Add-on cases in the endoscopy unit: Factors that affect volume.

BACKGROUND: Although most procedures in the endoscopy clinic are elective, emergency add-on cases in hospital-based endoscopy clinics are common, frequently consuming a great deal of time and resources relative to elective endoscopy procedures. OBJECTIVE: To determine which specific factors correlate with the high volume of add-on emergency cases in a tertiary care, hospital-based endoscopy unit. METHODS: A retrospective chart review of all gastrointestinal add-on, and electively booked cases of esophagastroduodenoscopy (EGD), colonoscopy(C) and flexible sigmoidoscopy(FS)procedures from September 2006 to May 2007, was conducted. The day of the week, month, type of procedure and physician were recorded. Emergency add-on procedures performed during the weekends were not assessed. These cases were then compared with elective cases during a similar time frame to determine differences in the aspects of add-on cases versus those that were elective. RESULTS: Seven hundred twenty-one add-on cases were reviewed (mean patient age 57.4 years; 46% women) and compared with 736 elective cases (mean age 56 years; 49% women; P not significant). Of the add-on cases, 377 (52%) were EGD, 216 C (30%) and 105 (15%) were FS, with 23 combined procedures (3.2%) versus 202 (27%) EGD, 442 (60%) C and 74 (10%) FS in the elective group. Add-on cases were more likely to be EGDs than elective cases (OR 2.7; 95% CI 1.8 to 4.3; P<0.0001) and less likely to be Cs (OR 0.24; 95% CI 0.15 to 0.38; P<0.0001). There were significantly more add-on cases on Mondays (OR 1.7; 95% CI 1.0 to 2.28; P>0.03). Conversely, there were significantly fewer procedures added on Fridays (OR 0.31; 95% CI 0.16 to 0.57; P=0.0001). There were statistically fewer add-on cases in September compared with the other months that were evaluated (OR 0.31; 95% CI 0.11 to 0.78; P=0.0006). CONCLUSION: With the present system of performing only emergency cases on the weekend, Monday tends to have more add-on cases. Consistent with the fact that upper gastrointestinal bleeding is the most common emergency condition, EGD is more common in add-on cases than with elective cases. Although speculative, the reasons for Friday having fewer add-on cases may be the result of a change of physician on call that day; consequently, most cases may be performed earlier in the week. For unknown reasons, fewer cases tend to be added on in September than in the other months evaluated. These data demonstrate that even in the same institution with similar patients, variability in the number of add-on cases likely is a result of many additional factors governing add-on cases, which require appropriate resource planning to ensure adequate allocation of services to ensure ideal patient care.

The use of infliximab for treatment of hospitalized patients with acute severe ulcerative colitis.

BACKGROUND/AIM: The use of infliximab in severe ulcerative colitis (UC) is established; however, its role in severe acute UC requires clarification. The present multicentre case series evaluated infliximab in hospitalized patients with steroid-refractory severe UC. METHODS: Patients from six hospitals were retrospectively evaluated. Data collection included demographics, duration of disease and previous treatments. The primary end point was response to in-hospital infliximab; defined as discharge without colectomy. RESULTS: Twenty-one patients (median age 26 years) were admitted between May 2006 and May 2008 with severe UC requiring intravenous steroids and given infliximab (median time to infusion eight days). Sixteen (76%) patients were discharged home without colectomy; three of these underwent colectomy at a later date. Of the remaining 13 patients (62%), all but two did not require further courses of steroids; six patients had infliximab as a bridge to azathioprine and seven patients were maintained on regular infliximab. Five patients required in-hospital colectomy after the initial infliximab. CONCLUSIONS: In this real-life experience of infliximab in patients with steroid-refractory severe UC, infliximab appears to be a viable rescue therapy. The majority of patients were discharged without surgery and 62% maintained response either as a bridge to azathioprine or maintenance infliximab.

Review article: Medical therapy for fistulizing Crohn's disease.

BACKGROUND: Fistulae will develop in approximately one-third of patients with Crohn's disease. With an expected spontaneous healing rate of only 10%, fistulizing Crohn's disease requires a comprehensive strategy with a medical and possible surgical approach. AIM: To summarize the current literature evaluating various medical options for treating patients with fistulizing Crohn's disease. METHODS: A literature review was conducted using PubMed (search terms: Crohn's disease and fistula) and manual search of references among the identified studies and relevant review papers to identify papers that present data on medical treatment of fistulizing Crohn's disease. RESULTS: The first line of medical therapy remains antibiotics (metronidazole and ciprofloxacin). Mercaptopurine and azathioprine are medications that are effective in treating fistulizing Crohn's disease. The current gold standard of medical treatment to induce and maintain remission for fistulizing Crohn's disease is infliximab. Used as induction therapy, infliximab produced a 62% clinical response, and a complete closure rate of 46%. A maintenance therapy trial demonstrated at 54 weeks, 46% of patients receiving infliximab continued to respond to treatment, compared with 23% in the placebo group (P = 0.001). CONCLUSION: Further research to find new therapies and to improve our existing medical treatment of fistulizing Crohn's disease is required.

Temporal response of brachial artery dilation after occlusion and nitroglycerin.

This study shows that a set time after cuff deflation or after nitroglycerin administration may not be suitable to capture peak, brachial artery dilatory responses in assessing endothelial dysfunction. Automated, continuous monitoring methods are required to simplify identification of peak responses and to standardize reporting.

Image-analysis-based assessment of the effects of the "Ca2+-jump" technique on sarcomere uniformity.

A new image analysis-based technique was used to quantitatively examine the effects of the "Ca2+-jump" activation protocol on the maintenance of fiber quality in skinned rabbit psoas muscle fiber segments. Specifically, contractions in pCa 4.6 were preceded by short-duration "preactivation" soaks in a solution in which EGTA was replaced with the low-Ca2+ buffering capacity analog hexamethylenediamine-N, N, N', N'-tetraacetate, which facilitated rapid Ca2+ equilibration within the fiber segments. Fiber quality was assessed by examining the Fourier spectra of the muscle fiber images before, during, and after activation. Segment lengths were typically below 500 micrometer, thus allowing the majority of the sarcomeres to be visualized in the field of view (x200 and x400 magnification). The preactivation protocol resulted in less deterioration of fiber quality with repetitive activation. In addition, there was also a significant reduction in the time required to reach the 50% level of maximum tension, with no significant change in the maximum tension level.

Noradrenaline stimulation of a membrane pump in frog skeletal muscle.

Resting membrane potentials were recorded from the frog sartorius before and during exposure to noradrenaline (NA; 10(-2) M) in the presence or absence of ouabain (10(-3) M) and during manipulation of the extracellular potassium concentration. In potassium-free Ringer, NA produced no significant change in the resting membrane potential. With the extracellular potassium concentration at 2.5 or 5mM, NA caused a hyperpolarization. This reversed to a depolarization when extracellular K+ was greater than 7 mM. In all cases NA-induced changes were blocked by ouabain. These effects suggest that NA stimulates a membrane cation pump, the Na : K coupling ratio of which is affected by the available ion concentrations.

A comparison of muscle stiffness measurements obtained with rapid releases or stretches of frog semitendinosus fibers.

The stiffness-tension relationship has been studied during the isometric twitch. All experiments were carried out at 0 degrees C using small fiber bundles from frog semitendinosus. Rapid shortening and lengthening steps of 3-6 nm/hs, complete in 500 mu sec were given at various times during the twitch. Instantaneous stiffness was measured as the ratio of delta P to delta L and expressed as a relative change to the maximum values recorded at the plateau of an isometric tetanus. The time course of the stiffness changes followed the tension for both releases and stretches. However, the stiffness measured with a rapid stretch was higher than when measured with a rapid release. This raises the possibility that the instantaneous elasticity is non-linear in stretches.

Suicide and drug abuse in the medical community.

In the United States each year the equivalent of an average-size medical school graduating class commits suicide, with the highest incidence occurring in the decade following the completion of training. Of these suicides, 20% to 30% are associated with drug abuse and 40% with alcoholism. Various problem areas are considered. Role strain, leading to excessive drug use in an attempt to increase work efficiency, is coupled with a denial of the physician's own dependency needs and gratification. The problem of identity occurs in relation to the exaggerated sense of duty and obligation the physician feels in attending to the demands of the patients and their families. Medicine as magical thinking is also discussed, revealing the physician's belief in his own immunity, which is strenuously tested when he actually sets up in practice. The community's high regard for the physician further complicates the situation. Too little has been done about working with emotional problems of medical students during their training and after they begin to practice. Unfortunately, physicians feel uncomfortable in turning to colleagues for help; rather, they tend to isolate themselves, resorting to alcohol and drugs. One should question the selection of medical students and their overall training, not only in terms of academic learning but also with more consideration for the stresses and strains of the future career.

Measurement of the position and displacement of a light beam with a spiral scanner.

A rotating spiral scanner interrupts an incident light beam for time intervals which are proportional to the position of the beam. This produces an electrical signal via a photodetector system which is independent of beam intensity. The device was used to measure the relative change in sarcomere spacing during the initial development of tension in a contracting frog sartorius muscle.

Review article: a clinician's guide for therapeutic drug monitoring of infliximab in inflammatory bowel disease.

BACKGROUND: Tumour necrosis factor (TNF)-antagonists have an established role in the treatment of inflammatory bowel diseases (IBDs), however, subtherapeutic drug levels and the formation of anti-drug antibodies (ADAs) may decrease their efficacy. AIM: The evidence supporting the use of therapeutic drug monitoring (TDM) based clinical algorithms for infliximab (IFX) and their role in clinical practice will be discussed. METHODS: The literature was reviewed to identify relevant articles on the measurement of IFX levels and antibodies-to-infliximab. RESULTS: Treatment algorithms for IBD have evolved from episodic monotherapy used in patients refractory to all other treatments, to long-term combination therapy initiated early in the disease course. Improved remission rates have been observed with this paradigm shift, nevertheless many patients ultimately lose response to therapy. Although empiric dose optimization or switching agents constitute the current standard of care for secondary failure, these interventions have not been applied in an evidence-based manner and are probably not cost-effective. Multiple TDM-based algorithms have been developed to identify patients that may benefit from measurement of IFX and ADA levels to guide adjustments to therapy. CONCLUSIONS: Therapeutic drug monitoring offers a rational approach to the management of secondary failure to IFX. This concept has gained momentum based on evidence from case series, cohort studies and post-hoc analyses of randomised controlled trials.

Setting priorities for comparative effectiveness research in inflammatory bowel disease: results of an international provider survey, expert RAND panel, and patient focus groups.

BACKGROUND: Comparative effectiveness research (CER) is an emerging field that compares the relative effectiveness of alternative strategies to prevent, diagnose, or treat patients who are typical of day-to-day practice. We developed a priority list of CER topics for inflammatory bowel disease (IBD). METHODS: Following the Institute of Medicine's approach, we developed and administered a survey to gastroenterologists asking for important CER topics in IBD. Two patient focus groups were convened to solicit additional CER studies. CER topics were presented to the expert panel using the RAND/UCLA methodology. Following initial ratings, the panel met to discuss and re-rate priorities. The top 10 CER topics were identified using a point-allocation system. RESULTS: Responses were collated into 234 CER topics across 21 categories, of which 87 were prioritized for discussion and re-rated. Disagreement regarding priorities was observed in 5 of 87 studies. We utilized a point-allocation system to prioritize the top-10 CER topics. These related to comparing the effectiveness of: biomarkers in IBD; withdrawal of anti-tumor necrosis factor (TNF) or immunomodulators for Crohn's disease in remission; mucosal healing as an endpoint of treatment; infliximab levels versus standard infliximab dosing; anti-TNF monotherapy versus combination therapy in patients failing thiopurines; safety of long-term treatment options; anti-TNF versus thiopurines for prevention of postoperative recurrence; and treatment options for steroid-refractory UC. CONCLUSIONS: We systematically developed a list of high-priority IBD topics for CER based on a survey of gastroenterologists, expert review, and patient input. This list may guide IBD research toward the most important CER studies.

Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections.

BACKGROUND: There remain concerns about the safety of infliximab therapy in patients with inflammatory bowel disease (IBD). AIM: To assess the association between the initiation of infliximab and other immunomodulating drugs and the risk of serious bacterial infection in the treatment of IBD. METHODS: We assembled a cohort study of patients with IBD, including Crohn's disease (CD) and ulcerative colitis (UC). All patients initiating an immunomodulating drug between January 2001 and April 2006 were identified in British Columbia from linked health care utilization databases. Exposure of interest was initiation of infliximab or corticosteroids compared with initiation of other immunosuppressive agents, including azathioprine, mercaptopurine (MP) and methotrexate (MTX). Outcome of interest was serious bacterial infections requiring hospitalization, including Clostridium difficile. RESULTS: Among 10 662 IBD patients, the incidence rate of bacteriaemia ranged from 3.8 per 1000 person-years (95% confidence interval 2.1-6.2) for other immunosuppressive agents to 7.4 (3.3-19.3) for infliximab with slightly higher rate for serious bacterial infections resulting in an adjusted relative risk 1.4 (0.47-4.24). Clostridium difficile infections occurred in 0/1000 (0-5.4) among 521 infliximab initiations and 14/1000 (10.6-18.2) for corticosteroids. Corticosteroid initiation tripled the risk of C. difficile infections (RR = 3.4; 1.9-6.1) compared with other immunosuppressant agents. This corticosteroid effect was neither dose-dependent nor duration-dependent. Bacteriaemia and other serious bacterial infections were not increased by corticosteroids or infliximab (5 events). CONCLUSIONS: In a population-based cohort of patients with IBD, we found no meaningful association between infliximab and serious bacterial infections, although some subgroups had few events. Corticosteroid initiation increased the risk for C. difficile infections in these patients.

Which patients with primary biliary cirrhosis or primary sclerosing cholangitis should undergo endoscopic screening for oesophageal varices detection?

BACKGROUND: Recent guidelines from an AASLD Single Topic Symposium suggest that patients with cirrhosis, including those with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC), should be screened for oesophageal varices when the platelet count is <140,000/mm3. AIM: To determine the validity of these guidelines in clinical practice in patients with PBC or PSC. METHODS: Retrospective review of individuals undergoing screening upper endoscopy for oesophageal varices at a single centre. Oesophageal varices were reported as being present or absent. RESULTS: A total of 235 patients with chronic liver disease, including 86 patients with PBC (n=79) or PSC (n=7), 104 patients with chronic viral hepatitis, and 45 with non-alcoholic cirrhosis of differing aetiologies, underwent a single screening endoscopy between 1996 and 2001. Oesophageal varices were detected in 26 (30%) of the PBC/PSC group, 38 (37%) of the viral hepatitis group, and 21 (47%) of the "other" group. Applying multiple logistic regression analysis to the data in the group with PBC/PSC, platelets <200,000/mm3 (odds ratio (OR) 5.85 (95% confidence interval (CI) 1.79-19.23)), albumin <40 g/l (OR 6.02 (95% CI 1.78-20.41)), and serum bilirubin >20 micromol/l (OR 3.66 (95% CI 1.07-12.47)) were shown to be independent risk factors for oesophageal varices. Prothrombin time was unhelpful. The values at these cut offs were not useful in predicting oesophageal varices in the other groups. CONCLUSION: We conclude that current guidelines recommended by the AASLD Single Topic symposium are invalid in our cohort of patients with PBC and PSC. Patients with a platelet count <200,000/mm3, an albumin level <40 g/l, and a bilirubin level >20 micromol/l should be screened for oesophageal varices.

The sarcomere length--isometric tension diagram of the toad Bufo bufo sartorius.

The sarcomere length--isometric tension diagram has been determined for the toad Bufo bufo sartorius using a laser diffraction technique to measure the sarcomere width. The sarcomere width at l0 was found to be 2.37 micron. At length shorter than l0 this whole muscle exhibits a steeper decline in tension than single fibres. This discrepancy in the shape of the tension-length diagram between single frog fibres and whole toad sartorii may be due to a difference in the magnitude of the internal force which appears only at short lengths.

Tension responses of frog skeletal muscle to ramp and step length changes.

Tension responses to ramp shortening of varying speed in whole muscle or single fibres from the plateau of an isometric tetanus, revealed at least two distinct phases. There was a fast initial drop in tension followed by a change of slope and a definite inflexion on the tension record. As the velocity of the imposed length change was increased, the inflexion point appeared at a lower tension. Similar inflexions were not observed during ramp releases to an elastic band or a segment of semitendinosus tendon. The tension records obtained with moderately fast ramp length changes to contracting muscle reflect the T1 and T2 phases of the tension transients.

Isometric tension and instantaneous stiffness in amphibian skeletal muscle exposed to solutions of increased tonicity.

The instantaneous elasticity and maximum isometric tetanic tension of isolated frog and toad sartorii have been measured in hypertonic Ringer solution. Although the mechanical response of contraction muscle continued to decrease as the tonicity of the bathing solution was increased to 1.26 X R, 1.52 X R, and 2.04 X R, a similar change in the instantaneous stiffness could not be shown. This finding was not expected on the basis of our current model of the cross-bridge mechanism which predicts that the instantaneous stiffness is a measure of the total number of tension-generating cross-bridges formed in a stimulated muscle. The compatability of our findings with an electrostatic theory of the cross-bridge mechanism proposed by Iwazumi (1970) is discussed.

Isometric contractile properties and instantaneous stiffness of amphibian skeletal muscle in the temperature range from 0 to 20 degrees C.

The isometric contractile properties of frog (Rana pipiens) and toad (Bufo bufo) sartorii have been studied over the temperature range from 0 to 20 degrees C. The isometric twitch tension was found to vary considerably between these two species and between muscles in the same species. Between 0 and 4 degrees C there was very little change in maximum isometric twitch tension. Between 4 and 12 degrees C several muscles from frog or toad showed a potentiation of twitch tension whereas others showed a decline. Over this temperature range the toad sartorii consistently demonstrated a greater potentiation. By 12 degrees C a steady decline in twitch tension in both muscles was seen as the temperature range the toad sartorii consistently demonstrated a greater potentiation. By 12 degrees C a steady decline in twitch tension in both muscles was seen as the temperature approached 20 degrees C. The maximum isometric tetanic tension recorded between 18 and 20 degrees C increased fractionally to an average of 1.504 +/- 0.029 (n = 4) for frog sartorii and to 1.377 +/- 0.008 (n = 5) for toad sartorii. The time to peak twitch tension and the half-relaxation time decreased markedly with an increase in temperature. Moreover, the half-relaxation time was reduced by a greater proportion than the time to peak twitch tension. Measurements of instantaneous stiffness by controlled velocity releases from the plateau of isometric tetani revealed that the large increase in isometric tetanus tension as the muscle was warmed was not accompanied by a corresponding increase in the total number of active cross-bridges. The possibility that a decreased availability of intracellular Ca2+ ions at the contractile sites contributing to the fall of isometric twitch tension at elevated temperatures is discussed. The possibility exists that at elevated temperatures a change inthe intrinsic contractile ability of the muscle occurs which produces an increased tension per cross-bridge.

Alterations in contractile properties of extensor digitorum longus muscle from C57BL/6J mice following denervation at 1 day of age.

Changes in contractile properties of developing fast-twitch skeletal muscle of the C57/BL6J mouse were studied following neonatal denervation. A sciatic neurectomy was performed at 1 day of age and then denervated and control muscles were examined at 7, 14, and 21 days postdenervation. In addition, normal muscles were studied at 1 day of age. The denervated muscles exhibited prolongation of time-to-peak twitch tension and half-relaxation time, a slowing of the maximum velocity of shortening, and a marked increase in resistance to fatigue compared with controls. Isometric tetanus tension was reduced compared to the control muscle both in absolute terms and when expressed relative to body weight at all ages studied. The absolute isometric twitch tension was reduced at 7 and 14 days, but was reduced only at 21 days when expressed as a fraction of the muscle weight. Post-tetanic twitch potentiation failed to appear in the denervated muscle. It would appear that neonatal denervation results in an uncoupling of the developmental pattern of skeletal muscle.