Serious events in older Ontario residents receiving bowel preparations for outpatient colonoscopy with various comorbidity profiles: a descriptive, population-based study

BACKGROUND:

Polyethylene glycol-based bowel preparations (PEGBPs) and sodium picosulfate (NaPS) are commonly used for bowel cleansing before colonoscopy. Little is known about adverse events associated with these preparations, particularly in older patients or patients with medical comorbidities.

OBJECTIVE:

To characterize the incidence of serious events following outpatient colonoscopy in patients using PEGBPs or NaPS.

METHODS:

The present population-based retrospective cohort study examined data from Ontario health care databases between April 1, 2005 and December 31, 2007, including patients ≥66 years of age who received either PEGBP or NaPS for an outpatient colonoscopy. Patients with cardiac or renal disease, long-term care residents or patients receiving concurrent diuretic therapy were identified as high risk for adverse events. The primary outcome was a serious event (SE) defined as a composite of nonelective hospitalization, emergency department visit or death within seven days of the colonoscopy.

RESULTS:

Of the 50,660 outpatients ≥66 years of age who underwent a colonoscopy, SEs were observed in 675 (2.4%) and 543 (2.4%) patients in the PEGBP and NaPS groups, respectively. Among high-risk patients (n=30,168), SEs occurred in 481 (2.8%) and 367 (2.8%) of patients receiving PEGBP and NaPS, respectively.

CONCLUSIONS:

The SE rate within seven days of outpatient colonoscopy was 24 per 1000 procedures, and among high-risk patients was 28 per 1000 procedures. The rates were similar for PEGBP and NaPS. Clinicians should be aware of the risks associated with colonoscopy in older patients with comorbidities.     

Management of perforation due to colonoscopy

Six patients who underwent emergency laparotomy for perforations secondary to colonoscopy or polypectomy are described. Three patients had the laceration closed primary, two required colostomy, and one needed resection. When contamination is minimal and the colon is mechanically prepared, primary closure without diversion is the treatment of choice. Colostomy is rarely indicated and may lead to increased morbidity, in view of the need for closure. However, resection should be considered if suspicion of carcinoma is great. Factors that contribute to perforation include sedation, forceful introduction of the colonoscope, inadequate equipment for hemorrhage control, and prolonged application of electrocoagulation to the colonic wall. The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the view of the Navy Department or the Naval service at large.     

Post-polypectomy bleeding after colonoscopy on uninterrupted aspirin/non steroideal antiflammatory drugs: Systematic review and meta-analysis

Background and aimThe aim of this systematic review and meta-analysis was to assess the risk of post-polypectomy bleeding (PPB) in patients that underwent colorectal polypectomy and exposed to ASA/NSAIDs.MethodsRelevant publications were identified in MEDLINE/EMBASE for the period 1950–2016. Studies with specified ASA/NSAIDs exposure and bleeding rate were included. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was based on fixed or random effect models in relation to the heterogeneity.Results11 studies (4 prospective and 7 retrospective) including 9307 patients were included in the analyses. Overall, 344 patients (OR 1.8; 95% CI 1.2–2.7; p-value 0.001, I² 52%) experienced rectal bleeding after procedure. While the rate of immediate PPB on aspirin and/or NSAIDs was not increased (OR 1.1; CI 95% 0.6–2.1; d.f. = 1, p = 0.64, I² 0%), the risk of delayed PPB was augmented (OR 1.7; 95% CI 1.2–2.2; d.f. = 8, p = 0.127, I² 36%).ConclusionsASA/NSAIDs are not a risk factor for immediate PPB but the chance of delayed is increased.     

The prevalence of adverse events associated with double-balloon enteroscopy from a single-centre dataset in Japan

BackgroundThere are few comprehensive reports detailing the prevalence of major adverse events associated with a double-balloon enteroscopy procedure.MethodsWe retrospectively investigated the prevalence of major adverse events in 538 patients (262 males and 276 females; median age, 65 years; age range, 12–95 years) who underwent double-balloon enteroscopy at our Institution between April 2008 and October 2011.ResultsOf the 17 adverse events recorded (3.2%), acute pancreatitis (n = 5; 0.9%) occurred during both diagnostic (n = 3) and therapeutic (n = 2) anterograde double-balloon enteroscopy, and all of them were treated conservatively. For these cases, the average duration of the examination was 135 min, which was longer than for the other patients (97 min) (P = 0.046). Intestinal bleeding (1.3%) was observed in 6 cases after endoscopic polypectomy and in 1 case following a biopsy procedure during a diagnostic double-balloon enteroscopy. The prevalence rates of intestinal perforation and other complications were 0.2% and 0.7%, respectively.ConclusionsThe rate of adverse events associated with double-balloon enteroscopy was high compared to that associated with conventional upper/lower gastrointestinal endoscopy (0.042%/0.078%). The occurrence of acute pancreatitis may be significantly dependent on the duration of double-balloon enteroscopy examination.     

Adverse events with bismuth salts for Helicobacter pylori eradication： Systematic review and meta-analysis

AIM： To assess the safety of bismuth used in Helicobacter pylori （H pylorl） eradication therapy regimens. METHODS： We conducted a systematic review and meta-analysis. MEDLINE and EMBASE were searched （up to October 2007） to identify randomised controlled tri- als comparing bismuth with placebo or no treatment, or bismuth salts in combination with antibiotics as part of eradication therapy with the same dose and duration of antibiotics alone or, in combination, with acid suppresion. Total numbers of adverse events were recorded. Data were pooled and expressed as relative risks with 95% confidence intervals （CI）.RESULTS： We identified 35 randomised controlled trials containing 4763 patients. There were no serious adverse events occurring with bismuth therapy. There was no statistically significant difference detected in total adverse events with bismuth rrelative risk （RR） = 1.01; 95% CI： 0.87-1.16], specific individual adverse events, with the exception of dark stools （RR = 5.06; 95% CI： 1.59-16.12）, or adverse events leading to withdrawal of therapy （RR = 0.86; 95% CI： 0.54-1.37）. CONCLUSION： Bismuth for the treatment of H py/ori is safe and well-tolerated. The only adverse event occurring significantly more commonly was dark stools.     

Artificial intelligence-aided colonoscopy: Recent developments and future perspectives

Artificial intelligence (AI) systems, especially after the successful application of Convolutional Neural Networks, are revolutionizing modern medicine. Gastrointestinal Endoscopy has shown to be a fertile terrain for the development of AI systems aiming to aid endoscopists in various aspects of their daily activity. Lesion detection can be one of the two main aspects in which AI can increase diagnostic yield and abilities of endoscopists. In colonoscopy, it is well known that a substantial rate of missed neoplasia is still present, representing the major cause of interval cancer. In addition, an extremely high variability in adenoma detection rate, the main key quality indicator in colonoscopy, has been extensively reported. The other domain in which AI is believed to have a considerable impact on everyday clinical practice is lesion characterization and aid in “optical diagnosis”. By predicting in vivo histology, such pathology costs may be averted by the implementation of two separate but synergistic strategies, namely the “leave-in-situ” strategy for < 5 mm hyperplastic lesions in the rectosigmoid tract, and “resect and discard” for the other diminutive lesions. In this opinion review we present current available evidence regarding the role of AI in improving lesions’ detection and characterization during colonoscopy.     

Quality indicators for colonoscopy: Current insights and caveats

Colonoscopy is the diagnostic modality of choice for investigation of symptoms suspected to be related to the colon and for the detection of polyps and colorectal cancer(CRC). Colonoscopy with removal of detected polyps has been shown to reduce the incidence and mortality of subsequent CRC. In many countries, population screening programs for CRC have been initiated, either by selection of patients for colonoscopy with fecal occult blood testing or by offering colonoscopy directly to average-risk individuals. Several endoscopy societies have formulated quality indicators for colonoscopy. These quality indicators are almost always incorporated as process indicators, rather than outcome measures. This review focuses on the quality indicators bowel preparation, cecal intubation rate, withdrawal time, adenoma detection rate, patient comfort, sedation and complication rate, and discusses the scientific evidence supporting them,as well as their potential shortcomings and issues that need to be addressed. For instance, there is still no clear and generally accepted definition of adequatebowel preparation, no robust scientific evidence is available supporting a cecal intubation rate ≥ 90% and the association between withdrawal time and occurrence of interval cancers has not been clarified. Adenoma detection rate is currently the only quality indicator that has been shown to be associated with interval colorectal cancer, but as an indicator it does not differentiate between subjects with one or more adenoma detected.     

Biological treatment in rheumatic diseases: results from a longitudinal surveillance: adverse events

The objective of this study was to assess the long-term safety and tolerability of biologicals in a clinical setting. Data on adverse events (AEs) have been collected over a 5-year period by means of detailed reports sent in to the National Register of Biological Treatment in Finland (ROB-FIN) and validated by information collected by the National Agency for Medicines. Three hundred and eight reports on AEs were filed, concerning a total of 248 patients; this corresponds to 17% of all patients in the ROB-FIN register who started biological treatments. Skin reactions and infections comprised 35 and 28% of the AEs, respectively. Some cases of tuberculosis and other infections, heart failure and demyelinating conditions were seen. Our work demonstrates no unexpected AEs in a Finnish patient cohort consisting of rheumatoid arthritis and spondylarthropathy patients, although many of them were treated with combination treatments in common use in Finland. Biological treatment appears safe in the hands of the Finnish rheumatologists.     

Perforated Colon Secondary to Virtual Colonoscopy: Report of a Case

We describe a case of a perforated colon secondary to a virtual colonoscopy in an 81-year-old female with ulcerative colitis. She underwent an emergent right hemicolectomy. The pathologic findings were described as ulcerative colitis with full-thickness perforation. To the best of our knowledge, this is the first complication from a virtual colonoscopy reported in the literature.     

Adverse events of thiopurine immunomodulators in patients with inflammatory bowel disease

Background

Thiopurine immunomodulators are the most commonly used immunosuppressants in inflammatory bowel disease.

Aims

To evaluate the incidence of adverse events (AE) in patients with inflammatory bowel disease treated with azathioprine (AZA) or 6-mercaptopurine (MP) in our hospital, the features of these effects, the distribution of socio-demographic factors, and the possible predisposing factors.

Methods

We included 377 patients with inflammatory bowel disease who were diagnosed through 2008 and who received AZA or MP during the course of their disease. We collected retrospective demographic, clinical, and laboratory data about their disease and detailed information on any AE.

Results

Fifty-one patients had some form of AE with AZA or MP (13.5%) and 11% discontinued therapy because of toxicity. Statistically significant association with Crohn's disease was found (P = .008). Myelotoxicity occurred in 18 patients (4.8%) with a mean time of laboratory abnormalities appearing after 16 months. Nine patients had hepatotoxicity secondary to these drugs (2.4%); one of them developed nodular regenerative hyperplasia and portal hypertension. Ten patients had acute pancreatitis (2.7%) with a mean time occurrence of 27 days and a statistically significant association with Crohn's disease (P = .03) and smoking (P = .01). Fifteen patients had gastrointestinal intolerance (4%) but 5 were able to continue with medication given in divided doses or switching to MP.

Conclusions

Thiopurine immunomodulators have a significant percentage of AE (13.5%), which, although usually mild, forced us to follow up all cases and sometimes even suspend treatment.     

Discontinuation due to adverse events in randomized trials of orlistat, sibutramine and rimonabant: a meta-analysis

The objective of this article was to estimate the risk of discontinuation due to adverse events in trials of orlistat, sibutramine and rimonabant. Medline, EMBASE, the Cochrane controlled trials register and reference lists of identified articles were searched from 1990 to May 2008. All randomized placebo-controlled trials of 12–24 months of duration on adults using licensed doses were included. Studies/study arms were excluded if they evaluated weight maintenance after weight loss. Trials were identified, subjected to inclusion and exclusion criteria and reviewed. Data on participants, interventions and discontinuation were extracted and trials rated for quality based on established criteria. A random effects model was used to estimate pooled risk ratios, risk differences and number needed to harm (NNH). A total of 28 trials met the inclusion criteria (16 orlistat, 7 sibutramine and 5 rimonabant). The risk ratios for discontinuation due to adverse events were significantly elevated for rimonabant (2.00; 1.66–2.41) and orlistat (1.59; 1.21–2.08), but not sibutramine (0.98, 0.68–1.41). Compared with placebo, the risk difference was the largest for rimonabant (7%, 5–9%; NNH 14, 11–19), followed by orlistat (3%, 1–4%; NNH 39, 25–83), while no significant difference was seen for sibutramine (0.2%, −3 to 4%; NNH 500). The most common adverse events leading to withdrawal were gastrointestinal for orlistat (40%) and psychiatric for rimonabant (47%). Corresponding information was unavailable for sibutramine. In conclusion, available weight loss drugs differ markedly regarding risk of discontinuation due to adverse events, as well as in underlying causes of these events. Given the large number of patients eligible for treatment, the low NNH for rimonabant is a concern.     

Adverse events and treatment discontinuations of antimuscarinics for the treatment of overactive bladder in older adults: A systematic review and meta-analysis

IntroductionAntimuscarinics should be used with caution in older adults with overactive bladder (OAB) due to anticholinergic adverse events (AEs). Systematic reviews and meta-analyses (SRMAs) have analyzed safety-related outcomes but have not specified risk in the elderly, the population at highest risk for AEs. The aim of this review is to explore and evaluate AEs and treatment discontinuations in adults 65 or older taking antimuscarinics for OAB.MethodsKeywords were searched in MEDLINE, EMBASE, SCOPUS, and Cochrane Central Register for Controlled Trials. Randomized controlled trials (RCTs) along with sub-analyses and pooled analyses that compared antimuscarinics to placebo or another antimuscarinic were performed in February 2015. Studies assessing AEs or treatment discontinuations in a population of adults 65 or older were included. The Jadad Criteria and McHarm Tool were used to assess the quality of the trials.ResultsA total of 16 studies met the inclusion criteria. Eighty AEs and 27 reasons for treatment discontinuation were described in the included studies and further explored. Anticholinergic AEs were more common in antimuscarinics compared to placebo. Incidence of dizziness, dyspepsia, and urinary retention with fesoterodine, headache with darifenacin, and urinary tract infections with solifenacin were significantly higher compared to placebo. Treatment discontinuation due to AEs and dry mouth were higher in the antimuscarinics when compared to placebo in older adults.ConclusionsTreatment for overactive bladder using antimuscarinics in adults aged 65 or older resulted in significant increases in risk for several AEs compared to placebo including anticholinergic and non-anticholinergic AEs.     

Carfilzomib-induced Cardiotoxicity: An Analysis of the FDA Adverse Event Reporting System (FAERS)

BackgroundCarfilzomib and other proteasome inhibitors (PIs) have revolutionized treatment of multiple myeloma (MM). PIs have proven to be highly effective, but are associated with significant cardiovascular adverse events (AEs). No prior study has compared the cardiotoxicity of carfilzomib against other PI’s and all other classes of medications.ObjectivesThe purpose of this study is to characterize the cardiotoxicity of carfilzomib with respect to other PIs and all classes of medications using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database and to define the observed cardiotoxicity profile.MethodsThe FAERS database was queried between years 2017 and 2020 to identify AEs associated with PIs. Data extracted included concomitant medications used, type and severity of AEs and patient characteristics including age, sex, and time from medication initiation to adverse event. Cardiotoxicities assessed included acute myocardial infarction, heart failure, and supraventricular tachycardia. The reporting odds ratio (ROR) and information component assessed the strength of association between PIs and cardiotoxicity.ResultsOver the study period, 21,026 adverse events were reported in patients taking carfilzomib among 55,195 total adverse events in patients taking PI’s were identified from 6,548,048 total events reported in the FAERS database. The most common AE associated with carfilzomib was development of heart failure (1116 adverse events); disproportionality analysis revealed a stronger association with hypertension and QT prolongation with carfilzomib than other PI’s.ConclusionsWhile they have demonstrated efficacy and revolutionized treatment of MM, carfilzomib and other PI’s are associated with cardiotoxicities.     

Adverse events of computed tomography colonography: An Italian National Survey

AimTo retrospectively study the frequency and magnitude of complications associated with computed tomography (CT) colonography in clinical practice.MethodsA questionnaire on complications of CT colonography was sent to Italian public radiology departments identified as practicing CT colonography with a reasonable level of training. The frequency of complications and possible risk factors were retrospectively determined. Responses were collated and row frequencies determined. A multivariate analysis of the factors causing adverse events was also performed.Results40,121 examinations were performed in13 centers during the study period. No deaths were reported. Bowel perforations occurred in 0.02% (7 exams). All perforations were asymptomatic and occurred in patients undergoing manual insufflation. Five perforations (71%) occurred in procedures performed following a recent colonoscopy. There was no significant difference between perforations associated with rectal balloon (0.017%) and those that were not (0.02%). Complications related to vasovagal reaction (either with or without spasmolytic) occurred in 0.16% (63 exams). All vasovagal reactions resolved in less than 3 h, without any sequelae.ConclusionsPerforation rate at CT colonography in Italy is comparable with elsewhere in the world, occurring regardless of the experience of radiology centers. Although the risk is very small, it may not be negligible when compared with the risk of diagnostic colonoscopy.     

Pediatric hypertension: recent trends and accomplishments, future challenges

Publication of the Fourth Report on high blood pressure (BP) in children and adolescents by the National High BP Education Program (NHBPEP) in 2004 has been followed by a remarkable increase in interest in pediatric hypertension. New data have emerged on the epidemiology of hypertension in the young, the influence of the childhood obesity epidemic on BP, how ambulatory BP monitoring (ABPM) can be used in evaluating elevated BP and the extent of hypertensive target-organ damage in the pediatric age group. Exciting new information on drug treatment of pediatric hypertension has been produced by industry-sponsored clinical trials of antihypertensive medications spurred by the FDA Modernization Act (FDAMA) and successor legislation. Despite these trends, recognition of elevated BP in children and adolescents by primary care providers remains problematic. This article will highlight these and other aspects of pediatric hypertension, hopefully providing a snapshot of where we are in early 2008, and pointing out areas where further work is needed in order to reduce the future burden of adult cardiovascular disease.