Randomised clinical trial: a 'nudge' strategy to modify endoscopic sedation practice

Aliment Pharmacol Ther 2011; 34: 229–234

Summary

Background In behavioural economics, a ‘nudge’ describes configuration of a choice to encourage a certain action without taking away freedom of choice. Aim To determine the impact of a ‘nudge’ strategy – prefilling either 3 mL or 5 mL syringes with midazolam – on endoscopic sedation practice. Methods Consecutive patients undergoing sedation for EGD or colonoscopy were enrolled. On alternate weeks, midazolam was prefilled in either 3 mL or 5 mL syringes. Preprocedure sedation was administered by the endoscopist to achieve moderate conscious sedation; dosages were at the discretion of the endoscopist. Meperidine was not prefilled. Results Overall, 120 patients received sedation for EGD [59 (5 mL), 61 (3 mL)] and 86 patients were sedated for colonoscopy [38 (5 mL), 48 (3 mL)]. For EGDs, average midazolam dose was significantly higher in the 5‐mL group (5.2 mg) vs. 3‐mL group (3.3 mg), (P < 0.0001); for colonoscopies, average midazolam dose was also significantly higher in the 5‐mL group (5.1 mg) vs. 3‐mL group (3.3 mg), (P < 0.0001). There was no significant difference in mean meperidine dose (42.1 mg vs. 42.8 mg, P = 0.9) administered to both colonoscopy groups. No adverse sedation‐related events occurred; no patient required reversal of sedation. Conclusions These findings demonstrate that ‘nudge’ strategies may hold promise in modifying endoscopic sedation practice. Further research is required to explore the utility of ‘nudges’ in impacting other aspects of endoscopic practice.     

Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11

We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation.     

Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations

Lynch syndrome or hereditary non-polyposis colorectal cancer is caused by mutations of DNA mismatch repair (MMR) genes. The extracolonic tumour spectrum includes endometrial, ovarian, gastric, small bowel, pancreatic, hepatobiliary, brain, and urothelial neoplasms. Families were referred on the basis of clinical criteria. Tumour immunohistochemistry and microsatellite testing were performed. Appropriate patients underwent sequencing of relevant exons of the MMR genes. Proven and obligate mutation carriers and first-degree relatives (FDRs) with a Lynch syndrome spectrum cancer were considered mutation carriers, as were a proportion of untested, unaffected FDRs based on the proportion of unaffected relatives testing positive in each age group. Kaplan–Meier analysis of risk to 70 years was calculated. One hundred and eighty-four Lynch syndrome spectrum extracolonic cancers in 839 proven, obligate, or assumed mutation carriers were analysed. Cumulative risk for females of an extracolonic tumour is 47.4% (95% CI 43.9–50.8). The risk to males is 26.5% (95% CI 22.6–30.4). There was no reduction in gynaecological malignancies due to gynaecological screening (examination, transvaginal ultrasound scan, hysteroscopy and endometrial biopsy). Males have a higher risk of gastric cancer than females (p = 0.0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic.     

Intra-articular analgesia for arthroscopic meniscectomy

Intra-articular morphine has been shown to provide prolonged analgesia after arthroscopic knee surgery; the addition of local anaesthetic agents has been reported to improve this analgesic effect. Pethidine possesses local anaesthetic properties, and therefore this study was designed to evaluate its analgesic efficacy after arthroscopic meniscectomy. Sixty patients were allocated randomly to receive intra- articular injections of pethidine 50 mg, morphine 5 mg or saline after elective arthroscopic meniscectomy. Postoperative pain was assessed using an interval visual analogue scale and measuring analgesic requirements. Both treatment groups had significantly lower pain scores compared with the control group. Patients in the pethidine group had lower pain scores than those in the morphine group at 0.5, 1 and 2 h, but significantly higher scores at 12 and 24 h. These observations suggest that the local anaesthetic effect of pethidine may be responsible for the improved early analgesia, but its duration of action appears to be less than that of morphine.      

Linkage of a familial platelet disorder with a propensity to develop myeloid malignancies to human chromosome 21q22.1-22.2

Linkage analysis was performed on a large pedigree with an autosomal dominant platelet disorder and a striking propensity in affected family members to develop hematologic malignancy, predominantly acute myelogenous leukemia. We report the linkage of the autosomal dominant platelet disorder to markers on chromosome 21q22. Four genetic markers completely cosegregate with the trait and yield maximum logarithm of difference scores ranging from 4.9 to 10.5 (theta = .001). Two flanking markers, D21S1265 and D21S167, define a critical region for the disease locus of 15.2 centimorgan. Further analysis of this locus may identify a gene product that affects platelet production and function and contributes to the molecular evolution of hematologic malignancy.     

Splenic lymphoma with villous lymphocytes involves B cells with extensively mutated Ig heavy chain variable region genes

Splenic lymphoma with villous lymphocytes (SLVL) is a recently defined subgroup of chronic B-cell lymphoproliferative diseases. The characteristic morphology of the tumor cells, together with phenotypic and cytogenetic findings, indicate that it is a distinct entity, but the nature of the cell or origin and its relationship to other low- grade lymphomas is unclear. For B-cell tumors, analysis of the variable region heavy chain (VH) genes used to encode the clonal Ig has shown marked differences between histologic categories, both in gene usage and extent of somatic mutation. An investigation of VH genes used in five typical cases of SLVL has shown somatic hypermutation from germline sequences in all cases, indicating that the cell of origin has been exposed to the hypermutation mechanism. However, no clonal heterogeneity was detectable, demonstrating that the tumor cell does not accumulate further mutations. These characteristics are similar to those found in mature postfollicular B cells, such as plasma cells. The distribution of mutations leading to replacement amino acids differed among the cases, with three of five cases showing clear evidence for antigen selection.     

Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency

Homocysteine can be methylated to form methionine by the cobalamin- (Cbl) and folate-dependent enzyme, methionine synthase; serum levels of total homocysteine are elevated in greater than 95% of patients with either Cbl or folate deficiency. Homocysteine can also condense with serine to form cystathionine in a pyridoxal phosphate-dependent reaction catalyzed by cystathionine beta-synthase. Cystathionine is subsequently cleaved to cysteine and alpha-ketobutyrate by the pyridoxal phosphate-dependent enzyme gamma-cystathionase. To assess levels of cystathionine in Cbl and folate deficiency, we developed a new capillary gas chromatographic-mass spectrometric assay and measured cystathionine in the serum of normal subjects and patients with clinically confirmed deficiencies of these vitamins. The normal range for serum cystathionine was 65 to 301 nmol/L (median = 126 nmol/L) for 50 normal blood donors. In 30 patients with clinically confirmed Cbl deficiency, values for cystathionine ranged from 208 nmol/L to 2,920 nmol/L (median = 816 nmol/L) and 26 (87%) had levels above the normal range. In 20 patients with clinically confirmed folate deficiency, cystathionine concentrations ranged from 138 nmol/L to 4,150 nmol/L (median = 1,560 nmol/L) and 19 (95%) had values above the normal range. Five homozygotes for cystathionine beta-synthase deficiency had high values for serum-total homocysteine and low or low-normal values for serum cystathionine that ranged from 30 nmol/L to 114 nmol/L even though they were on treatment with pyridoxine and had partially responded. One patient with a defect in the synthesis of 5-CH3- tetrahydrofolate and five patients with defects in the synthesis of CH3- Cbl had high values for serum-total homocysteine and high values for cystathionine that ranged from 311 nmol/L to 1,500 nmol/L even though they were on treatment with folic acid and Cbl, respectively, and had partially responded. We conclude that levels of cystathionine are evaluated in the serum of most patients with Cbl and folate deficiency and that they are useful in the differential diagnosis of an elevated serum-total homocysteine level.