To evaluate the perspective of gastroenterologists regarding the impact of fecal calprotectin (FC) on the management of patients with inflammatory bowel disease (IBD).
Patients with known IBD or symptoms suggestive of IBD for whom the physician identified that FC would be clinically useful were recruited. Physicians completed an online “pre survey” outlining their rationale for the test. After receipt of the test results, the physicians completed an online “post survey” to portray their perceived impact of the test result on patient management. Clinical outcomes for a subset of patients with follow-up data available beyond the completion of the “post survey” were collected and analyzed.
Of 373 test kits distributed, 290 were returned, resulting in 279 fully completed surveys. One hundred and ninety patients were known to have IBD; 147 (77%) with Crohn’s Disease, 43 (21%) Ulcerative Colitis and 5 (2%) IBD unclassified. Indications for FC testing included: 90 (32.2%) to differentiate a new diagnosis of IBD from Irritable Bowel Syndrome (IBS), 85 (30.5%) to distinguish symptoms of IBS from IBD in those known to have IBD and 104 (37.2%) as an objective measure of inflammation. FC levels resulted in a change in management 51.3% (143/279) of the time which included a significant reduction in the number of colonoscopies (118) performed (P < 0.001). Overall, 97.5% (272/279) of the time, the physicians found the test sufficiently useful that they would order it again in similar situations. Follow-up data was available for 172 patients with further support for the clinical utility of FC provided.
The FC test effected a change in management 51.3% of the time and receipt of the result was associated with a reduction in the number of colonoscopies performed.
Inflammatory bowel disease; Biomarkers; Fecal calprotectin; Colonoscopy; Physician perspective
Vedolizumab, an α4β7-integrin antagonist, is the first gut-selective monoclonal antibody that has been approved for the treatment of moderate-to-severe ulcerative colitis and Crohn’s disease in many countries in the world. However, questions still remain regarding its appropriate use and placement in current treatment algorithms. Therefore, we sought out to evaluate the existing literature on the use of vedolizumab in inflammatory bowel disease. From inception to 21 June 2015 we searched MEDLINE for phase III randomized control trials assessing the utility of vedolizumab in inflammatory bowel disease, of which three were identified. The GEMINI trials demonstrate that vedolizumab is an effective and safe treatment for patients suffering from moderate-to-severe ulcerative colitis (GEMINI I) and Crohn’s disease (GEMINI II and III). However, further studies are needed comparing its efficacy directly with anti-tumor necrosis factor therapies to allow for further delineation of current treatment algorithms as well as ensuring its long-term safety profile.
IBD; inflammatory bowel disease; integrins
Although endoscopy represents the gold-standard method for objective monitoring of disease extent and severity in inflammatory bowel disease, it is not always practical or feasible. This has prompted and driven the search for reliable surrogate biomarkers to assess inflammatory burden in the gut. Fecal calprotectin meets many of the criteria for ideal biomarkers for patients with the condition, and exceeds the sensitivity and specificity of traditional blood-based biomarkers. This article addresses several relevant questions regarding its use and the interpretation of test results.
Objective monitoring of the severity of inflammation in patients with inflammatory bowel disease (IBD) is an essential part of disease management. However, repeat endoscopy to define extent and severity of inflammation is not practical. Fecal calprotectin (FC) is a biomarker that can be used as a surrogate test to distinguish inflammatory from noninflammatory gastrointestinal disease.
A targeted search of the literature regarding FC, focusing primarily on the past three years, was conducted to develop practical clinical guidance on the current utility of FC in the routine management of IBD patients.
It is recommended that samples for FC testing be obtained from the first bowel excretion of the day. FC testing should be used as standard of care to accurately confirm inflammation and ‘real-time’ disease activity when a clinician suspects an IBD flare. Although FC is a reliable marker of inflammation, its role in routine monitoring in improving long-term outcomes has not yet been fully assessed. Based on available evidence, the authors suggest the following cut-off values and management strategies: when FC levels are <50 μg/g to 100 μg/g, quiescent disease is likely and therapy should be continued; when FC levels are >100 μg/g to 250 μg/g, inflammation is possible and further testing (eg, colonoscopy) is required to confirm inflammation; and when FC levels are >250 μg/g, active inflammation is likely and strategies to control inflammation should be initiated (eg, optimizing current therapies or switching to an alternative therapy).
FC is a useful biomarker to accurately assess the degree of inflammation and should be incorporated into the management of patients with IBD.
Disease activity; Fecal calprotectin; Inflammatory bowel disease; Monitoring
Background. Infliximab (IFX) therapeutic drug monitoring (TDM) allows for objective decision making in patients with inflammatory bowel disease (IBD) and loss of response. Questions remain about whether IFX TDM improves outcomes. Methods. Patients with IBD who had IFX TDM due to concerns for loss of response were considered for inclusion. Serum IFX trough concentration and anti-drug antibody (ADA) concentrations were measured. Patients were grouped by TDM results: group 1, low IFX/high ADA; group 2, low IFX/low ADA; group 3, therapeutic IFX. Changes in management were analyzed according to groupings; remission rates were assessed at 6 months. Results. 71 patients were included of whom 37% underwent an appropriate change in therapy. Groups 1 (67%) and 2 (83%) had high adherence compared to only 9% in group 3. At 6 months, 57% had achieved remission. More patients who underwent an appropriate change in therapy achieved remission, though this did not reach statistical significance (69% versus 49%; P = 0.098). Conclusions. A trend towards increased remission rates was associated with appropriate changes in management following TDM results. Many patients with therapeutic IFX concentrations did not undergo an appropriate change in management, potentially reflecting a lack of available out-of-class options at the time of TDM or due to uncertainty of the meaning of the reported therapeutic range.
Computed tomography (CT) scans are commonly used to diagnose acute diverticulitis, but there are overlapping features between diverticulitis and colorectal cancer (CRC) on imaging studies. Hence, colonoscopy is typically recommended after an episode of acute diverticulitis to rule out underlying malignancy. Currently, 64-slice multidetector CT scanners are capable of providing higher-resolution images and may be able to distinguish malignancy from diverticular inflammation. We aimed to determine the prevalence of CRC among patients with CT-diagnosed acute diverticulitis.
We performed a retrospective study of patients with acute diverticulitis diagnosed on CT scan between December 2005 and December 2010 at St. Paul’s Hospital, Vancouver, BC. Nonresidents were excluded. We reviewed CT scan reports that included the term “diverticulitis,” reports of follow-up colonic evaluation within 1 year of diagnosis and pathology results. We queried the provincial cancer registry to ensure no cases of CRC were missed.
A total of 293 patients had acute diverticulitis diagnosed on CT scan, but 8 were nonresidents and were excluded. Of the 285 included in the analysis, the mean age was 59.4 ± 15.1 years, and 167 (58.6%) were men. Among the 114 patients who underwent follow-up evaluation, malignancy was diagnosed in 4 (3.5%). The overall prevalence of malignancy among patients with CT-diagnosed diverticulitis was 1.4%.
Routine endoscopic evaluation after an episode of diverticulitis diagnosed with high-resolution CT scan does not appear to be necessary. Selective approach in patients with protracted clinical course or those with mass lesion/obstruction on CT scan may be of benefit.
We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn's disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously every second day, for a minimum of 2.5 months and a maximum of 11 months. All 10 patients reported improvement of symptoms while on the SSI QBECO treatment. Seven patients reported full resolution of clinical symptoms during a course of SSI QBECO of at least three months. Three patients have experienced ongoing sustained clinical remission after discontinuing all medications, including SSI treatment. The longest case of clinical remission is still ongoing (>4 years). No serious severe adverse clinical events were reported. Collectively, we conclude that treatment with the immunoactive SSI QBECO was well tolerated and effective for treatment of Crohn's disease in this case series.
According to a recent estimate, the direct medical costs of inflammatory bowel disease (IBD) in Canada exceed $1 billion annually. In addition, notable gaps between ideal and actual IBD care were exposed, as was the variability in prescription drug benefit plans and access to services across the provinces. The authors of this article identified 11 quality indicators reflective of the evidence base and expert opinion, and define the minimum that should be expected for IBD management.
There is a paucity of published data regarding the quality of care of inflammatory bowel disease (IBD) in Canada. Clinical quality indicators are quantitative end points used to guide, monitor and improve the quality of patient care. In Canada, where universal health care can vary significantly among provinces, quality indicators can be used to identify potential gaps in the delivery of IBD care and standardize the approach to interprovincial management.
The Emerging Practice in IBD Collaborative (EPIC) group generated a shortlist of IBD quality indicators based on a comprehensive literature review. An iterative voting process was used to select quality indicators to take forward. In a face-to-face meeting with the EPIC group, available evidence to support each quality indicator was presented by the EPIC member aligned to it, followed by group discussion to agree on the wording of the statements. The selected quality indicators were then ratified in a final vote by all EPIC members.
Eleven quality indicators for the management of IBD within the single-payer health care system of Canada were developed. These focus on accurate diagnosis, appropriate and timely management, disease monitoring, and prevention or treatment of complications of IBD or its therapy.
These quality indicators are measurable, reflective of the evidence base and expert opinion, and define a standard of care that is at least a minimum that should be expected for IBD management in Canada. The next steps for the EPIC group involve conducting research to assess current practice across Canada as it pertains to these quality indicators and to measure the impact of each of these indicators on patient outcomes.
Canada; Crohn disease; Delivery of health care; Process assessment; Quality indicators; Ulcerative colitis
Ulcerative colitis (UC)-associated pan-enteritis is a newly identified clinical entity that occurs almost exclusively after colectomy. Characterized by diffuse small bowel mucosal inflammation not compatible with Crohn's disease, the optimal treatment modality for this condition is unknown. Tacrolimus is a potent calcineurin inhibitor that has been successfully used in the treatment of UC. We describe a case of severe refractory pan-enteritis after colectomy for UC that was successfully treated with oral tacrolimus after failing intravenous corticosteroid treatment. Tacrolimus may be a safe and effective treatment modality for diffuse enteritis after colectomy in UC patients.
AIM: To evaluate the impact of medical therapy on Crohn’s disease patients undergoing their first surgical resection.
METHODS: We retrospectively evaluated all patients with Crohn’s disease undergoing their first surgical resection between years 1995 to 2000 and 2005 to 2010 at a tertiary academic hospital (St. Paul’s Hospital, Vancouver, Canada). Patients were identified from hospital administrative database using the International Classification of Diseases 9 codes. Patients’ hospital and available outpatient clinic records were independently reviewed and pertinent data were extracted. We explored relationships among time from disease diagnosis to surgery, patient phenotypes, medication usage, length of small bowel resected, surgical complications, and duration of hospital stay.
RESULTS: Total of 199 patients were included; 85 from years 1995 to 2000 (cohort A) and 114 from years 2005 to 2010 (cohort B). Compared to cohort A, cohort B had more patients on immunomodulators (cohort A vs cohort B: 21.4% vs 56.1%, P < 0.0001) and less patients on 5-aminosalysilic acid (53.6% vs 29.8%, P = 0.001). There was a shift from inflammatory to stricturing and penetrating phenotypes (B1/B2/B3 38.8% vs 12.3%, 31.8% vs 45.6%, 29.4% vs 42.1%, P < 0.0001). Both groups had similar median time to surgery. Within cohort B, 38 patients (33.3%) received anti-tumor necrosis factor (TNF) agent. No patient in cohort A was exposed to anti-TNF agent. Compared to patients not on anti-TNF agent, ones exposed were younger at diagnosis (anti-TNF vs without anti-TNF: A1/A2/A3 39.5% vs 11.8%, 50% vs 73.7%, 10.5% vs 14.5%, P = 0.003) and had longer median time to surgery (90 mo vs 48 mo, P = 0.02). Combination therapy further extended median time to surgery. Using time-dependent multivariate Cox proportional hazard model, patients who were treated with anti-TNF agents had a significantly higher risk to surgery (adjusted hazard ratio 3.57, 95%CI: 1.98-6.44, P < 0.0001) compared to those without while controlling for gender, disease phenotype, smoking status, and immunomodulator use.
CONCLUSION: Significant changes in patient phenotypes and medication exposures were observed between the two surgical cohorts separated by a decade.
Crohn’s disease; Surgery; Medication; Phenotype; Biologics; Anti-tumor necrosis factor; Immunomodulators; Inflammatory bowel disease
Endoscopic hemostasis is widely regarded as the primary objective in cases of nonvariceal upper gastrointestinal bleeding. However, although conventional modalities incorporating mechanical and thermal techniques have proven efficacy in a significant proportion of patients, rebleeding still occurs in a clinically significant number of cases. Therefore, alternative methods to achieve endoscopic hemostasis are being explored. This study evaluated a commercially available spray that achieves hemostasis by adhering to the bleeding site and promoting thrombus formation, and may be used as a temporary measure or a bridge toward more definitive therapy.
Hemospray (Cook Medical, USA) has recently been approved in Canada for the management of nonvariceal upper gastrointestional bleeding (UGIB).
To review the authors’ experience with the safety and efficacy of Hemospray for treating UGIB.
A retrospective chart review was performed on patients who required endoscopic evaluation for suspected UGIB and were treated with Hemospray.
From February 2012 to July 2013, 19 patients (mean age 67.6 years) with UGIB were treated with Hemospray. A bleeding lesion was identified in the esophagus in one (5.3%) patient, the stomach in five (26.3%) and duodenum in 13 (68.4%). Bleeding was secondary to peptic ulcers in 12 (63.2%) patients, Dieulafoy lesions in two (10.5%), mucosal erosion in one (5.3%), angiodysplastic lesions in one (5.3%), ampullectomy in one (5.3%), polypectomy in one (5.3%) and an unidentified lesion in one (5.3%). The lesions showed spurting hemorrhage in four (21.1%) patients, oozing hemorrhage in 11 (57.9%) and no active bleeding in four (21.1%). Hemospray was administered as monotherapy in two (10.5%) patients, first-line modality in one (5.3%) and rescue modality in 16 (84.2%). Hemospray was applied prophylactically to nonbleeding lesions in four (21.1%) patients and therapeutically to bleeding lesions in 15 (78.9%). Acute hemostasis was achieved in 14 of 15 (93.3%) patients. Rebleeding within seven days occurred in seven of 18 (38.9%) patients. Potential adverse events occurred in two (10.5%) patients and included visceral perforation and splenic infarct. Mortality occurred in five (26.3%) patients but the cause of death was unrelated to gastrointestinal bleeding with the exception of one patient who developed hemoperitoneum.
The high rates of both acute hemostasis and recurrent bleeding suggest that Hemospray may be used in high-risk cases as a temporary measure or a bridge toward more definitive therapy.
Efficacy; Hemospray; Safety; Upper gastrointestinal bleeding
Despite a high prevalence of complementary alternative medicine (CAM) use among inflammatory bowel disease (IBD) patients, there is a dearth of information about the attitudes and perceptions of CAM among the gastroenterologists who treat these patients.
To characterize the beliefs, perceptions and practices of gastroenterologists toward CAM use in patients with IBD.
A web-based survey was sent to member gastroenterologists of the Canadian Association of Gastroenterology. The survey included multiple-choice and Likert scale questions that queried physician knowledge and perceptions of CAM and their willingness to discuss CAM with patients.
Fifty-three per cent of respondents considered themselves to be IBD subspecialists. The majority (86%) of gastroenterologists reported that less than one-half of their patient population had mentioned the use of CAM. Only 8% of physicians reported initiating a conversation about CAM in the majority of their patient encounters. Approximately one-half (51%) of respondents were comfortable with discussing CAM with their patients, with lack of knowledge being cited as the most common reason for discomfort with the topic. Most gastroenterologists (79%) reported no formal education in CAM. While there was uncertainty as to whether CAM interfered with conventional medications, most gastroenterologists believed it could be effective as an adjunct treatment.
Our findings demonstrate that gastroenterologists were hesitant to initiate discussions about CAM with patients. Nearly one-half were uncomfortable or only somewhat comfortable with the topic, and most may benefit from CAM educational programs. Interestingly, most respondents appeared to be receptive to CAM as adjunct therapy alongside conventional IBD treatment.
CAM; Complementary alternative medicine; Crohn disease; IBD; Inflammatory bowel disease; Ulcerative colitis
AIM: To evaluate the effect of experience on the accuracy rate of computed tomography colonography (CTC) interpretation and patient preferences/satisfaction for CTC and colonoscopy.
METHODS: A prospective, non-randomized, observational study performed in a single, tertiary care center involving 90 adults who underwent CTC followed by colonoscopy on the same day. CTC was interpreted by an abdominal imaging radiologist and then a colonoscopy was performed utilizing segmental un-blinding and re-examination as required. A radiology resident and two gastroenterology (GI) fellows blinded to the results also interpreted the CTC datasets independently. Accuracy rates and trend changes were determined for each reader to assess for a learning curve.
RESULTS: Among 90 patients (57% male) aged 55 ± 8.9 years, 39 polyps ≥ 6 mm were detected in 20 patients and 13 polyps > 9 mm in 10 patients. Accuracy rates were 88.9% (≥ 6 mm) and 93.3% (> 9 mm) for the GI Radiologist, 89.8% (≥ 6 mm) and 98.9% (> 9 mm) for the Radiology Resident and 86.7% and 95.6% (≥ 6 mm) and 87.8% and 94.4% (> 9 mm) for each of the GI fellows respectively. The reader’s accuracy rate did not change significantly with the percentage change rate ranging between -1.7 to 0.9 (P = 0.12 to 0.56). Patients considered colonoscopy more satisfactory than CTC (30% vs 4%, P < 0.0001), they felt less anxiety during colonoscopy (36% vs 7%, P < 0.0001), they experienced less pain or discomfort during colonoscopy compared to CTC (69% vs 4%, P < 0.0001) and colonoscopy was preferred by 77% of the participants as a repeat screening test for the future.
CONCLUSION: No statistically significant learning curve was identified in CTC interpretation suggesting that further study is required to identify the necessary training to adequately interpret CTC scans.
Computed tomography colonography; Colonoscopy; Colorectal neoplasia; Colorectal cancer screening
AIM: To determine if early initiation of anti-tumor necrosis factor therapy affects the need for dose escalation.
METHODS: This was a retrospective review of patients receiving infliximab therapy for Crohn’s disease (CD) at two outpatient gastroenterology clinics during July 2009 to October 2010. All patients included in the study were biologic agent naïve and had moderate to severe CD (Harvey Bradshaw index > 8). Patients were divided into groups based on length of time between diagnosis to therapy initiation and concurrent immunosuppressant therapy. Kaplan-Meier survival analysis was used to compare the time to dose escalation for the four groups.
RESULTS: There were 68 patients, 51% female and 49% male, with an average age at diagnosis of 24.7 ± 11.9 years. The average age at infliximab initiation was 34.8 ± 14.8 years. Of the 68 patients, 19% initiated inflixiamb within 2 years of diagnosis, and 51% had concurrent immunosuppressant therapy at the time of therapy initiation. Fifty percent of patients required dose escalation and the median time from therapy initiation to dose escalation was 10 mo (interquartile range: 5.3-14.8). There was a statistically significant higher probability of requiring dose esclataion in patients who initiated biologic therapy within 2 years of diagnosis, without concurrent immunosuppressant therapy (P < 0.01).
CONCLUSION: Those who receive infliximab within 2 years of CD diagnosis require more intense immunosuppressant therapy than those who received infliximab later.
Crohn’s disease; Infliximab; Dose escalation
Elevation of liver biochemistry has been reported with anti-tumor necrosis factor agents, but overt liver failure rarely reported. Autoimmune hepatitis has been more commonly reported with infliximab than adalimumab (ADA). Our case, however, describes the first reported case of ADA-associated severe cholestatic injury. A 39-year-old female with Crohn’s disease developed severe jaundice after initiation of ADA. All serologic tests and imaging studies were normal. Liver biopsy showed prominent pericentral canalicular cholestasis, without features of steatosis or sclerosing cholangitis, consistent with drug-induced cholestasis. The serum total bilirubin peaked at 280 μmol/L, and improvement was seen after 5 wk with eventual normalization of liver enzymes at 10 wk. Our case describes the first reported case of ADA-associated severe cholestatic liver disease and the first histopathologic examination of this adverse drug effect. Clinicians need to be aware of this potential drug-induced liver injury when prescribing this commonly used biologic medication.
Crohn’s disease; Cholestasis; Adalimumab; Anti-tumor necrosis factor agents; Drug-induced liver injury
Adalimumab is a human monoclonal antibody against tumour necrosis factor-alpha that has been associated with acute lung toxicity, mainly in patients with rheumatoid arthritis. Descriptions of similar patterns of lung injury in patients treated with adalimumab for inflammatory bowel disease are emerging in the literature. A case involving a 45-year-old man with Crohn’s disease who developed a nonbronchiolitis inflammatory nodular pattern of lung injury after starting adalimumab is reported.
Acute drug reaction; Adalimumab; Antitumour necrosis factor-alpha; Drug-induced lung disease; Drug-induced lung toxicity; Interstitial lung disease
Mycobacterium avium paratuberculosis (MAP) is an obligate intracellular organism that has frequently been associated with Crohn’s disease (CD). Because CD is a chronic inflammatory condition, many researchers have speculated that an infectious agent must be the cause of CD. MAP has often been proposed to be one such agent; however, despite considerable research, the evidence remains inconclusive. Higher levels of MAP have been found in the tissues and blood of CD patients than in controls, forming the foundation for much of the research into the role of MAP in CD and the primary argument in support of a causative role for MAP in CD. MAP is a slow-growing and fastidious organism that is difficult to grow in culture and, therefore, challenging to detect in patients. As a result, there has been variability in the results of studies attempting to detect the presence of MAP in CD patients, and considerable controversy over whether this organism has a causative role in the etiology of CD. Two main hypotheses exist with respect to the role of MAP in CD. The first is that MAP is a principal cause of CD, while the second is that MAP is more prevalent because of the immune dysfunction seen in CD but does not play a causative role. Clinicians are often faced with questions regarding the role of this organism and the need to treat it. The present article attempts to provide an overview of the controversy including the nature of the mycobacterium, the difficulty in detecting it, the use of antimycobacterial agents to treat it and the effect of immunosuppressive agents – all from a clinician’s perspective. Although the role of MAP in CD remains controversial and an area of considerable research, it is currently only of academic interest because there is no clinically useful test to identify the presence of the organism, and no evidence to support the use of antibiotics to eradicate it for the treatment of CD.
Crohn’s disease; Infliximab; Mycobacterium avium paratuberculosis
For patients requiring colonoscopy while admitted to hospital, achieving adequate cleansing of the colon is often difficult.
To assess the impact of patient education, in the form of both counselling and written instructions, on bowel cleanliness at colonoscopy.
A total of 38 inpatients at a tertiary care hospital in Vancouver, British Columbia, who were referred to the gastroenterology service for colonoscopy were enrolled in the present study. Sixteen patients were randomly assigned to the intervention group, while 22 patients comprised the control group. Both groups received a clear liquid diet and 4 L of a commercially available bowel preparation. The intervention group also received a brief counselling session and written instructions outlining the methods and rationale for bowel preparation before colonoscopy. Bowel cleanliness was assessed by the endoscopist using a five-point rating scale.
The two groups were similar with respect to demographics, the indication for colonoscopy and findings at colonoscopy. The median bowel cleanliness scores in the control group and the enhanced-instruction group were 3.0 and 2.0, respectively (P=0.001).
Patient counselling and written instructions are inexpensive, safe and simple interventions. Such interventions are an effective means of optimizing colonoscopy preparation in the inpatient setting.
Bowel preparation; Colonoscopy; Inpatients
Recent concerns have been raised about the risk of gallbladder disease associated with the use of drospirenone, a fourth-generation progestin used in oral contraceptives. We conducted a study to determine the magnitude of this risk compared with other formulations of oral contraceptives.
We conducted a retrospective cohort study using the IMS LifeLink Health Plan Claims Database. We included women who were using an oral contraceptive containing ethinyl estradiol combined with a progestin during 1997–2009. To be eligible, women had to have been taking the oral contraceptive continuously for at least six months. We computed adjusted rate ratios (RRs) for gallbladder disease using a Cox proportional hazards model. In the primary analysis, gallbladder disease was defined as cholecystectomy; in a secondary analysis, it was defined as hospital admission secondary to gallbladder disease.
We included 2 721 014 women in the cohort, 27 087 of whom underwent surgical or laparoscopic cholecystectomy during the follow-up period. Compared with levonorgestrel, an older second-generation progestin, a small, statistically significant increase in the risk of gallbladder disease was associated with desogestrel (adjusted RR 1.05, 95% confidence interval [CI] 1.01–1.09), drospirenone (adjusted RR 1.20, 95% CI 1.16–1.26) and norethindrone (adjusted RR 1.10, 95% CI 1.06–1.14). No statistically significant increase in risk was associated with the other formulations of oral contraceptive (ethynodiol diacetate, norgestrel and norgestimate).
In a large cohort of women using oral contraceptives, we found a small, statistically significant increase in the risk of gallbladder disease associated with desogestrel, drospirenone and norethindrone compared with levonorgestrel. However, the small effect sizes compounded with the possibility of residual biases in this observational study make it unlikely that these differences are clinically significant.
Postpolypectomy bleeding and perforation are the most common complications of colonoscopy. A case of acute pancreatitis and ileus after colonoscopy is described. A 60-year-old woman underwent a gastroscopy and colonoscopy for investigation of iron deficiency anemia. Gastroscopy was normal; however, the colonoscope could not be advanced beyond the splenic flexure due to a tight angulation. Two polypectomies were performed in the descending colon. After the procedure, the patient developed a distended, tender abdomen. Bloodwork was remarkable for an elevated amylase level. An abdominal x-ray and computed tomography scan showed pancreatitis (particularly of the tail), a dilated cecum and a few air-fluid levels. The patient improved within 24 h of a repeat colonoscopy and decompression tube placement. The patient had no risk factors for pancreatitis. The causal mechanism of pancreatitis was uncertain but likely involved trauma to the tail of the pancreas during the procedure. Our patient developed ileus, likely secondary to pancreatitis. The present case is the first report of clinical pancreatitis and ileus associated with colonoscopy.
Colonoscopy; Ileus; Pancreatitis
To evaluate whether higher doses of peginterferon α-2a (40KD) [PEG-IFN α-2a (40KD)] can compensate for lower exposure observed among obese patients with chronic hepatitis C (CHC) treated with the standard dose of PEG-IFN α-2a (40KD).
Noncirrhotic, obese (body mass index ≥30 kg m−2) patients with CHC participated in a single-centre, open-label study. Patients were randomized to 180 or 270 µg week−1 PEG-IFN α-2a (40KD) + ribavirin (1000/1200 mg day−1) for 48 weeks. Blood samples were collected predose and up to 168 h after the first dose and at week 12 for pharmacokinetic analysis. Trough serum concentrations (Ctrough) were determined up to week 24.
In the 180 µg week−1 group mean ± SD steady-state (week 12) estimates of AUC0–168 (ng h−1 ml−1), Cmax (ng ml−1) and CL/F (l h−1) were 2154 ± 919, 13.8 ± 6.7 and 0.102 ± 0.051, respectively. In the 270 µg week−1 group, estimates were 3374 ± 1844, 23.4 ± 10.7 and 0.090 ± 0.042, respectively. The mean (range) Ctrough (ng ml−1) was 11.2 (4.4–18.5) in the 180 µg week−1 group and 16.1 (0.4–44.2) in the 270 µg week−1 group. Overall, 14 of 20 (70%) and 16 of 20 (80%) patients in the 180 µg week−1 and 270 µg week−1 groups were infected with hepatitis C virus genotype 1 or 4. In the 180 µg week−1 and 270 µg week−1 groups 14 of 20 (70%) and 15 of 19 (79%) patients, respectively, achieved a sustained viral response. Safety was similar between groups.
Mean PEG-IFN α-2a (40KD) exposure was dose proportional from 180 to 270 µg week−1. Increasing PEG-IFN α-2a (40KD) from 180 to 270 µg week−1 achieves higher serum drug exposure in obese patients.
CHC; hepatitis; obesity; peginterferon alfa