To probe the potential role of Th1 versus Th2 reactivity underlying the hygiene hypothesis, intrinsic levels of Th1‐associated and Th2‐associated antibodies in the serum of wild rodents were compared with that in various strains of laboratory rodents. Studies using rat lung antigens as a target indicated that wild rats have substantially greater levels of autoreactive, polyreactive immunoglobulin G (IgG), but not autoreactive, polyreactive IgM than do laboratory rats, both on a quantitative and qualitative basis. Increased levels of serum IgG and IgE were observed in both wild rats and wild mice relative to their laboratory‐raised counterparts, with the effect being most pronounced for IgE levels. Further, wild rats had greater intrinsic levels of both Th1‐ and Th2‐associated IgG subclasses than did lab rats. The habitat (wild versus laboratory raised) had a more substantial impact on immunoglobulin concentration than did age, strain or gender in the animals studied. The presence in wild rodents of increased intrinsic, presumably protective, non‐pathogenic responses similar to both autoimmune (autoreactive IgG, Th1‐associated) and allergic (IgE, Th2‐associated) reactions as well as increased levels of Th1‐associated and Th2‐associated IgG subclasses points toward a generally increased stimulation of the immune system in these animals rather than a shift in the nature of the immunoreactivity. It is concluded that, at least to the extent that feedback inhibition is a controlling element of immunoreactivity, an overly hygienic environment may affect the threshold of both types of immune responses more so than the balance between the different responses.

Summary Wild animals, unlike their laboratory counterparts, live amidst an abundance of pathogens and parasites. The presence of such immune stimulation from the time of birth likely has a profound effect on the development and stasis of the immune system. To probe potential differences between the immune systems of wild and laboratory animals, the response to mitogen (Con A) of splenocytes from wild rats was evaluated in vitro and compared with results from lab-rat-derived splenocytes. Although the response to mitogen is ubiquitous in splenocytes from laboratory animals regardless of strain or even species, splenocytes derived from wild rats were unresponsive to mitogen as judged by upregulation of activation markers and proliferation. Further, splenocytes from wild rats produced almost 10-fold less IL-2 and TNF-a in response to mitogen than did splenocytes from laboratory rats. In addition, mitogen stimulation resulted in an almost 100-fold greater production of IL-4 in wild-rat-derived splenocytes than in lab-rat-derived splenocytes. Perhaps surprisingly, these differences were observed in the absence of differences between wild and laboratory animals in the ratio of CD4 1 /CD8 1 T cells or in the relative numbers of T cells, B cells and monocytes in the splenocyte population. These observations may have substantial implications for the hygiene hypothesis and provide considerable insight into the roles played by the environment during immune system development and modulation.

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While many hospitalized patients have orders to fast in preparation for interventions, the extent to which these orders are necessary or adhere to evidence-based durations is unknown. In this study, we analyzed the length, indication, and associated outcomes of nil per os (NPO) orders for general medicine patients at an academic institution in the United States, and compared them to the best available evidence for recommended length of NPO. Of 924 NPO orders assessed, the indicated intervention was not performed for 183 (19.8%) orders, largely due to a change in plan (75/183, 41.0%) or scheduling barriers (43/183, 23.5%). When analyzed by indication, the median duration of NPO orders ranged from 8.3 hours for kidney ultrasound to 13.9 hours for upper endoscopy. For some indications, the literature suggested NPO orders may be unnecessary. Furthermore, in indications for which NPO was deemed necessary in the literature, the duration of most NPO orders was much longer than minimally required. These results suggest the need for establishing more robust practice guidelines or institutional protocols for NPO orders. Frequent and prolonged fasting can lead to patient dissatisfaction and distress. 1 It may also cause malnutrition and negatively affect outcomes in high-risk populations such as the elderly. 2 Evidence suggests that patients are commonly kept fasting longer than necessary. 3,4 However, the extent to which nil per os (NPO) orders are necessary or adhere to evidence-based duration is unknown.Our study showed half of patients admitted to the general medicine services experienced a period of fasting, and 1 in 4 NPO orders may be avoidable. 5 In this study, we aimed to provide action-oriented recommendations by 1) assessing why some interventions did not occur after NPO orders were placed and 2) analyzing NPO orders by indication and comparing them with the best available evidence. METHODSThis retrospective study was conducted at an academic medical center in the United States. The study protocol was approved by the Mayo Clinic Institutional Review Board.Detailed data handling and NPO order review processes have been described elsewhere. 5 Briefly, we identified 1200 NPO orders of 120 or more minutes' duration that were written for patients on the general medicine services at our institution in 2013. After blinded duplicate review, we excluded 70 orders written in the intensive care unit or on other services, 24 with unknown indications, 101 primarily indicated for clinical reasons, and 81 that had multiple indications. Consequently, 924 orders indicated for a single intervention (eg, imaging study, procedure, or operation) were included in the main analysis.We assessed if the indicated intervention was performed. If performed, we recorded the time when the intervention was started. If not performed, we assessed reasons why it was not performed. We also performed exploratory analyses to investigate factors associated with performing the indicated intervention. The variables were 1) NPO starting at midnight, 2) ...

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