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International audience; Introduction: The uptake of the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 chronic kidney disease (CKD) Guideline is not fully described in real-world nephrology practice across the world. Methods: We used baseline data from the CKD Outcomes and Practice Patterns Study (2013–2017), a 4-country cohort of patients with estimated glomerular filtration rate

International audience; In chronic kidney disease, anemia and disordered iron homeostasis are prevalent and associated with significant adverse consequences. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) issued an anemia guideline for managing the diagnosis, evaluation, and treatment of anemia in chronic kidney disease. Since then, new data have accrued from basic research, epidemiological studies, and randomized trials that warrant a re-examination of previous recommendations. Therefore, in 2019, KDIGO decided to convene 2 Controversies Conferences to review the latest evidence, explore new and ongoing controversies, assess change implications for the current KDIGO anemia guideline, and propose a research agenda. The first conference, described here, focused mainly on iron-related issues, including the contribution of disordered iron homeostasis to the anemia of chronic kidney disease, diagnostic challenges, available and emerging iron therapies, treatment targets, and patient outcomes. The second conference will discuss issues more specifically related to erythropoiesis-stimulating agents, including epoetins, and hypoxia-inducible factor-prolyl hydroxylase inhibitors. Here we provide a concise overview of the consensus points and controversies resulting from the first conference and prioritize key questions that need to be answered by future research.

Green chemistry is an important way of thinking in the field of chemistry and aims to conduct processes in accordance with the principles of sustainable development. It is the application of a wide range of principles that minimize the impact of both chemical processes and products on the environment. And what about analytical chemistry? There is no doubt that analytical chemistry plays an important role in the sustainable development of the planet. However, this only applies if analytical procedures are of high quality (sensitive, precise, and accurate) and also in line with the principles of environmental sustainability. This essay presents a brief discussion of the evolution of green chemistry and its multidimensional impacts, including the “industry” of analytical chemistry as well as academic education and research. We emphasize the difference between the term “sustainability” and “greenness.” Therefore, at least basic information on sustainability in analytical chemistry is provided. We hope that our considerations will inspire analytical chemists and will contribute to the further development of both green analytical chemistry and sustainable analytical chemistry.

We outline a low-order Lagrangian model for the inertial dynamics of spreading and imbibition of a spherical liquid cap on a plane featuring independent cylindrical capillaries without gravity. The analysis predicts the relative roles of radial and axial kinetic energy, reveals the critical Laplace number beyond which the drop oscillates, and attributes the exponent of the initial power-law for contact patch radius vs time to the form of capillary potential energy just after the liquid sphere touches the plate. This article is protected by copyright. All rights reserved.

Alfalfa leaf protein constitutes an important food ingredient and is widely used in food technology. Due to high nutritive value and high proteins content, alfalfa has a high application value for feed grass and human food. Conventionally, industrial leaf protein production from alfalfa requires complex operation process and high separation temperature (90 oC), which causes high energy cost, release of sensitive elements and protein denaturation. To overcome these issues, developing novel separation technologies with low energy consumption and high yield and purity is of paramount importance to meet the requirements of a green separation concept. In this review, some separation methods including acid heating method, pH method, salting method, organic solvent method, fermentation method and membrane separation are described. Among them, membrane separation has the best performance. Moreover, the feasibility of adopting conventional and new promising technology (membrane) to recover leaf protein from plant food materials from an environ-mental and economical point of view will be discussed.

This paper reports computational fluid dynamics (CFD) studies on the performance of flow inside a rotating disk filtration module. This module consists of a disk rotating at speeds between 1000 and 3000 rpm inside a cylindrical housing equipped with a stationary circular flat membrane. In order to investigate the influence of surface geometry, a smooth disk and a disk equipped with vanes were used. Commercial CFD software was utilized for the characterization of the flow inside the membrane module. The predicted results were compared at different values of rotating and inlet velocities with previous works and also with experimental ones obtained in the filtration of dairy effluent in the same conditions. The influence of the geometry of the disk was also evaluated. The obtained results show that an increase in rotating velocity leads to an increase in the pressure and shear stress at the membrane surface. The highest pressures were obtained when using disks equipped with vanes, this was due to the turbulent area created between the vanes visualized in animated views. It was also found that the presence of vanes on the surface of disk has a great effect on the shear stress; it contributes to the reduction in fouling and improvement in filtration flux.

BACKGROUND: During the natural history, the incidence HTLV-1 related diseases were 0.5% until 10% after decades of infection. Despite relative low lethality, previous study observed that HTLV-1 infection is associated with significantly increased mortality. For example, the incidence of ATLL and HAM/TSP, co-infections with HIV and HCV, parasitic co-infection with Strongyloides stercoralis may increase morbidity and mortality. OBJECTIVE: Determine the mortality rate and its major variables as possible risk factors, analyzing the HTLV Clinic at Emilio Ribas Institute, a continuous open cohort of HTLV patients since 1997. METHODS: This cohort open cohort possesses new patients added at a rate of approximately 50 patients/year. There were 1100 HTLV-infected subjects identified by September 30th 2018. All clinical data including clinical and laboratory data, which have been updated on a regular basis over the last 22 years, were entered into a specific REDCap database. The Ethical Board of the IIER approved the protocol. RESULTS: Along 22 years of clinical care in the HTLV-out clinic, 727 HTLV-1-infected subjects and 248 HAM/TSP cases. Four-hundred sixty-eight patients of whom remaining under active follow up. The mean follow-up time of the cohort was 12 years. Twenty-seven patients died (median age of 51,5 years old). From this total, 13 was asymptomatic carriers and 14 HAM/TSP subjects, 12 of asymptomatic and seven HAM/TSP possess co-infected with HIV or/and HCV. Other seven presented HAM/TSP without co-infection, and all was female, and sepsis was the majority cases the majority of cases of sepsis were related to infection of the urinary tract (p=0.058) and to ulcers of decubitus (p=0.021), and it was associated with risk factors for mortality. CONCLUSIONS: Overall, the mortality rate for HAM-TSP patients was six percent. The mean life expectancy in Brazil is about 78 years in 2018, twenty-two years higher than HAM/TSP patients without any other coinfection. This study highlights the possibility of higher death risk among HTLV-1-infected patients and HAM/TSP subjects in Brazil, and identified some risk factors for this outcome. Also, these patients may possess higher risk for morbidity, usually urinary tract infections and decubitus scars, which could increase risk for death.

Concentration polarization(CP) and membrane fouling are two major drawbacks for pressure-driven membrane filtration processes (PDMPs) because they cause severe flux decline, which requires effective control strategies. Many articles have proposed the diverse potential applications of various Control strategies in reducing CP and membrane fouling. This paper reviews various mechanisms and influencing factors on flux decline, as well as their control strategies in PDMPs. Nine effective control strategies are summarized, generalized, and compared in this paper. On the basis of their functions and influences, they can be also classified as the following: (1) modification: pretreatment of feed, modification of feed characteristics, selection and modification of membrane; (2) design: shear-enhanced filtration modules, applied field enhancement and CP drawer; (3) operation: optimization of operating parameters, hydraulic flushing and two-phase flow. Then, the general and practical guidelines are given. On the basis of this review, future research perspectives related to flux decline control strategies are proposed.

Segmental measurements of limb resistances permit to evaluate the regional distribution of fat-free-mass (FFM). As shown by Organ et al. (J Appl Physiol 1994;77:98–112) “virtual” limb resistances can be measured with only peripheral electrodes at ankle and wrist, which is faster and does not require undressing. This paper presents a different method for obtaining “virtual” limb resistances from peripheral electrodes and compares it with that of Organ et al. and with segmental measurements using same protocol. It is found that virtual arm resistances of both methods were overestimated as compared to segmental values, by 6.8% in men and 5.8% in women for our method and by 7.4% and 8% for Organ et al. one. Virtual leg resistances were found, for both methods, to be slightly lower than segmental leg resistances measured with proximal waist electrodes, which were a little overestimated. But after correcting this overestimation using Organ et al. data, we evaluated the overestimation of virtual leg resistances to be 2.3% in men and 2.8% in women by our method versus 4.4% and 5.9%, respectively, for Organ et al. one. An important finding was the strong correlation between virtual resistances of both methods and segmental ones, as their ratio had a small standard deviation between 0.019 and 0.024 for arms and legs. Thus, the overestimation of limb resistance is automatically corrected when FFM is determined by an equation calibrated with DXA segmental measurements.

This article compares the determination of body fat-free-mass (FFM) by impedance, using either hand-to-foot resistance (R₁₃) or foot-to-foot one (R₃₄) from comparison with dual X-ray absorptiometry (DXA) measurements in a normal population. The first goal was to see if the foot-to-foot resistance used in body fat analysers provides less accurate information for body FFM than the hand-to-foot one used by medical impedance-meters. Another goal was to compare the prediction accuracy of six different regression equations of FFM for each sex and for each resistance relatively to DXA. The impedancemeter used in this study was a Tefal prototype with 4 plantar electrodes and 4 additional electrodes for the hands and providing hand-to-foot and foot-to-foot resistances. Coefficients of these correlations were determined by comparison with FFM measured by DXA in a 1st cohort of 170 healthy adults. For an independent validation, these equations were tested in a 2nd cohort of 86 adults who underwent the same impedance and DXA protocols, using Student's paired t-tests. The accuracy of FFM prediction increased generally with the number of physiologic parameters included in the regression, but none of our equations gave FFM predictions significantly different from DXA. FFM calculated from the foot-to-foot resistance were closer to DXA values than those calculated from hand-to-foot resistance, as their average P-value of comparison with DXA was higher at 0.695 against 0.387 for R₁₃.

New concerns have appeared recently in regard to the increasingly complex relationship between physicians and the pharmaceutical or devices industry. The American Academy of Pain Medicine (AAPM) Council on Ethics has discussed the issue, especially focusing on the implication of conflicts of interest for Pain Medicine, and published several recommendations for specific professional situations that the Pain Medicine physician may encounter.

Regional body composition measurements may be achieved in a single operation with impedancemeters equipped with four plantar and four hand electrodes. By measuring sequentially the resistances of five current lines connecting the hands and feet and solving a system of five linear equations, it is possible to calculate the resistances of each limb and the trunk. The impedancemeter used in this study was a prototype with four plantar electrodes and four additional contact electrodes for the hands. Its electronic hardware was identical to that of a Tefal commercial foot-to-foot impedancemeter (FFI). The Tefal FFI was used for measuring weight, whole body fat-free mass (FFM) and fat tissue mass (FM). Impedance and DXA measurements were taken sequentially on a 1st cohort of 170 healthy adults, aged from 19 to 75 years, to obtain equations relating appendicular FFM measured by DXA to their resistances, subject weight and height. For appendicular FM, correlations of the body FM measured by the FFI, age and BMI were used. Trunk FFM was obtained by subtracting appendicular FFM from FFM of trunk + limbs obtained by the same method as that for appendicular FFM. For an independent validation, these equations were tested on a 2nd cohort of 87 subjects (18–74 years) who underwent the same impedance and DXA protocol. Comparison of FFM and FM by impedance and by DXA in the limbs and the trunk using paired Student's t-tests, showed that they were not significantly different both in the 1st and validation cohorts. Mean FFM differences between impedance and DXA were −0.018 ± 0.48 kg for right arms and −0.039 ± 0.85 kg for right legs of men in validation cohort. This work confirms that eight contact electrodes bioimpedance can measure appendicular and trunk FFM and FM in good agreement with DXA, at least in a healthy population.

Background In 2006, the authors observed a cluster of three deaths, which circumstances suggested were opioid-related, within 1 day after placement of intrathecal opioid pumps for noncancer pain. Further investigation suggested that mortality among such patients was higher than previously appreciated. The authors performed investigations to quantify that mortality and compare the results to control populations, including spinal cord stimulation and low back surgery. Methods After analyzing nine index cases--three sentinel cases and six identified by a prospective strategy--the authors used epidemiological methods to investigate whether mortality rates reflected patient- or therapy-related differences. Mortality rates after intrathecal opioid therapy and spinal cord stimulation were derived by correlating Medtronic device registration data with de-identified data from the Social Security Death Master File. Aggregate demographic and comorbidity data were obtained from Medicare and United Healthcare population databases to examine the influence of demographics and comorbidities on mortality. Results Device registration and Social Security analyses revealed an intrathecal opioid therapy mortality rate of 0.088% at 3 days after implantation, 0.39% at 1 month, and 3.89% at 1 yr-a higher mortality than after spinal cord stimulation implants or after lumbar diskectomy in community hospitals. Demographic, illness profile, and mortality analyses of large databases suggest, despite limitations, that excess mortality was related to intrathecal opioid therapy, and could not be fully explained by other factors. These findings were consistent with the nine index cases that revealed that respiratory arrest caused or contributed to death in all patients. No device malfunctions associated with overinfusion were identified among cases where data were available. Conclusions Patients with noncancer pain treated with intrathecal opioid therapy experience increased mortality compared to similar patients treated by using other therapies. Respiratory depression as a consequence of intrathecal drug overdosage or mixed intrathecal and systemic drug interactions is one plausible, but hypothetical mechanism. The exact causes for patient deaths and the proportion of those deaths attributable to intrathecal opioid therapy remain to be determined. These findings, although based on incomplete information, suggest that it may be possible to reduce mortality in noncancer intrathecal opioid therapy patients.

Current Status Since the 1950s, significant advances in the treatment of pain have resulted in greater relief for an increasing number of patients. However, the quality of pain care delivery in the United States continues to fall remarkably short of the current potential for optimal care. Pain medicine remains fragmented, and the absence of a unified organizational model of pain medicine hinders the effective provision of an integrated, cost-effective pain care, causing unnecessary and avoidable human suffering and societal expense. These consequences of fragmented care are unacceptable and threaten patient safety and well-being. Effective treatment of persistent pain requires the highest level of clinical reasoning, selectively coordinated medical skills, the strategic use of resources, and the orchestration of diverse areas of medical expertise. In order to close the gap between existing care and the potential for optimal pain care, significant institutional barriers to this goal must be addressed. To this end, the following position paper describes the history and context of this challenge, proposes recommendations to harness the collective abilities and knowledge within the discipline of pain medicine, and calls upon organized medicine to take action on behalf of patients and for the public health.

Our main goal was to test various impedance methods for measuring body composition in adolescents with anorexia nervosa (AN) during refeeding therapy. A specific objective was to compare the information provided by a foot-to-foot impedancemeter (FFI) with that supplied by a medical multifrequency impedancemeter and by dual X-ray absorptiometry (DXA). We have monitored 13 young AN subjects and 17 healthy controls of a similar age group using a Xitron 4200 multifrequency impedancemeter measuring extracellular (ECW) and total body water (TBW) volumes and a Tefal Bodymaster FFI measuring weight (W), fat-free-mass (FFM) and body fat mass (FM). This Tefal device has been modified to measure in addition ECW and TBW resistances permitting to calculate ECW and TBW volumes using appropriate algorithms. In addition FFM and FM were measured by DXA on AN subjects. FFM measured by the FFI and the Xitron in AN subjects were found to be respectively 7.8% and 4.5% lower than FFM measured by DXA. TBW measured by FFI was not significantly different from that measured by Xitron in AN subjects and in controls. ECW measured by the FFI was not significantly different from that measured by Xitron in controls, but was in AN subjects. The body cell mass to (height)2 ratio was found to be significantly different between AN subjects and controls. The modified FFI was found to be simpler and quicker to use than the Xitron, while giving similar information.

The purpose of this paper is to examine the relationship between dividend payments, firms’ decisions control and the nature of family firms, in order to assess whether large shareholders expropriate wealth from minority shareholders in Canada. Using data collected from various sources, we formulated and tested three hypotheses related to this issue using OLS and logit regression models. Our results indicate that in Canadian firms, dividends are used as a protective mechanism for minority shareholders against the possibility of expropriation by large shareholders. The protective power of dividend, however, seems less effective in Canadian family firms. The hidden reason is the control that families exert on the dividend payout policy. Overall, our results show no clear evidence of expropriation of wealth inflicted on small shareholders by large shareholders. This research has shown that the financial policies of Canadian firms in which a family represents the majority of the shareholders are insufficiently studied and deserve the attention of finance academia and professionals, due to their significant impact on corporate dividend policy

Treating postamputation pain is challenging because it probably comprises nociceptive and neuropathic components, and the neuropathic part probably has both peripheral and central elements. Nociceptive pain usually responds to traditional analgesics, but neuropathic pain is less responsive to most medications and is therefore more difficult to treat. Phantom limb pain (PLP) is by definition neuropathic. Satisfactory management of the pain is often difficult to achieve, although a systematic and empathic approach often improves outcomes. Controlled studies on the efficacy of treatments for postamputation pain are generally lacking, and even less evidence is available for postamputation pain resulting specifically from landmine injuries. In this chapter we will often extrapolate from evidence from other related diagnoses. Diagnostic imprecision in which PLP is not distinguished from stump pain or neuroma pain adds to the problems for both victim and caregiver. A proper diagnostic work-up can help establish the general cause of pain, provide hints as to mechanism, and thereby guide treatment decisions. To match the putative mechanism of pain with presumed mechanism of drug action is the ideal. Douleur Sans Frontieres developed a simple questionnaire to distinguish stump pain from PLP: 1. Do you have a sensation of the limb being present? 2. Do you sometimes fall down when you rise, thinking that your limb is still present? 3. Do you have pain in your missing limb? 4. Do you have stump pain (pain in the residual limb): 5. Does pain prevent you from using your prosthesis? Simply asking this series of questions will help the practitioner to distinguish between PLP and residual limb pain (RLP). The distinction of neuroma pain requires physical examination to detect a “Tinnel's sign” (an electrical/painful sensation elicited from the neuroma by a digital or reflex hammer percussion). Eliciting as many verbal descriptors of the pain …

BACKGROUND: Whereas the participation of alloreactive T cells sensitized by indirect allorecognition in graft rejection is well documented, the nature of recipient antigen presenting cells recognized by indirect pathway CD4(+) T cells within the graft has yet to be identified. The purpose of this study was to determine the role played by graft endothelium replacement in the immune recognition of cardiac allografts rejected by indirect pathway CD4(+) T cells. METHODS: Transgenic RAG2(-/-) mice expressing I-A(b)-restricted male antigen H-Y-specific TcR were studied for their capacity to reject H-2(k) male cardiac allografts. Chronic vascular rejection in this model was due to the indirect recognition of H-Y antigen shed from H-2(k) male allograft and presented by the recipient's own I-A(b) APC to transgenic T cells. RESULTS: Immunohistochemical analysis of rejected grafts revealed the presence of numerous microvascular endothelial cells (EC) that expressed recipient's I-A MHC class II molecules. This observation suggested that graft endothelium replacement by I-A(b)-positive cells of recipient origin could stimulate the rejection of male H-2(k) graft by I-A(b)--restricted H-Y--specific T cells. To investigate further this possibility, hearts from H-2(b)--into--H-2(k) irradiation bone marrow (BM) chimera were transplanted in transgenic recipients. A direct correlation was observed between the presence of I-A(b)-positive EC within myocardial microvessels and the induction of acute rejection of chimeric H-2(k) male cardiac allografts transplanted in transgenic recipients. CONCLUSIONS: We conclude that graft endothelium replacement by recipient-type cells is required for the rejection of cardiac allograft mediated by indirect pathway alloreactive CD4(+) T cells., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

The combination of increased life span and medical interventions has created sometimes a protracted dying process, which is the source of many ethical concerns at the end of life. Basic ethical principles, ie, autonomy, nonmaleficence, beneficence, justice, and double effect, are the cornerstones of decisions made at the end of life. Examples of items being discussed are: informed consent, advanced directives, surrogate, DNR, hospice and palliative care. New concepts such as “limit settings” on interventions at the end of life or “futility” are now applied. Those new trends have led to situations when patients are given by physicians the means to end their lives by themselves (physician-assisted suicide) or with the help of a health professional (euthanasia) to relieve patients’ suffering. Several professional medical organizations (AMA, ACP, AAHPM, for instance) provide ethical guidelines and may help solve end-of-life clinical problems which sometimes present some of the most challenging ethical dilemmas.

The article presents the results of in-depth interviews with key biotechnology executives and emphasizes the issues and challenges American investors face when investing venture capital funds in the Canadian biotechnology sector. The results show that, although capital suppliers feel that the quality of Canadian science is credible and that its biotechnology industry presents interesting investment opportunities, they must be careful to adjust their due diligence procedures to account for the specific characteristics of the Canadian environment. It is argued that specialized U.S. venture capital investors can capitalize on the sectorņs opportunities as long as the key issues are properly addressed.

We outline an algorithm to extract the mean and fluctuation velocities of identical spheres colliding in microgravity from a sequence of digital images. We analyze four kinds of intrinsic errors. The first two artificially reduce the apparent fluctuation velocity. They derive from the inability of the algorithm to track indistinguishable spheres moving with excessive speed, and from invisible collisions occurring between consecutive frames. The third is due to the finite pixel size. The resulting uncertainty in the position of the spheres increases the measured fluctuation velocity. The last arises from the partitioning of the flow domain in strips to calculate velocity profiles. While this last kind of error can always be reduced by increasing the number of images acquired, the first three cannot be made arbitrarily small without improving pixel resolution. Using microgravity experiments and numerical simulations of a shear flow, we illustrate insidious distortions of the mean and fluctuation velocity profiles that originate with the unavoidable errors that we have discussed.

Segmental measurements of limb resistances permit to evaluate fat-free mass (FFM) and body fat (BF) in the limbs and trunk and appendicular muscle mass. This is done using empirical correlations of...

Over the last 30 years, pain has become one of the most dynamic areas of medicine and a public health issue. According to a recent Institute of Medicine report, pain affects approximately 100 million Americans at an estimated annual economic cost of $560 to $635 billion and is poorly treated overall. The American Board of Medical Specialties (ABMS) recognizes a pain subspecialty, but pain care delivery has struggled with increasing demand and developed in an inconsistent and uncoordinated fashion. Pain education is insufficient and highly variable. Multiple pain professional organizations have led to fragmentation of the field and lack of interdisciplinary agreement, resulting in confusion regarding who speaks for pain medicine. In this Perspective, the authors argue that ABMS recognition of pain medicine as an independent medical specialty would provide much needed structure and oversight for the field and would generate credibility for the specialty and its providers among medical peers, payers, regulatory and legislative agencies, and the public at large. The existing system, managed by three ABMS boards, largely excludes other specialties that contribute to pain care, fails to provide leadership from a single professional organization, provides suboptimal training exposure to pain medicine, and lengthens training, which results in inefficient use of time and educational resources. The creation of a primary ABMS conjoint board in pain medicine with its own residency programs and departments would provide better coordinated training, ensure the highest degree of competence of pain medicine specialists, and improve the quality of pain care and patient safety.

Background: International asthma treatment guidelines recommend tapering inhaled corticosteroid (ICS) therapy to the lowest dose that provides the maximum effect. Montelukast, a leukotriene receptor antagonist with complementary anti-inflammatory actions, has been shown in a tightly controlled trial to allow effective tapering of ICS therapy. Objectives: The purpose of this naturalistic study was to assess whether administration of montelukast could assist in the tapering of ICS therapy in patients with established asthma and whether the reduced dose achieved at 12 weeks could be maintained at 48 weeks without loss of asthma control. Methods: Patients with proven chronic asthma who were being treated with moderate to high doses of ICS (beclomethasone equivalent of 600 to 3200 μg/d) and required, according to their physician, the prescribed dose to maintain asthma control, were given open-label oral montelukast (10 mg/d at bedtime) for 48 weeks. Patients who were clinically stable, based on a composite clinical performance score, had their ICS dose reduced by ∼25% at 2-week intervals for 12 weeks and at 6-week intervals for the remaining 36 weeks. The percentage reduction in final ICS dose associated with clinical stability was the primary end point of the study. Results: Five hundred eighty-one patients were enrolled (57% female; mean age, 41 years). At 12 weeks, the mean ICS dose had been tapered by 82.3% (from 959 μg/d to 172 μg/d) and a total of 345 patients (59.5%) had completely stopped ICS. At 48 weeks, mean ICS dose had been tapered by 81.3% (from 959 μg/d to 178 μg/d; P P P Conclusion: In patients with chronic asthma treated with ICS, the addition of montelukast to assist in ICS tapering can be applied in clinical practice without loss of asthma control.

The purpose of this study was to survey the membership of the American Pain Society and the American Academy of Pain Medicine to determine their beliefs about ethical dilemmas in pain management practice. Respondents rated ethical dilemmas for their importance as well as their own competence in dealing with these ethical issues. The survey also included an open-ended question that asked respondents to describe clinical situations in which they had encountered ethical dilemmas. A total of 1,105 surveys were analyzed, with physicians (N = 612), nurses (N = 189), and psychologists (N = 166) representing the professions with the greatest response. Management of pain at the end of life, general undertreatment of pain, and undertreatment of pain in the elderly were the most frequently encountered dilemmas. Qualitative data were analyzed to identify ethical issues in the case examples provided by the respondents. Major themes included inappropriate pain management, barriers to care, interactions and conflicts with others, regulatory/legal issues, euthanasia, assisted suicide, and research issues. We conclude that ethical dilemmas are common in pain management practice and that resolution of these dilemmas requires commitment by individual professionals as well as health systems.

Eosinophils release inflammatory mediators and cationic proteins that are instrumental in the pathogenesis of allergic diseases such as bronchial asthma. Here, we review experimental observations indicating that eosinophils are also involved in the rejection of allografts. We propose that their role as effectors of transplant damage becomes crucial when classical pathways of rejection are inhibited and T helper 2 (Th2) cells dominate the alloimmune response.

The physician's commitment to altruism, which puts the patients' interests first and is associated with scientific integrity and the absence of bias when making medical decisions, has traditionally constituted the cornerstone of medical ethics. In recent years, however, a flurry of federal prosecutions, class action lawsuits, and congressional investigations have underlined an increasing collusion between physicians and pharmaceutical and device manufacturers. When profit-seeking behavior overshadows concern for the patients' welfare, major conflicts ensue. In such cases, a conflict of interest may be defined as a set of conditions in which professional medical judgment concerning patients' welfare or the validity of research is unduly influenced by secondary interests. These can be financial, such as competition for research funding, or professional, such as professional retribution. Public anxiety about the interaction between physicians and the health industry has grown as a result of observing the increasing influence of money on the quality of patient care and the research process. The health industry has contributed to the discovery, development, and distribution of new drugs and devices that benefited patients. One offshoot of these activities has been the industry's commitment to medical education. However, the health industry's responsibility is ultimately to shareholders, who expect good financial returns on their investment. There is, obviously, a possibility for conflict between the positive and necessary help that the health industry provides to physicians in their educational and research activities and the requirement for that same industry to produce profits and create profit incentives. The very mechanism for profit incentives may be detrimental to patient welfare and may hamper the physician's ability to keep patients' interests as the primary priority. Americans spend about 200 billion dollars each year on prescription drugs. The industry spends 19 billion dollars per year on physician promotion of industrial products. Additionally, direct marketing to …

To determine what role non-culturable microorganisms play in the etiology of interstitial cystitis (IC).Thirty patients fulfilling NIH criteria for the diagnosis of interstitial cystitis and sixteen control patients with culture negative urine gave written informed consent and underwent bladder biopsy. Polymerase chain reaction (PCR) using two sets of universal primers for bacterial 16S rDNA was performed on urine from the cystoscope and on a cold cup bladder biopsy specimen. Of the PCR positive bladder biopsies, three patients with interstitial cystitis and three controls were randomly selected and cloned. Ten clones from each were sequenced and putative taxonomic assignments made.12/26 (46%) IC and 5/12 (42%) control urine specimens and 16/30 (53%) and 9/15 (60%) bladder biopsies were PCR positive, respectively. The bacterial populations in the two patient groups tested appeared to be different based upon analysis of the 16S rRNA sequences.Both IC and control patients had non-culturable bacteria in their bladders. A random sampling of the two populations revealed that the bacterial populations are different, suggesting a possible link between one or more bacterial species and IC.

A technique for continuous measurements of haematocrit and plasma volume in the arterial line of dialysed patients has been tested in vitro and in vivo. This method uses impedance measurements at 5 kHz and requires a single haematocrit measurement. It relies on two assumptions: that plasma resistivity does not change during dialysis and that blood resistivity obeys Hanai's model. Both assumptions are verified during in vitro tests. Haematocrits measured in vivo by this method are found to be in good agreement with direct measurements from blood samples. The haematocrit variation is then used to monitor changes in plasma volume, assuming conservation of erythrocyte volume. In addition, it is possible to obtain the variation in interstitial volume by combining these data with body impedance measurements.

Dynamic crossflow filtration increases membrane performance through the use of membrane shear rates that are much higher than in conventional crossflow filtration. The production of these high shear rates requires specific modules with metal disks or rotors rotating at high speed near fixed membranes or rotating or vibrating membranes. The advantages and drawbacks of dynamic crossflow filtration will be discussed and currently available pilots and industrial dynamic filtration modules will be described. Specific methods for calculating the shear rate at membranes, which is the key factor governing permeate flux, will be presented for various types of modules. Recent applications of dynamic filtration published in the scientific literature, together with industrial case studies and comparisons with conventional crossflow will be reviewed. These systems can be advantageous for end-of-pipe treatment when the goal is to maximize retentate concentration in order to reach at least 65% of solid concentration. In pharmaceutical and biotechnological applications, where a high purity is required, the higher membrane selectivity of dynamic filtration (better solute transmission in microfiltration and higher microsolute rejection in nanofiltration and reverse osmosis) is an important asset. Industrial strategies of manufacturers of modules, New Logic Research (CA, USA), which has sold over 376 industrial vibrating modules; Bokela (Germany), which produces the rotating disk Dyno filter; and Metso Paper (Finland), which sells the Optifilter with rotors between, will be summarized. Keywords: rotating and vibrating membranes; rotating disk modules; shear-enhanced filtration; energy considerations; review of industrial dynamic filtration modules

The volar locking plate is a popular implant for surgical management of unstable distal radial fractures. We routinely utilize this system for all distal radial fractures except for those with entrapped intra-articular fragments and fractures with a displaced dorsomedial facet fracture (which is hard to capture with the volar approach alone). In this video, we describe in detail the necessary steps for successful placement of the volar locking plate, starting with preoperative planning and ending with expected outcomes. The approach that we utilize is through the flexor carpi radialis tendon sheath and avoids the radial artery. In the video, we describe 4 variations on the application of a volar locking plate: (1) the standard technique after appropriate reduction and provisional fixation with Kirschner wires, (2) regaining length through a shortened distal radial fracture, (3) using the volar plate to assist in the reduction and regain volar tilt, and (4) intraoperative management of coronal shift of the distal fragment. Complications reported for the volar locking plate have decreased with newer low-profile plate designs; however, they still include volar tendon irritation and/or rupture and median neuropathy. Postoperatively, we advise a brief 2-week period of immobilization for wound-healing, which is followed by a period during which a removable wrist splint is used and patients are instructed on the performance of a hand therapy regimen.

Although the vast majority of patients with cancer pain receive effective analgesia from standard therapy, a few patients, particularly those with neuropathic pain, continue to experience severe pain despite large doses of systemic or intraspinal opioids. Animal studies suggest intraspinal alpha 2-adrenergic agonists may be effective in such cases. Eighty-five patients with severe cancer pain despite large doses of opioids or with therapy-limiting side effects from opioids were randomized to receive, in a double-blind manner, 30 micrograms/h epidural clonidine or placebo for 14 days, together with rescue epidural morphine. Pain was assessed by visual analog score (VAS), McGill Pain Questionnaire, and daily epidural morphine use. Success was defined as a decrease in either morphine use of VAS pain, with the alternative variable either decreasing or remaining constant. Blood pressure, heart rate, and degree of nausea and sedation were monitored. Successful analgesia was more common with epidural clonidine (45%) than with placebo (21%). This was particularly prominent in those with neuropathic pain (56% vs. 5%). Pain scores were lower at the end of the treatment period in patients with neuropathic pain treated with clonidine rather than placebo, whereas morphine use was unaffected. Clonidine, but not placebo, decreased blood pressure and heart rate. Hypotension was considered a serious complication in 2 patients receiving clonidine and in 1 patient receiving placebo. This study confirms the findings from previous animal studies which showed the effective, potent analgesic properties of intraspinal alpha 2-adrenergic agonists and suggests that epidural clonidine may provide effective relief for intractable cancer pain, particular of the neuropathic type.

Locally produced eicosanoids and endothelium-derived factors are believed to be the mediators of vascular tone of various vascular beds including the mesentery. Using a small vessel isometric myograph which allows direct measurement of microvascular reactivity, the interaction of eicosanoids and endothelium-derived relaxing factor (EDRF) in regulating vascular tone of mesenteric microcirculation of the rat was characterized. The microvascular response to various vasoactive agents before and after inhibition of prostacyclin production with indomethacin (INDO, 5 μM) and inhibition of EDRF synthesis with N ω-nitro-dcl026;-arginine methyl ester (dcl026;-NAME, 50 μM) was compared. Analysis of dose-response curves for prostaglandin F 2α (PGF 2α ), U46619, a stable thromboxane analog, and norepinephrine (NE) after pretreatment with INDO demonstrated that inhibition of endogenous eicosanoids significantly attenuated the vasoconstrictor response to PGF 2α and U46619 but not to NE. Inhibition of EDRF synthesis with dcl026;-NAME potentiated the vasoconstrictor response to PGF 2α , U46619, and NE. These results suggest that EDRF acts as the primary mediator of vasodilator tone in the mesenteric microcirculation rather than vasodilator cyclooxygenase products such as prostacyclin. It also appears that the vasoconstrictor action of PGF 2α and U46619 may be mediated by a release of an endogenous indomethacin-sensitive factor.

Among nonsteroidal anti-inflammatory drugs used in the treatment of adult asthma, sodium cromoglycate and nedocromil sodium are the most frequently prescribed. These medications have a similar efficacy profile in asthma although it has been suggested that nedocromil is more powerful than cromoglycate, particularly in its steroid sparing effects. Both drugs have been recommended as alternatives to steroids in the treatment of mild asthma. They are useful in the prevention of bronchospasm induced by exposure to allergens or to a variety of other stimuli. In comparison with theophylline or low dose inhaled steroids, cromoglycate and nedocromil have shown a similar antiasthmatic efficacy, although this is variable among patients.

Patrick Olivieri,1 Bruce Solitar,2,* Michel Dubois3,*1NYU School of Medicine, New York, NY, USA; 2Department of Rheumatology, 3Department of Pain Management, New York University Langone Medical Center, New York, NY, USA*These authors contributed equally to this workBackground: Fibromyalgia is a disease process without an obvious etiology. While some evidence suggests that adverse experiences in childhood contribute to its development, specific evidence has been equivocal.Methods: A total of 36 patients with fibromyalgia from the greater New York area were recruited and surveyed using the Centers for Disease Control's Behavioral Risk Factor Surveillance System survey, and questions from the section on adverse childhood experiences were administered. The results were compared to those obtained from over 400,000 people surveyed by the Centers for Disease control each year, and were monitored for statistically significant differences.Results: A statistically significant difference was noted among the control group, suggesting that individuals reported growing up with someone who was depressed when the respondents were between the ages of 0 and 18 years old. Moreover, respondents reported that they were hit by their parents in some way, were insulted or cursed at by their parents, and had been forced to have sex with someone at least 5 years older than them or with an adult. No correlation was found with the following variables and the development of fibromyalgia: growing up with divorced or separated parents; growing up with someone sentenced to serve time in jail; or having parents that abused each other. Additionally, statistically significant differences were found for the following categories: lack of emotional support; life dissatisfaction; fair or poor health; physical, mental or emotional disability; and being divorced or not married.Discussion: Using this well-validated survey, it became clear that at least six specific adverse childhood experiences were correlated with the development of fibromyalgia. Data pertaining to disability, quality of life, life satisfaction, number of days of depression, emotional support, and marriage status illustrated the extent of subjective disability that these patients feel every day.Keywords: fibromyalgia, adverse childhood events, risk factors

The investigation of the hydration process during the haemodialysis treatment sessions is very important for the development of methods for predicting the unbalanced fluid shifts and hypotension crisis hence improving the quality of the haemodialysis procedure. About 25% of patients who need haemodialysis treatment experience acute complications (haemodynamic instability) during the treatment sessions. These instabilities are related to the excess shift of fluids between the extracellular (ECW) and intracellular (ICW) spaces as shown in several publications during the past 10 years. The transcellular fluid shits during haemodialysis are not yet understood. In this work we propose a non-invasive method based on local multifrequency bioimpedance measurements that allow us to determine the fluid distribution and variations during haemodialysis. For this purpose a measurement system was developed for the measurement of the body fluid compartments during haemodialysis sessions. Clinical measurements were done using 10 HD patients during 60 HD sessions. Bioimpedance data, arterial blood pressure, blood volume and blood heamatocrit variations were recorded continuously during the HD sessions. Significant decrease in the ECW volumes were recorded during HD session for all patients, however ICW variations were not similar in all patients.

Moxibustion is a very old, commonly used treatment modality in traditional Chinese medicine, which is practically unknown in the United States. Like acupuncture, it is a technique of care that has existed almost unchanged for more than 2,000 years. It is still widely used today, not only in China and Tibet but also in Korea, Japan, Mongolia, and Vietnam. The recent advent of modern neuroscience in these countries has led scientists to attempt to assess the mechanisms of these ancient therapies. The present issue of Pain Medicine is publishing such an attempt, a neurophysiological study of moxibustion from the Neuroscience Research Institute in Beijing [1]. This article is part of the ongoing article-exchange program between the Chinese Journal of Pain Medicine and Pain Medicine . Moxibustion is a technique that involves the burning of mugwort (moxa, Artemisia argyi ), a small, spongy herb, to facilitate healing over specific acupuncture points. It is used to treat many medical conditions such as asthma, colds and influenza, breech pregnancy, irritable bowel syndrome, disorders of the spinal column, pain, and others. There are two types …

A fiber-optic sensor that measures the particle volume fraction in dense suspensions is calibrated against a quantitative capacitance probe. For homogeneous, dense, random suspensions of smooth, monodisperse, transparent dielectric spheres, the calibration is simulated by using a ray-tracing Monte Carlo algorithm that predicts systematic uncertainties of the sensor's output, the extent of its measurement volume, and the effects of changing its optical properties. The simulation shows that the output and accuracy of the sensor increase with a decreasing sphere diameter and with an increasing N.A. of the fiber. The output also increases when the ratio of the indices of refraction of the sphere and the suspending medium is increased. For small particles the measurement volume scales as the average interparticle distance.

Objective. The authors recently determined that early and longer term mortality after initiation or reinitiation of intrathecal opioid therapy is higher than previously appreciated: 0.088% within 3 days, 0.39% at 1 month, and 3.89% at 1 year. These rates were 7.5 (confidence interval, 5.7–9.8), 3.4 (confidence interval, 2.9–3.8), and 2.7 (confidence interval, 2.6–2.8) times higher, respectively, at each interval than expected based on the age- and gender-matched general U.S. population. A substantial portion of this excess mortality is probably therapy related and cannot be entirely accounted for by underlying demographic or patient-related factors, or by device malfunctions. We also analyzed multiple complementary internal, governmental, and insurance databases to quantify mortality and to identify medical practice patterns that appear to be associated with patient mortality risks, and to suggest measures for physicians and health care facilities to consider in order to reduce those risks. Both of those objectives involve judgments, which may be controversial and are subject to practical limitations. Results. Multiple clinical and patient- or therapy-related factors appear to increase the risk for early post-implant mortality. Specific risk mitigation measures associated with each factor include: close attention to the starting intrathecal opioid dose (or restarting dose after therapy interruption); avoidance of outpatient implant or other device procedures that involve less than 24-hour monitoring for respiratory depression; supervision of concomitant opioid, respiratory depressant, or other central nervous system active drug intake early post-implant and chronically in the outpatient setting; and careful programming or dosage calculations and decisions in order to avoid the unintentional administration of high intrathecal opioid drug doses. Conclusions. Mortality after initiation of or device interventions in intrathecal drug delivery patients appears to occur as a result of multiple factors that present possible mitigation opportunities for physicians and health care facilities.

In Ethics Forum , we will present clinical cases selected on the basis of diagnostic dilemmas and/or difficult therapeutic decisions that occur in the practice of pain medicine. We will ask several pain specialists to help identify the ethical issues raised in these cases and to give their opinions based on their perceptions and experience. Please send or e-mail (ch53@drexel.edu) your comments or remarks to Colleen Healy, Editorial Assistant, Pain Medicine , Pain Center, Graduate Hospital, 1800 Lombard Street, Philadelphia, PA 19146. Also, if you believe you have witnessed a case that presents an interesting ethical dilemma for examination, send it for possible inclusion in the Forum. The patient is a 69-year-old widowed white female with a 10-year history of chronic low back and leg pain. She has had two back surgeries in the past for presumed spinal stenosis. These did not produce significant pain relief. They were followed by multiple interventions to address her pain, including selective nerve root blocks, lumbar epidural steroid injections, facet injections, and rhizotomies. The patient did not experience any lasting pain relief from any of these procedures. The patient's overall functional status has deteriorated steadily since the beginning of treatment. Before her first surgery she played tennis regularly. Now she is essentially bedridden. Insurance coverage of her care is becoming more difficult, leaving more and more out-of-pocket expenses, which the patient can barely meet. The patient has been reading information on the Internet and now requests implantation of an intrathecal pump for opioids. The insurance company is balking at this expense, given her lack of response to other therapies. The patient wonders how they can deny her this last chance at relief. ### Comment no. 1: Mark Sullivan, MD, PhD This case raises a number of ethical issues. One concerns the insurance company's perspective on the case. Another concerns the nature and …

Background. Trigger point (TrPs) identification has become the mainstay of diagnosis for the treatment of Myofascial Pain Syndrome; however, manual pressure (MP) to identify TrPs by determining low-pressure pain threshold has low interrater reliability and may lack validity since it is done on inactive muscles. To elicit contractions and mimic an active muscle or movement that “causes” pain, a Muscle Pain Detection Device (MPDD) has been developed. A selected muscle is stimulated and painful muscles are precisely detected, allowing distinctions between primary and referred muscle pain as well as distinguishing other functional muscle pain thought to cause MPS. Methods. An IRB approved randomized controlled study is presented of MP (20 patients) control vs MPDD (20 patients) to identify which muscle(s) was the source of pain in subjects presenting to the NYU Pain Management Center with a minimum 3 months history of back pain. Patients were unaware of their diagnostic method. Subjects were injected in 1–3 sites identified via MP or MPDD by a separate, blinded physician. Prior to, and following treatment at one week and one month, the patients were administered Oswestry and visual analog scale pain questionnaires by a blinded evaluator, and their range of motion was measured by a blinded physical therapist. Results. The MPDD group reported significantly larger improvements in pain, mood and Oswestry scores compared with the control (P

To review various methods for measuring body composition by bioimpedance and their limitations, as well as available impedance meters, including body fat analyzers for home use.Bioimpedance spectroscopy, which requires multifrequency impedance meters, is preferable for fluid volume measurements, especially extracellular fluid, whereas bioimpedance analysis at 50 kHz is more widely used for measuring fat-free mass. A method for using bioimpedance spectroscopy equations with 50 kHz impedance meters has been recently proposed and successfully tested. Low cost foot-to-foot impedance meters (body fat analyzers) with plantar electrodes on a body scale, that are easy and fast to use, have been compared with medical impedance meters and with dual X-ray absorptiometry measurements and found reasonably accurate, except for individuals with very low or high BMI.Body composition by bioimpedance is gaining acceptance in nutrition, hemodialysis, gerontology and sports medicine. Body fat analyzers that have been validated by comparison with dual x-ray absorptiometry could be useful to general practitioners, nutritionists and cardiologists.

New and more efficient techniques of postoperative pain management have been recently introduced. Patient-controlled intravenous (and perhaps subcutaneous) administration of analgesics is an improvement over traditional intramuscular injection. Its efficacy, safety, and high acceptance by patients, surgeons, and nurses make this technique increasingly popular for routine management of postoperative pain. Epidural or intrathecal administration of narcotic agents, although more efficient in controlling pain than intravenous infusion, should probably be reserved for indications such as major thoracic and abdominal procedures. Spinal administration requires more routine surveillance and, when inadequately managed, has the potential for serious side effects and complications. Clinical investigations currently in progress are aimed at finding more successful and safer methods of postoperative pain control. The best methods will likely involve a multifaceted therapeutic approach rather than the simple effect of one "magic bullet."

This paper reviews various bioimpedance methods permitting to measure non-invasively, extracellular, intracellular and total body water (TBW) and compares BIA methods based on empirical equations of the wrist-ankle resistance or impedance at 50 kHz, height and weight with BIS methods which rely on an electrical model of tissues and resistances measured at zero and infinite frequencies. In order to compare these methods, impedance measurements were made with a multifrequency Xitron 4200 impedance meter on 57 healthy subjects which had undergone simultaneously a Dual X-ray absorptiometry examination (DXA), in order to estimate their TBW from their fat-free-mass. Extracellular (ECW) and TBW volumes were calculated for these subjects using the original BIS method and modifications of Matthie[Matthie JR. Second generation mixture theory equation for estimating intracellular water using bioimpedance spectroscopy. J Appl Physiol 2005;99:780-1], Jaffrin et al. [Jaffrin MY, Fenech M, Moreno MV, Kieffer R. Total body water measurement by a modification of the bioimpedance spectroscopy method. Med Bio Eng Comput 2006;44:873-82], Moissl et al. [Moissl UM, Wabel P, Chamney PW, Bosaeus I, Levin NW, et al. Body fluid volume determination via body composition spectroscopy in health and disease. Physiol Meas 2006;27:921-33] and their TBW resistivities were compared and discussed. ECW volumes were calculated by BIA methods of Sergi et al. [Sergi G, Bussolotto M, Perini P, Calliari I, et al. Accuracy of bioelectrical bioimpedance analysis for the assessment of extracellular space in healthy subjects and in fluid retention states. Ann Nutr Metab 1994;38(3):158-65] and Hannan et al. [Hannan WJ, Cowen SJ, Fearon KC, Plester CE, Falconer JS, Richardson RA. Evaluation of multi-frequency bio-impedance analysis for the assessment of extracellular and total body water in surgical patients. Clin Sci 1994;86:479-85] and TBW volumes by BIA methods of Kushner and Schoeller [Kushner RF, Schoeller DA. Estimation of total body water by bioelectrical impedance analysis. Am J Clin Nutr 1986;44(3):417-24], Lukaski et al. [Lukaski HC, Bolonchuk WW. Estimation of body fluid volumes using tetrapolar bioelectrical impedance measurements. Aviat Space Environ Med 1988;59:1163-9], Hannan et al. [Hannan WJ, Cowen SJ, Fearon KC, Plester CE, Falconer JS, Richardson RA. Evaluation of multi-frequency bio-impedance analysis for the assessment of extracellular and total body water in surgical patients. Clinical Science 1994;86:479-85], Deurenberg et al. [Deurenberg P, van der Koy K, Leenen R, Westrate JA, Seidell JC. Sex and age specific prediction formulas for estimating body composition from bioelectric impedance: a cross validation study. Int J Obesity 1991;15:17-25] These volumes were compared against those given by BIS method and, in the case of TBW, with those by DXA. For ECW, a good agreement was found between various BIS methods and that of Sergi while Hannan's values were higher. Both Matthie's and Moissl's methods gave mean TBW resistivities and volumes lower than those of Jaffrin's and DXA methods. Kushner et al. method gave values of TBW not significantly different from those of Jaffrin et al. and DXA, as Hannan's method in men, but Lukaski and Deurenberg methods led to an underestimation.

The efficacy and safety of intravenous (IV) esmolol to treat postoperative hypertension was studied in 30 adult patients, during emergence and recovery from anesthesia after general surgery. Esmolol was given as an IV infusion when the patient developed systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (OBP) ≥95 mm Hg and heart rate (HR) ≥70 beats/min in the recovery room. Patients received a dose ranging from 100 to 2,104 mg of esmolol. Mean duration of the infusion was 63.6 ± 28.3 minutes. There were statistically significant differences between the control measurements and the end of esmolol titration for SBP, DBP, and HR. Side effects such as HR less than 60 beats/min or a decrease in SBP greater than 25% were observed in 33% (10/30) of the patient population; however, these effects were temporary and self-limiting. Hypotension (SBP β -adrenergic blocker esmolol was 90% (27/30) efficacious (ie, at least a 10% decrease in SBP or DBP) in controlling postoperative hypertension. As a fastacting, short-lasting antihypertensive drug, it joins the armamentarium of other drugs in the treatment of postoperative hypertension during emergence from anesthesia after general surgery.

A technique to measure the effective dielectric permittivity of suspensions is described. In these measurements, test powders are suspended in petroleum jelly at any desired voidage. The technique is illustrated using spherical glass beads of various sizes, a catalyst powder with and without water contamination, metal spheres, and metal flakes. For each suspension, a model is selected to fit the data. In the context of metal flakes, a model is derived for the effective dielectric permittivity of a suspension of ellipsoids in an electric field of random orientation. For complex powders, the technique is shown to represent a necessary step towards quantitative measurements of voidage using capacitance diagnostics.