A study at 10 medical centers of the safety and efficacy of 48 flexible sigmoidoscopies and 8 colonoscopies during pregnancy with follow-up of fetal outcome and with comparison to control groups

To analyze the risks versus benefits of flexible sigmoidoscopy and colonoscopy to the pregnant female and fetus, we conducted a multiyear, retrospective study at 10 hospitals of 46 patients undergoing 48 sigmoidoscopies and 8 patients undergoing 8 colonoscopies during pregnancy. Sigmoidoscopy controls included two study control groups and the average American pregnancy outcomes. Sigmoidoscopy indications included hematochezia in 28, diarrhea in 10, abdominal pain in 4, and other in 3. Thirteen patients were in the first trimester of pregnancy, 18 were in the second trimester, and 15 were in the third trimester. Twenty-seven patients had a lesion diagnosed by sigmoidoscopy, including reactivated or newly diagnosed inflammatory bowel disease, bleeding internal hemorrhoids, and other colitidies. Twenty-two of 29 patients with rectal bleeding had a significant lesion identified by sigmoidoscopy. Sigmoidoscopy was significantly more frequently diagnostic for hematochezia than for other indications (p < 0.03, ²). No endoscopic complications occurred to the pregnant patients. Excluding 4 voluntary abortions and 1 unknown pregnancy outcome, 38 (93%) of 41 pregnant females delivered healthy babies (study control rate=93%; NS, Fisher's exact test). Mean live-born infant Apgar scores were 8.2 ± 1.5 (SD) at 1 min and 9.0 ± 0.2 at 5 min (control mean Apgar scores: 8.1 ± 1.7 at 1 min and 8.8 ± 1.0 at 5 min; NS, Student'st test). Three high-risk pregnancies ended with fetal demise at 8, 9, or 12 weeks after sigmoidoscopy, from causes unrelated to sigmoidoscopy. No fetal cardiac abnormalities were detected by fetal cardiac monitoring during two sigmoidoscopies. Eight pregnant females underwent colonoscopy, without complications. Pregnancy outcomes included six healthy babies delivered at full term, one voluntary abortion, and one fetal demise in a high-risk pregnancy 4 months after colonoscopy from causes unrelated to colonoscopy. This study suggests that sigmoidoscopy does not induce labor or result in congenital malformations, that sigmoidoscopy is not contraindicated during pregnancy, and that sigmoidoscopy may be beneficial in pregnant patients with significant lower gastrointestinal bleeding. Colonoscopy during pregnancy should be considered for life-threatening lower gastrointestinal bleeding or when the only alternative is surgery.A preliminary version of this paper was presented orally at the Annual Convention of the American Gastroenterology Association on May 15, 1995, in San Diego, California (1).     

The fetal safety and clinical efficacy of gastrointestinal endoscopy during pregnancy

More than 12,000 pregnant patients in the United States per annum have conditions that are normally evaluated by EGD. More than 6000 pregnant patients in the United States per annum have conditions that are normally evaluated by sigmoidoscopy or colonoscopy. About one thousand more have symptomatic choledocholithiasis during pregnancy, which is a strong indication for endoscopic sphincterotomy in nonpregnant patients. Endoscopy during pregnancy raises the unique issue of fetal safety. Endoscopic medications comprise a significant component of fetal endoscopic risks. Safety of EGD during pregnancy has been examined in a case-controlled study of 83 patients, a mailed survey of 73 patients, and 28 case reports. Safety of sigmoidoscopy during pregnancy has been examined in a case-controlled study of 46 patients, a mailed survey of 13 patients, and 10 case reports. Safety of therapeutic ERCP during pregnancy has been analyzed in studies of 23, 10, 6, and 5 patients, and in 32 case reports. These studies suggested that EGD, sigmoidoscopy, and ERCP should be performed when strongly indicated: EGD for significant upper gastrointestinal bleeding, sigmoidoscopy for nonhemorrhoidal rectal bleeding, and ERCP for symptomatic choledocholithiasis when sphincterotomy is contemplated. PEG and colonoscopy are currently considered experimental during pregnancy because of insufficient data on fetal safety. Several cases of PEG and colonoscopy were successfully performed during pregnancy. Performance of endoscopy during pregnancy should increase with further technical refinements, and greater awareness of procedure safety.     

Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy

OBJECTIVES: In this study we assessed the long-term efficacy and safety of disopyramide for patients with obstructive hypertrophic cardiomyopathy (HCM). BACKGROUND: It has been reported that disopyramide may reduce left ventricular outflow gradient and improve symptoms in patients with HCM. However, long-term efficacy and safety of disopyramide has not been shown in a large cohort. METHODS: Clinical and echocardiographic data were evaluated in 118 obstructive HCM patients treated with disopyramide at 4 HCM treatment centers. Mortality in the disopyramide-treated patients was compared with 373 obstructive HCM patients not treated with disopyramide. RESULTS: Patients were followed with disopyramide for 3.1 +/- 2.6 years; dose 432 +/- 181 mg/day (97% also received beta-blockers). Seventy-eight patients (66%) were maintained with disopyramide without the necessity for major non-pharmacologic intervention with surgical myectomy, alcohol ablation, or pacing; outflow gradient at rest decreased from 75 +/- 33 to 40 +/- 32 mm Hg (p < 0.0001) and mean New York Heart Association functional class from 2.3 +/- 0.7 to 1.7 +/- 0.6 (p < 0.0001). Forty other patients (34%) could not be satisfactorily managed with disopyramide and required major invasive interventions because of inadequate symptom and gradient control or vagolytic side effects. All-cause annual cardiac death rate between disopyramide and non-disopyramide-treated patients did not differ significantly, 1.4% versus 2.6%/year (p = 0.07). There was also no difference in sudden death rate, 1.0%/year versus 1.8%/year (p = 0.08). CONCLUSIONS: Two-thirds of obstructed HCM patients treated with disopyramide could be managed medically with amelioration of symptoms and about 50% reduction in subaortic gradient over >/=3 years. Disopyramide therapy does not appear to be proarrhythmic in HCM and should be considered before proceeding to surgical myectomy or alternate strategies.     

Safety and clinical efficacy of flexible sigmoidoscopy and colonoscopy for gastrointestinal bleeding after myocardial infarction

The risks versus benefits of flexible sigmoidoscopy and colonoscopy performed within three weeks of myocardial infarction were studied in nine consecutive patients who underwent sigmoidoscopy and in nine consecutive patients who underwent colonoscopy at two university hospitals. Indications for sigmoidoscopy were red blood per rectum in seven and occult blood in the stools in two. Sigmoidoscopy provided the diagnosis in three, including colon cancer in two and bleeding internal hemorrhoids in one, and provided helpful information in three. Sigmoidoscopy led to colon cancer surgery in two patients, and polypectomy of a 1-cm adenoma in one. Of two highly unstable patients before sigmoidoscopy, one developed second-degree heart block and frequent premature ventricular contractions 3 hr after sigmoidoscopy. No sigmoidoscopic complications occurred in the seven relatively clinically stable patients. Indications for colonoscopy included red blood per rectum in five, occult blood in the stools in three, and melena in one. Colonoscopy provided the diagnosis in five, including one each with colon cancer, internal hemorrhoids, large adenoma, ischemic colitis, and angiodysplasia. Colonoscopy resulted in colon cancer surgery in one patient and endoscopic polypectomies in three patients. Of two moderately unstable patients before colonoscopy, one developed asymptomatic bradycardia during colonoscopy. No colonoscopic complications occurred in the seven clinically stable patients. This study suggests that recent myocardial infarction is not an absolute contraindication to sigmoidoscopy or colonoscopy, that sigmoidoscopy is beneficial in medically stable patients with significant gastrointestinal bleeding, and that colonoscopy may be beneficial in selected, highly stable patients with significant gastrointestinal bleeding. Endoscopy should be performed with monitoring by electrocardiography and pulse oximetry after stabilization of vital signs, which may require transfusion of blood products and supplemental oxygen administration. Sigmoidoscopy in highly unstable patients and colonoscopy in moderately unstable patients may have a high complication rate.     

Colonoscopy and flexible sigmoidoscopy practice patterns in Ontario: a population-based study.

OBJECTIVE: To conduct a population-based study on the provision of large bowel endoscopic services in Ontario. METHODS: Data from the following databases were analyzed: the Ontario Health Insurance Plan, the Institute for Clinical Evaluative Sciences Physicians Database and Statistics Canada. The flexible sigmoidoscopy and colonoscopy rates per 10,000 persons (50 to 74 years of age) by region between April 1, 2001, and March 31, 2002, were calculated, as well as the numbers and types of physicians who performed each procedure. RESULTS: In 2001/2002, a total of 172,108 colonoscopies and 43,400 flexible sigmoidoscopies were performed in Ontario for all age groups. The colonoscopy rate was approximately five times that of flexible sigmoidoscopy; rates varied from 463.1 colonoscopies per 10,000 people in the north to 286.8 colonoscopies per 10,000 people in the east. Gastroenterologists in all regions tended to perform more procedures per physician, but because of the large number of general surgeons, the total number of procedures performed by each group was almost the same. CONCLUSION: Population-based rates of colonoscopies and flexible sigmoidoscopies are low in Ontario, as are the procedure volumes of approximately one-quarter of physicians.     

A case of thyroid hormone resistance: Prospective follow-up during pregnancy and obstetric outcome

We describe the case of a patient with resistance to thyroid hormone (R243W substitution) and her obstetric outcome. The patient gave birth to a healthy girl, unaffected by the R243W mutation. Two years later, following an uneventful pregnancy, a baby boy was born at term; he presented the same thyroid hormone receptor mutation as his mother. Follow-up of gestational thyroid hormone levels is reported during both pregnancies and related to obstetric outcome.     

胰岛素类似物在孕妇中使用的有效性及安全性

妊娠合并糖尿病的患者,若血糖控制良好,可减少母婴并发症的发生.孕期母体的生理改变使其对胰岛素的需求不同于一般患者.与当前广泛使用的常规人胰岛素相比,胰岛素类似物更能模拟胰岛索释放的生理特点,可将孕期血糖控制得更为理想.目前,短效胰岛素类似物的有效性及安全性已得到多个研究的证实,而长效胰岛素类似物虽然能减少夜间低血糖的发生,但其在孕妇中的有效性及安全性尚需大量基础及临床研究的支持.     

Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up

Patients with β-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged ≥ 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received ≥ 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with ≥ 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ± 11.2 mg Fe/g dry weight (dw; n = 103; P < .001) and 3.1 ± 7.9 mg Fe/g dw (n = 68; P < .001) in the deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n = 196; P < .001) and 371 ng/mL (n = 147; P < .001), respectively, after ≥ 4 years' exposure. Investigator-assessed, drug-related adverse events, including increased blood creatinine (11.2%), abdominal pain (9.0%), and nausea (7.4%), were generally mild to moderate, transient, and reduced in frequency over time. No adverse effect was observed on pediatric growth or adolescent sexual development. This first prospective study of long-term deferasirox use in pediatric and adult patients with β-thalassemia suggests treatment for ≤ 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials.gov as #NCT00171210.     

Uptake, yield of neoplasia, and adverse effects of flexible sigmoidoscopy screening

Background—A multicentre randomised controlledtrial to evaluate screening by "once only" flexible sigmoidoscopy(FS) for prevention of bowel cancer is in progress.
Aims—To pilot the trial protocol examining ratesof attendance, yield of neoplasia, and adverse effects.
Subjects—A total of 3540 subjects aged 55-64years in Welwyn Garden City (WGC) and 19 706 in Leicester (LE).
Methods—Subjects responding positively to an"interest in screening" questionnaire were randomised to invitationfor screening or control arms. Small polyps were removed duringscreening. Colonoscopy was undertaken for high risk polyps (more thantwo adenomas, size at least 1 cm, villous histology, severe dysplasia,or malignancy). The remainder were discharged.
Results—In WGC and LE respectively, 59% and 61%indicated an interest in screening, of which 74% and 75% attended.Adenomas were detected in 10% and 9%, respectively, and cancers in 7 per 1000 (in both centres), 55% at Dukes's stage A. The colonoscopy referral rate was 6% in both centres. Mild, short lived bleeding occurred in 3%. One person died following surgery.
Conclusions—Compliance rates, yield of adenomas,and referral rate for colonoscopy were as expected, but cancerdetection rates were higher. Adverse effects following sigmoidoscopy or colonoscopy were mild and transient, but there was one postoperative death. A randomised trial is necessary to evaluate fully the risks andbenefits of this intervention.

Keywords:screening; colorectal cancer; adenomas; sigmoidoscopy; endoscopy; randomised trial

     

Maternal and fetal outcome of lupus pregnancy: a prospective study of 29 pregnancies

The aim of this study was to analyse pregestational and pregnancy risk factors for adverse fetal and maternal outcome in lupus pregnancy. Twenty women with systemic lupus erythematosus (SLE) (29 pregnancies) were prospectively evaluated. Mean patient age was 29.5+/-4.7 years, and mean disease duration, 6.3+/-6.5 years. Twenty-two pregnancies (75.9%) ended in live births; preterm delivery occurred in 17.4%, intrauterine growth restriction in 50%, preeclampsia in 3.7%, and gestational hypertension in 8%. Six pregnancies (20.7%) ended in spontaneous abortions. Adverse live-birth outcome was significantly associated with low pregestational serum albumin level, elevated gestational anti-dsDNA antibody, and diabetes mellitus. Spontaneous abortion was directly associated with low levels of pregestational serum albumin, positive anticardiolipin IgA, anti-beta2-glycoprotein I IgM, and anti-La antibodies, and inversely associated with number of patients' children. Postgestational lupus flare-up was noted in six pregnancies. Risk factors included high pregestational SLE Disease Activity Index (SLEDAI), lower serum albumin, elevated serum antibody to dsDNA, proteinuria, and use of prednisone and hydroxychloroquine. We conclude that despite high rate of obstetrical complications and postpartum lupus flare-up, pregnancy poses low risk for the majority of women with SLE.     

Five French versus 6 French PCI: a case control study of efficacy,safety and outcome

We report our experience of percutaneous coronary intervention (PCI) with 5 French (Fr) guiding catheters in a retrospective analysis of consecutive cases undergoing ad hoc PCI. Results were compared with a cohort of 6 Fr PCI cases matched for age, sex and operator over the same study period. A total of 210 patients (311 lesions) underwent PCI using 5 Fr guiding catheters and 174 matched patients (300 lesions) underwent PCI with 6 Fr guiding catheters. Multivessel PCI was performed in 18% of patients in the 5 Fr group and in 26% of the 6 Fr group (p = 0.046). There was no difference in clinical, angiographic or procedural characteristics between groups. Technical success rate was superior in the 5 Fr group compared with the 6 Fr (99% versus 95%; p = 0.03). The rate of stent implantation did not differ and the 5 Fr guiding catheter did not prohibit the use of large or long stents/balloons. Failure of 5 Fr PCI in 3 cases was not due to inadequate guiding catheter support. In-hospital major adverse cardiac events (MACE) and serious femoral complications were rare and at 6-month follow-up did not differ between groups. However, compared with 6 Fr PCI, procedure time and contrast medium usage was significantly less in the 5 Fr group (contrast: 274 +/- 101 ml versus 313 +/- 124 ml; p = 0.0008; fluoroscopy time: 16 +/- 9 minutes versus 19 +/- 12 minutes; p = 0.006). We conclude that the use of 5 Fr guiding catheters is effective and safe in unselected patients undergoing PCI and may even confer certain advantages. The 5 Fr approach can be recommended for routine interventional practice.     

Significance of distal polyps detected with flexible sigmoidoscopy in asymptomatic patients.

BACKGROUND--Colorectal cancer is a frequent cause of death from cancer. To reduce the mortality associated with this disease, regular flexible sigmoidoscopy is recommended. However, the significance of diminutive polyps (adenomatous or hyperplastic) detected during flexible sigmoidoscopy remains controversial, as does the appropriate endoscope length (35 vs 60 cm) for colorectal cancer screening. METHODS--One hundred one consecutive patients with no history of colonic disease, gastrointestinal tract symptoms, or positive results of fecal occult blood testing underwent flexible sigmoidoscopy as part of a colorectal cancer screening program. All patients with distal polyps detected during flexible sigmoidoscopy underwent colonoscopy. RESULTS--More than 25% of these asymptomatic, predominantly male subjects had colonic neoplasms or polyps detected. Fifty percent more lesions could be detected with a 60-cm sigmoidoscope than with a 35-cm sigmoidoscope, and detection of any distal polyp, whether adenomatous or hyperplastic, was associated with at least one proximal colon adenoma in 20% of patients. "Extended flexible sigmoidoscopy" for colorectal cancer screening was well tolerated by patients, as evidenced by insertion to the hepatic flexure in 25% of patients, and provided significantly more information than could be obtained with a 35-cm sigmoidoscope. CONCLUSIONS--Colorectal cancer screening should be performed with a 60-cm flexible sigmoidoscope, and distal colonic polyps or neoplasms will be detected in 25% of asymptomatic patients.     

Patterns of use of flexible sigmoidoscopy, colonoscopy and gastroscopy: a population-based study in a Canadian province.

BACKGROUND & AIMS: Flexible sigmoidoscopy, colonoscopy and gastroscopy are important in the diagnosis and treatment of gastrointestinal (GI) diseases. Pressure on endoscopy resources is expected due to increased screening for GI cancers. The present study examined patterns of use of GI endoscopy in a Canadian province, Alberta, with universal health care insurance. METHODS: Data on physician payments from January 1, 1994 to March 31, 2002 were used to calculate age-sex adjusted rates and patterns of use. RESULTS: The gastroscopy rate increased by 17%, from 9.7 (95% CI 9.6 to 9.9) to 10.3 (95% CI 10.1 to 10.5). The colonoscopy rate increased by 105%, from 4.8 (95% CI 4.6 to 5.0) to 9.8 (95% CI 9.6 to 10.1). Flexible sigmoidoscopy rates declined by 10%, from 4.68 (95% CI 4.56 to 4.80) to 4.21 (95% CI 4.11 to 4.32). The increase in colonoscopy rates occurred in all age groups, whereas gastroscopy rates increased only in the older age groups. Regional variation in procedure rates was evident, but rural health regions did not have consistently lower rates than the large urban regions. A polypectomy was performed on 23.7% of male patients and 15.4% of female patients at time of colonoscopy. Rates of polypectomy for individual endoscopists ranged from 0% to 60%. CONCLUSIONS: There has been a marked increase in gastroscopy and colonoscopy rates, likely due to a broadening of indications rather than just increased use for cancer screening. Modest regional variation in rates exists, but there is no direct evidence of limited rural access to endoscopy. Reasonable polypectomy rates were seen but important variations between endoscopists exist.     

Prospective study of fetal DNA in serum and disease activity during pregnancy in women with inflammatory arthritis

OBJECTIVE: Rheumatoid arthritis (RA) usually improves during pregnancy and recurs postpartum. Fetal cells and cell-free DNA reach the maternal circulation during normal pregnancy. The present study investigated dynamic changes in levels of fetal DNA in serum from women with RA and inflammatory arthritis during and after pregnancy to test the hypothesis that the levels of circulating fetal DNA correlate with arthritis improvement. METHODS: Twenty-five pregnant patients were prospectively studied. A real-time quantitative polymerase chain reaction panel targeting unshared, paternally transmitted HLA sequences, a Y chromosome-specific sequence, or an insertion sequence within the glutathione S-transferase M1 gene was used to measure cell-free fetal DNA. Results were expressed as fetal genomic equivalents per milliliter (gE/ml) of maternal serum. Physical examinations were conducted during and after pregnancy. RESULTS: Levels of fetal DNA in women with improvement in or remission of arthritis were higher than those in women with active disease, especially in the third trimester. Overall, an inverse relationship between serum fetal DNA levels and disease activity was observed (P < 0.001). Serum fetal DNA increased with advancing gestation, reaching median levels of 24 gE/ml (range 0-334), 61 gE/ml (range 0-689), and 199 gE/ml (range 0-2,576) in the first, second, and third trimesters, respectively, with fetal DNA clearance observed postpartum. Arthritis improvement was initially noted in the first trimester for most patients, increased further or was sustained with advancing gestation, and was active postpartum. CONCLUSION: Changes in serum fetal DNA levels correlated with arthritis improvement during pregnancy and recurrence postpartum. Immunologic mechanisms by which pregnancy might modulate RA activity are described.     

Incomplete screening flexible sigmoidoscopy associated with female sex, age, and increased risk of colorectal cancer

BACKGROUND: Several previous studies have found that females and older individuals are at greater risk of having incomplete flexible sigmoidoscopy. However, no prior study has reported the subsequent risk of colorectal cancer (CRC) following incomplete sigmoidoscopy. METHODS: Using data from 55 791 individuals screened as part of the Colon Cancer Prevention (CoCaP) programme of Kaiser Permanente of Northern California, we evaluated the likelihood of having an inadequate (<40 cm) examination by age and sex, and estimated the risk of distal CRC according to depth of sigmoidoscope insertion at the baseline screening examination. Multivariate estimation of risks was performed using Poisson regression. RESULTS: Older individuals were at a much greater risk of having an inadequate examination (relative risk (RR) for age 80+ years compared with 50-59 years 2.6 (95% confidence interval (CI) 2.3-3.0)), as were females (RR 2.3 (95% CI 2.2-2.5)); these associations were attenuated but remained strong if Poisson models were further adjusted for examination limitations (pain, stool, and angulation). There was an approximate threefold increase in the risk of distal CRC if the baseline sigmoidoscopy did not reach a depth of at least 40 cm; a smaller increase in risk was observed for examinations that reached 40-59 cm. CONCLUSIONS: Older individuals and women are at an increased risk of having inadequate sigmoidoscopy. Because inadequate sigmoidoscopy results in an increased risk of subsequent CRC, physicians should consider steps to maximise the depth of insertion of the sigmoidoscope or, failing this, should consider an alternative screening test.     

Q fever during pregnancy: diagnosis, treatment, and follow-up

BACKGROUND: Q fever, caused by Coxiella burnetii, may result in abortions, premature deliveries, and stillbirths in infected pregnant women. OBJECTIVE: To evaluate the best treatment strategy for Q fever during pregnancy. METHODS: We evaluated the prognosis of 17 pregnant women who developed Q fever with and without co-trimoxazole (trimethoprim-sulfamethoxazole) treatment. RESULTS: The outcome of the pregnancy was found to depend on the trimester. Abortions occurred in 7 of 7 insufficiently treated patients infected during the first trimester vs 1 of 5 patients infected later. Co-trimoxazole given until delivery protected against abortion (0/4) but not against the development of chronic infections, and it did not significantly reduce the colonization of the placenta (2/4 vs 4/4). CONCLUSIONS: Our results show that C burnetii infections cause abortion and that women who develop Q fever while pregnant should be treated with co-trimoxazole for the duration of pregnancy, specifically when infected during the first trimester.