A brief review of complex regional pain syndrome and current management.

Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition that, although exceedingly rare, carries a significant burden for the affected patient population. The complex and ambiguous pathophysiology of this condition further complicates clinical management and therapeutic interventions. Furthermore, being a diagnosis of exclusion requires a diligent workup to ensure an accurate diagnosis and subsequent targeted management. The development of the Budapest diagnostic criteria helped to consolidate existing definitions of CRPS but extensive work remains in identifying the underlying pathways. Currently, two distinct types are identified by the presence (CRPS type 1) or absence (CRPS type 2) of neuronal injury. Current management directed at this disease is broad and growing, ranging from non-invasive modalities such as physical and psychological therapy to more invasive techniques such as dorsal root ganglion stimulation and potentially amputation. Ideal therapeutic interventions are multimodal in nature to address the likely multifactorial pathological development of CRPS. Regardless, a significant need remains for continued studies to elucidate the pathways involved in developing CRPS as well as more robust clinical trials for various treatment modalities.

Complex regional pain syndrome (CRPS) is a debilitating and complex condition that places a significant physical, psychological and emotional burden upon afflicted patients necessitating multi-modal approaches to treatment.The development of the Budapest criteria provided a robust and well-tested set of diagnostic criteria to aid clinicians in the diagnosis of CRPS.The pathophysiology of CRPS has been challenging to elucidate with numerous proposed mechanisms, altogether suggesting a multi-factorial process is involved in the development of this condition.Non-invasive treatments for CRPS are essential in addressing the physical limitations this disease can cause as well as addressing the significant psychological burden that involves increased incidence of depression and suicidal ideation.Invasive treatments offer promising results, especially when considering dorsal root ganglion stimulation; however, the need for more robust clinical trials remains, especially when considering a small portion of patients who have refractory CRPS resort to amputation to control their pain symptoms.

A Case Report of Acute Onset and Rapid Resolution of Atrioventricular Block After Sugammadex: Is the Autonomic System Involved?

Administering sugammadex to reverse neuromuscular blockade can cause marked bradycardia and rarely asystole. In this case, a rapid onset, biphasic heart rate response; slowing then speeding, after administering sugammadex was noted while at steady state, 1.3% end-tidal sevoflurane. On review of the electrocardiogram (ECG), the heart rate slowing coincided with the onset of a second-degree, Mobitz type I block that lasted 45 seconds. No other events, drugs, or stimuli coincided with the event. The acute onset and transient nature of the atrioventricular block without evidence of ischemia implies a brief parasympathetic effect on the atrioventricular node after sugammadex administration.

A Review of Chronic Pain and Device Interventions: Benefits and Future Directions.

Chronic pain is a debilitating condition with a growing prevalence both in the USA and globally. The complex nature of this condition necessitates a multimodal approach to pain management that extends beyond the established pharmaceutical interventions currently employed. A variety of devices comprising both invasive and noninvasive approaches are available to patients, serving as adjuvants to existing regimens. The benefits of these interventions are notable for their lack of addiction potential, potential for patient autonomy regarding self-administration, minimal to no drug interaction, and overall relative safety. However, there remains a need for further research and more robust clinical trials to assess the true efficacy of these interventions and elucidate if there is an underlying physiological mechanism to their benefit in treating chronic pain or if their effect is predominantly placebo in nature. Regardless, the field of device-based intervention and treatment remains an evolving field with much promise for the future chronic pain management.

Eptinezumab-jjmr, a humanized monoclonal specific to Calcitonin Gene Related Peptide, for the preventive treatment of migraine in adults.

Purpose of Review: Migraines are prevalent and cause significant morbidity, decline in quality of life and healthcare costs universally. Treatment options are varied, but efficacy is limited. This review centers on Eptinezumab-jjmr, a humanized monoclonal specific to CGRP for the prevention of migraines in adults. Herein presented are the science and mechanism of action, indication and clinical evidence for use. Recent Findings: Migraines are severe, recurrent headaches, which are either episodic or chronic in nature. The pain is severe, often accompanied by co-morbid symptoms, such as photophobia, phonophobia, nausea and emesis, and is limiting in nature. It is a prevalent disorder that causes significant, worldwide disability, morbidity, suffering, and costs.The pathophysiology of migraines is actively studied, though recent research points to an initiating event causing migraine generation, that is then propagated by other brain regions, a significant one being the trigeminocervical complex. This is driven by biochemical transmitters, chiefly CGRP. This discovery led to the development of CGRP-targeting drugs, including gepants (small molecular antagonists) and anti-CGRP antibodies, such as Eptinezumab-jjmr.Traditional therapy includes preventative and abortive treatment; however, adherence with preventative treatment has been historically poor, and certain types of abortive therapy carry risks and side effects that preclude them from a large patient population. Moreover, traditional therapy often falls short in migraine therapy. CGRP antagonist, including Eptinezumab, aims to cover the gaps in migraine therapy. We present here evidence to support the safe and effective use of Eptinezumab for the prevention of migraines. Summary: Migraines are a prevalent primary headache disorder causing significant morbidity worldwide. Traditional abortive and preventative treatments fall short for many patients. Eptinezumab is part of new generation of CGRP-targeting medications and has shown significant evidence to support its use for the prevention of migraines. Further research is required to properly compare eptinezumab with existing pharmacotherapy and update guidelines on the appropriate combinations of therapies that are not available and the correct patient selection for each.

Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors.

Monoamine oxidase inhibitors (MAOI) are a class of drugs that were originally developed for the treatment of depression but have since been expanded to be used in management of affective and neurological disorders, as well as stroke and aging-related neurocognitive changes. Ranging from irreversible to reversible and selective to non-selective, these drugs target the monoamine oxidase (MAO) enzyme and prevent the oxidative deamination of various monoamines and catecholamines such as serotonin and dopamine, respectively. Tyramine is a potent releaser of norepinephrine (NE) and is found in high concentrations in foods such as aged cheeses and meats. Under normal conditions, NE is unable to accumulate to toxic levels due to the presence of MAO-A, an enzyme that degrades neurotransmitters, including NE. When MAO-A is inhibited, the capacity to handle tyramine intake from the diet is significantly reduced causing the brain to be vulnerable to overstimulation of postsynaptic adrenergic receptors with as little as 8-10 mg of tyramine ingested and can result in life-threatening blood pressure elevations. In addition to adverse reactions with certain foods, both older and newer MAOIs can negatively interact with both sympathomimetic and serotonergic drugs. In general, patients on a MAOI want to avoid two types of medications: those that can elevate blood pressure via sympathomimetic actions (e.g., phenylephrine and oxymetazoline) and those that can increase serotonin levels via 5-HT reuptake inhibition (e.g., dextromethorphan, chlorpheniramine, and brompheniramine). Illicit drugs that stimulate the central nervous system such as ecstasy (MDMA, 3,4-methylenedioxymethamphetamine) act as serotonin releasers. Patient involvement is also crucial to ensure any interaction within the healthcare setting includes making other providers aware of a MAOI prescription as well as avoiding certain OTC medications that can interact adversely with MAOIs.

Buprenorphine and its formulations: a comprehensive review.

Buprenorphine, a novel long-acting analgesic, was developed with the intention of two purposes: analgesia and opioid use disorder. Regarding its pharmacodynamics, it is a partial agonist at mu receptors, an inverse agonist at kappa receptors, and an antagonist at delta receptors. For the purpose of analgesia, three formulations of buprenorphine were developed: IV/IM injectable formulation (Buprenex®), transdermal patch formulation (Butrans®), and buccal film formulation (Belbuca®). Related to opioid dependence, the formulations developed were subcutaneous extended release (Sublocade®), subdermal implant (Probuphine®), and sublingual tablets (Subutex®). Lastly, in order to avoid misuse of buprenorphine for opioid dependence, two combination formulations paired with naloxone were developed: film formulation (Suboxone®) and tablet formulation (Zubsolv®). In this review, we present details of each formulation along with their similarities and differences between each other and clinical considerations.

Clinical management of the pregnant patient undergoing non-obstetric surgery: Review of guidelines.

The management principles of non-obstetric surgery during pregnancy are important concepts for all health care providers to be cognizant of. The goals of non-obstetric surgery are to ensure maternal safety, maintain the pregnancy, and ensure fetal well-being. In this regard, organogenesis occurs roughly between days 7-57 and thus, certain medications have a higher incidence of fetal teratogenicity in this first trimester. Some examples of common surgeries performed urgently or emergently include appendectomies, ovarian detorsions, bowel obstruction, trauma, and cholecystectomies. The choice of anesthetic technique and the selection of appropriate anesthetic drugs should be guided by indication for surgery, the nature of the surgery, and the site of the surgical procedure. Many of the concerns for any patients undergoing urgent or emergent surgery must be considered by anesthesia providers along with steps to ensure the fetus has the best outcome.

Preoperative laboratory testing: Implications of "Choosing Wisely" guidelines.

Preoperative laboratory testing is often necessary and can be invaluable for diagnosis, assessment, and treatment. However, performing routine laboratory tests for patients who are considered otherwise healthy is not usually beneficial and is costly. It is estimated that $18 billion (U.S.) is spent annually on preoperative testing, although how much is wasteful remains unknown. Ideally, a targeted and comprehensive patient history and physical exam should largely determine whether preprocedure laboratory studies should be obtained. Healthcare providers, primarily anesthesiologists, should remain cost-conscious when ordering specific laboratory or imaging tests prior to surgery based on available literature. We review the overall evidence and key points from the Choosing Wisely guidelines, the identification of potential wasteful practices, possible harms of testing, and key clinical findings associated with preoperative laboratory testing.

Pharmacogenomics of Pain Management: The Impact of Specific Biological Polymorphisms on Drugs and Metabolism.

PURPOSE OF REVIEW: Pain is multifactorial and complex, often with a genetic component. Pharmacogenomics is a relative new field, which allows for the development of a truly unique and personalized therapeutic approach in the treatment of pain. RECENT FINDINGS: Until recently, drug mechanisms in humans were determined by testing that drug in a population and calculating response averages. However, some patients will inevitably fall outside of those averages, and it is nearly impossible to predict who those outliers might be. Pharmacogenetics considers a patient's unique genetic information and allows for anticipation of that individual's response to medication. Pharmacogenomic testing is steadily making progress in the management of pain by being able to identify individual differences in the perception of pain and susceptibility and sensitivity to drugs based on genetic markers. This has a huge potential to increase efficacy and reduce the incidence of iatrogenic drug dependence and addiction. The streamlining of relevant polymorphisms of genes encoding receptors, transporters, and drug-metabolizing enzymes influencing the pain phenotype can be an important guide to develop safe new strategies and approaches to personalized pain management. Additionally, some challenges still prevail and preclude adoption of pharmacogenomic testing universally. These include lack of knowledge about pharmacogenomic testing, inadequate standardization of the process of data handling, questionable benefits about the clinical and financial aspects of pharmacogenomic testing-guided therapy, discrepancies in clinical evidence supporting these tests, and doubtful reimbursement of the tests by health insurance agencies.

Ventilation rates and health: multidisciplinary review of the scientific literature.

UNLABELLED: The scientific literature through 2005 on the effects of ventilation rates on health in indoor environments has been reviewed by a multidisciplinary group. The group judged 27 papers published in peer-reviewed scientific journals as providing sufficient information on both ventilation rates and health effects to inform the relationship. Consistency was found across multiple investigations and different epidemiologic designs for different populations. Multiple health endpoints show similar relationships with ventilation rate. There is biological plausibility for an association of health outcomes with ventilation rates, although the literature does not provide clear evidence on particular agent(s) for the effects. Higher ventilation rates in offices, up to about 25 l/s per person, are associated with reduced prevalence of sick building syndrome (SBS) symptoms. The limited available data suggest that inflammation, respiratory infections, asthma symptoms and short-term sick leave increase with lower ventilation rates. Home ventilation rates above 0.5 air changes per hour (h(-1)) have been associated with a reduced risk of allergic manifestations among children in a Nordic climate. The need remains for more studies of the relationship between ventilation rates and health, especially in diverse climates, in locations with polluted outdoor air and in buildings other than offices. PRACTICAL IMPLICATIONS: Ventilation with outdoor air plays an important role influencing human exposures to indoor pollutants. This review and assessment indicates that increasing ventilation rates above currently adopted standards and guidelines should result in reduced prevalence of negative health outcomes. Building operators and designers should avoid low ventilation rates unless alternative effective measures, such as source control or air cleaning, are employed to limit indoor pollutant levels.

Olfactory detection of ozone and D-limonene: reactants in indoor spaces.

UNLABELLED: Young adult subjects who occupied a well-ventilated space with low background of level of ozone achieved via carbon-filtration could detect ozone odor at 7 ppb, lower than expected from archival compilations. The outcome was not inconsistent, however, with some observations of recognition, beyond mere detection, at about 15-20 ppb. Individual differences in sensitivity lay at or just below an order of magnitude, rare in olfactory testing and indicative of precision. In a study of d-limonene, subjects again showed high sensitivity and small individual differences. The subjects could detect the odor at 8 and 15 ppb, depending upon whether they occupied a space with or without carbon filtration, respectively. The results argue for use of carbon filtration to measure sensitivity most stringently, although absence of filtration seems not to incur a large penalty. The protocol used here, with collection of hundreds of judgments in a day, yet with little net exposure of the subject to odorant; with verifiably stable delivery; and with analytical confirmation of level should reduce tolerance for outcomes of large differences among subjects and among studies. PRACTICAL IMPLICATIONS: Humans manifested much higher sensitivity to ozone and D-limonene than commonly thought, a pattern revealing itself more broadly in olfactory studies as testing improves and analytical confirmation of delivery becomes more common. Published databases, with errors of +/-1000%, often badly underestimate sensitivity and can thereby encourage use of higher concentrations of compounds, particularly VOCs, than relevant in studies of reactive indoor chemistry.

Cutoff in detection of eye irritation from vapors of homologous carboxylic acids and aliphatic aldehydes.

Using neat vapors of selected homologous aldehydes (decanal, undecanal, dodecanal) and carboxylic acids (pentanoic, hexanoic, heptanoic, octanoic, nonanoic), we explored the point where a certain homolog (and all larger ones) becomes undetectable by eye irritation (i.e. by ocular chemesthesis). This phenomenon has been observed in other homologous series that also reach a break-point, or cutoff, in chemesthetic detection. Participants (11

Odor and chemesthesis from brief exposures to TXIB.

UNLABELLED: An experiment explored ability of subjects to detect vapors of the plasticizer TXIB (2,2,4-trimethyl-1,3-pentanediol diisobutyrate) and ethanol via olfaction and via ocular and nasal chemesthesis, i.e. chemically stimulated feel. Testing, tailored to the sensitivity of each subject, produced psychometric functions for individuals. Olfactory detection of TXIB began at concentrations below 1 ppb (v/v), with 50% correct detection at 1.2 ppb. (Comparable detection for ethanol occurred almost two orders of magnitude higher.) Chemesthetic detection of TXIB began at about 500 ppb, with 50% correct detection at 2.1 ppm for the eye and 4.6 ppm for the nose, both close to saturated vapor concentration. (Comparable detection for ethanol occurred essentially three orders of magnitude higher.) Suggestions that TXIB plays a role in generation of irritative symptoms at concentrations in the range of parts-per-billion need to reckon with a conservatively estimated 200-fold gap between the levels putatively 'responsible' for the symptoms and those even minimally detectable via chemesthesis. Neither the variable of exposure duration nor that of mixing offers a likely explanation. Inclusion of ethanol in the study allowed comparisons pertinent to issues of variability in human chemoreception. An interpretation of the psychometric functions for individuals across materials and perceptual continua led to the conclusion that use of concentration as the metric of detection in olfaction inflates individual differences. PRACTICAL IMPLICATIONS: This study indicated that the plasticizer TXIB could contribute odor at concentrations in the range of parts-per-billion, but could hardly contribute sensory irritation per se, as alleged in reports of some field studies where TXIB has existed amongst many other organic compounds.

Water Environment Research Foundation (WERF) anaerobic digestion and related processes, odour and health effects study.

Biosolids odour emissions can affect the ability of wastewater utilities to implement beneficial biosolids processing and reuse programs. Communities often become more sensitised and vocal about biosolids issues, once they experience odours emanating from a nearby site. Odour impacts from biosolids, including potential human health effects, have been targeted recently by many national and local newspapers, citizens' groups, and regulatory agencies, who have raised significant concerns, ranging from viable disposal methods/sites to outright bans. Many national and local regulatory agencies in the United States are considering biosolids disposal bans in their communities because of misinformation, poor science, and citizen pressure, but primarily because of odour impact concerns. The wastewater industry has a relatively poor understanding of the operations and treatment parameters that influence biosolids odour emissions. Thus, wastewater treatment plants are often unable to control the odour quality of the biosolids that are delivered into communities. A research study to demonstrate the influence of anaerobic digestion, mechanical dewatering, and storage design and operating parameters on the odour quality of the final product was performed and is the subject of this paper. Established and new sampling and analytical methods were used to measure biosolids odour emissions from 11 test sites in North America. By determining the impacts of these control variables on biosolids odour quality, design and operations of anaerobic digestion systems might be enhanced. This paper also summarises a corollary study performed as part of the WERF research study that addresses the health effects of biosolids odours.

Reduced hospitalization cost for patients with pectus excavatum treated using minimally invasive surgery.

BACKGROUND: Currently, few data exist regarding the relative costs associated with open and minimally invasive pectus excavatum repair. The aim of this study was to compare the surgical and hospitalization costs for these two surgical techniques and to identify factors responsible for cost differences. METHODS: A retrospective review of hospital charts, patient and parent questionnaires, and hospital accounting records was performed for 68 patients who underwent surgical correction of pectus excavatum between June 1996 and December 1999. RESULTS: In this series, 25 patients underwent open repair, whereas 43 patients underwent minimally invasive repair of pectus excavatum (MIRPE). The patient ages ranged from 4 to 19 years. The average ages for open repair (12 years) and MIRPE (11 years) did not differ significantly. As compared with open repair, MIRPE was associated with a 27% lower overall cost of hospitalization ( p < 0.05). The operating room costs were 12% higher for the patients who underwent MIRPE ( p < 0.05). The mean operative time for open repair was 3 h 15 min, whereas MIRPE required 1 h 10 min ( p < 0.001). The hospital stay for open repair averaged 4.4 days, as compared with 2.4 days for MIRPE ( p < 0.001). In contrast to other published series, the postoperative analgesia after MIRPE in this series consisted of narcotics, ketorolac, and methocarbamol. No patient received epidural analgesia, regardless of the repair technique selected. The postoperative complication rate was 4% in the open group and 14% in the MIRPE group. Most of the patients treated with either open or MIRPE reported postoperative oral narcotic usage for 2 weeks or less and returned to routine activities within 3 weeks. The patients and parents alike reported good to excellent overall outcomes in 85% or more of the open repair cases and 90% or more of the MIRPE cases. CONCLUSIONS: These data demonstrate for the first time that the use of an alternate pain management strategy including, narcotics, NSAIDs, and methocarbamol, but without epidural catheters, results in reduced hospital length of stay and decreased overall hospitalization costs for MIRPE, as compared with open pectus repair. This cost benefit was achieved without compromising pain management or patient satisfaction with surgical care.

The misconception of using floating patterns as an accurate means of measuring the contents of metered-dose inhaler devices.

BACKGROUND: Patients and physicians have searched for a reproducible method of determining the amount of medication that a metered-dose inhaler (MDI) contains as well as a reliable method of determining when their MDI is empty. Previously, patients have been instructed to float their canister in water, and depending upon the position attained, have been able to estimate the amount of medication within the canister. OBJECTIVE: To investigate whether the floating patterns of MDIs are a reliable method of determining the contents contained within an inhaler canister, including that of the newer devices containing the non-chlorofluorocarbon (CFC) propellant. METHODS: Fifteen albuterol sulfate MDIs (Proventil HFA; Schering, Kenilworth, NJ), 15 triamcinolone acetonide MDIs (Azmacort; Rhjne-Poulenc Rorer, Collegeville, PA), and 15 fluticasone propionate MDIs (Flovent; GlaxoSmith Kline, Research Triangle Park, NC) were obtained from their respective companies. Each device was floated in a clear container full of water before any actuations. The devices were then actuated into the air at 2-minute intervals and each subsequently floated following 25%, 50%, 75%, and 100% of the prescribed number of actuations and its position within the container observed. The canisters were then actuated until no visual spray was produced from the nozzle and again their floating positions within the container observed. RESULTS: Each of the three MDIs tested had unique floating patterns both before any actuation as well as throughout the various actuations. CONCLUSIONS: This study demonstrates that the floating method is not an accurate means by which patients can identify the amount of medication contained within an inhaler device. This includes both conventional MDIs containing CFC propellant, as well as the newer non-CFC MDIs.

The ability of the community pharmacist to learn the proper actuation techniques of inhaler devices.

Today, greater responsibility is placed on community pharmacists for the education of patients than ever before. Thus community pharmacists were recruited for this study and asked to demonstrate the proper steps in the actuation sequences of 3 inhaler devices. Baseline measurements were followed by an instructional session on the proper actuation technique, and then a posttest was conducted 4 to 6 weeks later. The mean changes between baseline and postinstruction percentage scores for the metered-dose inhaler device, the Turbuhaler, and the Diskus were (mean +/- SD) 17.1% +/- 15.4%, 22.6% +/- 18.7%, and 38.4% +/- 19.6%, respectively. This study demonstrates that a single instructional session can dramatically improve a community pharmacist's ability to demonstrate the correct method of actuation.

Orbital response indicates nasal pungency: analysis of biomechanical strain on the skin.

Stimulation of the human nasal passage with pungent vapor elicits motor responses in a zone around the eye. This investigation addressed whether quantification of such responses, particularly activity of the orbicularis oculi muscle, could yield a sensitive index of nasal pungency. We placed an array of small, high-contrast targets just beneath the lower eyelid and videotaped their movement to capture deformation of the skin atop the orbicularis oculi during 3 s stimulation with pungent concentrations of ethyl acetate. Eleven subjects participated. Analysis of the movements served to determine mechanical strain, which yielded a single index that we termed 'maximum strain'. This increased with concentration of the vapor and with time during and just after stimulation. Comparison with psychophysical data showed that the strain became evident at concentrations just detectable as pungent. Maximum strain measured on the skin shows promise as an objective index of pungency.

Ocular and nasal trigeminal detection of butyl acetate and toluene presented singly and in mixtures.

To probe into the rules of trigeminal chemosensory agonism in a binary mixture of chemicals we measured, first, the detectability (i.e., psychometric) function for eye irritation and for nasal pungency of butyl acetate and toluene, singly. (To avoid olfactory biases, nasal pungency was measured in a group of anosmics, i.e., persons lacking a functional sense of smell.) Then, based on the detectability function obtained for the individual chemicals, we prepared mixtures where the 2 components varied in their relative proportions but, if a simple rule of complete sensory agonism (in the sense of dose-additivity) were to hold, the mixtures should be as detectable as the reference concentration of each of the single chemicals. For both trigeminal endpoints (i.e., eye irritation and nasal pungency), the results showed that stimuli of relatively low detectability did show complete sensory agonism, whereas stimuli of relatively high detectability fell short of complete sensory agonism when compared with the detectability of the single substances. Further testing of additional binary and higher order mixtures will confirm whether or not a structure-activity model of trigeminal chemosensory impact of single chemicals, based on selected physicochemical parameters of the stimuli, can also be applied to chemical mixtures.

Human breathing and eye blink rate responses to airborne chemicals.

Increased levels of air pollution have been linked with morbidity and mortality, but mechanisms linking physiologic responses to quality of life and productivity issues remain largely unknown. Individuals often report irritation of the nose and/or eyes upon exposures to environmental contaminants. Evaluation of these self-reports would be greatly aided by the development of valid physiological markers. Chamber studies (unencumbered exposures) of nonsmoker responses to environmental tobacco smoke offer two candidate end points: (a) Tidal volume increases and breathing frequency declines with stimuli that elicit only moderate irritation. (b) Eye blink rate increases only with a concentration sufficiently high to cause progressive worsening of eye irritation with prolonged exposure. Experiments with very brief nasal-only presentations also suggest the value of breathing changes as sensitive markers of irritation: (a) Tidal volume is inversely related to perceived nasal irritation (NI) intensity in both normal and anosmic (lacking olfactory input) individuals, although normals exhibit greater NI sensitivity. (b) Inhalation duration, in both groups, declines only with trigeminal activation sufficient to cause readily perceptible NI in anosmics. Changes in eye blink rate and breathing may be useful in the investigation of irritation and other effects of air pollution, and could be quite useful in investigations of mixtures of volatile organic compounds.