and specific configurations of running common PK/PD programs such as NONMEM and R inside of the SCE are provided. The case study provides an example of an integrated repository that facilitates efficient data assembly for pharmacometrics analyses. The proposed platform encourages a good pharmacometrics working practice to maintain transparency, traceability, and reproducibility of PK/PD models and associated data in supporting drug development and regulatory decisions.