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Clinical diagnosis of complex regional pain syndrome (CRPS) is a dichotomous (yes/no) categorization, a format necessary for clinical decision making. Such dichotomous diagnostic categories do not convey an individual's subtle gradations in the severity of the condition over time and have poor statistical power when used as an outcome measure in research. This prospective, international, multicenter study slightly modified and further evaluated the validity of the CRPS Severity Score (CSS), a continuous index of CRPS severity. Using a prospective design, medical evaluations were conducted in 156 patients with CRPS to compare changes over time in CSS scores between patients initiating a new treatment program and patients on stable treatment regimens. New vs stable categorizations were supported by greater changes in pain and function in the former. Results indicated that CSS values in the stable CRPS treatment group exhibited much less change over time relative to the new treatment group, with intraclass correlations nearly twice as large in the former. A calculated smallest real difference value revealed that a change in the CSS of ≥4.9 scale points would indicate real differences in CRPS symptomatology (with 95% confidence). Across groups, larger changes in CRPS features on the CSS over time were associated in the expected direction with greater changes in pain intensity, fatigue, social functioning, ability to engage in physical roles, and general well-being. The overall pattern of findings further supports the validity of the CSS as a measure of CRPS severity and suggests it may prove useful in clinical monitoring and outcomes research.

SummaryBackgroundDespite a scarcity of supporting evidence, most surgeons recommend routine interval appendicectomy after successful non-operative treatment of an appendix mass in children. We aimed to compare routine interval appendicectomy with active observation.MethodsWe enrolled participants in the CHildren's INterval Appendicectomy (CHINA) study, a multicentre, open-label, randomised controlled study at 19 specialist paediatric surgery centres, 17 of which were in the UK, one in Sweden, and one in New Zealand. 106 children aged 3–15 years were assigned (1:1) by weighted minimisation to interval appendicectomy or active observation with minimisation for age, trial centre, sex, and presence of a faecolith on imaging. Eligible children had acute appendicitis with an appendix mass and were successfully treated without appendicectomy or other surgical intervention. Children were excluded from the study if they had coexisting gastrointestinal disease or had a substantial coexisting medical condition or immune defect. Because of the nature of the interventions, blinding was not possible. The primary outcome was the proportion of children developing histologically proven recurrent acute appendicitis or a clinical diagnosis of recurrent appendix mass within 1 year of enrolment after successful non-operative treatment of appendix mass (active observation group) and incidence of severe complications related to interval appendicectomy. Data were analysed on an intention-to-treat basis. This study is registered with ISRCTN, number 93815412.FindingsBetween Aug 8, 2011, and Dec 31, 2014, we randomly assigned 106 patients, 52 patients to interval appendicectomy and 54 to active observation. Two children in the interval appendicectomy group were withdrawn due to withdrawal of consent; two in the active observation group were withdrawn because they became ineligible after allocation. Six children under active observation had histologically proven recurrent acute appendicitis. Three children in the interval appendicectomy group had severe complications. Thus, the proportion of children with histologically proven recurrent acute appendicitis under active observation was 12% (95% CI 5–23) and the proportion of children with severe complications related to interval appendicectomy was 6% (95% CI 1–17).InterpretationMore than three-quarters of children could avoid appendicectomy during early follow-up after successful non-operative treatment of an appendix mass. Although the risk of complications after interval appendicectomy is low, complications can be severe. Adoption of a wait-and-see approach, reserving appendicectomy for those who develop recurrence or recurrent symptoms, results in fewer days in hospital, fewer days away from normal daily activity, and is cheaper than routine interval appendicectomy. These high-quality data will allow clinicians, parents, and children to make an evidence-based decision regarding the justification for interval appendicectomy.FundingBUPA Foundation.

Statistical inference for analyzing the results from several independent studies on the same quantity of interest has been investigated frequently in recent decades. Typically, any meta-analytic inference requires that the quantity of interest is available from each study together with an estimate of its variability. The current work is motivated by a meta-analysis on comparing two treatments (thoracoscopic and open) of congenital lung malformations in young children. Quantities of interest include continuous end-points such as length of operation or number of chest tube days. As studies only report mean values (and no standard errors or confidence intervals), the question arises how meta-analytic inference can be developed. We suggest two methods to estimate study-specific variances in such a meta-analysis, where only sample means and sample sizes are available in the treatment arms. A general likelihood ratio test is derived for testing equality of variances in two groups. By means of simulation studies, the bias and estimated standard error of the overall mean difference from both methodologies are evaluated and compared with two existing approaches: complete study analysis only and partial variance information. The performance of the test is evaluated in terms of type I error. Additionally, we illustrate these methods in the meta-analysis on comparing thoracoscopic and open surgery for congenital lung malformations and in a meta-analysis on the change in renal function after kidney donation. Copyright © 2017 John Wiley & Sons, Ltd.

Bilious (dark green) vomiting in the newborn is a surgical emergency as the underlying diagnosis may be volvulus of the entire midgut secondary to malrotation. This diagnosis is time critical as, untreated, volvulus will lead to midgut necrosis, resulting in short gut syndrome or death. While a range of other diagnoses are possible, transfer to a paediatric surgical centre should be undertaken urgently so that malrotation/volvulus can be excluded or treated. This review focuses on the causes, investigation and management of proximal bowel obstruction in the neonate that present primarily with bilious vomiting.

Section I General Considerations.- 1. Reflex sympathetic dystrophy: Clinical features.- 2. Reflex sympathetic dystrophy: Incidence and epidemiology.- 3. Chronic pain mechanisms.- 4. Sympathetically maintained pain principles of diagnosis and therapy.- 5. Psychosomatic aspects of reflex sympathetic dystrophy.- Summary of Section I.- Section II Basic Researches in Pathophysiology of RSD.- 6. Pathobiology of reflex sympathetic dystrophy: Some general considerations.- 7. Spinal hyperexcitability in sympathetically maintained pain.- 8. Neuropharmacologies aspects of reflex sympathetic dystrophy.- 9. Clinical and neurophysiological observations relating to pathophysiological mechanisms of reflex sympathetic dystrophy.- 10. Mechanisms and role of peripheral blood flow dysregulation in pain sensation and edema in reflex sympathetic dystrophy.- Summary of Section II.- Section III Therapeutic Techniques in BSD.- 11. Sympathetic nerve blocks: Their role in sympathetic pain.- 12. Intravenous regional sympathetic blocks.- 13. Reflex sympathetic dystrophy - Neurosurgical approaches.- 14. Peripheral nerve stimulator implant for treatment of RSD.- 15. Psychological support of the patient with reflex sympathetic dystrophy.- 16. Reflex sympathetic dystrophy non-invasive methods of treatment.- 17. Multi-disciplinary management of reflex sympathetic dystrophy.- Summary of Section III.- Section IV New Techniques.- 18. Three-phase bone scanning in reflex sympathetic dystrophy.- 19. An investigation of the role of clonidine in the treatment of reflex sympathetic dystrophy.- Summary of Section IV.- Summary Comments.- Proposed Definition of Reflex Sympathetic Dystrophy.

There is a paucity of data on outcomes and complications of colectomy for pediatric ulcerative colitis (UC). This study reports the experience of a regional center for 18years.Patients were identified from a prospective database and data obtained by note review. Median height/weight-SDS were calculated preoperatively and postoperatively. Data are expressed as median values (range).220 patients with UC (diagnosed17years) were identified, and 19 (9%) had undergone colectomy. Age at diagnosis was 11.6years (1.3-16.5), and 42% of patients were male. Time from diagnosis to surgery was 2.2years (0.1-13.1). All patients had failed maximal medical therapy. Fifteen patients had urgent scheduled operation, and 4 had emergency procedures, with 2 for (11%) acute-severe colitis (1 Clostridium difficile colitis) and 2 for acute-severe colitis with toxic dilatation. All initial procedures were subtotal-colectomy with ileostomy. Nine patients (47%) had early complications (during initial admission), 7 (37%) requiring reoperation. Six (32%) had late complications, with 5 requiring laparotomy. No patients had both early and late complications. Height-SDS was -0.27 before surgery and -0.23 (maximal follow-up). Weight-SDS was 0.32 and 0.05 (maximal follow-up).Approximately 1/11 children with UC required colectomy during childhood. Half of patients had acute complications, and 1/3 of patients required another operation during their first admission. 1/3 of patients developed late complications.

Background: anti-tumour necrosis factor-α (anti-TNF) therapy use has risen in paediatric-onset inflammatory bowel disease (PIBD). Whether this has translated into preventing/delaying childhood surgery is uncertain. The Wessex PIBD cohort were analysed for trends in anti-TNF-therapy and surgery. Design: all patients diagnosed with PIBD within Wessex from 1997-2017 were assessed. Prevalence of anti-TNF-therapy and yearly surgery rates (resection and perianal) during childhood (

This account of the condition now termed complex regional pain syndrome (CRPS) spans approximately 462 years since a description embodying similar clinical features was described by Ambroise Paré in 1557. While reviewing its historical origins, the text describes why it became necessary to change the taxonomies of two clinical syndromes with similar pathophysiologies to one which acknowledges this aspect but does not introduce any mechanistic overtones. Discussed at length is the role of the sympathetic component of the autonomic nervous system (ANS) and why its dysfunction has both directly and indirectly influenced our understanding of the inflammatory aspects of CRPS. As the following article will show, our knowledge has expanded in an exponential fashion to include musculoskeletal, immune, autoimmune, central and peripheral nervous system and ANS dysfunction, all of which increase the complexity of its clinical management. A burgeoning literature is beginning to shed light on the mechanistic aspects of these syndromes and the increasing evidence of a genetic influence on such factors as autoimmunity, and its importance is also discussed at length. An important aspect that has been missing from the diagnostic criteria is a measure of disease severity. The recent validation of a CRPS Severity Score is also included.

Sensory disturbances often spread beyond the site of injury in complex regional pain syndrome (CRPS) but whether this applies equally to CRPS I and II, or changes across the course of the disease, is unknown. Establishing this is important, because different symptom profiles in CRPS I and II, or in acute vs chronic CRPS, might infer different pathophysiology and treatment approaches. To explore these questions, sensory disturbances were assessed in the limbs and forehead of 71 patients with CRPS I and 33 patients with CRPS II. Pain had persisted up to 12 months in 32 patients, for 13 to 36 months in 29 patients, and for longer than this in 43 patients. Patients with CRPS I were more likely to be female, and pain was more likely to be present in an additional limb, than patients with CRPS II. Conversely, pain was more likely to be associated with sensory deficits and allodynia in patients with CRPS II than CRPS I. Nevertheless, heightened sensitivity, allodynia, and/or hyperalgesia to mechanical and thermal stimuli were detected in a hemisensory distribution ipsilateral to the affected limb in both forms of CRPS. Some of these hemisensory disturbances strengthened with chronicity of pain. These findings suggest that heightened excitability of nociceptive pathways in CRPS spreads to hemisensory convergence points in the brainstem or higher brain centres, possibly in association with compromised pain controls. The similarity of symptom profiles in chronic CRPS I and II implies shared mechanisms despite different triggers.

Two factors determine the outcome of peripheral nerve stimulation (PNS), namely the anatomy of the peripheral nerve and its physiologic response. The morphology of peripheral nerves described in this chapter suggests the manner by which a technical interface can deliver its electrical energy to a target nerve. The opportunities and limitations of PNS, reflecting on more than 40 years' observation, should be clear from this account. The final arbiter, the Hodgkin–Huxley neural tissue response to applied electric fields, is inextricably bound up with the anatomy and physiology of the peripheral nerve.

This chapter turns to the history of the beginnings of the societies that are important to the founding of a medically relevant paradigm, in this instance, neuromodulation. The International Neuromodulation Society (INS) was founded as an offshoot of the World Society of Functional and Stereotactic Neurosurgery (WSSFN), a society of neurosurgeons most interested in stereotactic surgery for cancer and functional neurosurgery, and Dr. Konstantin Slavin, past president of the American Society of Functional and Stereotactic Neurosurgery and secretary-treasurer of the WSSFN, will discuss the founding and beginnings of this society, followed by perspectives on the founding and beginnings of the INS by two of its past presidents, Dr. Giancarlo Barolat of the United States and Mr. Brian Simpson of Wales in the United Kingdom. Finally, because of its importance to the INS (largest and first INS chapter), I have asked Dr. Michael Stanton-Hicks to reminisce on the beginnings North American Neuromodulation Society.

BACKGROUND AND AIM: Acute severe colitis (ASC) is one of the few emergencies in pediatric gastroenterology. Tight monitoring and timely medical and surgical interventions may improve outcomes and minimize morbidity and mortality. We aimed to standardize daily treatment of ASC in children through detailed recommendations and practice points which are based on a systematic review of the literature and consensus of experts. METHODS: These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Fifteen predefined questions were addressed by working subgroups. An iterative consensus process, including 2 face-to-face meetings, was followed by voting of the national representatives of ECCO and all members of the Paediatric Inflammatory Bowel Disease (IBD) Porto group of ESPGHAN (43 voting experts). RESULTS: A total of 24 recommendations and 43 practice points were endorsed with a consensus rate of at least 91% regarding diagnosis, monitoring, and management of ASC in children. A summary flowchart is presented based on daily scoring of the Paediatric Ulcerative Colitis Activity Index. Several topics have been altered since the previous 2011 guidelines and from those published in adults. DISCUSSION: These guidelines standardize the management of ASC in children in an attempt to optimize outcomes of this intensive clinical scenario.

Complex regional pain syndrome (CRPS) has specific diagnostic criteria which set it apart from many pain syndromes. Thus CRPS patients can be studied to evaluate the efficacy of various interventions. Neurostimulation is an intervention that has been studied extensively in a variety of pain syndromes, demonstrating both safety and efficacy. This chapter provides a perspective on CRPS and gives a detailed description of the efficacy of neurostimulation for this syndrome. Since the publication of the last edition of this book, the only set of validated diagnostic criteria has been published. This has led to greater public awareness of CRPS and the development of more aggressive treatment for the syndrome. There is now approval for neurostimulation treatment specifically to address the problem of CRPS. With the above as a backdrop, this chapter reviews the literature evaluating the use of neurostimulation to treat CRPS and the novel therapies that have emerged during the last decade.

Congenital lung malformations comprise a group of anatomical abnormalities of the respiratory tree including congenital cystic malformations, bronchopulmonary sequestrations, bronchogenic cyst, bronchial atresia, and congenital lobar emphysema. These anomalies are detected with increasing frequency by pre-natal sonography, but may also present for the first time with symptoms in childhood or later life. When symptomatic, there is little controversy that resection is indicated, which is usually curative. When a lesion is asymptomatic there is greater debate regarding the benefit of resection versus continued observation. This article provides an overview of the spectrum of disorders, the management options available and the long-term outcomes associated with each treatment option.

The feasibility of utilising bacteria as vectors for gene therapy is becoming increasingly recognised. This is primarily due to a number of intrinsic properties of bacteria such as their tumour targeting capabilities, their ability to carry large genetic or protein loads and the availability of well-established genetic engineering tools for a range of common lab strains. However, a number of issues relating to the use of bacteria as vectors for gene therapy need to be addressed in order for the field to progress. Amongst these is the need for the development of non-invasive detection/imaging systems for bacteria within a living host. In vivo optical imaging has advanced preclinical research greatly, and typically involves engineering of bacteria with genetic expression constructs for luminescence (e.g. the lux operon) or fluorescent proteins (GFP etc.). This requirement for genetic modification can be restrictive, where engineering is not experimentally appropriate or technologically feasible (e.g. due to lack of suitable engineering tools). We describe a novel strategy exploiting endogenous bacterial enzymatic activity to specifically activate an exogenously administered fluorescent imaging probe. The red shifted, quenched fluorophore CytoCy5S is reduced to a fluorescent form by bacterial-specific nitroreductase (NTR) enzymes. NTR enzymes are present in a wide range of bacterial genera and absent in mammalian systems, permitting highly specific detection of Gram-negative and Gram-positive bacteria in vivo. In this study, dose-responsive bacterial-specific signals were observed in vitro from all genera examined - E. coli, Salmonella, Listeria, Bifidobacterium and Clostridium difficile. Examination of an NTR-knockout strain validated the enzyme specificity of the probe. In vivo whole-body imaging permitted specific, dose-responsive monitoring of bacteria over time in various infection models, and no toxicity to bacteria or host was observed. This study demonstrates the concept of exploiting innate NTR activity as a reporting strategy for wild-type bacteria using optical imaging, while the concept may also be extended to NTR-specific probes for use with other imaging modalities.

Acromioclavicular (AC) joint separation is a common injury seen in the young adult athletic population. Both the indications for surgical management and the best operative technique remain controversial. One of the most popular reconstruction techniques is the anatomic double-tunnel coracoclavicular (CC) ligament reconstruction. However, there have been several case reports of clavicle fractures with this technique. This article presents a single-tunnel reconstruction technique that aims to restore both the CC and AC ligament function, while minimizing fracture risk.

Aim To develop a paediatric endoscopy GRS (P-GRS) as a quality improvement tool which would also define standards for accreditation of paediatric endoscopy services. Methods A P-GRS working group was established in May 2015 and the membership of this group evolved to include representatives from the BSPGHAN endoscopy working group, district general hospital, paediatric surgery, allied health professional, and specialist input from the Joint Advisory Group in GI endoscopy. A draft P-GRS was developed following extensive discussion and communication between the P-GRS working group and the JAG and revised following a consultation period. Nine sites nationally piloted the P-GRS following a training day organised by JAG. Services are required to score a Level B in all standards. The first assessment against the P-GRS was completed in June 2016.A second assessment is to be completed in December 2016 and the results of this will be available before the meeting to present. Results Eight of the nine pilot sites completed a GRS assessment in June 2016. In the clinical quality domain, 12% of units achieved a level B or above in the leadership and organisation standard, 25% in safety, 63% in comfort, 25% in quality, 38% in appropriateness and 50% in results. In the quality of patient experience domain, 38% of the units achieved a level B or above in the respect and dignity standard, 24% in the consent process, 38% in the patient environment and equipment, 12% in access and booking, none in productivity and planning, 38% in aftercare and none in patient involvement. In the workforce domain, 12% of the units achieved a level B or above in the teamwork standards, 26% in workforce delivery, 38% in professional development. In the training domain, none of the units achieved a level B or above. Conclusion These results highlight a need for improvement and all pilot units agreed this was a positive experience which enabled the units to develop an action plan and share good practice. All pilot sites reflected on the measures in the P-GRS to ensure they were relevant to paediatric endoscopy services and fit for purpose.

Alcohol and drug addiction are major problems in today’s society, and specifically in the state of West Virginia. Chronic alcohol exposure has been shown to have various effects on cell proliferation, apoptosis, and DNA damage through oxidative stress. Neuronal stem cell populations in the adult brain help to support neuroplasticity improving short and long term memory. Chronic alcohol exposure reduces stem cell populations and suggests a link between alcoholism treatment paradigms and the damage induced to stem cells during use. Previous studies show as much as 40% reduction in stem cell numbers from chronic alcohol use and many cells experience substantial DNA damage. However, the mechanism repair mechanism used by exposed cells to repair DNA lesions is unknown. This study analyzes expression and localization of the CSB (ERCC6) protein responsible for recruitment and imitation of a Nucleotide Excision Repair (NER) mechanism necessary in DNA repair. Both alcohol treated and control stem cells were examined by immune-cytochemistry and western blot in order to analyze variations in protein expression and nuclear localization. We demonstrate changes in expression and increased localization to alcohol induced DNA lesions. This demonstrates a possible mechanism for Cellular losses in adult alcoholism.

CONTEXT:Nonoperative treatment (NOT) with antibiotics alone of acute uncomplicated appendicitis (AUA) in children has been proposed as an alternative to appendectomy.OBJECTIVE:To determine safety and efficacy of NOT based on current literature.DATA SOURCES:Three electronic databases.STUDY SELECTION:All articles reporting NOT for AUA in children.DATA EXTRACTION:Two reviewers independently verified study inclusion and extracted data.RESULTS:Ten articles reporting 413 children receiving NOT were included. Six, including 1 randomized controlled trial, compared NOT with appendectomy. The remaining 4 reported outcomes of children receiving NOT without a comparison group. NOT was effective as the initial treatment in 97% of children (95% confidence interval [CI] 96% to 99%). Initial length of hospital stay was shorter in children treated with appendectomy compared with NOT (mean difference 0.5 days [95% CI 0.2 to 0.8]; P = .002). At final reported follow-up (range 8 weeks to 4 years), NOT remained effective (no appendectomy performed) in 82% of children (95% CI 77% to 87%). Recurrent appendicitis occurred in 14% (95% CI 7% to 21%). Complications and total length of hospital stay during follow-up were similar for NOT and appendectomy. No serious adverse events related to NOT were reported.LIMITATIONS:The lack of prospective randomized studies limits definitive conclusions to influence clinical practice.CONCLUSIONS:Current data suggest that NOT is safe. It appears effective as initial treatment in 97% of children with AUA, and the rate of recurrent appendicitis is 14%. Longer-term clinical outcomes and cost-effectiveness of NOT compared with appendicectomy require further evaluation, preferably in large randomized trials, to reliably inform decision-making.

Laparoscopic-assistance for Hirschsprung disease (HD) pullthrough procedures has increased in popularity. This change has been associated in the UK, for example, with a shift from the Duhamel procedure, which had been performed most frequently, to an endorectal pull-through (ERPT) procedure that is being practiced more widely [1]. The concept of the transanal only approach was put forth by Langer and de la Torre, but this was using a Soave-like dissection, a problem noted by Swenson himself who originated this concept with the original repair for HD [2]. The use of the Swenson-like technique for ERPT has been popularized by Levitt and colleagues [3], who reported a series of 67 patients in 2013. The advantages of this approach are its simplicity, preservation of the pelvic nerves, and avoidance of the obstructing muscle cuff that may occur after the Soave-Boley procedure [4]. The procedure can be undertaken as a purely transanal operation for cases in which rectosigmoid aganglionosis is obvious from the contrast study, but initial laparoscopic colonic mobilization and biopsy are preferred in most cases.

Introduction The International Neuromodulation Society (INS) has determined that there is a need to provide an expert consensus that defines the appropriate use of neuromodulation technologies for appropriate patients. The Neuromodulation Appropriateness Consensus Committee (NACC) was formed to give guidance to current practice and insight into future developments. Methods The INS executive board selected members of the international scientific community to analyze scientific evidence for current and future innovations and to use clinical experience to fill in any gaps in information. The NACC used PubMed and Google Scholar to obtain current evidence in the field and used clinical and research experience to give a more complete picture of the innovations in the field. Results The NACC has determined that currently approved neurostimulation techniques and technologies have expanded our ability to treat patients in a more effective and specific fashion. Despite these advances, the NACC has identified several additional promising technologies and potential applications for neurostimulation that could move this field forward and expand the applicability of neuromodulation. Conclusions The NACC concludes that the field of neurostimulation is an evolving and rapidly changing one that will lead to improved patient access, safety, and outcomes.

Objective An international panel of pain specialists (anesthesiology, neurology, neurosurgery, and psychology) and research methodologists developed a screening tool to identify patients who may be suitable for spinal cord stimulation (SCS)—the Refractory Chronic Pain Screening Tool (RCPST) prototype. We describe a feasibility study to explore practicality and validity of this prototype. Design Consecutive outpatients were screened in two centers (United Kingdom and United States). Sixty chronic pain adults without satisfactory pain relief despite treatment were assessed using RCPST (by pain specialist without expertise in neurostimulation) and then evaluated by two pain specialists experienced in SCS implantation and management to determine whether the patient should be referred for SCS. To maintain blinding, the participating physicians did not inform each other or the patient of assessment outcome. Sensitivity and specificity of the RCPST prototype were calculated using implanters' judgment as “gold standard.” Results The average age of patients was 47.7 years; 53% were female. Fifty-seven patients completed the study (one withdrew consent, two lost to follow-up). The pain specialists agreed the prototype was easy to use and took

Cannabis is a substance that contains compounds that bind cannabinoid receptors, CB1 and CB2. Cannabis also contains substances that do not bind these receptors. Delta-9-tetrahydrocannabinol (THC) is the compound in cannabis responsible for its psychoactive effects and binding to cannabinoid receptors. Despite increasing popularity of the medical and recreational uses of cannabis, little attention has been paid to the adverse effects of the use of the substance. Evidence demonstrating an association between cannabis use and acute coronary syndromes has emerged with case reports and in vitro studies. This case report highlights an ST-segment myocardial infarction in a 27-year-old female with little cardiovascular risk factors, but a significant history of frequent cannabis use.

Some patients with chronic pain who are intolerant of or refractory to treatment with systemic analgesics may benefit from intrathecal therapy. Ziconotide is the first nonopioid analgesic approved by the United States Food and Drug Administration for intrathecal administration. Several randomized, double-blind, placebo-controlled clinical trials have demonstrated the efficacy and safety of ziconotide. However, the maximum recommended dosing and titration schedule provided in the prescribing information may be too aggressive for some patients, and experience has demonstrated that ziconotide is better tolerated with slower titration to a lower maximum dose. Efficacy can be assessed by an evaluation of changes in pain, functionality, and quality of life. Cognitive adverse events may be subtle; therefore, it is important that health care professionals not only monitor patients for signs and symptoms of cognitive adverse events, but also teach family members how to do the same. Careful patient assessment and monitoring can help optimize the potential benefit from treatment with ziconotide.

Chondral defects of the knee are quite common, affecting an estimated 10% to 12% of the population. Symptomatic chondral defects are thought to be persistent and possibly progressive. Less is known about the natural history of asymptomatic chondral lesions. Traditional treatment of chondral lesions has involved arthroscopic debridement with a mechanical shaver. Radiofrequency chondroplasty has been explored as a possible alternative or adjuvant to mechanical chondroplasty. The role of chondroplasty in the setting of knee osteoarthritis is more controversial. Early studies demonstrated promising results of arthroscopic debridement in the context of knee arthritis. However, publications in the last 10 to 15 years have brought into question the role of arthroscopic debridement in the setting of knee osteoarthritis. The purpose of this chapter is to explore the role of arthroscopic debridement in the treatment of chondral defects.

Statistical inference for analyzing the results from several independent studies on the same quantity of interest has been investigated frequently in recent decades. Typically, any meta-analytic inference requires that the quantity of interest is available from each study together with an estimate of its variability. The current work is motivated by a meta-analysis on comparing two treatments (thoracoscopic and open) of congenital lung malformations in young children. Quantities of interest include continuous end-points such as length of operation or number of chest tube days. As studies only report mean values (and no standard errors or confidence intervals), the question arises how meta-analytic inference can be developed. We suggest two methods to estimate study-specific variances in such a meta-analysis, where only sample means and sample sizes are available in the treatment arms. A general likelihood ratio test is derived for testing equality of variances in two groups. By means of simulation studies, the bias and estimated standard error of the overall mean difference from both methodologies are evaluated and compared with two existing approaches: complete study analysis only and partial variance information. The performance of the test is evaluated in terms of type I error. Additionally, we illustrate these methods in the meta-analysis on comparing thoracoscopic and open surgery for congenital lung malformations and in a meta-analysis on the change in renal function after kidney donation. Copyright © 2017 John WileySons, Ltd.

Limited research suggests that there may be Warm complex regional pain syndrome (CRPS) and Cold CRPS subtypes, with inflammatory mechanisms contributing most strongly to the former. This study for the first time used an unbiased statistical pattern recognition technique to evaluate whether distinct Warm vs Cold CRPS subtypes can be discerned in the clinical population. An international, multisite study was conducted using standardized procedures to evaluate signs and symptoms in 152 patients with clinical CRPS at baseline, with 3-month follow-up evaluations in 112 of these patients. Two-step cluster analysis using automated cluster selection identified a 2-cluster solution as optimal. Results revealed a Warm CRPS patient cluster characterized by a warm, red, edematous, and sweaty extremity and a Cold CRPS patient cluster characterized by a cold, blue, and less edematous extremity. Median pain duration was significantly (P < 0.001) shorter in the Warm CRPS (4.7 months) than in the Cold CRPS subtype (20 months), with pain intensity comparable. A derived total inflammatory score was significantly (P < 0.001) elevated in the Warm CRPS group (compared with Cold CRPS) at baseline but diminished significantly (P < 0.001) over the follow-up period, whereas this score did not diminish in the Cold CRPS group (time × subtype interaction: P < 0.001). Results support the existence of a Warm CRPS subtype common in patients with acute (

Summary Background With the Nordic consensus statement advocating orchidopexy at an earlier age, the present study sought to investigate the outcomes of primary paediatric orchidopexy at a tertiary UK centre. Objective To prospectively assess testicular atrophy following primary orchidopexy for undescended testes in a paediatric population. Secondary outcomes were complication rates and whether outcomes were dependent on grade of operating surgeon. Study design Prospective data regarding age at operation, classification of the undescended testis, length of follow-up, and subjective comparison of intraoperative and postoperative testicular volumes compared with the contralateral testis were collected. Testicular atrophy was defined as >50% loss of testicular volume or a postoperative testicular volume Results Data for 234 patients were analysed. Testicular atrophy occurred in 2.6% of cases. There was no reported testicular re-ascent. All secondary acquired cases underwent a previous ipsilateral hernia repair. There was no significant difference in outcomes comparing the grade of surgeon (consultant n = 8, trainee/staff-grade surgeon n = 7–8). There was a trend towards postoperative catch-up growth in approximately one fifth of cases. Discussion Previous studies have reported a testicular atrophy rate of 5%. The present study reported a similar rate of 2.6%. In agreement with a previous publication, it was also found that testicular atrophy was not dependent on the grade of operating surgeon. The mechanism for testicular catch-up growth is not well understood. Animal studies have supported the hypothesis that increased temperature has a detrimental effect on testicular volume. However, follow-up in the present cohort was short (median 6.9 months), making interpretation of this finding difficult. It is acknowledged that clinical palpation alone to determine testicular volume potentially introduces intra-observer and inter-observer error. However, prospective studies using ultrasound to determine testicular volumes following orchidopexy have reported catch-up growth. Conclusion This study represented one of the larger collections of prospective assessments of outcomes following primary orchidopexy. It was acknowledged that subjectively assessing testicular volume is not ideal; however, the data correlated with similar studies. Table . Testicular atrophy grouped by aetiology of undescended testis. Aetiology of undescended testis Age at operation, years (median) Length of follow-up, months (median) Testicular atrophy rate Overall (n = 234) 2.2 6.9 6 (2.6%) Congenital (n = 209) 1.8 7.1 6 (2.9%) Primary acquired (n = 21) 8.7 6.5 0% Secondary acquired (n = 4) 4.5 6.4 0%

Introduction: Targeted intrathecal drug infusion to treat moderate to severe chronic pain has become a standard part of treatment algorithms when more conservative options fail. This therapy is well established in the literature, has shown efficacy, and is an important tool for the treatment of both cancer and noncancer pain; however, it has become clear in recent years that intrathecal drug delivery is associated with risks for serious morbidity and mortality. Methods: The Polyanalgesic Consensus Conference is a meeting of experienced implanting physicians who strive to improve care in those receiving implantable devices. Employing data generated through an extensive literature search combined with clinical experience, this work group formulated recommendations regarding awareness, education, and mitigation of the morbidity and mortality associated with intrathecal therapy to establish best practices for targeted intrathecal drug delivery systems. Results: Best practices for improved patient care and outcomes with targeted intrathecal infusion are recommended to minimize the risk of morbidity and mortality. Areas of focus include respiratory depression, infection, granuloma, device-related complications, endocrinopathies, and human error. Specific guidance is given with each of these issues and the general use of the therapy. Conclusions: Targeted intrathecal drug delivery systems are associated with risks for morbidity and mortality that can be devastating. The panel has given guidance to treating physicians and healthcare providers to reduce the incidence of these problems and to improve outcomes when problems occur.

Introduction: Continuous intrathecal infusion of drugs to treat chronic pain and spasticity has become a standard part of the algorithm of care. The use of opioids has been associated with noninfectious inflammatory masses at the tip of the intrathecal catheter, which can result in neurologic complications. Methods: The Polyanalgesic Consensus Conference is a meeting of a group of well-published and experienced practitioners; the purpose of the meeting is to update the standard of care for intrathecal therapies to reflect current knowledge gleaned from literature and clinical experience. An exhaustive literature search was performed, and information from this search was provided to panel members. Analysis of the published literature was coupled with the clinical experience of panel participants to form recommendations regarding intrathecal inflammatory masses or granulomas. Results: The panel has made recommendations for the prevention, diagnosis, and management of intrathecal granulomas. Conclusion: The use of chronic infusions of intrathecal opioids is associated with the formation of inflammatory masses at the intrathecal catheter tip in a small minority of treated patients. Nonetheless, the appearance of these space-occupying lesions can lead to devastating neurologic sequelae. The prevention, early detection, and successful treatment of intraspinal granulomas are important considerations when offering intrathecal drug therapy to patients with chronic intractable pain.

Introduction: C8-root impingement by C7/T1 lesions on neuroimaging studies is not consistently observed in C8 radiculopathy. We hypothesized that C7 or T1 root lesions (with a pre- or postfixed plexus) or cervical myelopathy might explain some “C8 radiculopathies” without C8 root compression. Methods: Retrospective analysis of cervical neuroimaging in 31 consecutive patients with EMG-confirmed C8 radiculopathy. Results: Five patients (16%) had C8-root compression at C7/T1. Of those without C8-root compression, 5 (16%) had C7-root compression at C6/7, one (3%) had T1-root compression at T1/T2, 7 (23%) had cervical cord compression at or above the C6/7 level, 4 (13%) had intramedullary cervical lesions, and 9 (29%) had mild or nonspecific findings. Conclusions: C8 radiculopathy without C8-root compression may be due to C7-root compression in the setting of a “prefixed” brachial plexus, upper cervical cord compression with vascular compromise of the distal cervical spinal cord (“myelopathic hand”), or intramedullary cervical cord lesions. Muscle Nerve 45: 859–865, 2012

Introduction Spinal cord stimulation (SCS) is frequently used to treat chronic, intractable back, and leg pain. Implantation can be accomplished with percutaneous leads or paddle leads. Although there is an extensive literature on SCS, the long-term efficacy, particularly with paddle leads, remains poorly defined. Outcome measure choice is important when defining therapeutic efficacy for chronic pain. Numerical rating scales such as the NRS-11 remain the most common outcome measure in the literature, although they may not accurately correlate with quality of life improvements and overall satisfaction. Methods We reviewed the medical records of patients with failed back surgery syndrome (FBSS) or complex regional pain syndrome (CRPS) implanted with SCS systems using paddle leads between 1997 and 2008 at the Cleveland Clinic with a minimum six-month follow-up. Patients were contacted to fill out a questionnaire evaluating outcomes with the NRS-11 as well as overall satisfaction. Results A total of 35 eligible patients chose to participate. More than 50% of the patients with CRPS reported greater than 50% pain relief at a mean follow-up of 4.4 years. Approximately 30% of the FBSS patients reported a 50% or greater improvement at a mean follow-up of 3.8 years. However, 77.8% of patients with CRPS and 70.6% of patients with FBSS indicated that they would undergo SCS surgery again for the same outcome. Conclusion Patients with CRPS and FBSS have a high degree of satisfaction, indexed as willingness to undergo the same procedure again for the same outcome at a mean follow-up of approximately four years. The percentage of satisfaction with the SCS system is disproportionally greater than the percentage of patients reporting 50% pain relief, particularly among patients with FBSS. This suggests that the visual analog scale may not be the optimal measure to evaluate long-term outcomes in this patient population.

The aesthetic potentials of 4K digital cinema are an impetus for creative practitioners of cinematic arts to undertake full investigations of the methods and expressive possibilities of this end-to-end digital medium. This includes new approaches to production, distribution and the forum of theatrical experience. A group of artists, film-makers and computer scientists have been developing a series of 4K digital cinema projects that have diffused and grown the manner in which 4K cinema is experienced between Brazil, the US and Japan. The recent culmination of this was an event in July 2009 in which a 4K feature length movie had its world premiere on three continents, streamed from Brazil to the US and Japan. This was accompanied by an HD video teleconference (VTC) between the three sites. To the knowledge of the participants, this was both the first uncompressed HD VTC between the northern and southern hemispheres as well as the first feature length 4K film to be streamed across three continents. Through this work, the new creative affordances of 4K cinema were highlighted, along with the new capabilities of cinematic distribution, production and experience.

Objectives: Neuromodulation with spinal cord stimulation has become an increasingly employed intervention for treatment of a variety of neuropathic pain states. As prevalence increases, so does the incidence of complications. Currently, there is sparse literature describing spinal cord stimulation lead placement and stimulation characteristics in the subdural space. In this case report we describe subdural lead placement and the associated stimulation parameters, and provide evidence-based support to initiate a dialog to further reduce procedural morbidity and mortality. Materials and Methods: This study is a case report following lead placement during permanent percutaneous spinal cord stimulator placement and stimulation testing. The lead placement and stimulation characteristics were suggestive of extra-epidural lead placement. Results: Using the same cathode/anode configuration (1:anode, 3:cathode, 5:anode), frequency of 40 Hz and pulse width of 650 microseconds, sequential stimulation was performed. Summarizing, the testing demonstrated similar impedance for the left and right leads (within 30 ohms) of approximately 300 ohms, and a large discrepancy in current of 3.2 mA for the left and 0.9 mA for the right. The patient reported “painful intense” stimulation with right lead stimulation. Conclusions: Evidence suggesting subdural lead placement include the lack of cerebrospinal-fluid despite lavage, the absence of post-dural puncture headache, the recent evidence of intentional and reproducible subdural anesthesia, and the conductive properties of the dural spinal elements. It can be argued that subdural lead placement may occur unrecognized more frequently than originally anticipated.

Grids currently in production can be broadly classified as either service Grids, composed of dedicated resources, or opportunistic Grids that harvest the computing power of non-dedicated resources when they are idle. While a service Grid provides high and well defined levels of quality of service, an opportunistic Grid provides only a best-effort service. Nevertheless, since opportunistic Grids do not require resources to be fully dedicated to the Grid, they have the potential to assemble a much larger number of resources. Moreover, these Grids cater very well to the execution of the so-called embarrassingly parallel applications, a type of application that is frequently found in practice, and that comprises the largest portion of the typical workload processed in production Grid systems. The EELA-2 e-infrastructure is comprised of a service Grid and an opportunistic Grid that federates computing resources from scientific institutions in both Europe and Latin America. Due to the complementary characteristics of these two types of Grids, a lot of attention has recently been placed in how to interoperate them. In this paper we focus on the less studied problem of assessing the feasibility of such interoperation. We analyse different prioritisation policies that define when the resources of one Grid can be used to run jobs originating from the other. Our results show that in the absence of a suitable prioritisation policy, the benefits that the users of one Grid may have, frequently come with an important negative impact on the users of the other Grid. We also show that a simple reciprocation mechanism is capable of arbitrating the interoperation in such a way that, whenever possible, users profit from the interoperation and, in no case, this benefit leads to a noticeable reduction on the quality of service that the users would experience were the Grids not to interoperate. We conclude discussing how we have implemented, in the context of the EELA-2 project, this prioritisation mechanism, allowing the effective interoperation of a service Grid based on the gLite middleware with an opportunistic Grid that uses the OurGrid middleware.

Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy is a pain syndrome with an unclear pathophysiology and unpredictable clinical course. The disease is often therapy resistant, the natural course not always favorable. The diagnosis of CRPS is based on signs and symptoms derived from medical history and physical examination. Pharmacological pain management and physical rehabilitation of limb function are the main pillars of therapy and should be started as early as possible. If, however, there is no improvement of limb function and persistent severe pain, interventional pain management techniques may be considered. Intravenous regional blocks with guanethidine did not prove superior to placebo but frequent side effects occurred.Therefore this technique receives a negative recommendation (2 A-). Sympathetic block is the interventional treatment of first choice and has a 2 B+ rating. Ganglion stellatum (stellate ganglion) block with repeated local anesthetic injections or by radiofrequency denervation after positive diagnostic block is documented in prospective and retrospective trials in patients suffering from upper limb CRPS. Lumbar sympathetic blocks can be performed with repeated local anesthetic injections. For a more prolonged lumbar sympathetic block radiofrequency treatment is preferred over phenol neurolysis because effects are comparable whereas the risk for side effects is lower (2 B+). For patients suffering from CRPS refractory to conventional treatment and sympathetic blocks, plexus brachialis block or continuous epidural infusion analgesia coupled with exercise therapy may be tried (2 C+). Spinal cord stimulation is recommended if other treatments fail to improve pain and dysfunction (2 B+). Alternatively peripheral nerve stimulation can be considered, preferentially in study conditions (2 C+).

Complex regional pain syndrome I (CRPS I) is defined by the International Association for the Study of Pain (IASP) criteria to include pain that is disproportionate to the inciting event, sensory disturbances such as allodynia/ hyperalgesia, autonomic dysfunction, and motor dysfunction that usually occurs after trauma that is frequently trivial and generally expressed in an extremity. These symptoms are well described in the adult population, but there are relatively few data or reports of its prevalence in the pediatric population. Recent studies have demonstrated that unlike the adult population, about 90% of the cases reported are females in a range of 8 to 16 years, the youngest being 3 years old. There tends to be delay in recognizing the diagnosis, which may be as long as 4 months. In contrast to adults, the response to treatment, particularly exercise therapy with behavioral management will achieve almost 97% remission. While the pathophysiology is poorly understood, many features, particularly the neurologic abnormalities, suggest both peripheral and central nervous system involvement. Peripheral small fiber neuropathy as an etiology and inflammation involving small nerve fibers (neurogenic inflammatory pain) has been suggested. A tissue inflammatory etiology has been investigated over the past 25 years. However, these inflammatory aspects differ from those seen in other conditions involving tissue inflammation. The suggestion that CRPS in children is a different clinical entity than that seen in the adult, is probably incorrect, as recent evidence would suggest that the pathophysiology is most likely identical involving endocrine, behavioral, developmental, and environmental factors that distinguish clinical presentation in children from the adult. Behavioral management is a mandatory accompaniment of any program of exercise therapy and the sometimes extreme sensory disturbances and parental enmeshment do distinguish the clinical presentation from that in the adult. Interventional procedures may be required in the face of extreme allodynia preventing exercise therapy, and in occasional cases interruption of the sympathetic nerves may reverse this symptom in a few children. Occasionally, continuous analgesia techniques such as that which can be delivered by tunneled epidural catheter or an externalized neurostimulator (spinal cord stimulation) for short periods of time are effective.

(Headache 2010;50:1164-1174) Introduction.— Cluster headaches (CH) are primary headaches marked by repeated short-lasting attacks of severe, unilateral head pain and associated autonomic symptoms. Despite aggressive management with medications, oxygen therapy, nerve blocks, as well as various lesioning and neurostimulation therapies, a number of patients are incapacitated and suffering. The sphenopalatine ganglion (SPG) has been implicated in the pathophysiology of CH and has been a target for blocks, lesioning, and other surgical approaches. For this reason, it was selected as a target for an acute neurostimulation study. Methods.— Six patients with refractory chronic CH were treated with short-term (up to 1 hour) electrical stimulation of the SPG during an acute CH. Headaches were spontaneously present at the time of stimulation or were triggered with agents known to trigger clusters headache in each patient. A standard percutaneous infrazygomatic approach was used to place a needle at the ipsilateral SPG in the pterygopalatine fossa under fluoroscopic guidance. Electrical stimulation was performed using a temporary stimulating electrode. Stimulation was performed at various settings during maximal headache intensity. Results.— Five patients had CH during the initial evaluation. Three returned 3 months later for a second evaluation. There were 18 acute and distinct CH attacks with clinically maximal visual analog scale (VAS) intensity of 8 (out of 10) and above. SPG stimulation resulted in complete resolution of the headache in 11 attacks, partial resolution (>50% VAS reduction) in 3, and minimal to no relief in 4 attacks. Associated autonomic features of CH were resolved in each responder. Pain relief was noted within several minutes of stimulation. Conclusion.— Sphenopalatine ganglion stimulation can be effective in relieving acute severe CH pain and associated autonomic features. Chronic long-term outcome studies are needed to determine the utility of SPG stimulation for management and prevention of CH.

Background. Expert panels of physicians and nonphysicians, all expert in intrathecal (IT) therapies, convened in the years 2000 and 2003 to make recommendations for the rational use of IT analgesics, based on the preclinical and clinical literature known up to those times, presentations of the expert panels, discussions on current practice and standards, and the result of surveys of physicians using IT agents. An expert panel of physicians and nonphysicians has convened in 2007 to update information known regarding IT therapies and to update information on new and novel opioid and nonopioid analgesic compounds that might show promise for IT use. Methods. A review of preclinical and clinical published relevant studies from 2000 to 2006 was undertaken and disseminated to a convened expert panel of physicians and nonphysicians to discuss new and novel analgesic agents for IT use. Results. The panelists identified several agents that were worthy of future studies for the clinical and rational use of IT agents that are presented in this article. Conclusions. A list of nonopioid IT analgesics, including gabapentin, adenosine, octreotide, the χ-conopeptide, Xen2174, the conopeptide, neurotensis 1 agonist, CGX-1160, the ω-conotoxin, AM-336, and physostigmine, were identified as worthy of future research by the panelists.

Background. Expert panels of physicians and nonphysicians in the field of intrathecal therapies convened in 2000 and 2003 to make recommendations for the rational use of intrathecal analgesics based on the preclinical and clinical literature known up to those times. An expert panel of physicians convened in 2007 to update previous recommendations and to form guidelines for the rational use of intrathecal opioid and nonopioid agents. Methods. A review of preclinical and clinical published relevant studies from 2000 to 2006 was undertaken and disseminated to a convened expert panel of physicians and nonphysicians. Focused discussions were held on the rational use of intrathecal agents and a survey asking questions regarding intrathecal therapies management was given to the panelists. Results. The panelists, after review of the literature from 2000 to 2006 and discussion, created an updated algorithm for the rational use of intrathecal opioid and nonopioid agents in patients with nonmalignant and end-of-life pain. Of note is that the panelists felt that ziconotide, based on new and relevant literature and experience, should be updated to a line one intrathecal drug.

Sympathetic blockade is often undertaken to diagnose or treat sympathetically maintained pain in painful extremities. A thorough understanding of the anatomy and physiology of the sympathetic nervous system is essential to understand complications that may arise as a result of sympathetic blocks and to develop strategies to prevent them. Complications of sympathetic blockade vary depending on the sympathetic ganglia blocked, the location, the approach, and the agents used. Complications related to sympathetic blocks can be generally divided into unwanted results related to blockade of sympathetic fibers and untoward events related to injuring other organs as a result of the procedure. This article describes complications that may occur with sympathetic blocks performed for extremity pain and potential strategies to minimize such events.

Although the application of CT-guided fluoroscopy techniques for interventional radiology have become more popular, a majority of practitioners in health care remain unfamiliar with their possibilities. Accurate imaging accompanied by guided techniques increase the precision of analgetic procedures, improving results and reducing complications. Main focuses of CT fluoroscopy use in pain management are axial spinal procedures, including zygapophyseal (ZAJ) (facet) joint injection, medial branch rhizolysis, sacroiliac joint injection, transforaminal nerve root block and peri-radicular infiltration, dorsal interlaminar epidural injection, costotransverse and costovertebral joint injections, and blocks of the sympathetic nerve ganglia, splanchnic, and celiac plexus nerve blocks.