Has laparoscopic cholecystectomy changed patterns of practice and patient outcome in Ontario?

OBJECTIVE: To examine the effect of the introduction of laparoscopic cholecystectomy (LC) on patterns of practice (number of cholecystectomy procedures, case-mix and length of hospital stay) and patient outcomes in Ontario. DESIGN: Cross-sectional population-based time trends using hospital discharge data. SETTING: All acute care hospitals in Ontario where cholecystectomy was provided. PATIENTS: All 119,821 Ontario residents who underwent cholecystectomy between 1989-90 and 1993-94. After exclusions (initial bile duct exploration, cancer, incidental cholecystectomy, or missing codes for age, sex or residence) 108,442 patients remained. OUTCOME MEASURES: Number of cholecystectomy procedures, proportion of patients with acute or chronic gallstone disease, length of hospital stay, and rates of death, readmission, and bile duct injury and other in-hospital complications after cholecystectomy by year. RESULTS: The number of cholecystectomy procedures increased by 30.4% between 1989-90 and 1993-94. The number of patients with chronic gallstone disease increased by 33.6%, and the number who underwent elective surgery increased by 48.3%. The proportion of procedures performed as LC increased from 1.0% in 1990-91 to 85.6% in 1993-94. Patients who received LC tended to be younger female patients with chronic gallstone disease with no coexisting conditions undergoing elective operations. The mean length of stay, adjusted for case-mix differences, was significantly lower in 1993-94 than in 1989-90 (2.6 days v. 7.5 days) (p < 0.05); the values for LC and open cholecystectomy in 1993-94 were 1.8 days and 7.3 days respectively. The decrease in the crude death rate over the study period (0.3% to 0.2%) was not significant (relative odds 1.10, 95% confidence interval [CI] 0.72 to 1.69). In 1993-94 the adjusted risk of readmission to hospital within 30 days was 1.38 (95% CI 1.19 to 1.58) as compared with 1989-90. Over the 5 years the rate of bile duct injuries tripled (0.3% in 1989-90 v. 0.9% in 1993-94). The adjusted risk of having at least one complication after cholecystectomy in 1993-94 was 1.90 (95% CI 1.75 to 2.07) as compared with 1989-90. CONCLUSIONS: LC has had a substantial effect on the number of cholecystectomy procedures performed, the type of patient having the gallbladder removed and the length of hospital stay. Death rates are unchanged, but the odds of readmission and in-hospital complications are both increased. Future research should be directed toward determining the reasons for the overall increase in rates, developing methods to reduce bile duct injuries and identifying other relevant outcomes, such as patient satisfaction with the procedure.     

Has the code for protein translocation been broken?

Polypeptides chains are segregated by the translocon channel into secreted or membrane-inserted proteins. Recent reports claim that an in vivo system has been used to break the "amino acid code" used by translocons to make the determination of protein type (i.e. secreted or membrane-inserted). However, the experimental setup used in these studies could have confused the derivation of this code, in particular for polar amino acids. These residues are likely to undergo stabilizing interactions with other protein components in the experiment, shielding them from direct contact with the inhospitable membrane. Hence, it is our view that the "code" for protein translocation has not yet been deciphered and that further experiments are required for teasing apart the various energetic factors contributing to protein translocation.     

Has water limited our imagination for aridland biogeochemistry?

The classic ecological paradigm for deserts, that all processes are controlled by water availability, has limited our imagination for exploring other controls on the cycling of carbon and nutrients in aridland ecosystems. This review of recent studies identifies alternative mechanisms that challenge the idea that all soil processes in aridlands are proximately water-limited, and highlights the significance of photodegradation of aboveground litter and the overriding importance of spatial heterogeneity as a modulator of biotic responses to water availability. Aridlands currently occupy >30% of the terrestrial land surface and are expanding. It is therefore critical to incorporate these previously unappreciated mechanisms in our understanding of aridland biogeochemistry to mitigate the effects of desertification and global change.     

Interferon-beta for treatment of rheumatoid arthritis?

IFN-beta treatment is emerging as a potentially effective form of therapy in various immune-mediated conditions. The present review addresses the possible role of IFN-beta in immune-mediated diseases such as multiple sclerosis and rheumatoid arthritis. Several placebo-controlled trials are discussed, as are the available immunological data that are relevant to this field. Review of these data provides evidence that IFN-beta has some beneficial therapeutic effect in patients with relapsing-remitting multiple sclerosis and might also have antirheumatic potential. This notion is supported by recent studies showing a critical role for IFN-beta in bone homeostasis.     

How has extracorporeal shock-wave lithotripsy changed the treatment of urinary stones in Quebec?

OBJECTIVES: To determine the number of people who underwent treatment of urinary stones in Quebec before and after the introduction of extracorporeal shock-wave lithotripsy (ESWL) and to determine how the introduction of ESWL influenced resource utilization. DESIGN: Before-after study; data were obtained from administrative databases and hospital-based cost estimates. SETTING: The 68 acute care hospitals in Quebec in which treatment of urinary stones is undertaken. PATIENTS: Quebec residents admitted to hospital for treatment of urinary stones between the fiscal years 1984 and 1992. OUTCOME MEASURES: Number of people treated for urinary stones per year, total number of procedures per year (including open surgery, percutaneous procedures, retrograde procedures and ESWL), and annual resources (including number of hospital bed-days and direct costs) for treatment of urinary stones used overall and in hospitals with and without ESWL services. RESULTS: Over the study period the number of people treated for urinary stones increased by 59%. As well, the combined frequency of ESWL and surgery (the two main treatment methods) increased by 107%. These increases were largely due to rates of treatment that grew by 52% among women and by 34% among men. The total number of hospital bed-days decreased by 28%, which reflected shorter hospital stays for ESWL. However, despite this decrease, the total direct annual costs were 7% higher in 1992 than in 1984 because of the increased numbers of people treated and procedures performed. In the three hospitals that offered ESWL the number of hospital bed-days and the direct costs of treating urinary stones increased by 49% and $2.5 million respectively. In the 65 other hospitals these figures decreased by 41% and about $2.9 million respectively. CONCLUSIONS: Because of increased intervention rates the total cost of treating urinary stones has risen since the introduction of ESWL. The introduction of ESWL has also been associated with a shift in the use of resources for treating urinary stones to hospitals with a lithotriptor. The reasons for the increased intervention rates are unknown. However, given the possibility of negative health effects and the increased costs, studies to determine whether the increased rates improve health outcomes are warranted.     

Cotrimoxazole for prenatal treatment of congenital toxoplasmosis?

Congenital toxoplasmosis is still one of the most frequent causes of fetal death. Despite a significant improvement in diagnosis, particularly in utero diagnosis, maternal treatment is only partially effective in preventing transmission to the fetus and treating fetal infection. Maternal treatment is based on drugs developed 50 years ago, which may have limited efficacy (spiramycin) or serious side-effects (pyrimethamine). Data on the use of cotrimoxazole in mouse models of toxoplasmosis and for preventing toxoplasmic encephalitis in patients suffering from AIDS have led Francis Derouin and colleagues to consider the potential of cotrimoxazole for prenatal prevention and treatment of toxoplasmic fetal death.     

VGLUTs--potential targets for the treatment of seizures?

Vesicular glutamate transporters (VGLUTs) load glutamate into synaptic vesicles. In this issue of Neuron, Juge et?al. report that ketone bodies compete with chloride-dependent activation of VGLUTs, leading to suppression of glutamate release and seizures. These findings provide a surprising explanation for the efficacy of the ketogenic diet in controlling epilepsy.     

Interferon-β for treatment of rheumatoid arthritis?

IFN-β treatment is emerging as a potentially effective form of therapy in various immune-mediated conditions. The present review addresses the possible role of IFN-β in immune-mediated diseases such as multiple sclerosis and rheumatoid arthritis. Several placebo-controlled trials are discussed, as are the available immunological data that are relevant to this field. Review of these data provides evidence that IFN-β has some beneficial therapeutic effect in patients with relapsing-remitting multiple sclerosis and might also have antirheumatic potential. This notion is supported by recent studies showing a critical role for IFN-β in bone homeostasis.     

Has the Time Come for Big Science in Wildlife Health?

The consequences of wildlife emerging diseases are global and profound with increased burden on the public health system, negative impacts on the global economy, declines and extinctions of wildlife species, and subsequent loss of ecological integrity. Examples of health threats to wildlife include Batrachochytrium dendrobatidis, which causes a cutaneous fungal infection of amphibians and is linked to declines of amphibians globally; and the recently discovered Pseudogymnoascus (Geomyces) destructans, the etiologic agent of white nose syndrome which has caused precipitous declines of North American bat species. Of particular concern are the novel pathogens that have emerged as they are particularly devastating and challenging to manage. A big science approach to wildlife health research is needed if we are to make significant and enduring progress in managing these diseases. The advent of new analytical models and bench assays will provide us with the mathematical and molecular tools to identify and anticipate threats to wildlife, and understand the ecology and epidemiology of these diseases. Specifically, new molecular diagnostic techniques have opened up avenues for pathogen discovery, and the application of spatially referenced databases allows for risk assessments that can assist in targeting surveillance. Long-term, systematic collection of data for wildlife health and integration with other datasets is also essential. Multidisciplinary research programs should be expanded to increase our understanding of the drivers of emerging diseases and allow for the development of better disease prevention and management tools, such as vaccines. Finally, we need to create a National Fish and Wildlife Health Network that provides the operational framework (governance, policies, procedures, etc.) by which entities with a stake in wildlife health cooperate and collaborate to achieve optimal outcomes for human, animal, and ecosystem health.     

Has Selection for Improved Agronomic Traits Made Reed Canarygrass Invasive?

Plant breeders have played an essential role in improving agricultural crops, and their efforts will be critical to meet the increasing demand for cellulosic bioenergy feedstocks. However, a major concern is the potential development of novel invasive species that result from breeders' efforts to improve agronomic traits in a crop. We use reed canarygrass as a case study to evaluate the potential of plant breeding to give rise to invasive species. Reed canarygrass has been improved by breeders for use as a forage crop, but it is unclear whether breeding efforts have given rise to more vigorous populations of the species. We evaluated cultivars, European wild, and North American invader populations in upland and wetland environments to identify differences in vigor between the groups of populations. While cultivars were among the most vigorous populations in an agricultural environment (upland soils with nitrogen addition), there were no differences in above- or below-ground production between any populations in wetland environments. These results suggest that breeding has only marginally increased vigor in upland environments and that these gains are not maintained in wetland environments. Breeding focuses on selection for improvements of a specific target population of environments, and stability across a wide range of environments has proved elusive for even the most intensively bred crops. We conclude that breeding efforts are not responsible for wetland invasion by reed canarygrass and offer guidelines that will help reduce the possibility of breeding programs releasing cultivars that will become invasive.     

Is immunotherapy an effective treatment for Alzheimer's disease?

Immunotherapy in patients with Alzheimer's disease (AD) is rapidly becoming a hot topic of modern geriatric and clinical gerontology. Current views see immunization with Aβ peptide, the amyloidogenic protein found in senile plaque of AD patient's brains, or the infusion of preformed antibody specific for human Aβ, as possible therapeutic approaches to improve the cognitive status in the disease. Animal models of the disease have provided positive results from both approaches. Thus, an initial clinical trial using immunization with human Aβ in AD patients was started, but then shortly halted because of an unusually high incidence (6%) of meningoencephalitis. A long and currently ongoing debate in the scientific community about the pro or contra of vaccination or passive immunization with Aβ in AD is thereafter started. Here, the authors would like to stress few points of concern regarding these approaches in clinical practice.     

Increasing the options for inflammatory bowel disease treatment?

Curative treatment of an experimentally induced colitis by a CD44 variant V7-specific antibodyWittig, B. et al. (1998)J. Immunol. 161, 1069–1073     

RNA interference: new mechanisms for targeted treatment?

Nucleic acid-based sequence-specific therapeutic intervention offers the potential for treatment of particular cancers without side effects. RNA interference (RNAi) induced by small interfering RNA (siRNA) (19-21 bp) is a normal cellular mechanism leading to highly specific and extraordinarily efficient degradation of the corresponding mRNA. The mechanism of RNAi as well as strategies for the design and delivery of siRNA are described. The growing role of RNAi in target validation for cancer-specific genetic aberrations is discussed. We attempt an early assessment of the potential for using RNAi technologies to treat cancer directly, especially hematologic malignancies. Promising targets for specific gene silencing in hematologic oncology include oncogenic fusion proteins and oncogenes activated by point mutations. Potency and specificity of gene silencing are the major advantages of the new RNAi technology over other nucleic acid-based gene targeting approaches. Crucial questions for pharmaceutical interventions remain. Advances in the areas of delivery, systemic spreading and duration of the silencing effect are necessary before the methodology can enter clinical oncology.     

Diet as prophylaxis and treatment for venous thromboembolism?

Background

Both prophylaxis and treatment of venous thromboembolism (VTE: deep venous thrombosis (DVT) and pulmonary emboli (PE)) with anticoagulants are associated with significant risks of major and fatal hemorrhage. Anticoagulation treatment of VTE has been the standard of care in the USA since before 1962 when the U.S. Food and Drug Administration began requiring randomized controlled clinical trials (RCTs) showing efficacy, so efficacy trials were never required for FDA approval. In clinical trials of 'high VTE risk' surgical patients before the 1980s, anticoagulant prophylaxis was clearly beneficial (fatal pulmonary emboli (FPE) without anticoagulants = 0.99%, FPE with anticoagulants = 0.31%). However, observational studies and RCTs of 'high VTE risk' surgical patients from the 1980s until 2010 show that FPE deaths without anticoagulants are about one-fourth the rate that occurs during prophylaxis with anticoagulants (FPE without anticoagulants = 0.023%, FPE while receiving anticoagulant prophylaxis = 0.10%). Additionally, an FPE rate of about 0.012% (35/28,400) in patients receiving prophylactic anticoagulants can be attributed to 'rebound hypercoagulation' in the two months after stopping anticoagulants. Alternatives to anticoagulant prophylaxis should be explored.

Methods and Findings

The literature concerning dietary influences on VTE incidence was reviewed. Hypotheses concerning the etiology of VTE were critiqued in relationship to the rationale for dietary versus anticoagulant approaches to prophylaxis and treatment. Epidemiological evidence suggests that a diet with ample fruits and vegetables and little meat may substantially reduce the risk of VTE; vegetarian, vegan, or Mediterranean diets favorably affect serum markers of hemostasis and inflammation. The valve cusp hypoxia hypothesis of DVT/VTE etiology is consistent with the development of VTE being affected directly or indirectly by diet. However, it is less consistent with the rationale of using anticoagulants as VTE prophylaxis. For both prophylaxis and treatment of VTE, we propose RCTs comparing standard anticoagulation with low VTE risk diets, and we discuss the statistical considerations for an example of such a trial.

Conclusions

Because of (a) the risks of biochemical anticoagulation as anti-VTE prophylaxis or treatment, (b) the lack of placebo-controlled efficacy data supporting anticoagulant treatment of VTE, (c) dramatically reduced hospital-acquired FPE incidence in surgical patients without anticoagulant prophylaxis from 1980 - 2010 relative to the 1960s and 1970s, and (d) evidence that VTE incidence and outcomes may be influenced by diet, randomized controlled non-inferiority clinical trials are proposed to compare standard anticoagulant treatment with potentially low VTE risk diets. We call upon the U. S. National Institutes of Health and the U.K. National Institute for Health and Clinical Excellence to design and fund those trials.     

A silver bullet for the treatment of depression?

The search for a rapid-acting antidepressant has been a subject of intense research interest for several decades. The article by Lucas and colleagues in this issue of Neuron provides compelling evidence from preclinical animal models that drugs acting at the serotonin 5-HT(4) receptor could finally achieve this goal. However, caution is warranted, as results from animal studies are not always predictive of therapeutic actions in humans.