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Carhartt Camouflage Seat Covers SSC7366CAXG
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The image of an African servant and a bunch of flowers is very significant to mid-nineteenth-century French painting. It features in a number of the period's most challenging paintings, including Edouard Manet's notorious Olympia (1863).
African Woman with Peonies is among Bazille's most sophisticated canvases, and sadly one of his last. The servant arranges the bunch of flowers in an image that makes clear Bazille's art historical credentials. The density and clarity of the flowers recall the Dutch tradition of floral still lifes, and the application of paint and the subject itself refer to Bazille's keen interest in Manet and Gustave Courbet. But the painting also indicates Bazille's own important contribution to both art history and to French politics. He reminds us that the African servant, the bunch of flowers, and the highly glazed earthenware pot were all equally objects of beauty and commercial exchange.


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Executive Summary – Dec. 19, 2011
Effectiveness of Early Diagnosis, Prevention, and Treatment of Clostridium difficile Infection
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Table of Contents
- Introduction
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Clostridium difficile infection (CDI) is a serious healthcare-associated infection and a growing health care problem. C. difficile is a Gram-positive, spore-forming, anaerobic bacterium that, when ingested, can cause CDI if it is a toxigenic strain. CDI symptoms include varying levels of diarrhea severity, as well as pseudomembranous colitis and toxic megacolon. CDI incidence is estimated at 6.5 cases per 10,000 patient days in hospital.1 About 250,000 hospitalizations were associated with CDI in 2005.2 Direct attributable mortality from CDI has been reported to be as high as 6.9 percent of cases.3 Elderly people in hospitals account for the vast majority of severe morbidity and mortality.4-6 Residents of long-term care facilities are also at higher risk.7,8 Incidence rates may increase by fourfold or fivefold during outbreaks.9 In addition to institutional care environments, C. difficile is also common in the community, being easily isolated from soil and water samples.10 Community-associated CDI rates are generally much lower, accounting for 27 percent of all CDI cases in a recent prevalence study,9 but are also on the rise.11 However, the source of the C. difficile organisms responsible for cases of CDI in the community is not well understood.
In order for CDI to develop, a person must be infected with a strain of C. difficile capable of making toxin in the person's colon. Toxigenic strains are those that make toxin B (a cytotoxin), with or without toxin A (an enterotoxin). Approximately 1–2 percent of healthy individuals are colonized with C. difficile.12 If these people have usual, healthy colonic flora, the risk of CDI is very low. There is a small risk of CDI if the colon flora becomes disturbed, commonly through antibiotic use, while the person is colonized with a toxigenic strain. Antibiotics that disturb colon flora enough to allow CDI to develop must get into the colon, and they are associated with alterations in relative amounts of colon bacterial constituents.13,14 The immune status of the patient also contributes to the risk of developing CDI and the experienced severity.15 Other risk factors include increasing age, female gender, comorbidities, gastrointestinal procedures, and use of gastric acid suppression medications.16-25 Risk profiles for recurrent CDI are similar.21 One study, which statistically modeled CDI within the hospital setting, suggested that reducing patient susceptibility to infection is more effective in reducing CDI cases than lowering transmission rates.26
New, more virulent strains have emerged since 2000. Characteristics associated with hypervirulent strains can include increased toxin production (due to a deletion in a toxin regulatory gene), an additional binary toxin, whose role in disease etiology is not well understood, hypersporulation, and high-level resistance to fluoroquinolone antibiotics.27 These new strains affect a wider population, often people with a lack of established risk factors for CDI based on older strains, such as previous hospitalization or antibiotic use, and include children, pregnant women, and other healthy adults.28 With hypervirulent strains, the time from symptom development to septic shock may be reduced, making quick diagnosis and proactive treatment regimens critical for positive outcomes.
The highly virulent strain associated with the epidemic of CDI described in the early 2000s may be decreasing in prevalence in limited locations.29 Recent analysis of an archived collection of C. difficile isolates revealed that predominant strains shifted from year to year among a population served at a single institution,30 suggesting that this strain shift may occur on a larger scale. However, this phenomenon potentially cuts both ways as strains drift toward lesser or higher virulence, and the possible future risks and costs of CDI remain significant.
Scope and Key Questions
The purpose of this systematic review was to provide an overarching assessment of the evidence for comparing the accuracy of diagnostic tests and the effectiveness of prevention and treatment interventions on initial and recurrent CDI-related patient outcomes in adult patients. This purpose was developed during the project's topic refinement stage. There was consensus among key informants that this systematic review's single greatest contribution to the field could be to provide a comprehensive review by an independent organization that covered the major concerns of the field. CDI is an active topic in the literature as well as a vital clinical concern. The consensus opinion included the idea that clinicians and researchers both would be well served by a reaffirmation of what is and is not supported by evidence in the literature, and at what level of evidence, to balance against this activity level.
The major impetus of this review is the presence of clinical disease, not asymptomatic carriage of the C. difficile organism. While we were interested in how treatment of CDI varies by organism strain, molecular epidemiology studies whose main purpose was to identify the strains of C. difficile present in the population are also outside the scope of this review. The review focuses on adult patients because adults, and particularly elderly adults, carry the large majority of the morbidity and mortality burden.
The following Key Questions (KQs) form the basis for this review:
- KQ 1. How do different methods for detection of toxigenic C. difficile to assist with diagnosis of CDI compare in their sensitivity and specificity?
- Do the differences in performance measures vary with sample characteristics?
- KQ 2. What are effective prevention strategies?
- What is the effectiveness of current prevention strategies?
- What are the harms associated with prevention strategies?
- How sustainable are prevention practices in health care (outpatient, hospital inpatient, extended care) and community settings?
- KQ 3. What are the comparative effectiveness and harms of different antibiotic treatments?
- Does effectiveness vary by disease severity or strain?
- Does effectiveness vary by patient characteristics: age, gender, comorbidity, hospital- versus community-acquired setting?
- How do prevention and treatment of CDI affect resistance of other pathogens?
- KQ 4. What are the effectiveness and harms of nonstandard adjunctive interventions?
- In patients with relapse/recurrent CDI?
We used the key word "difficile" to identify all articles related to C. difficile. Articles were limited to English language and humans. No date limits were applied. We searched MEDLINE, AMED, the Cochrane Library, and ClinicalTrials.gov. For systematic reviews, we searched MEDLINE, the Cochrane Database of Systematic Reviews, and the Web sites of the National Institute for Clinical Excellence, Guidelines.gov, and the National Health Service Health Technology Assessment Programme. We also manually searched reference lists of review articles and articles that were read for the review. Searches were conducted in February 2010 and updated in March and June 2010. An updated search was performed specifically for KQ 3 (standard treatment) in Auguest 2011, because of a new study that led to FDA approval of fidaxomicin in May 2011.
For KQ 1, we included studies that used clinical stool specimens from patients suspected to have CDI. We included studies that concurrently compared at least two diagnostic tests in the same laboratory using the same stool samples and using the same reference standard to reduce heterogeneity in the estimates. Studies must have used toxigenic culture, cell cytotoxicity assay, or combinations of tests as the reference test for toxigenic CDI. Direct comparisons of diagnostic tests without a reference test were not included. We sought studies that included patient outcomes or outcomes related to changes in therapy. We present study results in positive terms, that is, true positives (sensitivity) and false positives (1 minus specificity).
For KQ 2, we included studies that examined the effects of prevention strategies aimed at breaking routes of transmission within institutional settings or reducing susceptibility to CDI through antibiotic prescribing practices. We included only studies with CDI incidence, or other measures of CDI, as an outcome. We excluded studies that used only intermediate outcomes, such as reduced spore count in environmental samples. Accepted study designs included randomized controlled trials (RCTs), prospective cohort, retrospective cohort, time series, and before/after trials. We also identified good quality studies that identified specific risk factors for development of CDI in general hospital inpatients to facilitate infectious disease control efforts to target likely effective preventive strategies.
For KQ 3, we included RCTs that compared two active antimicrobial treatments, including vancomycin, metronidazole, bacitracin, nitazoxanide, rifaximin, fidaxomicin, and rifampin, on adult patients. We also included placebo-controlled trials for vancomycin or metronidazole, the agents of most interest. We included initial cure, recurrence (variably defined by symptoms with or without a positive test for C. difficile), and mortality, which are outcomes of interest to clinicians and are reported in most studies. We also included time to resolution of diarrhea.
For KQ 4, we included all studies that examined any nonstandard intervention, such as toxin binding agents, probiotics, vaccinations, or other treatments aimed at enhancing a patient's resilience. Outcomes included resolution of symptoms and recurrence.
Diagnostics (KQ1) Results
We found 13 references that provided comparative data about diagnostic tests of interest.31-43 The number and type of paired (within study) comparisons available for each diagnostic test varied considerably, and not all possible comparisons were available.
Sixteen paired comparisons of seven commonly used immunoassays for toxins A and B provided low-strength evidence that the test sensitivities do not differ. There was moderate-strength evidence for no differences in test specificities for two comparisons and for a difference of 2 percent in one comparison. Otherwise, there was only low-strength evidence for or against differences in test specificities. There was insufficient evidence of differences between all tests that were not directly compared.
Nine comparisons of two toxin gene detection tests that focus on toxin B to toxin immunoassays provided only low-strength evidence that the gene-based tests are substantially more sensitive. There was moderate evidence that the test specificities in one comparison did not differ. Otherwise, there was only low-strength evidence for differences in either direction between test specificities. There was insufficient evidence of differences between all tests that were not directly compared.
There was no evidence to determine whether any differences in sensitivity or specificity between diagnostic tests depend on patient or specimen characteristics or the clinical scenarios that lead to testing for toxigenic CDI.
Prevention (KQ2) Results
We found 1 Cochrane review, 44 4 studies on antibiotic prescribing restrictions,45-48 11 on single preventive practices aimed at transmission interruption,49-58 and 10 studies that bundled multiple practices into a prevention strategy.59-68 We updated a previous systematic review and found 11 studies examining risk factors that met the inclusion criteria.20
Overall, the evidence available to link prevention strategies to clinically important outcomes, such as CDI incidence, is of low quality and is not extensive.
Four observational studies45-48 and one Cochrane review44 found that prescribing practice interventions decreasing the use of high-risk antimicrobials are associated with decreased CDI incidence. Prescribing practices were also used in multicomponent interventions credited with reducing CDI incidence; however, it is difficult to isolate the specific effects of the prescribing practices.
One controlled trial found glove use significantly reduced CDI incidence in the hospital setting.49 Likewise, three observational studies, including two controlled, found that disposable thermometer use is likely to reduce CDI incidence.50-52
No study examined the effect of handwashing on CDI incidence. Four studies found use of alcohol gels as interventions for other infectious diseases, presumably in the presence of common protocols requiring handwashing in the presence of CDI or visible soiling, did not increase CDI incidence.53-55,69
Four single-component intervention studies provide low evidence that disinfection with a chemical compound that kills C. difficile spores in thehospital environment prevents CDI, at least in epidemic or hyperendemic settings.56-58,70 Seven studies included disinfection in multicomponent interventions.60,62,63,66,71 Disinfection agents examined included hypochlorite solution, hydrogen peroxide, aldehydes, and detergent.
Ten time series/before–after studies have examined bundled multiple interventions using before–after study designs.59-68,71 All of the studies described the use of the measures to bring epidemic CDI, or endemic CDI which was felt to be excessive, under control. The number of interventions, and the specific nature of any particular intervention, varied widely. Studies employed between two and nine different types of interventions. Study design and intervention complexity, along with the fact that many outbreaks naturally diminish, made it difficult to conclude whether the reduced CDI prevalence was due to one or more intervention components, or entirely independent.
Risk factors for developing CDI include antibiotic use, substantial chronic illness, hospitalization in an ICU, acid suppression, and age.
No data on patient harms or harms to hospital staff due to preventive interventions were reported. Likewise, no studies assessed the sustainability of a prevention program beyond an intervention period.
Standard Treatment (KQ3) Results
Eleven randomized clinical trials were identified that evaluated different antimicrobials (or different doses of a single drug) available for treatment of CDI in the United States.72-82 These 11 studies enrolled 1,463 patients and reported efficacy analysis on 1,239 patients.
Overall, study quality is low. Vancomycin and metronidazole, the most frequently clinically used antimicrobials, were also the most frequently compared antimicrobials. Three RCT comparisons of vancomycin to metronidazole, with a total of 335 pooled subjects, found no significant differences in any examined outcome.73,76,79 One RCT comparing vancomycin to metronidazole, using a prespecified subgroup analysis of 69 patients, found a small but significant increase in the proportion of subjects with severe CDI who achieved initial clinical cure with vancomycin, using a treatment-received analysis.73 The significance of this difference did not persist when a strict intention-to-treat analysis was performed.
Moderate-strength evidence from one large, high-quality study demonstrated that vancomycin and fidaxomicin performed equally well for initial cure, but that recurrence was significantly decreased with fidaxomicin versus vancomycin.82 No other head-to-head trial demonstrated superiority of any single antimicrobial for initial clinical cure, clinical recurrence, or mean days to resolution of diarrhea. Combination therapy with rifampin and metronidazole resulted in significantly higher mortality when compared to treatment with metronidazole only.74 Pooled data of 104 subjects comparing vancomycin to bacitracin showed significantly higher rates of organism or toxin clearance for vancomycin.77,80
Harms were not reported with sufficient detail to compare the risks of any particular antimicrobial with another antimicrobial. When harms were reported, they were generally not serious (e.g. nausea, emesis) and transient.
A single study assessed initial cure and recurrence by strain, categorized as North American pulsed-field gel electrophoresis type 1 (NAP1) versus non-NAP1.82 Strain data was available for 324 of 629 (51.5%) participants. For initial cure, no significant difference was observed, regardless of strain. However, among patients with non-NAP1 strains, those treated with fidaxomicin recurred less frequently than those treated with vancomycin (10% vs. 28%; P < 0.001), whereas among patients with the NAP1 strain, recurrence was similarly frequent regardless of treatment.82
Nonstandard Treatment (KQ4) Results
Five RCTs on nonstandard adjunctive treatments of CDI and 13 studies that addressed prevention of CDI formed the basis of this analysis. Four of the studies on treatment of CDI compared a nonstandard intervention with an active control, that is, a standard antibiotic treatment for CDI, oral vancomycin or metronidazole.83-86 One study compared a nonstandard intervention with placebo.87 All of the 13 prevention studies compared the nonstandard intervention with placebo rather than with another intervention, reflecting the current state of the science in this area. Five of the 13 prevention studies analyzed antibiotic-acquired diarrhea as a primary outcome and CDI as a secondary outcome.83-86 Numerous published case reports, as well as nonexperimental studies, describe additional nonstandard approaches for treatment of CDI and their possible harms. As found with the other Key Questions, overall, study quality was low. Definitions of CDI with regard to diarrhea, that is, number and consistency of stools, were inconsistent across studies.
For treatment of CDI, C. difficile immune whey that binds C. difficile toxin A is similar to metronidazole in a small study of 38 patients with recurrent CDI.85 Colestipol, an absorptive resin, is not more effective in treating CDI than placebo.87 Probiotics administered as an adjunct to antibiotic treatment were not more effective than treatment with antibiotics alone.83,84,86
There is low-strength limited evidence that the probiotic88-93 interventions in this review are not more effective than placebo for primary prevention of CDI. There is low-strength limited evidence from one subgroup analysis that a prebiotic may reduce diarrhea recurrence in patients treated for CDI more so than placebo with standard antibiotics.94,95 Fungemia is a serious potential harm associated with administration of probiotics for CDI in critically ill patients.96,97 In one review, 46 percent of 60 critically ill patients who developed fungemia had been administered a probiotic containing Saccharomyces boulardii and 5 more patients were in the vicinity of an administered probiotic. Seventeen patients subsequently died.96
There is limited moderate-strength evidence from one study that monoclonal antibodies are effective in preventing recurrence of CDI.98
There is limited low-strength evidence from two case series that fecal flora reconstitution is effective in treating recurrent CDI for up to 1 year.99,100
There is very limited high-strength evidence to support the diagnostic, preventive, and treatment practices for CDI carried out by providers in hospital, long-term care, and outpatient settings. Table A provides a summary of the evidence and results presented in this review. Inconsistency in definitions of diarrhea, severity, resolution of symptoms, recurrence, or cure contributes to the difficulty in drawing conclusions from the evidence.
In general, there is little evidence that the sensitivities of commonly used immunoassays for toxins A and B differ, and any differences in their percent of false positives (1 minus specificity) most likely are small (3 percent or less). However, the strength of the evidence is low due to the number of studies that have directly compared various immunoassays in the literature. Future research possibly could impact the findings. The available comparative data does not rule out the possibility of larger differences in test sensitivities between some of the immunoassays that have or have not been directly compared in adequate numbers. While the precision of the findings is such that we cannot rule out the possibility of differences in sensitivity on the order of 3 to 5 percent, it is unclear whether such differences would affect clinical decisionmaking.
Gene detection tests that focus on toxin B tended to have better sensitivity than immunoassays for toxins A and B. Results, however, should be viewed with caution, given rather imprecise confidence intervals on the estimated differences. Further study of the differences in false positives, if any, is needed, too. Few studies contributed to the findings, and many direct comparisons were not found. Furthermore, variation in the stability of the toxins in stool specimens as they were collected, stored, and processed may have contributed to the observed variation between studies in the estimates of the sensitivities of the immunoassays, whereas detection of amplified toxin gene fragments could be less susceptible to specimen degradation and more susceptible to contamination of specimens. Differences in the sensitivities of the reference tests could affect the estimated sensitivity for immunoassays to greater degrees than gene detection tests as well.
The immunoassays and gene detection tests require varying skills, equipment, and time to carry out, and heterogeneity is a significant factor in reviewing the literature. Previous reviews by Planche et al.101 and Crobach et al.102 encountered difficulty comparing the sensitivities and specificities of immunoassays in large part because there was too much variation between studies in the estimates of the sensitivity and specificity of a particular test. We attempted to control for the heterogeneity between studies by examining the differences in sensitivity and specificity in stool samples tested within the same lab using the sample patient stool specimens and reference test, and we did not find strong evidence of differences between tests within several immunoassays for toxins type A and B. The extent of any publication bias for these comparisons is unknown.
A clinically important question is whether the potential differences in the accuracy of the diagnostic tests being employed in practice would translate into differences in clinical behaviors or patient outcomes. Indeed, how well clinicians actually know the sensitivity and specificity of the test(s) for toxigenic C. difficile employed by their laboratories and incorporate this information into their patient care decisions is not clear. If test results are combined with pretest probabilities that patients have toxigenic C. difficile using Bayes' formula, then the differences in post-test probabilities might not lead to different clinical decisions even if there are substantial differences in the sensitivities and specificities of tests for toxigenic C. difficile.
Very little evidence connects prevention strategies and techniques directly to patient-related outcomes, such as CDI incidence. Available evidence is generally from before–after study designs or limited time series. Hospital settings with outbreaks or hyperendemic episodes further limit applicability of the findings and leave open the question of the relative contribution of regression to the mean (i.e., that CDI rates returned to baseline rates even in the absence of effective interventions). The studies also varied in the degree to which they described CDI surveillance, diagnostic accuracy, or laboratory performance. In most, surveillance was passive and depended on a positive toxin test on a stool specimen sent by clinicians caring for a patient with diarrhea. Unknown numbers of cases might have been missed or misdiagnosed. Additionally, attention has not been given to describing a prevention strategy's potential harm (e.g., increase in other pathogens, reduction in direct patient care contact due to isolation or restrictive contact requirements, increased costs) or the long-term sustainability of a practice.
There is low-strength evidence that antibiotic prescribing practices appear to reduce CDI incidence, a finding consistent with the Cochrane review.44 None of the studies explicitly addressed the potential harms of changes in antibiotic use policy, but there are several theoretical harms. They include the possibility that preferred drugs will be less effective than drugs that physicians are discouraged from using, or drugs that are made unavailable for treating infections other than CDI. Preferred antimicrobials might have greater costs or greater toxicities unrelated to CDI. C. difficile strains might evolve to develop resistance to the preferred antibiotics, which might increase the likelihood that the recommended antibiotics might induce CDI.
While several studies found increased risk with specific antibiotics or antibiotic classes, the antibiotics that confer greater risk for CDI have changed over time and vary by location because of differences in prevalent toxigenic strains and especially the susceptibility patterns of those strains.103 Clindamycin resistance was identified soon after the role of C. difficile in pathogenesis was discovered.49,104,105 More recently, quinolones have assumed greater importance because strains have become more resistant over time.106
Fewer studies are available to support prevention practices aimed at breaking transmission. There was limited low-strength evidence that gloves, disposable thermometers, handwashing, and intensive disinfection solutions help to reduce CDI incidence. In addition, the presence and use of alcohol gel to prevent other hospital-acquired infections, such as MRSA, did not increase the rate of CDI incidence as might be expected if alcohol gel use replaced handwashing.
Similar to the antibiotic prescribing practice research, none of the studies aimed at breaking transmission addressed potential harms for other prevention practices. Costs of disinfection, time to perform disinfection, and the possible harm to surfaces and equipment should be anticipated. Failures with vapor disinfection systems would be possible and might lead to toxic exposures of personnel or patients. Nor is there evidence to inform infection control professionals whether such practices are sustainable after an intervention period. That is, we cannot answer whether environmental cleaning staff will have developed professional habits that will continue when the intense monitoring related to an intervention period discontinues.
The potential for prevention research is often compromised by the swift uptake of newly described prevention strategies with the belief that these will improve institutional practices and health care quality and will reduce CDI morbidity and mortality. Current prevention strategies often rely on studies using intermediate outcomes such as process. Newly acquired strategies are then added to current practice, bundling them into multiple component interventions. When introduced in outbreak or hyperendemic situations, these "bundled" multipronged prevention efforts in natural settings have been associated with reduction in CDI incidence. The bundles appear to be beneficial, but from a research standpoint, it is challenging to design research that would tease out the relative contributions of single components to the overall bundle of prevention strategies to determine which ones are essential or what might be added.
The available evidence is insufficient to say whether any antimicrobial treatment is better than another, including the two most commonly used treatments, metronidazole and vancomycin. The total number of subjects from comparative studies on metronidazole and vancomycin is just 335 patients. This raises the possibility that, although a significant difference in effectiveness has not been detected, a true difference may exist. There is moderate strength of evidence that recurrence is less frequent with fidaxomicin than with vancomycin, and that these two agents are not significantly different from one another for initial cure. Otherwise, there is no evidence for a difference in effectiveness for other agents, but again the possibility remains that such a difference exists. However, at this time, any claims that one agent is superior to another for all cases of CDI are not supported by available evidence. The findings apply to general adult inpatients. Bias due to selectively reporting outcomes is possible if cut-points are changed for CDI definitions, for example, number or consistency of stools. The clinical differences of changes in cut-points are also unknown, however, so the clinical significance could remain.
We found insufficient evidence that vancomycin was superior to metronidazole for subjects classified as having severe disease. One subgroup analysis of a single trial used a prespecified analysis, and the severity classification appears to have been made before treatment allocation. However, the superiority of vancomycin over metronidazole does not persist when a strict intention-to-treat analysis is used.
We sought to document the range of treatments under investigation for treatment and prevention of CDI, particularly recurrent CDI. The evidence for effectiveness of nonstandard interventions for treating CDI shows that probiotics, prebiotics, C. difficile immune whey, and colestipol are not more effective in treating CDI than standard antibiotic treatment with oral vancomycin or metronidazole or compared with placebo. The evidence supporting this conclusion is limited and of low strength.
Prevention of CDI, both initial and recurrent cases, through interventions intended to improve gut flora and host immunity is also a very active topic in the literature. There is limited, low-strength evidence that the nonstandard prevention interventions are not more effective than placebo for primary prevention of CDI. There is limited evidence of low strength that administering the prebiotic oligofructose or a monoclonal antibody to C. difficile toxins A and B along with standard antibiotics for CDI are better than placebo and active control in preventing recurrence of CDI in patients treated for CDI. Although the studies for both treatment and prevention of CDI using a nonstandard intervention included components of experimental designs, few had adequate rigor to yield high-quality findings or power to detect a significant difference between the interventions (or placebo) compared. In some studies, a low rate of CDI precluded statistical testing.
Caution is recommended regarding new, nonstandard treatments and not extrapolating study findings beyond the data. For example, one cannot assume that if a probiotic treatment is effective for antibiotic-associated diarrhea, it will be effective for CDI. Likewise, attention should be paid to which patients were included and excluded in probiotic treatment studies. Such studies generally exclude high-risk patients. Thus, there is no evidence for the use of probiotics in high-risk patients.
Future Research
A number of important questions need to be addressed regarding diagnostic testing, prevention, and treatment of CDI. Table B summarizes the research recommendations.
Diagnostic Tests
It is difficult to apply the available evidence from comparative studies to help select the best diagnostic test(s) for clinical applications. The reviewed comparative studies did not clearly define the testing scenario including the setting, disease prevalence, patient selection criteria, patient characteristics, or signs and symptoms of the suspected CDI, making it difficult to judge to whom the study results might apply. Ultimately, the clinical importance of estimated differences in sensitivity (true positives), false positives, specificity (true negatives), and false negatives depends on how these types of test results would affect clinical decisions, hence patient outcomes.
More research is needed to understand how test sensitivities and specificities are used to make decisions in clinical practice, and to define clinically meaningful differences based on their effects on clinical decisions and patient outcomes. Multicenter studies that (1) consistently use the most clinically relevant reference test, (2) use explicit clinical criteria to select patients and stool specimens to be tested, (3) randomly assign patients to different diagnostic tests, and (4) use key clinical outcomes as study endpoints are needed to fill this major gap in knowledge about diagnostic tests for toxigenic C. difficile.
Questions about whether the newer toxin gene amplification and detection tests are more consistent across laboratories, and more sensitive than the currently used toxin immunoassays for toxin without substantial loss of specificity, need further study. Most importantly, studies are needed to demonstrate that use of tests that detect genetic residue related to C. difficile toxin production rather than the toxins per se lead to better patient outcomes.
A number of potential prevention strategies can and should be investigated as a single intervention in a controlled trial in order to understand its potential contribution to a prevention program. However, the main obstacle to research in this area is the contextual setting.
Prevention happens within an institutional environment, as a comprehensive approach for preventing multiple potential hospital-acquired infectious agents and attending to multiple potential vectors of transmission and host susceptibility. Researchers and decisionmakers may need to consider another approach to inform decisionmaking: a collaborative research process in which consensus agreements are reached for minimum datasets and followup periods, and definitions of interventions are agreed to in order to facilitate pooling data across organizations. For example, minimum datasets might be those that would yield statistically significant results in a controlled trial if the intervention arm could prevent 10 to 20 percent of CDI cases. Datasets of this nature could allow for employing more sophisticated epidemiological and decision analytic techniques to tease apart the relative contributions of different prevention strategies. The nature of the decisions faced by infection control professionals is qualitatively different from a physician's clinical decisions for an individual CDI patient. Decision analytic techniques may be particularly valuable in this venue.
Standard Treatment
The greatest needs for future studies for CDI treatment are consistent definitions and reporting of outcomes, a uniform and clinically relevant definition of disease severity, and trials with adequate power to detect clinically meaningful differences in outcomes. In particular, trials need to include adequate numbers of subjects to allow stratification by patient characteristics such as age, gender, and comorbid conditions in order to address questions regarding the most effective therapy for CDI. A well-validated and clinically meaningful severity score would also assist in treatment decisions. Although most agents for CDI appear to be well tolerated, explicit reporting of adverse events by treatment allocation is another area where future research can improve our understanding of optimal management of this disease.
Although identifying the strain of C. difficile is of great relevance to researchers and can offer useful information to hospital epidemiologists, at present, strain identification is rarely performed in clinical settings. Thus, few clinicians treating CDI are aware of which strain of C. difficile is causing an individual patient's disease and can, at most, make an assumption as to the strain type based on current epidemiology reported in the literature. This limitation makes any difference by strain in treatment efficacy of uncertain relevance.
Nonstandard Treatment
Additional research on nonstandard interventions as adjunctive or alternatives to standard antibiotics for preventing and treating CDI is needed and encouraged. Studies to prevent recurrence of C. difficile are a priority of prevention. As no single approach has been shown to be superior, promoting studies of different types of interventions is reasonable at this time.
Fecal flora reconstitution is one novel therapy for which continued research is supported. Of all the nonstandard interventions, probiotics have been investigated in the most studies, and the results are not encouraging. Unlike fecal flora reconstitution, probiotics provide only a single strain or a few strains of bacteria, and thus may be insufficient to correct alterations in the complex and extensive microbiome to the extent needed to be therapeutic. The genomic mapping of indigenous microflora may offer new information to guide future formulation of a probiotic that can effectively target alterations in the microbiome in CDI and other diseases of the colon. A third strategy related to modifying microbial ecology in CDI for which additional research is supported is administration of a nontoxigenic strain of C. difficile.
Developing agents to treat severe cases of refractory CDI is another area in need of research. Identifying new antibiotics may be one approach. Two of the larger case series of immunoglobulin use are in severely ill patients, and results are inconsistent.107,108 Whether immunoglobulin might confer greater benefit if initiated earlier in the course of CDI prior to extensive systemic involvement is an area for further study.
Studies are needed to determine whether some patients might be more likely to respond to nonstandard interventions. Sampling in current studies of nonstandard interventions varies considerably, ranging from individuals who are just starting antibiotics for infections other than C. difficile, to those who have had multiple failures of antibiotic treatment for CDI itself, to those who have had C. difficile in the past. Whether any one type of nonstandard intervention is effective in all of these types of cases is a question. More information is needed about patients who are at high risk for recurrence of CDI.
The effect of sequencing therapies (antibiotic as well as nonstandard) on the resolution of CDI merits further research. Studies show a variety of procedures for administering probiotics to prevent CDI, for example, such as during standard antibiotic therapy or for a period after standard treatment is completed. Determining the optimal timing to introduce nonstandard interventions to possibly maximize their effect is recommended.
Methodological Improvements
It is essential that future studies of a nonstandard intervention for treatment or prevention of CDI be supported by a power analysis, adequate sample size, and an intent-to-treat analysis, in addition to other standard quality components of experimental design. Study designs must separate interventions for prevention versus treatment of recurrent CDI if this approach is desired. Multicenter studies may be necessary to achieve adequate sample sizes. Laboratory confirmation of a pathogenic C. difficile organism (e.g., by toxin testing) and clinical symptoms of disease (e.g., diarrhea) are essential not only for study eligibility but for determination of recurrence in long-term followup. Adoption of a standard definition of diarrhea as part of the definition of CDI is strongly recommended. Similarly, a standard definition of CDI resolution should be adopted. RCTs that compare more than one type of nonstandard intervention are suggested for efficiency.
|Key Questions
|Level of Evidence
|CDI = Clostridium difficile infection; RCT = randomized controlled trial
|Key Question 1 - Diagnostics
|Immunoassays for toxins A and B
|Low to moderate
|Gene detection tests versus immunoassays for toxins A and B
|Low to moderate
|Patient characteristics
|Insufficient patient information was provided in reports of comparative data.
|Key Question 2 - Prevention
|Antibiotic use
|One controlled trial found use of gloves in hospital settings reduced CDI incidence.
|Disposable thermometer
|Three time series/before–after studies, two with controls, found use of disposable thermometers in hospital settings reduced CDI incidence.
|Handwashing/ alcohol gel
|Thirteen before–after studies of outbreaks or endemic hospital settings found intensive disinfection with a chemical compound that kills C. difficile spores reduced CDI incidence.
|No evidence was available.
|Risk factors
|Multiple component strategies
|Key Question 3 - Antibiotic Treatment
|Vancomycin versus metronidazole
|Moderate for clinical cure, low for all other outcomes
|Severe disease, vancomycin versus metronidazole
|One RCT examined a prespecified subgroup of 69 subjects with severe CDI; improved clinical cure was based on per-protocol analysis, but not with strict intention-to-treat analysis
|Fidaxomycin versus vancomycin
|One large, high-quality RCT demonstrated decreased recurrence among those receiving fidaxomicin.
|All other comparisons of standard treatments
|Moderate for vancomycin versus fidaxomicin, low for all other comparisons
|There were eight trials examining: vancomycin versus bacitracin (two trials), vancomycin versus fidaxomicin, vancomycin versus nitazoxanide, vancomycin high versus low dose, vancomycin versus placebo, metronidazole versus nitazoxanide, and metronidazole versus metronidazole plus rifampin (one each). No differences.
|Strain of organism
|One RCT (fidaxomicin vs. vancomycin) demonstrated decreased recurrence among those receiving fidaxomicin when the infecting organism was a non-NAP1 strain.
|Patient characteristics
|No comparative data were available.
|Resistance of other pathogens
|No data were available.
|Key Question 4 - Nonstandard Treatment
|Treating CDI, active control
|Probiotics, prebiotics, C. difficile immune whey, and colestipol are not more effective in treating CDI than standard antibiotic treatment with oral vancomycin or metronidazole or placebo.
|Treating CDI, placebo
|Administration of a probiotic with live bacteria to treat CDI in critically ill patients increases risk for greater morbidity and mortality from fungemia without any known benefit.
|Treating recurrent CDI
|There is limited evidence from two case series that fecal flora reconstitution is effective in treating recurrent CDI for up to 1 year.
|Preventing CDI
|There is limited evidence that the nonstandard interventions in this review are not more effective than placebo for primary prevention of CDI.
|Preventing recurrent CDI
|Low to moderate
|Key Question
|Research Gaps
|Types of Studies Needed to Answer Questions
|Future Research Recommendation
|CDI = Clostridium difficile infection
|Key Question 1. How do different methods for detection of toxigenic C. difficile compare in their sensitivity, specificity, and predictive values?
|Document stool sample characteristics, patient selection criteria, patient characteristics, and signs and symptoms of suspected CDI
|Key Question 2. What are effective prevention strategies?
|Little evidence available with clinically important outcomes
|Key Question 3. What are the comparative effectiveness and harms of different antibiotic treatments?
|Limited evidence available on whether vancomycin is more effective for severe CDI.
|High-quality comparative studies with adequate power to detect significance in a priori subgroups
|Key Question 4. What are the effectiveness and harms of nonstandard adjunctive interventions?
|High-quality comparative studies with adequate power
|Umbrella issues
|Adoption of standard definitions for diarrhea, CDI resolution
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Full Report
This executive summary is part of the following document: Butler M, Bliss D, Drekonja D, Filice G, Rector T, MacDonald R, Wilt T. Effectiveness of Early Diagnosis, Prevention, and Treatment of Clostridium difficile Infection. Comparative Effectiveness Review No. 31. (Prepared by the Minnesota Evidence-based Practice Center under Contract No. 290-02-0009.) AHRQ Publication No. 11(12)-EHC051-EF. Rockville, MD: Agency for Healthcare Research and Quality. December 2011. www.effectivehealthcare.ahrq.gov/reports/final.cfm.
For More Copies
For more copies of Effectiveness of Early Diagnosis, Prevention, and Treatment of Clostridium difficile Infection: Comparative Effectiveness Review Executive Summary No. 31 (AHRQ Pub. No. 11(12)-EHC051-1), please call the AHRQ Clearinghouse at 1-800-358-9295 or email firstname.lastname@example.com.


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Four members of the Hope College women's soccer team have received all-conference honors from the Michigan Intercollegiate Athletic Association (MIAA), including the league's top honor.
Senior midfielder Allison Van Beek of Libertyville, Ill. (Libertyville HS), pictured right, has been named the MIAA's most valuable player by conference coaches.
She is joined on the All-MIAA first team by sophomore defender Courtney Cook of Grand Rapids, Mich. (Forest Hills Central HS). Van Beek is being honored on the first team for the third consecutive year while Cook is being recognized for the second time.
Hope players named to the All-MIAA second team are sophomore midfielder Kristen Schwenk of Midland, Mich. (Dow HS) and senior forward Sarah Sosolik of Oswego, Ill. (Oswego HS).
Van Beek led Hope in scoring this fall with 12 goals and two assists. Over her four-year career she scored 31 goals and had 16 assists.
She is the third Hope player to receive MIAA MVP honors joining Tina Gill (1996) and Dawn Gillam (2004).
Coach Leigh Sears' Flying Dutch posted a 13-6 season record and finished third in the MIAA standings.


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Anyone's Guess for 2010 Eagles
Posted on 23 Oct 2010 by Christopher Rowe.
Does anyone really have a clue what is happening with the Philadelphia Eagles? They lose when they should win, they win when they should lose. Their offensive line leaks live a sieve and then plays a solid game with patchwork players. Their defense is suspect one week and then devastating the following week. Heading into Week 7 of the NFL season, there is no way to tell whether the Eagles are e...


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Vector image of Jesus Christ captive for cutting plotter and engraving
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|the Rod Rack Rod Builder's Forum
|Topic Review (Newest First)
|Gregory DeFoe
Off center cork grip
It sounds like the inletted bore of the cork ring was not concentric to the ring and/or the reel seat was not centered. When finished this would be the thinnest cork on the handle and minor errors could show up as you describe. While it is probably me, I do not fully understand your description of the method you used. If you would care to PM me with contact info perhaps I could talk you thru it. I build 2handers and turn all grips on the blank and have yet to have a problem like that.
Greg DeFoe
Can't center cork grip turned on blank
I glued-up my first grip ever on a blank and when I turned it in the drill lathe the seat hood showed through on one side. Obviously the grip became offcentered somehow. The reel seat is a REC with a round hood. I epoxied in a threaded REC fighting butt insert and then used a headless bolt threaded into the insert chucked into drill lathe. I did notice a little wobble that disappeared after a while. My thought was that the fighting butt insert or the reel seat itself was not centered. The difference between the width of the edge of the cork ring arround the hood is over 1mm. I would have noticed that difference if the reel seat was off by that much.
I then glued up another cork grip on another rod. Same model seat but without the fighting butt insert. I used the bushing made for the seat and it was centered perfectly on the blank. I bushed an old blank and inserted it into the butt end of the blank I was turning and it fit perfectly. Before I started I noticed that the cork ring over the hood was symmetrical at the aft end. When I started turning the grip the same thing happened. While I was careful not to exrose the hood like the former one, it still wanted to become offset. I sanded the high spot bringing the grip back to symmetrical. After I finished the grip is great but the ring over the hood is still offset.
To produce a straight stick of cork I epoxied 60 grit paper to a smooth board and applied it carefully to knock down the high spots. I use a Flex Coat lathe with 2 steadies.
I can't figure what I am I doing wrong.
Advise would be appreciated.
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if each solenoid is 12v I will need a total of 60v then
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By Sam Mamudi
Credit card company stocks have enjoyed a bountiful 2012, as this chart illustrates:
Not bad at all — but not the end of the story, at least according to analysts at Nomura. In a note published Monday, they argue that this year's gains shouldn't mean you cash out of your credit card stocks. In fact, Nomura has a Buy rating for MasterCard (MA), Discover Financial Services (DFS), Visa (V) and American Express (AXP).
Based on new price targets, the Nomura analysts foresee gains in the next 12 months of 26%, 23% 17% and 22% for each company, respectively. The reason, they argue, is less the macro picture than the companies themselves:
As we look ahead to 2013, we anticipate a tough revenue growth environment, given our outlook for rather muted spending growth and continued lack of consumer appetite for credit. The ability to grow revenues faster than expenses will be key to delivering strong performance. Both our estimates and consensus show the cards and payments stocks delivering positive operating leverage in 2013.


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Absolutely NO! Gas prices are up as are NC gas taxes. Food prices have gone way up and I definitely spend more time checking the grocery ads and comparing prices in the store. My house has gone down in value but my property taxes have gone up. The same for my rental properties. The houses are worth less but I pay more in property taxes. NC state sales tax has gone up. I smoke (yeah yeah I know) and both the federal and state tax on a pack of smokes has gone way up. Beer and wine tax has gone up. The price of dog food has gone way up and I have 4 dogs. The list goes on and on.
Hihope Hiland Heathen of Perth CD, RE, CGC, TDI. (RIP)
teracroft Clan Piper of Perth CGC TDI (RIP)
Boyne's Fast Break of Perth RN CGC CGCU( munchin in training)
To paraphrase some here, "That all depends on how you qualify the question".
Wages? No.
Job likability? No.
Taxes? No.
Cost of living? No.
Love of and appreciation for family & friends? YES!
Thanks to Divine Providence for things that could be worse, aren't YES!
Getting rid of "stuff" and simplifying? YES!
Getting more active in political process/re-learning American History? YES!
"It's not that government is inherently stupid, although that's a debatable question."
Rand Paul CPAC speech 2011
I would rather be exposed to the inconveniences attending too much liberty than to those attending too small a degree of it. Thomas Jefferson to Archibald Stuart, 1791
Proud partner of (HR) WR SR Brian's 44Magnum Monster
co-owned by HR Rianne's 2nd Chance Hurricane Rebel
With the US being $14,000,000,000,000 in the hole, even if you think you are better off, you are not.
Health insurance agent and consultant, oil and gas investor, real estate investor, son who is a real estate agent - no, we are not better off.
M&K's HR UH Tucker of Texoma JH
M&K's SHR Prime Black Angus
M&K's Miss Jessie Girl JH
Sir Jacob of Lakeview-Jake
Freeway JYD
Mike Whitworth
And let's keep on increasing the entitlement programs and adding more of them, especially those that encourage more non working slime to cross our borders and breed even more of the same. They may be parasites on society but hey they can vote and we all know who'll get those votes in exchange for promises of even more free shit. After all we can always keep taxing the rich to pay for it all....
Julie R., Hope Springs Farm
Chesapeake Bay Retrievers since 1981
That is what is wrong with this country. Not one word about quit spending money. With that attitude I could come up with a long list of taxable actions.
A tax for every pound a person is overweight would be a good start. Notice I do not advocate a tax on soda or chips because if you work out and burn it off you should not pay for the 600lb person that walks across the floor and shakes the building.
Hihope Hiland Heathen of Perth CD, RE, CGC, TDI. (RIP)
teracroft Clan Piper of Perth CGC TDI (RIP)
Boyne's Fast Break of Perth RN CGC CGCU( munchin in training)


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BONUS AUDIO: Author Robert J. Sawyer explains why Ponter Boddit is his favorite among all the characters he's created.
Hunt and gather: listen to more in the Neanderthal Parallax trilogy.
©2002 by Robert J. Sawyer; (P)2008 Audible, Inc.
"Sawyer is a writer of boundless confidence and bold scientific extrapolation." (The New York Times)
My taste differs from kid books to gory horror books.
"Good Science Fiction"
I am a fan of Robert J. Sawyer and this is another great read. This is Science Fiction in it's purest form. We are talking Neanderthals, parallel universes and a little physics thrown in. Character development not the best. Mainly it has neat stuff in it that leads to a lot of deep thought.
Don't you just love a great story well told?
"Scicen Fiction Can Be Literature"
I found the book fast paced, well narrated and well edited. Some complain of the politics and religion but this is literature. Since we can't discuss these things at "polite gatherings" literature is appropriate except for those who wish pure escapism (While concise, entertaining and compelling certainly this is not a 'light' read).
It won the Hugo award (Science Fiction Writer's "Oscar" as most likely know), and only rarely are such prizes awarded to art without any merit.
Much fuss is made by some about the graphic sexual assault which is brief but absolutely key to distinguishing two cultures and a woman's feelings about a more sensitive being.
My only critique, is I found the verisimilitude lacking in the other culture regarding their belief system. I would think any being that could contemplate its death might have different views. A line or two more explaining their reasons would have helped. That is my only critique.
Finally, remember this is fiction. If one finds FICTION so offensive why bother reading? I can understand political or religious NON-fiction being offensive but isn't the joy of fiction that it's just "make believe?"
The price is right considering its length.
"Great idea, execution a bit flat"
The first in a series; great concept and a fun vision of what a "modern" neanderthal culture might be like. Even so the plot speed, complexity, and execution are a bit slow and even at times predictable. A fun read overall and worth the time.
"Canada's answer to Clark and Asimov"
This was the first book I ever listened to on Audible, and I still recall the magic of the experience, how I was longing to discover more even before it was over, and looking back on it all, I couldn't have picked a more perfect book to start than this. Mr. Sawyer does a wonderful job of combining cutting edge science, likeable and believable characters, and even crafts and alternate world that's totally alien, yet still relatable and easy to comprehend. I also loved the vivid descriptions of Canada (both from our world, and the alternate world of the Neanderthals), that almost made it feel like I was there with the characters, though I suppose Sawyer had an advantage as a native (and proud) Canadian. I loved how Sawyer introduces the book, and gives it the quality of being like an old friend when you've read all the books (like I have), and Jonathan Davis did a superb job narrating. For me, this was the start of a wonderful experience that still continues to this day, I only hope this book will do the same for my fellow listeners.
"Without Good and Evil"
I'm very glad I listened to this Hominids Book 1 without regard to the numerous member reviews that clearly were blinded by their own hidebound perspectives.
The beauty of this book is that it shows us two entirely different civilizations each of which is in many ways blind to its own flaws and yet each of which has its own strengths and humanity.
It's clearly not by accident that the Neanderthals call themselves human and that the Homo Sapiens call themselves human and that as a whole each civilization is short sighted.
The flaws of the Neanderthals really are both potential and present flaws of our society, too. And the flaws of the Homosapiens are parallel flaws of our own.
It's a book without good or evil. Each society is both compassionate and prejudiced, and each side is worthy of existing and interacting with the other.
Finally, the main characters are for good reason benevolent and often wise. Thus individuals redeem their societies.
Some reviewers are caught up on one side or another, on one character or another, on trivia that misses the whole point. Be willing to accept the evil to appreciate the good.
"Very thoughtful"
While this is a very interesting book, listeners/readers should be warned that it isn't fast paced, and the story unfolds slowly - this is not a criticism, but if you are impatient, you may not enjoy this. However, if you are willing to commit, it should be pretty enjoyable.
"Ended too soon"
I guess that's what sequels are for, but the only thing disappointing about this book is that it ends. This is a eminently believable and intimately humanistic work of science fiction. The beginning is a bit dense, because there is quite a bit to set up. But for all the technical detail and description, this is ultimately a story about personal connections.
I've had this in my library for years. I don't remember why I bought it, and I'm not sure why I have only read it now after eyeing it curiously every month or so. I only wish I would have read it sooner, because it probably would have given me plenty of time to read it again.
It isn't something that's often -- if ever -- said about science fiction, but this book is just lovely. And the only other book I can recall being similarly wonderful is Stephen King's 11/22/63.
Show me your paso doble.
Seriously! Freaking awesome! I can totally understand why it won a Hugo award. I would have driveway moments just as I got home from work listening to the book in my parked car. It is a good sci-fi book because it focuses on the characters and their interaction to the technology. The sci-fi part itself is spectacular and raises a bunch of what-if questions. It is the kinda sci-fi where it seems like it could almost happen, that it is not so much of a stretch. Another great thing about it, is that the storyline is episodic, so you almost get several stories at once. My next Audible purchase is going to be the next book in this series. I might actually put this up there with Ender's Game, and Starship Troopers, as one of my favorite books.
I really don't see what other people do in this novel. The premise itself I found excellent. The author really started well, but the novel really turned into a vehicle to cram the author's social ideas onto the reader. That wouldn't necessarily be so bad if it were not for the fact that the guy posits caricatures of people to criticize them. For instance, he uses an allegedly Catholic character to contrast with his atheist neanderthals, and yet NOTHING that comes out of that character's thoughts and words reflects any reasonable representation of what a lifelong Catholic would think or believe. It was almost like the characters were taken as cartoon characters from one of the vapid New Atheist books. Yes, I realize bitter atheists will thumb down my review because they only vote for their dogma over any criticism, but this book truly was a poor attempt at positing a valid alternate society. For instance, if you read one of Orson Scott Card's novels, even the characters with whose beliefs he would never agree are given a fair place. In short, this is NOT a 21st century Stranger in a Strange Land. To do so it would need accurate human beings with which to contrast the alternate ideas. Instead you get a lot of straw characters that have little to nothing in common with the beliefs of actual people. If it were not for that, I think the novel would have so much more merit.
The most interesting aspect of the story is the depth with which the author developed this alternate society. He developed a basic naming language to make it more realistic. He built a solid culture and everything. The least interesting aspect is that he failed to accurate represent homo sapiens.
"Brilliant book - going straight to the next one!"
I'm glad I chose to ignore some of the less good reviews this book got because I really really enjoyed it. It's a great story that shines a (not always flattering) light on our own society as well as exploring an interesting fictional world as well.
I've gotten so involved in this novel that I've listened (unusually for me) at all sorts of times outside of my normal commute and that I'm going straight on to book 2 as soon as my next credit becomes active!
"Really Good"
I had no real preconceptions about this title, I'd never heard of the writer and only got it because I have an interest in Neanderthals - but I wasn't disappointed at all! I'm not really interested in science fiction in general, Star Trek and Star Wars leave me cold! But this is really a human interest story, looking at an outsiders view of our humanity, as well as exploring what our lives might be like if our ancestors had made different descisions - for example what would we be like without religion?
I thoroughly reccomend; it is gripping, thrilling and really gets you going and wanting more! I'd want to carry on listening even when I was not driving or down the gym!
The thing that got me was that there was loads of science in it, real detailed information that was accurate and relevant to the story and that thoroughly interested me.
The world Ponter comes from is explained in vivid detail and you want to go there and see it for yourself - however, when Ponter asks Mary, Louise and Reuben about our lack of conservation and how we've destroyed our habitat it really makes you question humanity's motives and mistakes. If you want to feel positve about your species this is probably not the best book - if you want a bit of science fiction and romance this is for you!
"most enjoyable"
This book was much more interesting than the title lead me to expect. How the neanderthals structured their society gave me much food for thought.
I like science - not people. I like ideas too - not fantasies. I especially alternative histories. And this story absolutely gripped me with the brilliant way it asks questions, using science and the excellently conceived alternative world of the Neanderthals. It also explores people and their issues - so you might like it too! Fascinating attack on religion with a few novel ideas to interweave makes this an entertaining yet thought-provoking listen.
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Property owners would be to elitists. Just because someone cant of does not own property does not mean they are incapable of casting an educated vote. I think there are many, many, many non property owners that are definitely capable of voting. I would be interested in why you would think that one?
I dont think all felons are created equally and I am not sure why the right to vote must be given up in most cases. Maybe if your felony involved election fraud, but really why should someone with felony not be allowed to vote. What are you afraid of? Paid the price why cant they vote? I dont necessarily feel the same about gun laws regarding felons, but I think not having the right to vote is kind of silly in most cases.
Now I do totally agree that it has been made too easy to vote. If you are too lazy to go and register you probably should not be voting because you are probably too lazy to take the time to know much about the candidates. I dont like the idea of people sitting outside stores trying to recruit votes to register. I also would not be against a raise in the age to vote. I have been voting since I was 20, but I will be the first to admit that I knew very little about the world at that age.


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ACHICA > Elodie Details > Elodie Details Stroller Bag - Classic Wool
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Elodie Details Stroller Bag - Classic Wool
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Features: Wind- and water-resistant surface that keeps rain and snow safely on the outside, Openings for 5-point belt, compatible with most stroller models, Elastic top end that can be folded around the backrest, or used as a hood in windy or cold conditions, Detachable top piece with zipper that opens at both ends - perfect when moving from outdoor to indoor conditions, Darts at foot end allow movement of the feet and increased comfort.
Dimensions: 53 x 110 cm.
Easy maintenance, machine wash and tumble dry.
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Product Code 103510
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