The 91% to 98% clinician compliance indicates eProtocol-insulin is an exportable instrument that can establish a replicable experimental method for clinical trials of blood glucose management in critically ill adults. Control of blood glucose was better with eProtocol-insulin than with a simple clinical guideline or a paper-based protocol.
Purpose: Although the mutator phenotype, including genetic and epigenetic alterations of the mismatch repair (MMR) system, seems to be pronounced in familial colorectal cancer, there have been few integrative studies comprising the entire mutator pathway. This study was done to identify the entire mutator pathway determining risk factors in patients with familial colorectal cancer not fulfilling the Amsterdam criteria.Experimental Design: We consecutively recruited 134 colorectal cancer patients with a family history of accompanying cancers. Patients with hereditary nonpolyposis colorectal cancer meeting the Amsterdam criteria, familial adenomatous polyposis, or those receiving preoperative radiotherapy were excluded. Mutator phenotype was assessed by assaying microsatellite instability (MSI) at 24 markers, hMLH1-promoter methylation, mutations at MMR genes (hMLH1, hMSH2, hMSH6, and hPMS2), and immune staining of MMR proteins (hMLH1, hMSH2, hMSH6, hPMS1, and hPMS2).Results: Of the 208 cancers in first-degree and/or second-degree relatives of patients, colorectal and gastric cancers (81%) were most common. Of the 134 proband colorectal cancers, 23 (17%) were MSI in high level, and 32 (24%) were MSI in low level. MMR alterations, including known polymorphism and splicing substitution, were identified in eight patients (6%). Twenty-eight tumors with mutator phenotype were further identified by hMLH1-promoter methylation and/or loss of MMR protein expression. In 51 tumors (38%), mutator phenotype was associated with right-sided colon cancer (P < 0.001) and younger age at onset (P ؍ 0.032), but the number of patients with a mutator phenotype did not differ with respect to inheritance patterns of accompanying cancers, either successive or horizontal transmission (P ؍ 0.815). Familial impact value, which differentially associated the degree of relatives with all accompanying cancers, effectively discriminated MSI in high level from microsatellite stable/MSI in low level tumors.Conclusion: Familial colorectal cancer may be associated with multiple occurrences of colorectal or accompanying cancers inherited by dominant or recessive transmission. MMR gene mutations, however, are less associated with mutator phenotype in familial colorectal cancer.
Clinical decision-making is based on knowledge, expertise, and authority, with clinicians approving almost every intervention—the starting point for delivery of “All the right care, but only the right care,” an unachieved healthcare quality improvement goal. Unaided clinicians suffer from human cognitive limitations and biases when decisions are based only on their training, expertise, and experience. Electronic health records (EHRs) could improve healthcare with robust decision-support tools that reduce unwarranted variation of clinician decisions and actions. Current EHRs, focused on results review, documentation, and accounting, are awkward, time-consuming, and contribute to clinician stress and burnout. Decision-support tools could reduce clinician burden and enable replicable clinician decisions and actions that personalize patient care. Most current clinical decision-support tools or aids lack detail and neither reduce burden nor enable replicable actions. Clinicians must provide subjective interpretation and missing logic, thus introducing personal biases and mindless, unwarranted, variation from evidence-based practice. Replicability occurs when different clinicians, with the same patient information and context, come to the same decision and action. We propose a feasible subset of therapeutic decision-support tools based on credible clinical outcome evidence: computer protocols leading to replicable clinician actions (eActions). eActions enable different clinicians to make consistent decisions and actions when faced with the same patient input data. eActions embrace good everyday decision-making informed by evidence, experience, EHR data, and individual patient status. eActions can reduce unwarranted variation, increase quality of clinical care and research, reduce EHR noise, and could enable a learning healthcare system.
Acute unilateral lung injury in the dog results in increased NO production that is compartmentalized to the injured lung. The increase in exhaled NO after injury is transient and does not allow one to monitor the progress of lung injury.
To the Editors:The risk for developing de novo hepatitis B from liver donors was recently highlighted by a study from Spain, 1 where there is a greater background of antibody to hepatitis B core antigen (anti-HBc) positivity (10%). 2 Their study concluded that the risk for having an antiHBc-positive liver donor (12% in their study) increased with age and was related to a significant rate of de novo hepatitis B if the donor was anti-HBc positive (50%). 1 In an earlier study from the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database, the rate of de novo hepatitis B was even greater (78%) 3 for their anti-HBc-positive donors. The Pittsburgh data had a similar rate of infection of 72% with 25 such liver transplants. 4 We examined the results from our small transplant series 5 over the last 5 years in Singapore, and our results are strikingly different from those in the Western series. We had only 30 cadaveric donors in this period, and performed 32 liver transplantations with 2 split transplants. Sixteen of the 30 donors (53%) had anti-HBc positivity (Microparticle Immunoassay; Abbott Axsym, Abbott Park, IL). We performed transplantation on 11 hepatitis B surface antigen-negative patients from 11 (58%) anti-HBc-positive donors. Only 3 of these patients had significant antibody to hepatitis B surface antigen titers. However, with a median follow-up of 18 months and no prophylactic treatment, there were only 2 de novo hepatitis B cases (18%) and no cases of de novo hepatitis B in patients receiving a graft from antiHBc-negative donors. Similar to the Spanish findings (Table 1), the group with anti-HBc positivity was significantly older than the anti-HBc-negative group (41 Ϯ 13.6 v 29 Ϯ 14.3 years; t-test P ϭ .026).A recent seroepidemiological survey performed in Singapore among healthy volunteers from March 1998 to June 1999 showed a 27.1% (95 of 350 volunteers) rate of anti-HBc positivity in unvaccinated individuals aged from 5 years to older than 45 years. 6 An older survey in 1981 among children aged younger than 12 years had an even greater rate of anti-HBc positivity for those with Chinese ethnicity (30.2%). 7 In view of the high prevalence rate of anti-HBc positivity, we ensure that our transplant recipients are vaccinated for hepatitis B if they are not naturally immune or have hepatitis B. The reason for the much lower de novo hepatitis B rate is unclear and warrants further investigation.
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