The cardiovascular benefits of indiscriminate supplementation of omega-3 fatty acids; meta-analysis and decision-making approach.

AIM: The meta-analysis was conducted to estimate of the cardiovascular benefits of indiscriminate supplementation of omega-3 capsules. The results, expressed in terms of quality adjusted life years (QALY) intuitively understood by the general public, can be the basis for the (personal) decision on whether to take omega-3 supplements. METHODS: The results of meta-analysis of eight double-blind, placebo-controlled clinical trials are expressed in terms of QALY, using the Markov model and Monte Carlo simulations. RESULTS: Omega-3 supplementation results in a 8% decrease of the risk of cardiac death, unless the patients are treated by statins. Results indicate that omega-3 supplementation may prolong QALY by about a month. Old people gain less, whereas DM-2 patients and people with history of CV events gain more. DISCUSSION: Our analysis yielded an algorithm for estimating benefit from omega-3 supplementation, based on the age and the individual risk of CV events of the patient.

The outcome of ulcerative colitis patients undergoing pouch surgery is determined by pre-surgical factors.

BACKGROUND: Pouch surgery, a common intervention for ulcerative colitis (UC) complications, is often associated with the development of pouchitis. AIM: To identify predictors of pouch outcome in a cohort of patients with UC. METHODS: We conducted a retrospective unmatched case-cohort study in a tertiary IBD referral centre. Adult patients with UC were classified into the worst phenotype throughout follow-up: normal pouch, a form of chronic pouchitis (either chronic pouchitis or Crohn's like disease of pouch [CLDP]), or episodic recurrent acute pouchitis (RAP). Risk factors for pouchitis (chronic forms) were detected using statistical models. RESULTS: Two hundred and fifty-three pouch patients were followed up for 13.1±7.3 years. Only 71 patients (28.1%) maintained a favourable outcome of a sustained normal pouch. These patients were older at UC diagnosis (27.8±12.5 vs 23.0±11.4 years), had longer UC duration until surgery (13.4±9.5 vs 8.2±7.9 years), and had higher rates of referral to surgery due to nonrefractory (dysplasia/neoplasia) complications (42.3% vs 16.2%) compared with pouchitis patients. Median survival for sustained normal pouch was 10.8 years (95% CI 8.9-12.7 years), and it was longer in the nonrefractory group (20.3 vs 9.4 years for the refractory group, HR=2.37, 95% CI 1.25-3.52, P=.004). CONCLUSIONS: Most patients with UC undergoing pouch surgery will develop pouchitis. Patients operated for nonrefractory indications have a more favourable outcome. These results may contribute to pre- and post-surgical decision-making. The findings imply that the processes determining UC severity may be similar to that causing pouchitis.

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 2.

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.

Strategies to manage hepatitis C virus (HCV) infection disease burden - volume 2.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.

The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2.

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.

Assessment of the underestimation of childhood diarrhoeal disease burden in Israel.

We determined the extent by which mandatory reporting on isolates of Shigella and Salmonella underestimates the burden of diarrhoeal diseases in individuals aged <17 years in Israel and examined paediatricians' knowledge, attitudes and practices related to patient visits with diarrhoeal diseases. Sources of data were a nationwide population-based telephone survey for presence of diarrhoeal diseases, Maccabi Healthcare Services databases and a mail survey among its paediatricians. Monte Carlo simulation and rate estimates for all stages, from visit to physician to reporting on a culture-confirmed case of shigellosis or salmonellosis, were used to determine the underestimation factor. Of 1492 children, 5·7% reported a diarrhoeal episode during the 2 weeks prior to interview. The rate of visiting a physician with and without fever was 86% and 16%, respectively. A stool culture was performed for around 20% of patients and the isolation rates were 7·1% for Shigella and 2·1% for Salmonella. Paediatricians (n=214) ranked very young age of patient and the complaint 'bloody diarrhoea' as the most important determinants. We estimated that one reported isolate of Shigella or Salmonella represented 152 diarrhoeal episodes of all aetiologies. This estimate is important for further assessments of the true burden of diarrhoeal diseases.

Cost effectiveness of mass screening for coeliac disease is determined by time-delay to diagnosis and quality of life on a gluten-free diet.

BACKGROUND: Coeliac disease is frequently diagnosed after a long delay resulting in increased morbidity and mortality. AIMS: To define the parameters which have the highest impact on the cost-effectiveness of mass screening for coeliac disease. METHODS: A Markov model examined a coeliac disease screening programme of the healthy young-adult general population compared with a no-screening strategy. The main outcome measures were quality adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). Effects of variables were examined using sensitivity analyses. RESULTS: The screening strategy resulted in a gain of 0.0027 QALYs. The ICER of screening vs. no-screening strategy was US$48,960/QALYs. The variables with the largest impact on cost effectiveness were: the time delay from symptom onset to diagnosis, the utility of adherence to a gluten-free diet (GFD) and the prevalence of coeliac disease. Screening would be cost-effective if the time delay to diagnosis is longer than 6 years and utility of GFD adherence is greater than 0.978. CONCLUSIONS: Our model suggests that mass screening for coeliac disease of the young-adult general population is associated with improved QALYs and is a cost effectiveness strategy. Shortening of the time-delay to diagnosis by heightened awareness of health-care professionals may be a valid alternative to screening.

Can patients at high risk for significant colorectal neoplasms and having normal quantitative faecal occult blood test postpone elective colonoscopy?

BACKGROUND: Common reasons for elective screening and surveillance colonoscopy, at predetermined intervals, are family or personal history of colorectal cancer (CRC) or advanced adenoma (AAP). Quantified, human haemoglobin (Hb)-specific, immunochemical faecal occult blood tests (I-FOBT) detect bleeding. AIM: To determine I-FOBT sensitivity for CRC or AAP before elective colonoscopy in patients at high-risk of cancer or advanced adenoma. METHODS: Prospective double-blind study of 1000 ambulatory asymptomatic high-risk patients (555 family history of CRC, 445 surveillance for past neoplasm), who prepared three I-FOBTs before elective colonoscopy. I-FOBTs quantified as ngHb/mL of buffer by OC-MICRO instrument and results >or=50 ngHb/mL considered positive. RESULTS: At colonoscopy, eight patients had CRC, 64 others had AAP. Sensitivity for CRC and/or AAP was the highest, 65.3% (95% CI 54.3, 76.3), when any of the three I-FOBTs was >or=50 ngHb (15.4%), with specificity of 87.5% (95% CI 86.4, 90.5) identifying all CRCs and 62% of AAPs. CONCLUSIONS: All cancers or an AAP were detected every third I-FOBT-positive colonoscopy (47/154), so colonoscopy was potentially not needed at this time in 84.6% (846 patients). I-FOBT screening might provide effective supervision of high-risk patients, delaying unnecessary elective colonoscopies. This favourable evaluation needs confirmation and cost-benefit study by risk-group.

Identification of colorectal adenomas by a quantitative immunochemical faecal occult blood screening test depends on adenoma characteristics, development threshold used and number of tests performed.

BACKGROUND: Faecal occult blood tests (FOBT) are faulted by low sensitivity for advanced adenomatous polyps (AAP). Quantified, immunochemical, haemoglobin (Hb)-specific immunochemical FOBT (I-FOBT) measurements are now used for colorectal screening. AIMS: To correlate adenoma characteristics to amount of faecal Hb lost and to evaluate sensitivity and specificity for AAP by faecal Hb development threshold used and number of I-FOBTs collected. METHODS: Three daily I-FOBTs were collected and analysed in 1221 patients scheduled for colonoscopy. Faecal Hb was analysed as ngHb/mL of buffer and the highest result related to colonoscopy findings. RESULTS: In 1204 patients without cancer, colonoscopy identified adenomas in 294, 99 with AAPs. Adenoma patients had elevated faecal Hb increasing with advanced histology, size, pedunculated shape and multiplicity (P < 0.001 for all). At 50 ngHb/mL threshold, sensitivity and specificity for AAPs were 54.5% (95%CI 44.7, 64.7) and 88.1% (95%CI 86.2, 90.1) for three tests. At higher thresholds, sensitivity decreased, but was significantly higher with more samples collected. Conversely, specificity increased at higher thresholds, but decreased with more samples. CONCLUSIONS: Faecal Hb loss from adenomas is significantly associated with size, number and advanced features. Sensitivity and specificity for AAPs are determined by test threshold chosen and number of samples collected; these determine the number of colonoscopies needed for positive tests.

Clinical trial: evaluation of a clinical decision-support model for upper abdominal complaints in primary-care practice.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) and dyspepsia affect 25-40% of the general population. In the absence of alarm symptoms, the current recommended policy in young dyspeptic patients is a 'test and treat' strategy for Helicobacter pylori; in GERD patients, a therapeutic trial with proton pump inhibitors is the treatment of choice. AIM: To create a short and simple clinical algorithm, for the diagnosis and treatment of patients with upper gastrointestinal complaints. METHODS: The clinical usefulness and cost-effectiveness of the new algorithm were evaluated in a controlled clinical trial, held in primary-care clinics in Israel. Clinical and economical treatment outcomes were evaluated after 1, 3 and 6 months comparing doctors who used the algorithm (cases) vs. those who did not (controls). RESULTS: 78 cases and 54 controls completed the 6 months of follow up. The improvement in symptom severity and quality of life was greater in the cases than in the controls (P < 0.05). General practitioner clinics visits (P = 0.04), gastroenterology clinics visits (P = 0.02) and medication costs (P = 0.004) were all significantly reduced among cases. Controls underwent also more imaging tests (computerized tomography, ultrasound and X-ray) and endoscopies. The average cost for 6 months' treatment and follow-up was $US 199 for cases compared with an average of $US 336 in the control group. CONCLUSION: The use of a clinical decision-support tool can facilitate and promote the implementation of management guidelines by general practitioners. The short algorithm presented in the study was found to be useful and easy to apply in clinical practice. Its effectiveness can be further increased by implementing it in computerized medical systems.

Halitosis and gastroesophageal reflux disease: a possible association.

OBJECTIVE: Previous reports have suggested that gastrointestinal (GI) diseases may cause halitosis. The aim of this study was to evaluate the relationship between upper GI conditions, especially gastroesophageal reflux disease (GERD), and halitosis. PATIENTS AND METHODS: One hundred and thirty two consecutive patients complaining of upper GI symptoms were included in the study. All the patients completed a validated questionnaire that was designed to characterize and measure the severity of their symptoms. The questionnaire also contained questions about awareness and severity of oral bad breath. Following the filling of the questionnaire, the patients were physically examined and subjected to an upper GI endoscopy. RESULTS: The final diagnosis among the 132 patients (M/F = 70/62, mean age 45.2 years, range 20-87 years) was GERD in 72 patients (55%), Functional dyspepsia in 52 (39%), Peptic ulcer in seven patients (5%) and gastric cancer in one patient (1%). Halitosis was significantly associated with the occurrence and severity of heartburn (P = 0.027), regurgitation (P = 0.002) sour taste (P < 0.001), belching (P = 0.001) and burburigmus (P = 0.006). Halitosis was not associated with upper abdominal pain, bloating, early satiety and chest pain. In relation to the final diagnosis, halitosis was significantly associated only with GERD (P = 0.002) but not with functional dyspepsia (P = 0.855) and peptic ulcer disease (0.765). No correlation was found between Helicobacter pylori infection status and halitosis occurrence and severity (analysis of variance F = 0.001, P = 0.977). CONCLUSIONS: Halitosis is a frequent symptom of GERD and may be considered as an extra-esophageal manifestation of GERD. On the other hand, we did not find an association between functional dyspepsia, peptic ulcer disease and H. pylori infection with halitosis occurrence or severity.

Sporadic adenomatous polyp regression with exisulind is effective but toxic: a randomised, double blind, placebo controlled, dose-response study.

BACKGROUND AND AIMS: A 12 month, multicentre, randomised, double blind, placebo controlled, phase 3, dose-response study was carried out. Exisulind inhibits tumour growth by induction of apoptosis. The aim of our study was to investigate if exisulind induces regression of sporadic colonic adenomas. PATIENTS AND METHODS: A 12 month multicentre randomised double blind placebo controlled phase 3 dose response study was carried out. At baseline colonoscopy, left sided polyps (3-10 mm) were tattooed, measured, and left in place. Subjects received exisulind 200 or 400 mg, or placebo daily. Follow up sigmoidoscopy was performed after six months, and removal of any remaining polyps at the 12 month colonoscopy. The primary efficacy variable was change in polyp size from baseline. RESULTS: A total of 281 patients were enrolled and randomised; 155 (55%) fulfilled the criteria for the intention to treat (ITT) analysis and 114 (41%) fulfilled the criteria for the efficacy evaluation analysis (patients who underwent the 12 month colonoscopy). The decrease in median polyp size was significantly greater (p=0.03) in patients who received exisulind 400 mg (-10 mm2) compared with those who received placebo (-4 mm2). Complete or partial response was significantly higher in the exisulind 400 mg group (54.6%) compared with the placebo group (30.2%), and disease progression was significantly lower (6.1% v 27.9%) (p=0.04 and 0.02, respectively). Increased liver enzymes (8.4%) and abdominal pain (14.7%) were also reported at a greater frequency in the exisulind 400 mg group. CONCLUSION: Exisulind caused significant regression of sporadic adenomatous polyps but was associated with more toxicity. This model of polyp regression, short in its term and involving a comparatively small patient sample size, may be the best available tool to assess a therapeutic regimen before launching into large preventive clinical studies.

[Cost-effectiveness of imaging procedures in knee injuries].

It is clear to experts in the health care industry that with regard to medical decision-making, considering costs of medical devices is not a good index, but it is highly important to include medical aspects. This approach guarantees an advance and an appropriate method. We present a cost-effectiveness analysis to target the optimal strategy of how to use medical diagnostic devices in cases of knee injuries. Today, one of the more common medical emergency referrals seen worldwide is in the area of orthopedics, knee injuries in particular. They can harm soft tissue, bone tissue, or both simultaneously. The diagnosis of soft tissue injury is difficult at best. Among the devices helping the clinician make an accurate diagnosis are MRI and ultrasound (US). We conclude that US is superior to MRI in this condition. This is especially true when the orthopedic examination leads to the suggestion of arthroscopy. The results were not modified, and a sensitive study of the parameters that influence the decision-making process was undertaken. Decision-makers should not consider medical outcome alone, but should take into account the costs. A clinical study should validate the assumption on which this study was based.

Inappropriateness of cataract extraction: an analysis in two Israeli hospital settings.

OBJECTIVE: To assess and compare the appropriateness of cataract extraction in two Israeli regional hospitals. SETTINGS: Two Israeli hospitals located in different geographic areas. DESIGN: A randomized sample of 150 patients was drawn from a list of all patients who underwent cataract surgery at the two study hospitals during 1995. Detailed extraction of hospital medical records was performed. The appropriateness of cataract surgery was assessed using the Medical Review System, an interactive expert system that assesses the appropriateness of selected medical and surgical procedures. RESULTS: The rates of cataract surgery in the two hospitals were 0.54 and 0.59 operations per 1,000 population, respectively, and the age-adjusted rates per 1,000 population were 5.7 and 6.2, respectively. The percentage of patients with only light perception or hand-motion perception in the operated eye before the operation was 62.2%, with no difference in the two hospitals. There was not a significant difference in the distribution of visual acuity before the operation; however, there was a significant difference in the distribution of visual acuity after the surgery. Rates of inappropriate surgeries in the two hospitals were found to be similar to the inappropriate rate in the United States (1.3%). The preoperative visual acuity of patients undergoing cataract surgery in Israel was inferior to the visual acuity of patients undergoing cataract surgery in the United States. CONCLUSION: To increase quality and cost-effectiveness in the Israeli medical system, future studies of this type are warranted in connection with surgical procedures.