REDCap on FHIR: Clinical Data Interoperability Services.

BACKGROUND: Despite widespread use of electronic data capture (EDC) systems for research and electronic health records (EHR), most transfer of data between EHR and EDC systems is manual and error prone. Increased adoption of Health Level Seven Fast Healthcare Interoperability Resource (FHIR) application programming interfaces (APIs) in recent years by EHR systems has increased the availability of patient data for external applications such as REDCap. OBJECTIVE: Describe the development of the REDCap Clinical Data Interoperability Services (CDIS) module that provides seamless data exchange between the REDCap research EDC and any EHR system with a FHIR API. CDIS enables end users to independently set up their data collection projects, map EHR data to fields, and adjudicate data transfer without project-by-project involvement from Health Information Technology staff. METHODS: We identified two use cases for EHR data transfer into REDCap. Clinical Data Pull (CDP) automatically pulls EHR data into user-defined REDCap fields and replaces the workflow of having to transcribe or copy and paste data from the EHR. Clinical Data Mart (CDM) collects all specified data for a patient over a given time period and replaces the process of importing EHR data for registries from research databases. With an iterative process, we designed our access control, authentication, variable selection, and mapping interfaces in such a way that end users could easily set up and use CDIS. RESULTS: Since its release, the REDCap CDIS has been used to pull over 19.5 million data points for 82 projects at Vanderbilt University Medical Center. Software and documentation are available through the REDCap Consortium. CONCLUSIONS: The new REDCap Clinical Data and Interoperability Services (CDIS) module leverages the FHIR standard to enable real-time and direct data extraction from the EHR. Researchers can self-service the mapping and adjudication of EHR data into REDCap. The uptake of CDIS at VUMC and other REDCap consortium sites is improving the accuracy and efficiency of EHR data collection by reducing the need for manual transcription and flat file uploads.

Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome.

Germline mutations in the LKB1/STK11 tumour suppressor gene cause Peutz-Jeghers syndrome (PJS), a rare dominant disorder. In addition to typical hamartomatous gastrointestinal polyps and pigmented perioral lesions, PJS is associated with an increased risk of tumours at multiple sites. Follow-up information on carriers is limited and genetic heterogeneity makes counselling and management in PJS difficult. Here we report the analysis of the LKB1/STK11 locus in a series of 33 PJS families, and estimation of cancer risks in carriers and noncarriers. Germline mutations of LKB1/STK11 were identified in 52% of cases. This observation reinforces the hypothesis of a second PJS locus. In carriers of LKB1/STK11 mutations, the risk of cancer was markedly elevated. The risk of developing any cancer in carriers by age 65 years was 47% (95% CI: 27-73%) with elevated risks of both gastrointestinal and breast cancer. PJS with germline mutations in LKB1/STK11 are at a very high relative and absolute risk of multiple gastrointestinal and nongastrointestinal cancers. To obtain precise estimates of risk associated with PJS requires further studies of genotype-phenotype especially with respect to LKB1/STK11 negative cases, as this group is likely to be heterogeneous.

Compartment syndrome following pelvic surgery in the lithotomy position.

We report the cases of two patients who developed compartment syndrome following pelvic surgery in the lithotomy position. These cases highlight this important and potentially devastating complication.

Radioimmunoguided surgery in colorectal cancer using a genetically engineered anti-CEA single-chain Fv antibody.

In radioimmunoguided surgery (RIGS), a radiolabeled antibody is given i.v. before surgery and a hand-held gamma-detecting probe is used to locate tumor in the operative field. The rapid blood clearance and good tumor penetration of single-chain Fv antibodies (scFv) offer potential advantages over larger antibody molecules used previously for RIGS. A Phase I clinical trial is reported on RIGS with scFv (MFE-23-his) to carcinoembryonic antigen (CEA). Thirty-four patients undergoing surgery for colorectal carcinoma (17 primary tumors, 16 liver metastases, and 1 anastomotic recurrence) and 1 patient with liver metastases of pancreatic carcinoma received 125I-labeled MFE-23-his scFv (125I-MFE-23-his) 24, 48, 72, or 96 h before operation. 125I-MFE-23-his showed biexponential blood clearance with alpha and beta half-lives of 0.32 and 10.95 h, respectively. The abdomen was scanned during surgery with a hand-held gamma detecting probe (Neoprobe Corp.). 125I-MFE-23-his showed good tumor localization; comparison with histology showed overall accuracy of 84%. Highest median ratios for tumor:normal tissue and tumor:blood were recorded 72 or 96 h after scFv injection for patients undergoing resection of liver metastases. High levels of radioactivity were found in the kidneys. Five patients had grade 1 fever, and three had a grade 1 rise in blood pressure according to the Common Toxicity Criteria. There was a significant correlation between these ratios and those measured in excised tissues using a laboratory gamma counter (P < 0.001). MFE-23-his scFv antibody localizes in CEA-producing carcinomas. The short interval between injection and operation, the lack of significant toxicity, and the relatively simple production in bacteria make MFE-23-his scFv suitable for RIGS.

Should air contrast computed tomography become the first investigation of the colon of frail or elderly patients?

OBJECTIVE: Air contrast computed tomography (ACCT) is an alternative test to barium enema or colonoscopy. We review our experience of this test as the first investigation of frail, elderly patients with lower gastrointestinal symptoms, and record the subsequent clinical course of these patients to evaluate the efficacy of the technique. PATIENTS AND METHODS: We performed 109 ACCT studies on frail patients aged 70 years or over with lower gastrointestinal symptoms. The findings were correlated with subsequent investigations and surgical findings. Patients with normal scans were followed up in out-patients or by their GP. Average follow up was 17 months. RESULTS: A good quality complete examination of the colon was achieved in 97% of patients. Of 109 examinations 34 (31%) were reported as normal, 65 (60%) as diverticular disease, nine (8%) as demonstrating a colonic malignancy and one (1%) showed a benign polyp. One sigmoid tumour was missed initially but diagnosed on a repeat ACCT study. CONCLUSION: ACCT is a reliable, well-tolerated technique in elderly frail patients.

Side-to-side stapled anastomosis may delay recurrence in Crohn's disease.

PURPOSE: Perianastomotic recurrence after resection in Crohn's disease may be related to ischemia and subacute obstruction at the anastomosis. A technique designed to minimize these factors currently is being evaluated. METHODS: From 1984 to 1997 69 patients underwent resection and primary anastomosis for symptomatic Crohn's disease (17 jejunal or ileal, 72 ileocolic, and 7 colocolic resections). Of these, 42 patients underwent functional end-to-end anastomoses with the use of linear cutting staplers (Proximate 75 mm or GIA 228 80 mm) and 27 patients underwent end-to-end sutured anastomoses. RESULTS: In the stapled anastomosis group one (2 percent) patient required reoperation for recurrent symptoms at 46 months. Complications occurred in four (8 percent) patients (one enterocutaneous fistula, one wound infection, one abscess, and one ileus). There were no anastomotic leaks. The median postoperative stay was seven (range, 5-26) days. In the sutured anastomosis group 14 (43 percent) patients required 15 further resections for symptomatic recurrence at a median of 46 (range, 4-91) months. Complications occurred in six (17 percent) patients (two anastomotic leaks, two fistulas, one stricture, and one pulmonary embolus). The median postoperative stay was 10 (range, 6-28) days. CONCLUSIONS: Functional end-to-end stapled anastomoses after resection for Crohn's disease may be associated with fewer complications than sutured anastomoses and may delay reoperation for symptomatic recurrence. Further evaluation of the technique is indicated.

Prospective randomized trial of Ivalon sponge versus sutured rectopexy for full-thickness rectal prolapse.

Ivalon sponge rectopexy is a safe reliable procedure in the management of rectal prolapse. Sutured rectopexy is simpler and avoids the use of foreign material. Sutured rectopexy is mandatory if synchronous resection is to be considered. Sixty-three patients (62 women) with full-thickness rectal prolapse were entered into a prospective randomized trial of Ivalon sponge rectopexy (31 patients) versus sutured rectopexy (32). Twenty patients (32 per cent) had coexistent incontinence (ten in each group). The operation was performed in the standard manner with a sutured rectangle of sponge or sutures alone placed along the length of the sacrum. Postoperative morbidity occurred in nine patients (14 per cent) of whom three underwent a sutured procedure and six Ivalon rectopexy: wound infection in three, chest infection in two, urinary tract infection in two and thromboembolism in two. There were no deaths within 30 days. At a median follow-up of 47 months prolapse had recurred in two patients (3 per cent), one in each group, 14 (22 per cent) suffered from incontinence (of whom five had undergone a sutured procedure), while 25 (40 per cent) had developed constipation (of whom 15 had received Ivalon rectopexy). The medium-term results of rectopexy by suture alone are equivalent to those obtained following the conventional Ivalon procedure. These data suggest that Ivalon rectopexy could now be abandoned.

Long-term results of large-dose, single-session phenol injection sclerotherapy for hemorrhoids.

PURPOSE: The aim of our study was to assess the medium to long-term outcome following single session large dose injection sclerotherapy for symptomatic hemorrhoids. METHODS: One hundred eighty-nine patients (male = 106, female = 83, median age, 51; range, 20-85 years) were assessed following single-session, large-dose (3 x 5 ml) phenol injection therapy. The most frequent complaint was bleeding (100 percent). RESULTS: At four-year follow-up, 53 patients (28.0 percent) were cured, 26 (13.7 percent) were improved, 35 (18.5 percent) remained unchanged, 59 (31.2 percent) deteriorated, and 16 (8.5 percent) required surgical intervention. Among the patients who were not cured, symptoms were minimal in 50 percent. Sclerotherapy was associated with a reduced incidence of bleeding (P < 0.05) but an increase in difficulty in perineal cleaning was observed (P < 0.05). CONCLUSION: Large-dose, single-session sclerotherapy provides only short-term benefits in the majority of patients with symptomatic hemorrhoids.

Crohn's disease and anastomotic recurrence: microvascular ischaemia and anastomotic healing in an animal model.

Microvascular injury and ischaemia may be factors in anastomotic recurrence after resection for Crohn's disease. This hypothesis was explored in a ferret model of multifocal intestinal infarction. At laparotomy, isolated loops of small intestine were injected intraarterially with styrene microspheres (test loop) or saline (control). At a second laparotomy 72 h later, test and control loops were divided and an end-to-end anastomosis performed between test loops (n = 2), test and control loops (n = 9) or control loops (n = 2). Abnormalities including chronic transmural inflammation, ulceration and granuloma formation were identified 2 weeks after the second operation in ten of the 11 surviving animals; changes were confined to the test loops and were more prominent adjacent to the anastomosis. No abnormalities were seen in control loops. The combination of two self-limiting ischaemic insults can produce a pattern of intestinal inflammation similar to that seen in anastomotic recurrence in Crohn's disease.

Granulomatous vasculitis in Crohn's disease.

This study investigated a possible vascular origin for granulomas in Crohn's disease. Twenty-four consecutive resected specimens of small and large intestinal Crohn's disease were preserved by arterial perfusion-fixation with 10% formol saline, at mean arterial pressure (100 mm Hg). Fifteen specimens contained granulomas on routine examination of H&E-stained sections. These 15 specimens were examined in detail using a range of immunohistochemical staining techniques to identify vascular structures and granulomas. A total of 485 granulomas were found, 85% of which were identified as being directly involved in vascular injury. The majority (77%) of granulomas were deep to the mucosa; they were found most frequently in the submucosa (42%). The techniques used in this study enhanced the recognition of granulomatous vasculitis. The results suggest that the majority of granulomas in Crohn's disease form within walls of blood vessels. Vascular localization of granulomatous inflammation suggests that the intestinal microvasculature contains an early element in the pathogenesis of Crohn's disease.

Pathogenesis of Crohn's disease: multifocal gastrointestinal infarction.

In a prospective study, specimens of resected small and large intestine from fifteen patients with Crohn's disease were prepared by heparin-saline vascular perfusion, followed by either resin casting of the mesenteric vascular supply and tissue maceration or glutaraldehyde perfusion-fixation, resin casting, and tissue clearance. The specimens were examined by macrophotography, histopathology, and either scanning or transmission electronmicroscopy. A pathogenetic sequence of events in Crohn's disease was seen--vascular injury, focal arteritis, fibrin deposition, arterial occlusion mainly at the level of the muscularis propria, followed by tissue infarction or neovascularisation. These features were confined to segments of intestine affected by Crohn's disease and did not occur in normal bowel. The findings suggest that Crohn's disease is mediated by multifocal gastrointestinal infarction. This pathogenetic process is compatible with many of the clinical features of Crohn's disease, and its recognition has important implications for the identification of the primary cause of the illness and advances in clinical management.

Measurement of cell kinetics in human tumours in vivo using bromodeoxyuridine incorporation and flow cytometry.

The proliferative potential of human solid tumours, in vivo, was investigated using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry (FCM). Patients with solid tumours from a variety of sites were injected with 500 mg BrdUrd, intravenously, several hours prior to biopsy or surgical excision. The labelling index (LI), duration of S-phase (Ts) and thus the potential doubling time (Tpot) could be measured within 24 h of sampling. The results show that both the LI and Ts vary greatly between tumours (Ts ranges from 5.8 to 30.7 h). However, within this study of 26 evaluable patients, tumours of the same tissue origin tended to have similar Ts values. Melanomas had the shortest Ts (8.8 h), nine patients with head and neck cancer had Ts values ranging from 5.8 to 18.8 h (median 12.5 h). The longest Ts values (24 h) were found in lung and rectum. The estimates of Tpot ranged from only 3.2 days in an oat cell carcinoma to 23.2 days in a lymphoma. The striking feature of the study was that 38% of the tumours had a potential doubling time of 5 days or less. We found no relationship between proliferation and histopathological differentiation or DNA ploidy. It should now be possible to assess the prognostic significance of pretreatment cell kinetic measurements which may, in the future, aid in the selection of treatment schedules for the individual patient.

Resection for colorectal cancer in the very old: are the risks too high?

Altogether 277 consecutive patients aged 70 or more who were admitted for resection of colorectal cancer between 1975 and 1985 were studied. The postoperative complications and mortality in the 175 patients aged 70-79 were compared with those in the 102 patients aged 80 or more. The overall mortality was 11%. Mortality was significantly higher after resection in the older age group even when deaths from widespread malignancy were excluded from the analysis. After curative resection mortality was 2% (2/120) in the younger group and 7% (4/60) in the older group, but after palliative resection of tumours with local or distant spread mortality was significantly higher, at 21% (9/44) and 38% (12/32), respectively. An equal but high proportion of patients in both age groups suffered major complications, but complications caused significantly more deaths in the older group. The length of stay in hospital was not significantly different between the age groups. Patients should not be denied resection of a colorectal cancer because of age alone, especially if a curative operation is possible. The increased risk of death from major complications, particularly after palliative resection, should, however, be taken into account when an operation on patients over 80 is being considered.