Complex regional pain syndrome - Autoimmune or functional neurologic syndrome.

Complex regional pain syndrome (CRPS) purports to explain extremity pain accompanied by a variety of subjective complaints, including sensitivity to touch, fatigue, burning sensations, allodynia and signs consistent with voluntary immobilization, including skin changes, edema and trophic changes. By its own definition, CRPS pain is disproportionate to any inciting event or underlying pathology, which means that the syndrome describes non-anatomic and exaggerated symptoms. Although CRPS was coined in the early 1990s, physicians have described unexplained exaggerated pain for centuries. Before a small group of researchers assigned this historical phenomenon with the name CRPS, other physicians in various subspecialties investigated the existence of a common pathophysiologic mechanism but found none. The literature was searched for evidence of a reproducible pathologic mechanism for CRPS. Although some have suggested that CRPS is an autoimmune disease, there is a paucity of evidence to support this. While cytokines such as IL-1ß, IL-6 and TNF-α have been detected during the early phases of CRPS, this cannot lead to the conclusion that CRPS is an autoimmune disease, nor that it is an autoinflammatory disorder. Moreover, intravenous immunoglobulin has showed inconsistent results in the treatment of CRPS. On the other hand, CRPS has been found to meet at least three out of four criteria of malingering, which was previously a DSM-IV diagnosis; and its diagnostic criteria are virtually identical to current DSM-5 Functional Neurological Disorder ("FND"), and proposed ICD-11 classification, which includes FND as a distinct neurological diagnosis apart from any psychiatric condition. Unfortunately, the creation of CPRS is not merely misguided brand marketing. It has serious social and health issues. At least in part, the existence of CRPS has led to the labeling of many patients with a diagnosis that allows the inappropriate use of invasive surgery, addictive opioids, and ketamine. The CRPS hypothesis also ignores the nature and purpose of pain, as a symptom of some organic or psychological process. Physicians have long encountered patients who voice symptoms that cannot be biologically explained. Terminology historically used to describe this phenomenon have been medically unexplained symptoms ("MUS"), hysterical, somatic, non-organic, psychogenic, conversion disorder, or dissociative symptoms. The more recent trend describes disorders where there is a functional, rather than structural cause of the symptoms, as "functional disorders." Physicians report high success treating functional neurological symptoms with reassurance, physiotherapy, and cognitive behavior therapy measured in terms of functional improvement. The CRPS label, however, neither leads to functional improvement in these patients nor resolution of symptoms. Under principles of evidence-based medicine, the CRPS label should be abandoned and the syndrome should simply be considered a subset of FNDs, specifically Functional Pain Disorder; and treated appropriately.

Administration of Human Non-Diabetic Mesenchymal Stromal Cells to a Murine Model of Diabetic Fracture Repair: A Pilot Study.

Individuals living with type 1 diabetes mellitus may experience an increased risk of long bone fracture. These fractures are often slow to heal, resulting in delayed reunion or non-union. It is reasonable to theorize that the underlying cause of these diabetes-associated osteopathies is faulty repair dynamics as a result of compromised bone marrow progenitor cell function. Here it was hypothesized that the administration of non-diabetic, human adult bone marrow-derived mesenchymal stromal cells (MSCs) would enhance diabetic fracture healing. Human MSCs were locally introduced to femur fractures in streptozotocin-induced diabetic mice, and the quality of de novo bone was assessed eight weeks later. Biodistribution analysis demonstrated that the cells remained in situ for three days following administration. Bone bridging was evident in all animals. However, a large reparative callus was retained, indicating non-union. µCT analysis elucidated comparable callus dimensions, bone mineral density, bone volume/total volume, and volume of mature bone in all groups that received cells as compared to the saline-treated controls. Four-point bending evaluation of flexural strength, flexural modulus, and total energy to re-fracture did not indicate a statistically significant change as a result of cellular administration. An ex vivo lymphocytic proliferation recall assay indicated that the xenogeneic administration of human cells did not result in an immune response by the murine recipient. Due to this dataset, the administration of non-diabetic bone marrow-derived MSCs did not support fracture healing in this pilot study.

Complex regional pain syndrome - False hopes and miscommunications.

Complex regional pain syndrome (CRPS) has been considered to be an autoimmune disease and there have been clinical trials with intravenous immunoglobulin. Often the etiology of the so-called CRPS diagnosis cannot be discerned and there are no validated instruments that provide functional metrics. The term complex regional pain syndrome (CRPS), coined in 1994 to describe patients in whom the pain is out of proportion to the injury, was actually a diagnosis proposed during the American Civil War, but was originally known as causalgia. Physicians have long observed similar sensitivity and inflammatory symptoms following periods of immobilization and disuse, which generally resolve within a few months of remobilization. Following the original description, persistent disproportionate pain would come to be known under many other names until researchers theorized that it was related to dysfunction in the sympathetic nervous system, after which it acquired the moniker, Reflex Sympathetic Dystrophy ("RSD"). In the latter quarter of the twentieth century, after researchers failed to prove the connection between the pain and the sympathetic nervous system, a small cadre of physicians-without rigorous science-invented CRPS. This new descriptor, CRPS, has become not only a diagnosis without objective data but with proposed criteria involving ambiguous signs and symptoms with low specificity. It has led to patients being treated erroneously with sympatholytic drugs, with or without pharmaceutical or surgical blockade of the sympathetic nervous system, unwarranted use of ketamine infusions, inappropriate use of narcotics and nerve stimulation. Intravenous immunoglobulin infusions have not been effective in the treatment of chronic pain. The indiscriminate use of pain medications to treat subjective symptoms of unclear diagnoses can be a risk factor for opioid and analgesic misuse or abuse.

A novel drug management system in the Febuxostat versus Allopurinol Streamlined Trial: A description of a pharmacy system designed to supply medications directly to patients within a prospective multicenter randomised clinical trial.

BACKGROUND: Trials of investigational medicinal products are required to adhere to strict guidelines with regard to the handling and supply of medication. Information technology offers opportunities to approach clinical trial methodology in new ways. This report summarises a novel pharmacy system designed to supply trial medications directly to patients by post in the Febuxostat versus Allopurinol Streamlined Trial. METHOD: A bespoke web-based software package was designed to facilitate the direct supply of trial medications to Febuxostat versus Allopurinol Streamlined Trial participants from a pharmacy based in the Medicines Monitoring Unit, University of Dundee. RESULTS: To date, 65,467 packs of medication have been dispensed using the system to 3978 patients. Up to 238 packs per day have been dispensed. CONCLUSION: The Medicines Monitoring Unit Febuxostat versus Allopurinol Streamlined Trial drug management system is an effective method of administering the complex drug supply requirements of a large-scale clinical trial with advantages over existing arrangements. A low rate of loss to follow-up in the Febuxostat versus Allopurinol Streamlined Trial may be attributable to the drug management system.

Influenza H1N1 (swine flu) vaccination: a safety surveillance feasibility study using self-reporting of serious adverse events and pregnancy outcomes.

AIMS: During the global H1N1 influenza A (swine flu) pandemic 2009-2010, swine flu vaccines were expeditiously licensed and a mass vaccination programme for high risk groups, including pregnant women, was introduced in the UK. This pilot active safety surveillance study was performed to establish the feasibility of rapidly monitoring the new swine flu vaccines in large patient numbers receiving or offered the vaccination under normal conditions of use within a short time frame. METHODS: A cohort design with safety data capture through modern technologies was carried out in Scotland, UK during the winter swine flu vaccination programme 2009-2010 in individuals receiving or offered the swine flu vaccination. The main outcome measures were self-reported serious adverse events (SAEs) and pregnancy outcomes. RESULTS: The cohort comprised 4066 people; 3754 vaccinated and 312 offered the vaccination but not vaccinated. There were 939 self-reported events (838 different events), 53 judged to fit SAE criteria by the investigators, with nine judged as possibly, probably or definitely vaccine related. None of the seven deaths (six in vaccinees) were judged as vaccine related. One hundred and twenty-eight women reported 130 pregnancies during the study with 117 pregnant at study start. There were reports of four miscarriages in three women and six possible congenital abnormalities in live births. CONCLUSIONS: Overall, no significant safety issues were identified. The methodology and use of modern technologies to collect safety data from large numbers of patients was successful and could be used again in similar safety studies.

Managing security and privacy concerns over data storage in healthcare research.

PURPOSE: Issues surrounding data security and privacy are of great importance when handling sensitive health-related data for research. The emphasis in the past has been on balancing the risks to individuals with the benefit to society of the use of databases for research. However, a new way of looking at such issues is that by optimising procedures and policies regarding security and privacy of data to the extent that there is no appreciable risk to the privacy of individuals, we can create a 'win-win' situation in which everyone benefits, and pharmacoepidemiological research can flourish with public support. We discuss holistic measures, involving both information technology and people, taken to improve the security and privacy of data storage. METHODS: After an internal review, we commissioned an external audit by an independent consultant with a view to optimising our data storage and handling procedures. RESULTS: Improvements to our policies and procedures were implemented as a result of the audit. CONCLUSIONS: By optimising our storage of data, we hope to inspire public confidence and hence cooperation with the use of health care data in research.

Influence of incrementally substituting dietary soya bean meal for rapeseed meal on nutrient digestibility, nitrogen excretion, growth performance and ammonia emissions from growing-finishing pigs.

A completely randomised design experiment was performed to examine the effects of replacing different levels of soya bean meal (SBM) with rapeseed meal (RSM) on the growth performance, carcass characteristics, apparent nutrient digestibility, nitrogen (N) balance and manure ammonia emissions of growing-finishing pigs. Pigs (n = 336; mean live weight 42.1 kg) were assigned to one of four dietary treatments containing per kg diet: 210 g SBM; 140 g SBM and 70 g RSM; 70 g SBM and 140 g RSM; and 210 g RSM. All diets were formulated on an ileal digestible amino acid, net energy and available phosphorus basis. There was no significant treatment effect on average daily gain, feed intake, feed conversion ratio and carcass characteristics. There was a linear decrease in gross energy digestibility (p < 0.01) as RSM increased at the expense of SBM in the diet. There was a linear decrease in urinary N excretion (p < 0.01), N digestibility (p < 0.05), total N excretion (p < 0.05) and N retention (p < 0.05) with increasing levels of RSM. There was no effect of dietary treatment on manure ammonia emissions. The results of this study indicate that RSM can be used as a direct replacement for SBM with no associated depression in performance, when formulated on an ileal digestible amino acid and net energy basis. Consumption of diets containing incremental levels of RSM linearly decreased urinary N and total N excretion, reflecting the associated decrease in crude protein concentrations.

Detecting deviations from pure EOF during CE separations.

CE separations are known for their high separation efficiencies. In systems with EOF, the high efficiencies benefit from the flat, plug profile that is characteristic of EOF. When a velocity gradient is present, such as in separations which have nonuniform buffer ionic strength, surface adsorption or differences in the height of the ends of the capillary, a parabolic flow component is introduced. This deviation from purely EOF yields increased peak dispersion and a subsequent decrease in separation performance. This work details a rapid method for detecting deviations from ideal plug flow during the course of a separation using the radially averaged flow profile of a photobleached fluorophore added to the BGE. By comparing the ratio of two different data analysis procedures, deviations from ideal plug flow can be detected. This method allows rapid measurement of flow character and does not interfere with the concurrent separation. We demonstrate easy detection of the onset of hydrodynamic flow induced by both gravity siphoning and an ionic strength buffer discontinuity. A brief analysis of the radially averaged peak shapes is also presented.

Building individualized medicine: prevention of adverse reactions to warfarin therapy.

Warfarin is the most widely used oral anticoagulant in the world for patients with venous thrombosis, pulmonary embolism, chronic atrial fibrillation, and prosthetic heart valves. Approximately 30 genes contribute to therapeutic effects of warfarin, and genetic polymorphisms in these genes may modulate its anticoagulant activity. In contrast to monogenic pharmacogenetic traits, warfarin drug response is a polygenic trait, and development of diagnostic tools predictive of adverse reactions to warfarin requires a novel approach. A combination of two strategies, biochemical isolation of allelic variants and linkage disequilibrium association studies, was used to find an association between genetic polymorphisms in the candidate genes and warfarin response. A strong association was found between genetic polymorphisms in six genes, including VKORC1, CYP2C9, PROC, EPHX1, GGCX, and ORM1, and interindividual variability in the anticoagulant effect of warfarin; the strongest predictors were VKORC1 and CYP2C9. Generation of single nucleotide polymorphism (SNP)-based dense genetic maps made it possible to identify haplotypes associated with drugresponse phenotypes. Discrimination between haplotypes associated with warfarin dose phenotypes can be achieved by a limited set of informative polymorphisms (tag SNPs). The use of tag SNPs in pharmacogenomic analysis provides a promising tool for dissecting polygenic traits of drug response.

Anaphylactic reaction to a dietary supplement containing willow bark.

OBJECTIVE: To report a case of anaphylaxis resulting from the use of a willow bark-containing dietary supplement in a patient with a history of an aspirin allergy. CASE SUMMARY: A 25-year-old white woman presented to the emergency department of a community teaching hospital with anaphylaxis requiring epinephrine, diphenhydramine, methylprednisolone, and volume resuscitation to which she responded favorably. Medication history revealed that she had ingested 2 capsules of Stacker 2 (NVE Pharmaceuticals, Newton, NJ), a dietary supplement promoted for weight loss, prior to experiencing her initial symptoms. Among other active ingredients, this product contains willow bark. Of significance is that this patient also reported a history of allergy to acetylsalicylic acid. No other causes for anaphylaxis were identified. She continued to receive routine supportive care and the remaining hospital course was uncomplicated. DISCUSSION: Dietary supplements, including herbal products, are used by many individuals who consider them to be inherently safe despite limited regulatory oversight by the Food and Drug Administration. While there may be value to specific botanical ingredients, a potential for adverse effects also exists. The popular product consumed by our patient is used for weight loss and contains willow bark, a source of salicylates. Based on the Naranjo probability scale, it is probable that this case of anaphylaxis was due to this dietary supplement. CONCLUSIONS: The use of any willow bark-containing dietary supplement may present a risk of anaphylactic reaction to patients with a history of allergy to salicylates. Clinicians need to recognize the potential for adverse effects from dietary supplements.

Hospital admissions resulting from preventable adverse drug reactions.

BACKGROUND: Adverse drug reactions (ADRs) are a significant cause of hospital admissions. These events can lead to significant morbidity and mortality and financial costs. ADRs that may be preventable might be considered a form of medication error. OBJECTIVE: To assess the potential preventability of ADRs directly related to a patient's hospital admission. METHODS: A retrospective chart review of 437 ADRs occurring during an 11-month period was conducted at a university hospital. A subset of these events leading to hospital admissions was identified for further review. Those that resulted in admission were further examined to determine probability of causality, severity, and preventability. RESULTS: Over 11 months, 158 ADRs were directly related to hospital admission. The relationship of these admissions to drug exposure was determined to be probable or highly probable in 154 (97.4%) of these cases. From this group, 96 (62.3%) of these events were considered potentially preventable, with 23 (24%) considered severe to life-threatening. Characteristics associated with these ADRs included documentation of a toxic drug concentration or abnormal laboratory value (80%), inadequate monitoring of a patient's drug therapy (67%), inappropriate dose (51%), patient noncompliance (33%), drug-drug interaction (26%), contraindication to therapy (3%), and documented allergy (1%). These ADRs resulted in 595 hospital days, with an average length of stay of 6.1 days. CONCLUSIONS: ADRs leading to hospital admissions are often preventable. Approximately 25% of these events were serious to life-threatening. Most resulted from inadequate monitoring of therapy or inappropriate dosing. Patient noncompliance and drug interactions were also common causes. Multidisciplinary prevention strategies among physicians, pharmacists, other healthcare professionals, and patients focusing on communication and education should be targeted.