Substantial Reduction In Risk Research Articles

Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients

AbstractThe impact of early human cytomegalovirus (HCMV) replication on leukemic recurrence was evaluated in 266 consecutive adult (median age, 47 years; range, 18-73 years) acute myeloid leukemia patients, who underwent allogeneic stem cell transplantation (alloSCT) from 10 of 10 high-resolution human leukocyte Ag-identical unrelated (n = 148) or sibling (n = 118) donors. A total of 63% of patients (n = 167) were at risk for HCMV reactivation by patient and donor pretransplantation HCMV serostatus. In 77 patients, first HCMV replication as detected by pp65-antigenemia assay developed at a median of 46 days (range, 25-108 days) after alloSCT. Taking all relevant competing risk factors into account, the cumulative incidence of hematologic relapse at 10 years after alloSCT was 42% (95% confidence interval [CI], 35%-51%) in patients without opposed to 9% (95% CI, 4%-19%) in patients with early pp65-antigenemia (P < .0001). A substantial and independent reduction of the relapse risk associated with early HCMV replication was confirmed by multivariate analysis using time-dependent covariate functions for grades II to IV acute and chronic graft-versus-host disease, and pp65-antigenemia (hazard ratio = 0.2; 95% CI, 0.1-0.4, P < .0001). This is the first report that demonstrates an independent and substantial reduction of the leukemic relapse risk after early replicative HCMV infection in a homogeneous population of adult acute myeloid leukemia patients.

Association of Physical Activity and Atrial Fibrillation

There is controversy regarding the association of physical activity (PA) and atrial fibrillation (AF). This systematic review aims to summarize the evidence regarding the association of PA at different levels and AF. A structured search of databases was performed until December 2009. Studies that investigated the association between PA and AF were included and assessed by 2 researchers according to selection criteria and methodological quality. The overall quality of evidence was rated according to the Grade system. Of 855 publications, 10 met the inclusion criteria. The risk of uncontrolled bias and confounding was profound and there was substantial heterogeneity regarding observed associations. One methodologically rigorous study reported substantial risk reductions associated with moderate intensity PA. Another indicated modest increases in risk with high levels of vigorous PA. Five methodologically less reliable studies reported large increases in risk due to regular sport practice. The overall quality of evidence indicating increases in risk of AF is low. Most reports of large increases in risk appear to be overestimated substantially. In light of the public health importance of regular PA, contradictory recommendations concerning the participation in PA should be considered cautiously before more rigorous studies have investigated this issue.

Does achieving an intensive versus usual blood pressure level prevent stroke?

The purpose of this study was to compare the impact of achieving tight versus usual systolic blood pressure (SBP) control on stroke prevention through meta-analysis of randomized controlled trials. We searched PubMed and bibliographies of recent review articles. Relative risk with 95% confidence interval was used as a measure of the association between an active treatment group with achieved SBP <130 mmHg versus a comparator group with achieved SBP 130 to 139 mmHg, and risk of stroke after pooling data across trials. The search identified 11 studies with 42,572 participants and 794 stroke events. The final SBPs, weighted for trial size, were a mean of 126.5 mmHg in the intensive treatment arms and 132.6 mmHg in the conventional arms (mean SBP reduction, 6.1 mmHg). Achieving a tight SBP level was associated with a lower stroke risk (relative risk, 0.80; 95% confidence interval, 0.70-0.92; p < 0.01) and a lower risk of major vascular events (0.91; 0.86-0.96; p < 0.001). In subgroup analyses, subjects with risk factors but no established cardiovascular disease showed substantial reduction of future stroke risk with tight control (0.49; 0.34-0.69), but those with established cardiovascular disease at entry did not experience stroke risk reduction with tight control (0.92; 0.83-1.03). Achieving an SBP <130 mmHg compared to 130 to 139 mmHg appears to provide additional stroke protection only among people with risk factors but no established cardiovascular disease.

Review and management of side effects associated with antiplatelet therapy for prevention of recurrent cerebrovascular events

The risk of secondary events following noncardioembolic ischemic stroke or transient ischemic attack (TIA) is high and especially pronounced in the first days and weeks following the initial event; to reduce this risk, it is recommended that antiplatelet therapy be initiated immediately. Although the risk and impact of antiplatelet-associated side effects are generally far less substantial than those of secondary events, some (especially bleeding) can be severe and even life-threatening, and others may reduce adherence to antiplatelet regimens. Therefore, clinicians should implement strategies to reduce the risk of side effects and to manage those that occur. Three antiplatelet regimens have demonstrated substantial reductions in secondary event risk and are currently recommended by consensus panels: aspirin monotherapy at 50-325 mg/day; the combination of aspirin plus extended-release dipyridamole (ER-DP); and clopidogrel monotherapy. Bleeding is potentially the most significant antiplatelet-associated side effect. As bleeding risk with aspirin monotherapy is dose dependent, while preventive efficacy appears similar at all doses above 50 mg/day, aspirin doses should be kept as low as possible. Clopidogrel bleeding risk is similar to aspirin, although a reduced incidence of gastrointestinal bleeding events suggests lower gastrotoxicity. Clopidogrel should not be combined with aspirin after stroke or TIA, as the combination increases bleeding risk without improving antiplatelet efficacy. Patients should be assessed for bleeding risk (especially gastrointestinal bleeding) before initiating antiplatelet therapy; those at elevated risk should be made aware of the signs and symptoms of bleeding events to facilitate prompt treatment. The addition of ER-DP to aspirin does not increase bleeding risk, although ER-DP is associated with risk of headache, which may be severe. The prevalence of headache drops rapidly following initiation of ER-DP, suggesting most patients are able to "push through" this side effect; for those who find headache intolerable, short-term use of a reduced-dose regimen may be helpful.

Assessing the effectiveness of non-structural flood management measures in the Thames Estuary under conditions of socio-economic and environmental change

Risk analysis and appraisal of the benefits of structural flood risk management measures such as embankments is well established. Here, a method to quantify, over extended timescales, the effectiveness of non-structural measures such as land use spatial planning, insurance and flood resilient construction is presented. The integrated approach couples socio-economic and climate change scenarios with long term land use modelling and flood risk analysis to generate maps and time series of expected annual damages. The analysis has been applied on a case study in the Thames Estuary in the UK. Stakeholders helped develop a number of scenarios that might lead to substantial changes in existing planning and insurance policies in the UK. The effectiveness of these changes was analysed and showed the substantial benefits in terms of reduction of future flood risks that are achievable with changes in planning policy, financial incentives and resilient property construction in the floodplain. Moreover, the reward can be increased through earlier action. Subsequently, the benefits of a range of policies are explored under the UK Foresight socio-economic scenarios. Different structural and non structural flood management interventions are tested and the results demonstrate that despite the potential for large increases in flood risk in the Thames Estuary, in all scenarios substantial flood risk reductions are possible. The effectiveness of non-structural measures is however sensitive to socio-economic changes and governance arrangements. The analysis described here will help to identify portfolios of non-structural and structural options that are robust to uncertainties.

Deploying e-health service innovations &amp;ndash; an early stage business model engineering and regulatory validation approach

The objective of this study was to design a viable business model for commercially deploying an e-health service innovation - i.e. a so-called myofeedback-based teletreatment service - in the R&D deployment phase. In this paper, the business model and regulatory validation strategy used to conceptualise the deployment of this e-health service innovation is described, analysed and evaluated. Insights from surveys, desk research, expert interviews, workshops and quantitative modelling were combined to engineer the business model and consequently refine it in four design cycles. The business model engineering strategy led to critical deployment insights that would otherwise be unknown or learned at a much later phase of the development process. Based on this result, it is concluded that our approach may lead to substantial risk reduction as well as substantial savings in costs and resources related to service innovation deployment.

The importance of risk reduction in critically ill patients

Intensive care patients are per definition at risk for an unfavourable outcome while at the same time being exposed to the risks of a very complex and invasive process of care. This review addresses this extrinsic risk with respect to causative factors and strategies for risk reduction. A growing amount of evidence shows that the actual risk of an unfavourable outcome in critically ill patients depends on the quality of the process of care. Several domains have been identified in which changes in infrastructure, process, and culture can result in a substantial risk reduction and increased patient safety. Important examples refer to work environment and workload of intensive care professionals, safety climate, information flow, and continuity of care. Recent studies have demonstrated that routine procedures in intensive care are amenable to considerable improvement. This review discusses recent findings related to the reduction of risk in critically ill patients with respect to the process of intensive care medicine and the conditions under which that care is provided.

Niacin's role in the statin era

Importance of the field: The combination use of niacin and HMG Co-A reductases (statins) is increasing. While statin therapy reduces the risk of adverse cardiovascular events, additional therapies are needed to decrease event rates further. High-density lipoprotein cholesterol (HDL-C) is of interest as a potential therapeutic target as epidemiologic evidence demonstrates that low HDL-C is a strong predictor of incident coronary events. Niacin is the most effective agent available at present to increase HDL-C.Areas covered in this review: This review focuses on the efficacy and safety of niacin in combination with statins, along with the combination's effects on cardiovascular end points and clinical outcomes. We systematically reviewed studies, dating from 2001 to the present, identified through MEDLINE and searches of reference lists, which contained a combination statin and niacin group.What the reader will gain: The reader will gain an understanding of the rationale and results of using niacin and statin therapy concurrently.Take home message: The addition of niacin to statin therapy results in multiple favorable effects on lipid levels, and the combination seems to be as safe as the individual drugs separately. Current evidence indicates that adding niacin to statin therapy has the potential to result in substantial reductions in risk for adverse cardiovascular events. However, large-scale clinical outcome trials are needed to confirm the benefits of this combination.

Do inferior vena cava filters reduce the risk of acute pulmonary embolism in preoperative patients with venous thromboembolism?

Although prophylactic anticoagulants reduce the risk of acute pulmonary embolism (PE), inferior vena cava filters (IVCF) remain elusive in prophylactic use. This study investigated whether IVCF in addition to anticoagulants augment the prophylactic effect on acute PE in the highest-risk patients. This study included patients with existing venous thromboembolism (VTE) or a history of previous PE, who underwent subsequent surgery for the underlying disease. The hospital records of the patients were reviewed. Forty-nine consecutive patients treated from October 2001 to June 2007 were assessed, including 13 men and 36 women with a mean age of 58.1 years. The underlying diseases that required surgery included malignancy in 23, orthopedic disorder in 14, and others in 12. All patients received anticoagulants, with perioperative IVCF in 31 patients or without in 18. Neither group had any fatal complications. The no-filter group had no cases of recurrent PE, whereas the filter group had one case of recurrent PE just after placement of the filter. Moreover, 5 cases in the filter group had filter-related complications. This study suggested that the addition of IVCF to anticoagulants does not provide a substantial risk reduction for perioperative patients with VTE prior to surgery.

Primary Prevention of Colorectal Cancer

Colorectal cancer has been strongly associated with a Western lifestyle. In the past several decades, much has been learned about the dietary, lifestyle, and medication risk factors for this malignancy. Although there is controversy about the role of specific nutritional factors, consideration of dietary pattern as a whole appears useful for formulating recommendations. For example, several studies have shown that high intake of red and processed meats, highly refined grains and starches, and sugars is related to increased risk of colorectal cancer. Replacing these factors with poultry, fish, and plant sources as the primary source of protein; unsaturated fats as the primary source of fat; and unrefined grains, legumes and fruits as the primary source of carbohydrates is likely to lower risk of colorectal cancer. Although a role for supplements, including vitamin D, folate, and vitamin B6, remains uncertain, calcium supplementation is likely to be at least modestly beneficial. With respect to lifestyle, compelling evidence indicates that avoidance of smoking and heavy alcohol use, prevention of weight gain, and maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and nonsteroidal anti-inflammatory drugs and postmenopausal hormones for women are associated with substantial reductions in colorectal cancer risk, though their utility is affected by associated risks. Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence.

Prevention of Alzheimer's disease in high risk groups: statin therapy in subjects with PSEN1 mutations or heterozygosity for apolipoprotein E epsilon 4

Because cerebrospinal fluid (CSF) abnormalities in presymptomatic subjects with PSEN1 (presenilin 1) mutations may be observed 4 to 12 years prior to the estimated age at onset, it is possible to test putative therapies on the CSF analytes that correlate with neurodegeneration during this presymptomatic window of clinical opportunity. It is also possible to test the same therapy on a comparison group with increased risk status conferred by both hyperlipidemia and heterozygosity for apolipoprotein Eε4. To our knowledge, the only putative therapy thus far tested in such a common design has been statin therapy. The results of these tests show increases in soluble amyloid precursor protein (sAPP)α correlating with statin-induced decreases in serum cholesterol levels in the non-PSEN1 subjects. This result could be one functional correlate for part of the substantial risk reduction for late onset Alzheimer's disease recently reported in the Rotterdam study, a large, long-term prospective statin trial. Statin therapy significantly decreased both sAPPα and sAPPβ in presymptomatic PSEN1 subjects. Initially, elevated phospho-tau levels in PSEN1 subjects did not further increase during the 2 to 3 years of statin therapy, possibly indicative of a prophylactic effect. These results suggest that large and longer term trials of statin therapy correlating changes in CSF biomarker levels with clinical course may be warranted in both presymptomatic PSEN1 and non-PSEN1 subjects.

Postmenopausal Breast Cancer Risk and Dietary Patterns in the E3N-EPIC Prospective Cohort Study

Since evidence relating diet to breast cancer risk is not sufficiently consistent to elaborate preventive proposals, the authors examined the association between dietary patterns and breast cancer risk in a large French cohort study. The analyses included 2,381 postmenopausal invasive breast cancer cases diagnosed during a median 9.7-year follow-up period (1993-2005) among 65,374 women from the E3N-EPIC cohort. Scores for dietary patterns were obtained by factor analysis, and breast cancer hazard ratios were estimated by Cox proportional hazards regression for the highest quartile of dietary pattern score versus the lowest. Two dietary patterns were identified: "alcohol/Western" (essentially meat products, French fries, appetizers, rice/pasta, potatoes, pulses, pizza/pies, canned fish, eggs, alcoholic beverages, cakes, mayonnaise, and butter/cream) and "healthy/Mediterranean" (essentially vegetables, fruits, seafood, olive oil, and sunflower oil). The first pattern was positively associated with breast cancer risk (hazard ratio = 1.20, 95% confidence interval (CI): 1.03, 1.38; P = 0.007 for linear trend), especially when tumors were estrogen receptor-positive/progesterone receptor-positive. The "healthy/Mediterranean" pattern was negatively associated with breast cancer risk (hazard ratio = 0.85, 95% CI: 0.75, 0.95; P = 0.003 for linear trend), especially when tumors were estrogen receptor-positive/progesterone receptor-negative. Adherence to a diet comprising mostly fruits, vegetables, fish, and olive/sunflower oil, along with avoidance of Western-type foods, may contribute to a substantial reduction in postmenopausal breast cancer risk.

A graded association of exercise capacity and all-cause mortality in males with high-normal blood pressure

Introduction. Information regarding the effect of exercise capacity on mortality risk in individuals with high-normal blood pressure is severely limited. Thus, we evaluated the association of exercise capacity and all-cause mortality in individuals with high-normal blood pressure. Methods. Exercise test was performed in 1727 males with high-normal blood pressure at two Veteran sites (Washington, DC, and Palo Alto, CA). Fitness status was assessed in metabolic equivalents (METs) at exercise peak. All-cause mortality was recorded for a mean follow-up period of 9.8±6.0 years. Results. Exercise capacity was inversely associated with all-cause mortality, and the association was independent of traditional cardiovascular risk factors. For each 1 MET increase in exercise capacity, the adjusted mortality risk was reduced by 13%, underscoring the strong predictive value of exercise capacity that was confirmed by ROC analysis. Data analysis according to fitness levels revealed a threshold level of 4 METs, over which the mortality risk was progressively reduced by 30% (hazard ratio=0.70; CI 0.51–0.95) for those who achieved 4.1–6.0 METs and 61% (hazard ratio=0.39; CI 0.26–0.57) for those who achieved 8.1–10 METs. No additional reductions in risk were noted until the MET level achieved exceeded 12 METs. Conclusions. We observed a strong, inverse, graded and independent association between exercise capacity and all-cause mortality in individuals with high-normal blood pressure. Our findings indicate that a shift of the fitness curve to the right is associated with significant survival benefits, and even slight differences in fitness levels are associated with substantial reductions in mortality risk.

Breastfeeding and risk of epithelial ovarian cancer

Several studies have found inverse associations between breastfeeding and ovarian cancer occurrence but there are inconsistencies. The relationship with breastfeeding duration is unclear, and it is uncertain whether the association varies according to histological subtype of ovarian cancer. We sought to clarify these issues. Parous women who participated in an Australia-wide population-based case-control study of epithelial ovarian cancer between 2001 and 2005 (1,092 cases and 1,288 controls) completed a reproductive/lifestyle questionnaire. Logistic regression was used to calculate odds ratios and 95% confidence intervals to investigate relations between breastfeeding and ovarian cancer. We found a strong inverse association between total duration of breastfeeding (all episodes combined) and ovarian cancer occurrence (OR = 0.986, 95% CI 0.978-0.994 per month of breastfeeding) that appeared to be independent of parity. However, individual episodes of lactation beyond 12 months conferred no appreciable additional benefit. The relation with breastfeeding appeared to vary by histological subtype such that we saw no association between duration of breastfeeding and borderline serous cancers or mucinous cancers, but inverse associations for the other subtypes, although these were not always statistically significant. A long total duration of breastfeeding appears to be associated with a substantial reduction in the overall risk of ovarian cancer, independent of the decrease in risk due to childbirth, but this may vary according to histological subtype.

Influence of Race/Ethnicity on Genetic Counseling and Testing for Hereditary Breast and Ovarian Cancer

Risk assessment coupled with genetic counseling and testing for the cancer predisposition genes BRCA1 and BRCA2 (BRCA1/2) has become an integral element of comprehensive patient evaluation and cancer risk management in the United States for individuals meeting high-risk criteria for hereditary breast and ovarian cancer (HBOC). For mutation carriers, several options for risk modification have achieved substantial reductions in future cancer risk. However, several recent studies have shown lower rates of BRCA1/2 counseling and testing among minority populations. Here, we explore the role of race/ethnicity in cancer risk assessment, genetic counseling and genetic testing for HBOC and the BRCA1/2 cancer predisposition genes. Barriers to genetic services related to race/ethnicity and underserved populations, including socioeconomic barriers (e.g., time, access, geographic, language/cultural, awareness, cost) and psychosocial barriers (e.g., medical mistrust, perceived disadvantages to genetic services), as well as additional barriers to care once mutation carriers are identified, will be reviewed.

Is international diversification really beneficial?

Previous research claims that low constant correlations among international stock indices create substantial risk-reduction from diversification. We contend that only using constant correlations is too simplistic an approach. We examine international diversification by: (1) using conditional correlations, (2) evaluating tail risk, including the effect of skewness and kurtosis, and (3) examining the possible tradeoffs of standard deviation with correlation, skewness, and kurtosis. We show that conclusions concerning diversification based solely on constant correlations across markets can be misleading, since the diversification benefits are time-varying, are affected by non-normality, and depend on the benchmark (country) employed. Finally, tradeoffs do exist between standard deviation and the other risk factors.

Do vegetables and fruits reduce the risk of chronic obstructive pulmonary disease? A case–control study in Japan

Objective To investigate the relationship between vegetable and fruit consumption and the risk of chronic obstructive pulmonary disease (COPD), a case–control study was conducted in central Japan in 2006. Methods A total of 278 referred patients with COPD diagnosed within the past four years and 340 community-based controls undertook spirometric measurements of respiratory function. A structured questionnaire was administered face-to-face to obtain information on demographics, lifestyle and habitual food consumption. Results The mean vegetable and fruit intakes of cases (155.62 (SD 88.84) and 248.32 (SD 188.17) g/day) were significantly lower ( p < 0.01) than controls (199.14 (SD 121.41) and 304.09 (SD 253.72) g/day). A substantial reduction in COPD risk was found by increasing daily total vegetable intake, p for trend = 0.037. The prevalence of breathlessness also decreased with vegetable consumption, the adjusted odds ratio being 0.49 (95% CI 0.27–0.88) for the highest versus lowest quartile of intake. However, the effects of fruit consumption were not significant. Among the nutrients contained in vegetables and fruits, vitamin A was particularly significant ( p = 0.008) with an estimated 52% reduction in COPD risk at the highest level of intake. Conclusion The study provided evidence of an inverse association between vegetable consumption and the risk of COPD for Japanese adults.

High high-density lipoprotein-cholesterol reduces risk and extent of percutaneous coronary intervention-related myocardial infarction and improves long-term outcome in patients undergoing elective percutaneous coronary intervention

The study tested whether high-density lipoprotein-cholesterol (HDL-C) has an effect on percutaneous coronary intervention (PCI)-induced myocardial infarction and its prognosis. Elevation of cardiac troponin I (cTnI) > 3x upper normal limit after PCI is defined as PCI-related myocardial infarction (PMI) and is associated with a negative prognosis. No data exist on the relationship of HDL-C to PMI and PMI-related outcome. Pre-procedural HDL-C levels and post-procedural peak cTnI levels were collected in 350 patients undergoing PCI. Data were analysed for PMI and for acute myocardial infarction (AMI) during follow-up. Patients with PMI (n = 115) had lower HDL-C levels than patients without PMI [n = 235; 1.17 mmol/L (0.75-2.51) vs. 1.27 mmol/L (0.70-2.87), P < 0.001]. Pre-procedural HDL-C levels were inversely related to the occurrence of PMI [odds ratio for PMI: 0.884, 95% CI: 0.80, 0.98; P = 0.02 for an HDL-C-increment of 5 mg/dL (0.13 mmol/L)] and to AMI during follow-up [hazard ratio (HR): 0.697, 95% CI: 0.54, 0.90; P = 0.005]. The occurrence of PMI was associated with an elevated HR for AMI (4.702, 95% CI: 1.79, 12.37; P = 0.002). Low-risk levels of pre-procedural HDL-C [men >or=40 mg/dL (>or=1.03 mmol/L), women >or=45 mg/dL (>or=1.16 mmol/L)] did not influence the negative effects of PMI on outcome (HR: 5.510, 95% CI: 1.43, 21.31; P = 0.013) and reduction of AMI-free survival [mean AMI-free survival time with PMI: 1167.5 days (95% CI: 1098.27, 1236.67) vs. 1240.7 days (95% CI: 1220.94, 1290.49) without PMI; log-rank P = 0.005]. Conclusion Small increases in HDL-C in patients undergoing elective PCI convert into a substantial reduction of risk for PMI, which has adverse effects on the long-term prognosis. Patients with PMI are at a high risk for AMI at any HDL-C level and therefore should receive particular monitoring by the treating physician over a long period after PCI.

Cost–benefit comparisons of investments in improved water supply and cholera vaccination programs

This paper presents the first cost–benefit comparison of improved water supply investments and cholera vaccination programs. Specifically, we compare two water supply interventions – deep wells with public hand pumps and biosand filters (an in-house, point-of-use water treatment technology) – with two types of cholera immunization programs with new-generation vaccines – general community-based and targeted and school-based programs. In addition to these four stand-alone investments, we also analyze five combinations of water and vaccine interventions: (1) borehole + hand pump and community-based cholera vaccination, (2) borehole + hand pump and school-based cholera vaccination, (3) biosand filter and community-based cholera vaccination, (4) biosand filter and school-based cholera vaccination, and (5) biosand filter and borehole + hand pump. Using recent data applicable to developing country locations for parameters such as disease incidence, the effectiveness of vaccine and water supply interventions against diarrheal diseases, and the value of a statistical life, we construct cost–benefit models for evaluating these interventions. We then employ probabilistic sensitivity analysis to estimate a frequency distribution of benefit–cost ratios for all four interventions, given a wide variety of possible parameter combinations. Our results demonstrate that there are many plausible conditions in developing countries under which these interventions will be attractive, but that the two improved water supply interventions and the targeted cholera vaccination program are much more likely to yield attractive cost–benefit outcomes than a community-based vaccination program. We show that implementing community-based cholera vaccination programs after borehole + hand pump or biosand filters have already been installed will rarely be justified. This is especially true when the biosand filters are already in place, because these achieve substantial cholera risk reductions on their own. On the other hand, implementing school-based cholera vaccination programs after the installation of boreholes with hand pump is more likely to be economically attractive. Also, if policymakers were to first invest in cholera vaccinations, then subsequently investing in water interventions is still likely to yield positive economic outcomes. This is because point-of-use water treatment delivers health benefits other than reduced cholera, and deep boreholes + hand pumps often yield non-health benefits such as time savings. However, cholera vaccination programs are much cheaper than the water supply interventions on a household basis. Donors and governments with limited budgets may thus determine that cholera vaccination programs are more equitable than water supply interventions because more people can receive benefits with a given budget. Practical considerations may also favor cholera vaccination programs in the densely crowded slums of South Asian and African cities where there may be insufficient space in housing units for some point-of-use technologies, and where non-networked water supply options are limited.

Questioning Conventional Wisdom

In science, what seems obvious may not be true, and what is accepted as conventional wisdom, may sometimes be based on flawed assumptions. What is more obvious than the fact that the sun revolves around the earth? Each day the sun rises in the eastern horizon, and we observe it moving across the sky until it retires in the west. And yet, it is not true that the earth is the center of the universe. Galileo de’ Galilei, the scientist born in Pisa, was persecuted for questioning such conventional wisdom and supporting the theory proposed by Nicolaus Copernicus of a heliocentric universe. Ultimately, the truth could not be suppressed. We have many examples of progress that resulted from the questioning of strongly held beliefs that once seemed so obvious. Who anticipated that a gastric ulcer could be considered an infectious disease?1 Who expected that drugs that effectively suppressed premature ventricular beats in patients with ischemic heart disease would cause harm?2 Who believed that treatment strategies associated with substantial risk reduction might be poorly adopted into practice even 10 years after the publication of the trials establishing their efficacy?3 Who could …