An evidence-based treatment algorithm for colorectal polyp cancers: results from the Scottish Screen-detected Polyp Cancer Study (SSPoCS).

OBJECTIVES: Colorectal polyp cancers present clinicians with a treatment dilemma. Decisions regarding whether to offer segmental resection or endoscopic surveillance are often taken without reference to good quality evidence. The aim of this study was to develop a treatment algorithm for patients with screen-detected polyp cancers. DESIGN: This national cohort study included all patients with a polyp cancer identified through the Scottish Bowel Screening Programme between 2000 and 2012. Multivariate regression analysis was used to assess the impact of clinical, endoscopic and pathological variables on the rate of adverse events (residual tumour in patients undergoing segmental resection or cancer-related death or disease recurrence in any patient). These data were used to develop a clinically relevant treatment algorithm. RESULTS: 485 patients with polyp cancers were included. 186/485 (38%) underwent segmental resection and residual tumour was identified in 41/186 (22%). The only factor associated with an increased risk of residual tumour in the bowel wall was incomplete excision of the original polyp (OR 5.61, p=0.001), while only lymphovascular invasion was associated with an increased risk of lymph node metastases (OR 5.95, p=0.002). When patients undergoing segmental resection or endoscopic surveillance were considered together, the risk of adverse events was significantly higher in patients with incomplete excision (OR 10.23, p<0.001) or lymphovascular invasion (OR 2.65, p=0.023). CONCLUSION: A policy of surveillance is adequate for the majority of patients with screen-detected colorectal polyp cancers. Consideration of segmental resection should be reserved for those with incomplete excision or evidence of lymphovascular invasion.

A minimum estimate for the incidence of gastric cancer in Eastern Kenya.

We documented available information concerning incident cases of gastric cancer in part of Kenya's Eastern Province between 1991 and 1993. By reviewing the records of all major health facilities in the area, 200 cases of gastric carcinoma were found giving an annual average crude incidence rate of 7.01 per 100 000 males and 3.7 for females (world age-standardised rates, 14.3 for males and 7.1 for females). There is likely to be underascertainment of cases especially among those aged over 65 years. Previous incidence estimates for the same area of Kenya were reviewed and a 10-fold increase in the recorded indirectly standardised incidence rate between the periods 1965-70 and 1991-93 was noted but this may be due to improved diagnostic facilities. The recent rates in this part of Kenya are comparable to Eastern European rates and similar to those recorded in other highland regions of Africa.

A prepaid healthcare scheme in rural Africa.

Healthcare providers in Africa are having to increasingly rely on the resources of the populations they serve. An 8-year experience with one of the first rural-based health insurance schemes in East Africa is described. Initial difficulties included adverse selection of members with chronic ill health, fraudulent claims and overuse of health services, leading to considerable financial losses. External technical assistance introduced member tracking and regular reports, reduced adverse selection, fraud and overuse of services to a minimum, and achieved financial stability. Local market research and a comprehensive marketing plan is essential for the overall success of an insurance plan. Health insurance in this part of Africa is likely to assist middle income earners rather than the poor.

Trends over time in Helicobacter pylori gastritis in Kenya.

OBJECTIVE AND DESIGN: There is increasing evidence to link infection of the gastric mucosa by Helicobacter pylori with the subsequent development of gastric cancer. This study was undertaken to document the progression of H. pylori gastritis in a rural Kenyan population with a moderate gastric cancer risk. METHOD: Biopsy follow-up study of 51 H. pylori-positive patients over an average of 5.5 years. RESULTS: In the study group, the number of individuals with moderate to severe atrophy rose from 17 (33%) to 22 (43%), an annual increase of 1.8% [95% confidence interval (CI) -0.9% to 4.4%]. There was significant progression of atrophy (P< 0.05) in those with low overall scores for graded morphological variables at initial endoscopy. Intestinal metaplasia did not progress; indeed four out of 12 patients initially diagnosed with intestinal metaplasia showed no evidence of it in their follow-up biopsies. CONCLUSIONS: H. pylori gastritis with atrophy may provide a suitable environment within the gastric mucosa for the development of gastric cancer but it is likely that other factors in this population determine further progress towards dysplasia and cancer.

A controlled trial of an educational pamphlet to prevent disability after occupational low back injury.

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To test the ability of an educational pamphlet to improve recovery in terms of pain, work status, and health care utilization after occupational low back injury. BACKGROUND: Low back pain and disability persist as occupational health problems of epidemic proportions. Because interventions based on biomechanical models have had limited impact, recent educational approaches to preventing back problems have stressed psychosocial recovery issues. METHODS: A pamphlet was developed by compiling activity resumption, self-care, and attitudinal advice from recent publications. The pamphlet was sent at random to half of all consenting workers reporting back pain within 11 days of occupational injury between 7/96 and 6/97. Three and 6 months later, back pain, work status, health care use, and pamphlet impact outcomes were assessed through structured telephone interviews. RESULTS: Of the 726 eligible workers, 486 consented to participate. Consenters and nonconsenters and intervention and control groups were similar in initial demographic variables. The pamphlet had no statistically significant impact at the 0.05 significance level on pain severity or reduction, health care visits, or work absence. Of the 229 pamphlet recipients, 129 thought it had provided useful information, but only 25 thought it had helped them return to work more quickly. CONCLUSIONS: In this trial, a pamphlet stressing psychosocial recovery issues did not prevent or reduce postinjury pain, health care use, or work absence.

Design and SAR of novel potassium channel openers targeted for urge urinary incontinence. 2. Selective and potent benzylamino cyclobutenediones.

A novel series of benzylamine, potassium channel openers (KCOs) is presented as part of our program toward designing new, bladder-selective compounds for the treatment of urge urinary incontinence (UUI). We have found that the in vitro potency of (R)-4-[3,4-dioxo-2-(1,2, 2-trimethyl-propylamino)-cyclobut-1-enylamino]-3-ethyl-benzo nitrile 1 in the relaxation of precontracted rat detrusor strips can also be obtained with cyanobenzylamine derivative 4 (IC(50) = 0.29 microM) (Figure 3). Addition of a 2-Cl substituted benzylamine moiety and changing the alkylamino substituent of 4 to a t-Bu amine gives 31 (IC(50) = 0.14 microM)-a compound with similar in vitro potency as 4 as well as relaxant activity on bladder smooth muscle in vivo when administered orally (31, ED(50) = 3 mg/kg) in a rodent model of bladder instability. Further modifications, particularly the replacement of the t-Bu amino substituent with a tert-amylamine, gave a similarly active compound 60 (IC(50) = 0.10 microM) which shows excellent in vivo efficacy (ED(50) = 0.6 mg/kg). Moreover, 60, 3-(2,4-dichloro-6-methyl-benzylamino)-4-(1, 1-dimethyl-propylamino)-cyclobut-3-ene-1,2-dione (WAY-151616), shows excellent tissue selectivity for bladder K channels over arterial tissue (60, MAP ED(20) = 100 mg/kg; selectivity: MAP ED(20)/bladder ED(50) = 166). Other manipulations of the benzylamino cyclobutenediones, acylation of the benzylamine, conversion of the benzylamine substituent to a benzamide, homologation of the benzylamine to a phenethylamine, and incorporation of a methyl group at the benzyl carbon, all led to substantial loss of in vitro activity, although some in vivo activity was maintained in the acylated analogues. Compound 60 represents an attractive candidate for development in the treatment of UUI.

Abdominal cocoon: report of five cases.

Abdominal cocoon (idiopathic sclerosing peritonitis) has now been reported in many parts of the world but remains principally a disease of the tropics and sub-tropics. Five cases diagnosed at a rural Kenyan hospital between 1993 and 1998 are presented and the operative findings and management is discussed. Although the condition normally occurs in adolescent girls, one patient was noted to be forty two years of age, and was subsequently found to have AIDS.

Reduced risk of AIDS lymphoma in individuals heterozygous for the CCR5-delta32 mutation.

Non-Hodgkin's lymphoma (NHL) has been increasing in frequency in the industrialized world, but the environmental and genetic factors that contribute to susceptibility are not known. B-cell lymphomas represent a major cause of morbidity and mortality in HIV-infected individuals. The identification of a deletion in the CCR5 chemokine receptor gene that alters the risk for infection and progression to AIDS led us to examine a potential role of this gene in AIDS lymphoma. A matched case-control analysis was performed using all eligible NHL cases in the Multicenter AIDS Cohort Study. Patients were matched for age, study center, time AIDS-free, and slope of the CD4+ T-cell decline. The CCR5-delta32 allele was found to be associated with a 3-fold lower risk of NHL among individuals after controlling for time of infection and progression toward AIDS. The CCR5 gene was not associated with a difference in risk for Kaposi's sarcoma, another common malignancy in AIDS patients, or opportunistic infections. Costimulation of normal phorbol 12-myristate 13-acetate-treated B cells with the CCR5 ligand RANTES induced a proliferative response, indicating that RANTES is a mitogen for B cells. Taken together, these findings suggest that the CCR5 gene plays a role in the risk of NHL in HIV-infected patients, perhaps through a mechanism involving a decreased response of B cells to the mitogenic activity of RANTES.

Combination antiretroviral therapy improves psychomotor speed performance in HIV-seropositive homosexual men. Multicenter AIDS Cohort Study (MACS).

BACKGROUND: Combination antiretroviral therapy including protease inhibitors (combo+PI) is effective in suppressing systemic viral load in HIV infection, but its impact on HIV-associated cognitive impairment is unclear. OBJECTIVE: To determine whether psychomotor speed, a sensitive measure of impairment in HIV dementia, improves with combo+PI compared with other antiretroviral treatments. METHODS: A total of 411 HIV-seropositive (HIV+) homosexual men (with longitudinal neuropsychological testing) in the Multicenter AIDS Cohort Study and, in a separate analysis, 282 HIV+ homosexual men with psychomotor slowing at baseline were classified by treatment into four groups: antiretroviral naive (no antiretroviral medication treatment), monotherapy, combination antiretroviral therapy without protease inhibitors (combo-noPI), and combo+PI. We compared longitudinal performance on three tests of psychomotor speed: the Grooved Pegboard (GP) (nondominant and dominant hands), Trail Making Test B, and the Symbol Digit Modalities Test (SDMT). RESULTS: Relative to antiretroviral-naïve and monotherapy participants, on the GP nondominant hand test, combo+PI participants with abnormal baseline neuropsychological testing showed improved performance (difference = +0.63 standard deviation [SD], p = 0.02). For the SDMT, both combo+PI participants (difference = +0.26 SD, p = 0.03) and combo-noPI participants (difference = +0.29 SD, p = 0.01) with abnormal baseline neuropsychological testing improved compared with antiretroviral-naïve and monotherapy groups. CONCLUSION: Combo+PI and combo-noPI are associated with improved psychomotor speed performance in HIV+ homosexual men with abnormal neuropsychological testing.

Effectiveness of potent antiretroviral therapy on time to AIDS and death in men with known HIV infection duration. Multicenter AIDS Cohort Study Investigators.

CONTEXT: Time to development of acquired immunodeficiency syndrome (AIDS) and time to death have been extended with the increased use of combination therapy and protease inhibitors. Cohort studies following up persons with human immunodeficiency virus (HIV) infection in periods characterized by different therapies offer the opportunity to estimate therapy effectiveness at the population level. OBJECTIVE: To assess the effectiveness of self-reported, long-term potent antiretroviral therapy in a cohort of 536 men whose duration of HIV infection was known (seroconverters). DESIGN: Cohort study. The cohort was compared for time to development of AIDS and time to death in 1984 to 1990, 1990 to 1993, 1993 to July 1995, and July 1995 to July 1997 when the major treatments were no therapy, monotherapy, combined therapy, and potent antiretroviral therapy, respectively. Survival analysis methods with time zero set as the date of seroconversion and incorporating staggered entries into each period were used. Mean CD4 cell change, stratified by infection duration, was determined for each period using a random effects model. SETTING: The Multicenter AIDS Cohort Study (MACS) in 4 urban areas (Baltimore, Md; Chicago, III; Los Angeles, Calif; and Pittsburgh, Pa). PARTICIPANTS: A total of 5622 men who were 18 years or older were enrolled into MACS. Of the 5622, there were 2191 HIV-positive individuals at enrollment. Of the 3431 men who were HIV-negative, 536 were observed to seroconvert and were followed up for up to 13 years. The group of 536 who seroconverted constituted the study population. MAIN OUTCOME MEASURES: Time from seroconversion to development of AIDS and to death and change in CD4 cell count. RESULTS: A total of 231 seroconverters developed AIDS, and 200 men died. Using 1990 to 1993 as the reference period, the relative hazard of AIDS was 1.04 (95% confidence interval [CI], 0.73-1.48) during 1993 to July 1995 and 0.35 (95% CI, 0.20-0.61) during July 1995 to July 1997. Relative hazards of death were 0.87 (95% CI, 0.58-1.31) and 0.62 (95% CI, 0.38-1.01 ) for the same periods. The relative time (the factor by which times are contracted or expanded) to development of AIDS was 0.97 (95% CI, 0.86-1.09) for 1993 to July 1995 and 1.63 (95% CI, 1.40-1.89) for July 1995 to July 1997. Relative survival time for 1993 to July 1995 was 1.01 (95% CI, 0.91-1.12) and for July 1995 to July 1997 was 1.21 (95% CI, 1.07-1.36) relative to 1990 to 1993. The rate of CD4 cell count decline in July 1995 to July 1997 was significantly lower (P<.05) compared with the previous 2 periods. CONCLUSIONS: In the calendar period when potent antiretroviral therapy was introduced, the time to development of AIDS and time to death were extended, and rate of CD4 cell count decline was arrested.

Prevalence of abdominal aortic aneurysms in patients undergoing coronary artery bypass.

Although several studies describe the prevalence of coronary artery disease in patients with abdominal aortic aneurysms (AAA), the opposite relationship is virtually unexplored. It is the purpose of this study to determine the prevalence of AAA in patients with severe coronary artery disease undergoing bypass grafting (CABG). Patients scheduled for elective CABG underwent aortic ultrasound (US) preoperatively. A control group of patients without cardiovascular disease also underwent US. An AAA was defined as a maximal diameter > or =3.0 cm. US was performed on 192 CABG patients and 140 controls. The overall prevalence (previously repaired AAA and new cases) of AAA in CABG patients was 18.2%. The prevalence of new cases of AAA was 13.0% compared to 1.4% in controls (p = 0.0001). Ten patients had an AAA greater than 5.0 cm in size (5.2%). Logistic regression identified age > or =65 years and smoking as significant risk factors for AAA in the CABG population. The higher prevalence of AAA in CABG patients was confirmed by a case-control analysis of 73 age-matched patients. This study provides the first convincing evidence that the prevalence of AAA is higher in patients undergoing CABG than in the control population in Vermont. Consideration should be given to screening patients for AAA who are undergoing CABG, particularly older, smoking males.

Helicobacter pylori and gastric cancer.

BACKGROUND: Considerable progress has been made over the past two decades in understanding gastric carcinogenesis. Genetic and environmental factors have been shown to play a part. Infection with Helicobacter pylori leads to chronic gastritis and evidence is accumulating to link this disease with the subsequent development of gastric cancer. METHOD: A literature review was undertaken using Medline (National Library of Medicine, Washington DC, USA) searches of the headings gastrointestinal neoplasms and H. pylori for the years 1993-1997; further relevant references were examined. RESULTS: H. pylori is implicated in gastric carcinogenesis. Proposed mechanisms centre on the inflammatory response of the gastric mucosa to the bacterium. CONCLUSION: Investigation is still required to elucidate the exact role of H. pylori in the development of gastric carcinoma. Eradication of the organism in high-risk groups might lead to a reduction in the incidence of gastric cancer.

Desktop teleradiology in support of rural orthopedic trauma care.

UNLABELLED: Research has shown that diagnostic quality images for most teleradiology applications requires a sophisticated telemedicine system and access to a large amount of bandwidth. While the ideal standards have been set by those involved in evaluating teleradiology, these standards are impractical for many small rural health centers which deliver routine trauma care. While there is no disagreement about the ultimate need for this level of teleradiology support, the purpose of this research was to determine whether Orthopedists would be able to read plain radiographs of orthopedic trauma injuries using a desktop teleradiology system in support of rural trauma care. METHOD: Two radiology residents and two orthopedic residents viewed forty radiographs, twenty through a desktop teleradiology system and twenty in person. Diagnostic findings and certainty of diagnosis were recorded. FINDINGS: There was no statistically significant difference between modalities in orthopedic residents' ability to correctly diagnose orthopedic trauma injuries. Further, for those instances when the diagnosis was imprecise, the residents were aware of their inability to make an accurate diagnosis. CONCLUSION: Although the study was relatively limited and further research needs to be done, the use of desktop teleradiology in support of rural orthopedic trauma consultation is a promising alternative to the more expensive forms of telemedicine technology.

Early physician notification of patient disability risk and clinical guidelines after low back injury: a randomized, controlled trial.

STUDY DESIGN: Back-injured workers with high disability risk scores on a predictive questionnaire participated in a randomized, controlled trial of physician notification, with outcomes follow-up 3 months after injury. OBJECTIVES: To test whether physician intervention improves return to work and self-assessment outcomes for people at relatively high risk for disability. SUMMARY OF BACKGROUND DATA: Only a small number of back-injured workers suffer significant disability. Quick identification of these people would facilitate more efficient targeting and trials of interventions. Controlling variations in practice through practice guidelines has been recommended as a promising strategy for improving care and reducing disability. METHODS: Workers filing back injury reports responded to a disability prediction questionnaire. Those with high risk scores were randomly assigned to control or intervention groups. Patient-designated physicians in the intervention group received two letters identifying the patient's risk and making recommendations for care, including the Agency for Health Care Policy and Research's algorithms for acute low back pain. Predictive accuracy of the questionnaire and efficacy of physician intervention were evaluated on the basis of work status and self-assessments 3 months after injury. RESULTS: Of the 268 workers completing the questionnaire portion of the study, 32 (12%) were out of work because of back pain 3 months after injury. The questionnaire's predictive accuracy included maximum kappa of 0.277 and a receiver operating curve area of 0.78. Fifty-three people completed the physician intervention trial. The intervention had no significant impact on return to work, self-assessed pain, or satisfaction with health care. CONCLUSIONS: Stratification of back-injured people according to disability risk can can increase intervention efficiency by identifying those who require treatment and sparing those who do not. The apparent failure of risk notification and practice guidelines to reduce disability in this study may be improved by different application methods in the future.

Education strategy for the implementation of computerized nursing documentation.

Educators at The Toronto Hospital took an innovative approach to providing education and support to nursing staff prior to, during, and after the implementation of computerized nursing documentation. The education strategy included a combination of formal classroom training, inservices on the unit, a self-learning package and an electronic scavenger hunt. Resources such as Clinical Teachers, Clinical Nurse Specialists and Information Systems Analysts and Educators who provided support during the implementation phase received additional education to prepare for their role on the nursing units. Nurses were provided intensive twenty-four hour support for a period of four weeks, and a documentation checklist helped monitor the progress of individual nurses during the implementation. This strategy was designed to maximize consistent support and to minimize cost.

Efficient optical frequency-comb generator.

We have demonstrated a method that efficiently transfers the power from a single-frequency laser into a wideband frequency comb. The comb was produced by a 2.7-GHz electro-optic modulator in a resonant optical cavity. A coupled cavity technique was used to transfer 8.5% of the laser power into a comb with a span of 400 modes, or more than 1 THz.

Hepatitis B control in Toronto classrooms for the mentally retarded: a seroprevalence survey.

A seroepidemiologic hepatitis B survey of students and staff at schools for the mentally retarded in the City of Toronto found 2.5% of students to be carriers, 5% to be immune without being immunized, 11.3% to have immunization underway or complete, and 81.2% to be susceptible. The first two groups were older and more likely to have been born in countries with intermediate or high hepatitis B marker prevalence. Among staff tested, 4.1% were immune without immunization while all others were susceptible. Because hepatitis B control recommendations could not be made on the basis of these results alone, local Medical Officers of Health also considered other studies and practical experience to recommend the following: (1) Use Ontario Ministry of Health Guidelines for mentally retarded hepatitis B carriers in regular schools; (2) Offer hepatitis B vaccine to all susceptible students and staff in schools specifically for the mentally retarded.

Antihypertensive therapy in diabetic patients. The use of indapamide.

Abnormalities in glucose tolerance in nondiabetic patients and rapid alteration in non-insulin-dependent diabetics have been reported with antihypertensive drugs such as beta-blockers or thiazide diuretics. Such deleterious effects on a cardiovascular risk factor could limit the long-term benefit of an antihypertensive treatment. Indapamide is a nonthiazide antihypertensive agent that appears to respect the glucose tolerance in hypertensive patients. The present study was conducted to assess the effects of indapamide 2.5 mg in 10 hypertensive non-insulin-dependent diabetic patients treated for a one-year period. Glucose tolerance was evaluated using a 50-g oral glucose test, with measurements of plasma glucose and insulin before and after treatment. At the end of the one-year treatment, both systolic and diastolic blood pressure were significantly reduced, whereas there was no significant alteration in either plasma glucose or plasma insulin levels. Thus, indapamide appears as an effective antihypertensive agent in the diabetic patient, with no adverse effects on the glucose tolerance.