A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

Cost utility analysis of HIV pre exposure prophylaxis among men who have sex with men in Israel.

BACKGROUND: Between 2011 and 2015, Men who have sex with men (MSM) accounted for nearly half of new HIV cases among men in Israel. This study carries out a cost-utility analysis of PrEP (HIV Pre Exposure Prophylaxis), an antiretroviral medication that can protect against the acquisition of HIV infection, whose incidence rate in Israel is around 1.74 per 1000 MSM. METHOD: Epidemiological, demographic, health service utilisation and economic data were integrated into a spread-sheet model in order to calculate the cost per averted disability-adjusted life year (DALY) of the intervention from a societal perspective, in mid-2018 US$ using a 3% discount rate. Cost utility analyses were performed for both types of PrEP delivery (continuous regimen and on-demand), together with sensitivity analyses on numbers of condom users who take up PrEP (baseline 25%) and subsequently abandon condom use (baseline 75%), PrEP efficacy (baseline 86%), PrEP prices and monitoring costs. RESULTS: Around 21.3% of MSM are high risk (as defined by having unprotected anal intercourse). Offering PrEP to this group would have a ten year net cost of around 1563 million USD, preventing 493 persons from becoming HIV-positive, averting around 1616 DALYs at a cost per averted DALY of around 967,744 USD. This will render the intervention to be not cost-effective. PrEP drug prices would have to fall dramatically (by 90.7%) for the intervention to become cost-effective (i.e. having a cost per averted DALY less than thrice GNP per capita) in Israel. PrEP remains not cost-effective (at 475,673 USD per averted DALY) even if intervention costs were reduced by using an "on demand" instead of a daily schedule. Even if there were no changes in condom use, the resultant 411,694 USD cost-utility ratio is still not cost-effective. CONCLUSIONS: Despite PrEPs high effectiveness against HIV, PrEP was found not to be cost-effective in the Israeli context because of a combination of relatively low HIV incidence, high PrEP costs, with a likelyhood that some low-risk MSM (ie: who use condoms) may well begin taking PrEP and as a consequence many of these will abandon condom use. Therefore, ways of minimizing these last two phenomena need to be found.

Comparison of carcinogenic potency across life stages: implications for the assessment of transplacental cancer risk.

Cancer development from in utero exposure has been documented for a variety of agents with the most commonly studied compounds exhibiting mutagenic and genotoxic carcinogen properties. Age-dependent adjustment factors (ADAFs) are applied by the US Environmental Protection Agency to many such carcinogens when assessing cancer risk from early postnatal (PN) exposures; however, this approach has not been widely considered for transplacental (TP) exposure. To explore this question and further evaluate prenatal susceptibility a database of early life animal studies developed by California Office of Environmental Health Hazard Assessment (OEHHA) enhanced with additional literature searching was evaluated. Nine genotoxic carcinogens and one mixture (cigarette smoke) have data available via TP only, PN only and adult-only protocols. Potency comparisons across these lifestages displayed similarly greater potency in male liver and brain compared to adult-only exposure. Both TP and PN exposures were not markedly different than adult-only for other targets such as female liver and blood-borne tumors. Similarity in TP and PN targets and potency for carcinogen action suggests that a 10-fold ADAF may be applied for TP exposure as is currently applied to PN exposure. A similar conclusion was reached by OEHHA. The implications of this heightened TP vulnerability are greatest for less-than-lifetime exposure and this approach might be used to assess the level of cancer risk from exposures during pregnancy. A case example employing a mutagenic flame retardant was used to exemplify application of a TP ADAF for evaluating risks during pregnancy.

Adherence to the 2011 American Gastroenterological Association medical position statement for the diagnosis and management of Barrett's esophagus.

Considerable variability exists in adherence to practice guidelines for Barrett's esophagus (BE). Rapid advances in management approaches to BE led to a new American Gastroenterological Association (AGA) medical position statement in 2011. Our aim was to assess how well members of the AGA Clinical Practice section adhered to these guidelines. A self-administered survey incorporating questions on diagnostic criteria, cancer risk estimates, screening, surveillance, and therapeutics for BE was distributed electronically to 5850 North American members of the AGA Clinical Practice section. The response rate was 470 of 2040 opened e-mails (23%). Intestinal metaplasia was required for diagnosis of BE by 90%, but the Prague classification was used by only 53% of those aware of it. The annual risk of progression to esophageal adenocarcinoma was reported as 0.1-0.5% by 76%. Screening practices were variable, with 35% screening all patients with chronic gastroesophageal reflux disease and 15% repeating endoscopy in patients with gastroesophageal reflux disease following a negative screening. Surveillance guidelines were followed by 79% for nondysplastic BE and 86% for low-grade dysplasia, with expert pathology confirmation of dysplasia reported by 86%. Proton pump inhibitor dosing was variable, with 18% administering twice-daily doses and 30% titrating dose to symptoms. Ablation therapy was recommended by 6% for nondysplastic BE, 38% for low-grade dysplasia, and 52% for high-grade dysplasia. There is satisfactory adherence to the new AGA guidelines with respect to diagnosis, cancer risk estimates, and surveillance intervals in a select group of respondents. However, adherence continues to be variable in the use of the Prague classification, screening, and dosing of antisecretory therapy. Use of ablation therapy increases with grade of dysplasia. The reason for continued variability in adherence to BE practice guidelines remains unclear, and more evidence-based guidance is required to enhance clinical practice.

Methylmercury-induced inhibition of paraoxonase-1 (PON1)-implications for cardiovascular risk.

Methylmercury (MeHg) has been associated with increased risk for cardiovascular disease in some but not all epidemiology studies. These inconsistent results may stem from the fact that exposure typically occurs in the context of fish consumption, which is also associated with cardioprotective factors such as omega-3 fatty acids. Mechanistic information may help to understand whether MeHg represents a risk to cardiovascular health. MeHg is a pro-oxidant that inactivates protein sulfhydryls. These biochemical effects may diminish critical antioxidant defense mechanism(s) involved in protecting against atherosclerosis. One such defense mechanism is paraoxonase-1 (PON1), an enzyme present on high-density lipoproteins and that prevents the oxidation of blood lipids and their deposition in vascular endothelium. PON1 is potentially useful as a clinical biomarker of cardiovascular risk, as well as a critical enzyme in the detoxification of certain organophosphate oxons. MeHg and other metals are known to inhibit PON1 activity in vitro. MeHg is associated with lowered serum PON1 activity in a fish-eating population. The implications of lowering PON1 are evaluated by predicting the shift in PON1 population distribution induced by various doses of MeHg. An MeHg dose of 0.3 µg/kg/d is estimated to decrease the population average PON1 level by 6.1% and to increase population risk of acute cardiovascular events by 9.7%. This evaluation provides a plausible mechanism for MeHg-induced cardiovascular risk and suggests means to quantify the risk. This case study exemplifies the use of upstream disease biomarkers to evaluate the additive effect of chemical toxicity with background disease processes in assessing human risk.

Risk of malignancy in resected cystic tumors of the pancreas < or =3 cm in size: is it safe to observe asymptomatic patients? A multi-institutional report.

Recent international consensus guidelines propose that cystic pancreatic tumors less than 3 cm in size in asymptomatic patients with no radiographic features concerning for malignancy are safe to observe; however, there is little published data to support this recommendation. The purpose of this study was to determine the prevalence of malignancy in this group of patients using pancreatic resection databases from five high-volume pancreatic centers to assess the appropriateness of these guidelines. All pancreatic resections performed for cystic neoplasms < or =3 cm in size were evaluated over the time period of 1998-2006. One hundred sixty-six cases were identified, and the clinical, radiographic, and pathological data were reviewed. The correlation with age, gender, and symptoms (abdominal pain, nausea and vomiting, jaundice, presence of pancreatitis, unexplained weight loss, and anorexia), radiographic features suggestive of malignancy by either computed tomography, magnetic resonance imaging, or endoscopic ultrasound (presence of solid component, lymphadenopathy, or dilated main pancreatic duct or common bile duct), and the presence of malignancy was assessed using univariate and multivariate analysis. Among the 166 pancreatic resections for cystic pancreatic tumors < or =3 cm, 135 cases were benign [38 serous cystadenomas, 35 mucinous cystic neoplasms, 60 intraductal papillary mucinous neoplasms (IPMN), 1 cystic papillary tumor, and 1 cystic islet cell tumor], whereas 31 cases were malignant (14 mucinous cystic adenocarcinomas and 13 invasive carcinomas and 4 in situ carcinomas arising in the setting of IPMN). A greater incidence of cystic neoplasms was seen in female patients (99/166, 60%). Gender was a predictor of malignant pathology, with male patients having a higher incidence of malignancy (19/67, 28%) compared to female patients (12/99, 12%; p < 0.02). Older age was associated with malignancy (mean age 67 years in patients with malignant disease vs 62 years in patients with benign lesions (p < 0.05). A majority of the patients with malignancy were symptomatic (28/31, 90%). Symptoms that correlated with malignancy included jaundice (p < 0.001), weight loss (p < 0.003), and anorexia (p < 0.05). Radiographic features that correlated with malignancy were presence of a solid component (p < 0.0001), main pancreatic duct dilation (p = 0.002), common bile duct dilation (p < 0.001), and lymphadenopathy (p < 0.002). Twenty-seven of 31(87%) patients with malignant lesions had at least one radiographic feature concerning for malignancy. Forty-five patients (27%) were identified as having asymptomatic cystic neoplasms. All but three (6.6%) of the patients in this group had benign disease. Of the patients that had no symptoms and no radiographic features, 1 out of 30 (3.3%) had malignancy (carcinoma in situ arising in a side branch IPMN). Malignancy in cystic neoplasms < or =3 cm in size was associated with older age, male gender, presence of symptoms (jaundice, weight loss, and anorexia), and presence of concerning radiographic features (solid component, main pancreatic duct dilation, common bile duct dilation, and lymphadenopathy). Among asymptomatic patients that displayed no discernable radiographic features suggestive of malignancy who underwent resection, the incidence of occult malignancy was 3.3%. This study suggests that a group of patients with small cystic pancreatic neoplasms who have low risk of malignancy can be identified, and selective resection of these lesions may be appropriate.

Relationship between intragastric acid control and healing status in the treatment of moderate to severe erosive oesophagitis.

AIM: To assess the relationship between the percentage of time intragastric pH >4.0 and healing of erosive oesophagitis. METHODS: In this proof-of-concept study, adults with endoscopically verified Los Angeles grade C or grade D erosive oesophagitis were randomly assigned to oral esomeprazole 10 or 40 mg once daily for 4 weeks. On day 5, patients underwent 24-h pH monitoring. At 4 weeks, erosive oesophagitis healing status was endoscopically assessed. Investigators scored gastro-oesophageal reflux disease symptoms on a 4-point scale [none to severe (0-3)] before and 4 weeks after treatment. The percentage of time intragastric pH was >4.0 and healing status were correlated and tested for significance using a Spearman rank correlation (r). RESULTS: 103 patients had evaluable data (mean age, 48.7 years; 65% men). Mean percentages of time with intragastric pH >4.0 on day 5 in patients with healed and unhealed erosive oesophagitis were 61% and 42%, respectively (P = 0.0002), indicating that erosive oesophagitis healing rates were positively related to the percentage of time intragastric pH was >4.0. Greater intragastric acid control correlated with lower final daytime and night-time heartburn and acid regurgitation symptom scores (r = -0.029, -0.029 and -0.021; P = 0.003, 0.003 and 0.032, respectively). CONCLUSION: A positive relationship between intragastric acid control and erosive oesophagitis healing was demonstrated.

DNA adduct formation in mouse tissues in relation to serum levels of benzo(a)pyrene-diol-epoxide after injection of benzo(a)pyrene or the diol-epoxide.

Previous studies have shown that the carcinogenic metabolite of benzo(a)pyrene [B(a)P], B(a)P-7,8-diol-9,10-epoxide (BPDE), is transported in serum after B(a)P injection in mice. It is possible that serum transport is an important source of carcinogenic metabolite and results in DNA adduct formation in tissues. This possibility was studied by comparing the time course for BPDE appearance in serum with that for BPDE/DNA adduct formation after B(a)P i.p. injection (2, 20, or 200 mg/kg) into female C57BL/6 x C3H F1 mice. Additionally, BPDE was injected i.v. (8.25 nmol), and its disappearance from serum and adduction of tissue DNA were followed. BPDE serum levels and DNA adduct levels were measured by 32P-postlabeling analysis. Results indicate that, after a 200-mg B(a)P/kg i.p. injection, BPDE/DNA adduct levels rose sharply in liver, lung, kidney, stomach, and spleen through 5 h and then more gradually through 24 h. Adduct levels were similar in all tissues at 24 h. BPDE levels in serum reached a plateau within 2.5 h and remained constant thereafter (10 to 11 nM). B(a)P levels in serum fell steadily from 1980 nM at 1 h to 350 nM by 24 h. Levels of serum BPDE and DNA adducts showed a similar dose dependency at 10- and 100-fold lower B(a)P i.p. doses. After BPDE i.v. injection, BPDE levels in serum decreased to 0.16% of the initial level within 5 min. By this time, BPDE/DNA adducts were at peak levels in all tissues assayed. Lung adduct levels were 10 to 100 times greater than those in the other tissues. These results support a role for serum transport of BPDE in the production of DNA adducts after B(a)P since BPDE was available in serum throughout the time course for DNA adduct formation. Further, injected BPDE rapidly formed DNA adducts and this occurred primarily in the lung, which had the greatest access to the transported carcinogen.

Endoscopic ultrasound-guided real-time fine-needle aspiration biopsy of the pancreas in cancer patients with pancreatic lesions.

BACKGROUND: Endoscopic ultrasound (EUS) is an important new tool in the staging of pancreatic malignancies. Using new curved linear-array instruments, real-time fine-needle aspiration biopsy (RTFNA) of pancreatic lesions can be performed. METHODS: Forty-five patients with pancreatic lesions (22 males and 23 females) underwent staging with the Olympus EUM-20 (Olympus America Corp, Melville, NY) followed by EUS-RTFNA with the Pentax FG-32PUA (Pentax-Precision Instrument Corp, Orangeburg, NY) and the 22-gauge GIP needle (GIP Medizin Technik, Grassau, Germany). RESULTS: EUS tumor stages were as follows: TO, n = 1; T1, n = 8; T2, n = 9; and T3 n = 27. Aspiration attempts were unsuccessful in four patients (two technical failures and two inadequate specimens). The remaining 41 lesions (mean size, 3.3 cm) were aspirated under EUS guidance (median passes, three) and the cytologic diagnoses were 25 definite adenocarcinoma, five suspicious for adenocarcinoma (three subsequently confirmed and two clinical course consistent with adenocarcinoma), and 11 negative for malignancy. Of 11 negatives, two were found to have adenocarcinoma, seven were confirmed benign at surgery (four cystadenomas and three inflammatory), one had a benign pseudocyst, and one had abundant inflammatory cells on RTFNA and follow-up time greater than 12 months with computed tomographic (CT) scans consistent with resolving inflammation. There were no false-positive RTFNAs. There were no procedure-related complications. Among those with diagnostic EUS-RTFNA (91%), the sensitivity for malignancy (confirmed plus suspicious) was 94% and negative predictive value 82%. CONCLUSION: EUS-guided RTFNA is a safe and accurate method for performing pancreatic biopsy. It should be considered in patients with suspected pancreatic malignancies in whom a tissue diagnosis is required or when other modalities have failed. EUS-RTFNA allows for local staging and tissue diagnosis in one procedure.

The siesta in the elderly: risk factor for mortality?

BACKGROUND: During the siesta, blood pressure declines like it does during night sleep. Because cardiovascular and cerebrovascular events cluster during the morning hours, when hemodynamic changes from nocturnal baseline are maximal, we hypothesized that an additional sleep period during the day (the siesta) may increase cardiovascular and cerebrovascular events, and thus mortality. METHODS: A prospective population-based cohort study of 455 70-year-old residents of Jerusalem, Israel, using self-reported siesta at baseline and 6 1/2 years of total mortality data. RESULTS: The prevalence of the practice of the siesta was 60.7%. It was more prevalent among men than women (68% vs 51%, P<.001) and in survivors of previous myocardial infarction than in those without previous myocardial infarction (78% vs 58%, P = .009). After 6 1/2 years of follow-up (1990-1996), 75 subjects died. For those who practiced the siesta, total mortality was 20% vs 11% for those who did not (P = .01; risk odds ratio, 2.0; 95% confidence interval, 1.1-3.4). In a multiple logistic regression model that included several lifestyle descriptors, risk factors, and diseases, the siesta remained predictive of mortality (P = .03; risk odds ratio, 2.1; 95% confidence interval, 1.1-3.9).

Phenylpropanolamine OROS (Acutrim) vs. placebo in combination with caloric restriction and physician-managed behavior modification.

We added phenylpropanolamine OROS (Acutrim; Ciba-Geigy Corp.) or placebo to a physician-managed behavior modification, mild caloric restriction, and exercise weight control program. One hundred six healthy, overweight (115% to 130% ideal body weight) women participated in this 14-week double-blind clinical trial. On average, the participants who took Acutrim lost significantly more weight (X +/- SE; 6.1 +/- 0.6 kg; 8.0% +/- 0.8%) than did those taking placebo (4.3 +/- 0.7 kg; 5.5% +/- 0.8%; P less than 0.05). Those taking Actrim continued to lose weight over the Christmas holiday, while the placebo group gained weight. Fifteen participants taking placebo withdrew, three because of adverse drug reactions (ADRs). Thirteen of 53 participants in the Acutrim group left the study, two because of ADRs. Dry mouth was the most frequent complaint from participants taking Acutrim. No serious cardiovascular effects occurred. Both complaints and the number of participants reporting ADRs decreased with continued dosing. We conclude that Acutrim is a safe, modestly effective adjunct to a physician-managed, integrated weight control program.

Long-term weight control study. II (weeks 34 to 104). An open-label study of continuous fenfluramine plus phentermine versus targeted intermittent medication as adjuncts to behavior modification, caloric restriction, and exercise.

Between weeks 34 and 104, we explored different schema for administering fenfluramine plus phentermine in open-label fashion. At week 34, the original placebo group participants began taking fenfluramine plus phentermine (placebo-to-active group). Those receiving fenfluramine plus phentermine between weeks 6 and 34 either continued to receive medication or began targeted intermittent therapy. Participants who did not lose 10% of initial weight received an augmented dose (60 mg fenfluramine plus 30 mg phentermine. The placebo-to-active group lost an additional 9.1 +/- 0.8 kg (mean +/- SEM) in the period from week 34 to week 60. At week 60, they were assigned to either continue medication, intermittent therapy, or augmented therapy. More than 68% (83) of the original participants completed up to study week 104. At that point, overall weight loss was 10.8 +/- 0.7 kg (11.6 +/- 0.8% of initial weight); participants who continued to receive fenfluramine plus phentermine lost 11.6 +/- 0.8 kg, participants receiving intermittent therapy lost 11.6 +/- 1.3 kg, and participants receiving augmented therapy lost 6.5 +/- 1.5 kg. Although 41% of the participants complained of dry mouth, neither serious adverse effects nor evidence of medication abuse appeared. There were 29 dropouts in the period from weeks 34 to 104. Sixteen of those were related to medication (adverse effects, lack of efficacy, and fear of medication). Overall, fenfluramine plus phentermine used in conjunction with behavior modification, caloric restriction, and exercise continued to be efficacious for up to 2 years.

Decreased hospital utilization by older adults attributable to a home hospitalization program.

OBJECTIVE: To evaluate the cost effectiveness of a short-term home health care program for older people, Home Hospitalization (HH), compared with the alternative of regular ambulatory care with general or geriatric hospitalization as necessary. SETTING: Our HH was initiated in November 1991 to serve Jerusalem residents. Program staff included physicians, nurses, and paramedical professionals. Other medical/hospital services were provided nonselectively by the general medical personnel of the various hospitals in Jerusalem. STUDY DESIGN: Patients over the age of 65 were either referred to the HH program (study group, n = 36,500) or to routine medical care (control group; n = 9000) depending on their Sick Fund assignment. Hospital utilization rates per enrollee were studied prospectively and compared both between the two groups and with hospitalization rates in the year before the initiation of the program. RESULTS: During the first 26 months of operations, the HH program cared for 741 older persons for a total of 37,290 days' care at an average daily costs of $30.06 (1992) and $23.64 (1993). Annual general hospitalization rates per person declined in the study group from 2.80 days in the 1991 baseline period to 2.65 days in 1992 and to 2.54 days in 1993. Hospitalization rates in the control group increased from 2.62 in 1991 to 2.70 days/member and 2.71 days/member in 1992 and 1993, respectively. Annual geriatric hospitalization rates declined considerably in the study group from the 1991 baseline of 1.49 to 1.34 (1992) to 1.33 (1993). The control group experienced a small decrease from 1.64 (1991) to 1.58 (1992) and then a rise to 1.68 days per member in 1993. For the 26-month duration of the program, estimated savings of 20,773 general hospital days ($5.54 million) and 8486 geriatric hospital days ($0.98 million) exceeded its costs ($0.97 million), providing a cost/benefit ratio of 5.7/1. In addition, patient satisfaction was high. CONCLUSION: The HH program provided a cost effective substitute for care in a geriatric or general hospital for Jerusalem's elderly.

Spontaneous mediastinal hemorrhage associated with renovascular hypertension.

We report on a patient with severe renovascular hypertension associated with massive spontaneous mediastinal hemorrhage. Differentiation of this entity from aortic dissection, as well as establishing the cause of the severe hypertension, was possible only through the aid of angiography. Following exploratory thoracotomy, renal artery revascularization was carried out, with resolution of the hypertension. To our knowledge, this complication of renovascular hypertension has not been reported. Prompt recognition and appropriate therapy were possible only after angiographic evaluation.

Cost-benefit analysis of a nationwide neonatal inoculation programme against hepatitis B in an area of intermediate endemicity.

STUDY OBJECTIVE: The aim was to estimate the costs and benefits of a nationwide neonatal vaccination campaign against hepatitis B in Israel for the 1990-2034 period. DESIGN: Using morbidity, mortality, utilisation, and cost data from Israeli and international sources, a spreadsheet model was constructed to carry out the cost-benefit analysis. SETTING: The entire State of Israel, an area of intermediate endemicity. PARTICIPANTS: The population of Israel from 1990-2034. MAIN RESULTS: A policy of immunising all Israeli neonates would, for a cost of $13.8 million, reduce the number of cases of hepatitis B during the 1990-2035 period in the cohort from 359,000 to 166,000 and save the nation around $21.5 million in health resources alone, $16.6 million in averted work absences, and a further $0.6 million in averted premature mortality costs. Even when the savings to the health services ($0.6 million) arising from the reduction in hepatocellular carcinoma are excluded, the direct benefit to cost ratio is 1.51/1, still in excess of unity. CONCLUSIONS: The decision to adopt a nationwide neonatal inoculation policy, starting in January 1992, appears to be not only medically but also economically justifiable.

Costs and benefits of a second measles inoculation of children in Israel, the West Bank, and Gaza.

STUDY OBJECTIVE: Measles has been targeted by the WHO as a disease which should be eradicated. Use of existing vaccines during infancy has resulted in a substantial decline in cases in Israel, the West Bank, and Gaza. However the disease continues to occur in epidemic waves with large scale morbidity and mortality in all of these populations. This paper estimates the costs and benefits of three alternative strategies of adding immunisation at school age, and during young adult life to the present vaccination at 15 months. MEASUREMENTS AND MAIN RESULTS: A policy of immunising all Israeli children aged 6 (option A) would cost around $1 million and have estimated benefits of $4.5 million, yielding a benefit cost ratio of 4.53/1. Despite relatively lower medical care costs and work absence costs (as a result of the lower per capita GNP and lower female participation rate in the workforce), the West Bank and Gaza situations yield benefit to cost ratios of 5.74/1 and 9.59/1 respectively because of their relatively higher incidence rates. If implemented in Israel, a vaccination programme (such as option A) would prevent, over the next 10 years, approximately 28,700 simple cases, 3400 hospital admissions, eight non-fatal cases of encephalitis, and 2.2 cases of SSPE. It would save 28 lives. The adoption of option A, is expected to reduce incidence and mortality by around 13,600 and 32 cases in the West Bank, and by 18,000 and 64 cases in Gaza. CONCLUSION: The adoption of a two dose policy appears to be economically justifiable.

Cost benefit analysis of Haemophilus influenzae type b vaccination programme in Israel.

STUDY OBJECTIVE: The recent availability of Haemophilus influenzae type b (HIB) conjugate vaccines prompted an examination of the costs and benefits of four and three dose HIB prevention programmes targeting all newborns in Israel. MEASUREMENTS AND MAIN RESULTS: A four dose programme would reduce the number of childhood (aged 0-13) HIB cases from 184.2 to 31.3 per year, yielding a benefit ($1.03 million) to cost ($3.55 million) ratio of just 0.29/l for health services only, based on a vaccine price of $7.74 per dose. When benefits resulting from a reduction in mild handicaps and severe neurological sequelae are included, the benefit ($4.48 million) to cost ratio rises to 1.26/l and it reaches 1.45/l when the $0.66 million indirect benefits of reduced work absences and mortality are also included. Break even vaccine costs are $2.24 when health service benefits only are considered and $11.21 when all the benefits are included. CONCLUSION: In the absence of other projects with higher benefit to cost ratios, Israel should start to provide a nationwide HIB vaccination programme since the monetary benefits to society of such a programme will exceed the costs to society. A barrier to implementation may occur, however, because the costs of the programme exceed the benefits to the health services alone.

Resource savings from non-pharmacological control of hypertension.

Treatment of acute cardiovascular illness is expensive, and a preventative approach may be cheaper. Since pharmacological costs account for a large proportion of costs in prevention programmes, a non-pharmacological approach such as that used by us in Ashkelon on mild hypertensives, relying on stress management, weight management and exercise aimed at reducing risk factors, might prove to be more cost-effective. After six months on a 1,000 calorie/day diet, 69 obese subjects (initial body mass index greater than 28 kg/m2) had reduced their weight by an average of 7.3 kg (P less than 0.005). This weight reduction contributed to a significant decrease in systolic blood pressure (SBP) from 157.3 to 137.6 mmHg (P less than 0.005) and diastolic blood pressure (DBP) from 101.1 to 85.2 mmHg (P less than 0.005), which was sustained at two-year follow-up. Pharmacological treatment could be stopped in about one-quarter of these cases. In non-obese mild-hypertensives, deep muscle relaxation and biofeedback techniques were prescribed. Significant decreases in SBP (153.1 to 138.3 mmHg, P less than 0.005) and DBP (101.2 to 90.1 mmHg, P less than 0.005) were achieved at six months. In nine out of 19 cases pharmacological treatment was stopped after six to eight months. Smoking cessation was achieved by individual instruction together with stress management techniques, physical exercise and a nicotine-based chewing gum. After six months 18 out of 30 heavy smokers had stopped smoking, and the remaining 12 had reduced their cigarette consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Partial cost-benefit analysis of two different modes of nonpharmacological control of hypertension in the community.

In the Dan and Ashkelon areas of Israel, 28 male and 24 female mild to moderate hypertensives without target organ damage aged 35-65 years were randomly assigned to treatment programmes (based on nutritional management, exercise and stress management techniques) either on an individual basis administered by physician-nurse teams (PN) or on a group basis from a team of paramedical professionals (PP) consisting of a psychologist, nutritionist and physical activity instructor. At 11 and 24 months follow-up, there were similar significant improvements in both treatment modes for such risk factors as body mass index, caloric intake and physical activity levels. There was a significant decrease in drug use from $36.28 a month at baseline to $18.94 a month at 11 month follow-up (P = 0.01) and to an estimated $20.48 at 24 months. Mean BP remained unchanged, despite the reduction in drug use, indicating a reduction in the underlying BP. The net present value (NPV) of the reduction in drug utilisation totalled $740 per person over a five year time horizon and a 7.5% discount rate. The total extra costs of treatment, training, case-note writing, travelling and follow-up booster sessions, amounted to $95 per patient for the PN mode and $234 per patient for the PP mode, yielding benefit to cost ratios of 7.79/1 and 3.16/l, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-benefit analysis of risperidone and clozapine in the treatment of schizophrenia in Israel.

In this study, the benefits and costs of treating schizophrenia with either risperidone or clozapine were examined. The lifetime drug-treatment cost incurred by a patient with schizophrenia in Israel was $US7561 (1996 values) with an initial 6-month trial with risperidone, compared with $US6326 with clozapine and $US3360 with typical antipsychotics. Total lifetime costs of psychiatric health services (excluding medications) by individuals who were continuously receiving typical antipsychotics were $US181,555 per patient. Assuming a 6.3% decrease in hospital use with typical antipsychotics and an absolute 30% decrease with risperidone or clozapine, the use of clozapine or risperidone reduced hospitalisation costs by $US7159 per patient, but increased community-care costs by $US1627 per patient, giving health-service benefit:cost ratios of 1.87:1 and 1.32:1, respectively. After adding indirect benefits resulting from increased work productivity (minus indirect costs related to increases in transport costs because of visits for blood monitoring during clozapine therapy), the benefit:cost ratios increased to 2.04:1 and 1.48:1, respectively. Assuming that clozapine caused a 30% decrease in hospital use by patients with new-onset schizophrenia, risperidone would have to decrease hospital use by 43.2% (i.e. a 13.2% relative advantage) for its societal benefits to justify its increased costs.