Interdisciplinary rehabilitation after whiplash injury: an observational prospective outcome study

To examine the state of, and change in, biopsycho-social health and quality of life of patients after whiplash injury, before and after an inpatient interdisciplinary pain management programme.

Schmerzmanagement bei Kindern in der Schweiz

Hintergrund Schmerzen bei stationär aufgenommenen Kindern werden häufig unzureichend behandelt. Bisher gab es keine Informationen zum Schmerzmanagement von Kinderkrankenhäusern in der Schweiz. Ziel der vorliegenden Studie war, den aktuellen Stand der Schmerzerfassung, -interpretation und -behandlung zu bestimmen. Studiendesign Ein Fragebogen wurde an alle pädiatrischen Krankenhäuser in der Schweiz gesendet. Ergebnisse Insgesamt antworteten 27 von 45 Einheiten (Antwortrate: 60%). Die meisten Abteilungen verwenden Schmerzerfassungstools (96%) und führten diesbezügliche Leitlinien ein (78%). Die Behandlung von Schmerzen erfolgt ebenfalls meist nach hausinterner Leitlinie (78%). Prozedurale und postoperative Schmerzen werden stets (100%) analgetisch behandelt. Bei Frühgeborenen und Kindern auf Intensivpflegestationen werden bei invasiven Eingriffen häufig Analgetika (> 87%) verwendet. Auf Intensivstationen liegen in 44% diesbezügliche Leitlinien vor. Resümee Der Nutzen eines effektiven Schmerzmanagements bei Kindern ist eindeutig belegt. Viele Ansätze zur Verbesserung werden in der Schweiz gut umgesetzt. Vor allem im internationalen Vergleich verbesserte sich das Schmerzmanagement. Es gibt aber noch Optimierungsmöglichkeiten. Beispielsweise besitzen weniger als die Hälfte aller schweizerischen Intensivstationen eine Leitlinie für die Behandlung von Schmerzen bei invasiven Eingriffen.

The well-being model: a new drug interaction model for positive and negative effects

BACKGROUND: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account. METHODS: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs. RESULTS: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed. CONCLUSIONS: The model is consistent with clinical knowledge and supports previously published experimental results on optimal drug combinations. This new framework improves understanding of the characteristics of drug combinations used in clinical practice and can be used in clinical research to identify optimal drug dosing.

Sensory innervation of the dorsal longitudinal ligament and the meninges in the lumbar spine of the dog

Although intervertebral disc herniation is a well-known disease in dogs, pain management for this condition has remained a challenge. The goal of the present study is to address the lack of information regarding the innervation of anatomical structures within the canine vertebral canal. Immunolabeling was performed with antibodies against protein gene product 9.5, Tuj-1 (neuron-specific class III β-tubulin), calcitonin gene-related peptide, and neuropeptide Y in combination with the lectin from Lycopersicon esculentum as a marker for blood vessels. Staining was indicative of both sensory and sympathetic fibers. Innervation density was the highest in lateral areas, intermediate in dorsal areas, and the lowest in ventral areas. In the dorsal longitudinal ligament (DLL), the highest innervation density was observed in the lateral regions. Innervation was lower at mid-vertebral levels than at intervertebral levels. The presence of sensory and sympathetic fibers in the canine dura and DLL suggests that pain may originate from both these structures. Due to these regional differences in sensory innervation patterns, trauma to intervertebral DLL and lateral dura is expected to be particularly painful. The results ought to provide a better basis for the assessment of medicinal and surgical procedures.

Nerve Stimulator–Guided Sciatic-Femoral Block in Pet Rabbits (Oryctolagus cuniculus) Undergoing Hind Limb Surgery: A Case Series

This article describes the clinical applicability of a nerve stimulator–guided technique, previously described in dogs, to block the sciatic and the femoral nerves in 4 pet rabbits (Oryctolagus cuniculus) undergoing hind limb surgeries. Preanesthetic intramuscular doses of medetomidine (0.08 mg/kg), ketamine (15 mg/kg), and buprenorphine (0.03 mg/kg) were administered to the rabbit patients. The rabbits were intubated and general anesthesia was maintained using isoflurane in oxygen. The sciatic-femoral nerve block was performed with 2% lidocaine at a volume of 0.05 mL/kg/nerve. Sciatic-femoral block was feasible in rabbits, and the motoric responses following electrical stimulation of both nerves were consistent with those reported in dogs after successful nerve location. Iatrogenic complications, namely nerve damage and local anesthetic toxicity, did not occur. Based on these results, the authors conclude that the sciatic-femoral nerve block described in dogs can be safely performed in rabbits. Clinical trials are required to assess the analgesic efficacy of the combined sciatic-femoral nerve block in rabbits as a part of multimodal pain management.

Influencing factors on the length of stay in lumbar spine surgery: analysis of the German spine registry

INTRODUCTION Spinal disc herniation, lumbar spinal stenosis and spondylolisthesis are known to be leading causes of lumbar back pain. The cost of low back pain management and related operations are continuously increasing in the healthcare sector. There are many studies regarding complications after spine surgery but little is known about the factors predicting the length of stay in hospital. The purpose of this study was to identify these factors in lumbar spine surgery in order to adapt the postoperative treatment. MATERIAL AND METHODS The current study was carried out as a post hoc analysis on the basis of the German spine registry. Patients who underwent lumbar spine surgery by posterior surgical access and with posterior fusion and/or rigid stabilization, whereby procedures with dynamic stabilization were excluded. Patient characteristics were tested for association with length of stay (LOS) using bivariate and multivariate analyses. RESULTS A total of 356 patients met the inclusion criteria. The average age of all patients was 64.6 years and the mean LOS was 11.9 ± 6.0 days with a range of 2-44 days. Independent factors that were influencing LOS were increased age at the time of surgery, higher body mass index, male gender, blood transfusion of 1-2 erythrocyte concentrates and the presence of surgical complications. CONCLUSION Identification of predictive factors for prolonged LOS may allow for estimation of patient hospitalization time and for optimization of postoperative care. In individual cases this may result of a reduction in the LOS.

European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa

Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axillae, inguinal and anogenital regions. A mean disease incidence of 6.0 per 100,000 person-years and an average prevalence of 1% has been reported in Europe. HS has the highest impact on patients' quality of life among all assessed dermatological diseases. HS is associated with a variety of concomitant and secondary diseases, such as obesity, metabolic syndrome, inflammatory bowel disease, e.g. Crohn's disease, spondyloarthropathy, follicular occlusion syndrome and other hyperergic diseases. The central pathogenic event in HS is believed to be the occlusion of the upper part of the hair follicle leading to a perifollicular lympho-histiocytic inflammation. A highly significant association between the prevalence of HS and current smoking (Odds ratio 12.55) and overweight (Odds ratio 1.1 for each body mass index unit) has been documented. The European S1 HS guideline suggests that the disease should be treated based on its individual subjective impact and objective severity. Locally recurring lesions can be treated by classical surgery or LASER techniques, whereas medical treatment either as monotherapy or in combination with radical surgery is more appropriate for widely spread lesions. Medical therapy may include antibiotics (clindamycin plus rifampicine, tetracyclines), acitretin and biologics (adalimumab, infliximab). A Hurley severity grade-relevant treatment of HS is recommended by the expert group following a treatment algorithm. Adjuvant measurements, such as pain management, treatment of superinfections, weight loss and tobacco abstinence have to be considered.

Studies on behavioral regulations of morphine tolerance in rats

Opioids remain the drugs of choice in chronic pain treatment, but opioid tolerance, defined as a decrease in analgesic effect after prolonged or repeated use, dramatically limits their clinical utility. Opioid tolerance has classically been studied by implanting spinal catheters in animals for drug administration. This procedure has significant morbidity and mortality, as well as causing an inflammatory response which decreases the potency of opioid analgesia and possibly affects tolerance development. Therefore, we developed and validated a new method, intermittent lumbar puncture (Dautzenberg et al.), for the study of opioid analgesia and tolerance. Using this method, opioid tolerance was reliably induced without detectable morbidity. The dose of morphine needed to induce analgesia and tolerance using this method was about 100-fold lower than that required when using an intrathecal catheter. Only slight inflammation was found at the injection site, dissipated within seven mm. ^ DAMGO, an opioid μ receptor agonist, has been reported to inhibit morphine tolerance, but results from different studies are inconclusive. We evaluated the effect of DAMGO on morphine tolerance using our newly-developed ILP method, as well as other intrathecal catheter paradigms. We found that co-administration of sub-analgesic DAMGO with morphine using ILP did not inhibit morphine tolerance, but instead blocked the analgesic effects of morphine. Tolerance to morphine still developed. Tolerance to morphine can only be blocked by sub-analgesic dose of DAMGO when administered in a lumbar catheter, but not in cervical catheter settings. ^ Finally, we evaluated the effects of Gabapentin (GBP) on analgesia and morphine tolerance. We demonstrated that GBP enhanced analgesia mediated by both subanalgesic and analgesic doses of morphine although GBP itself was not analgesic. GBP increased potency and efficacy of morphine. GBP inhibited the expression, but not the development, of morphine tolerance. GBP blocked tolerance to analgesic morphine but not to subanalgesic morphine. GBP reversed the expression of morphine tolerance even after tolerance was established. These studies may begin to provide new insights into mechanisms of morphine tolerance development and improve clinical chronic pain management. ^

Why does low dose morphine augment fentanyl analgesia?

Opioids dominate the field of pain management because of their ability to provide analgesia in many medical circumstances. However, side effects including respiratory depression, constipation, tolerance, physical dependence, and the risk of addiction limit their clinical utility. Fear of these side effects results in the under-treatment of acute pain. For many years, research has focused on ways to improve the therapeutic index (the ratio of desirable analgesic effects to undesirable side effects) of opioids. One strategy, combining opioid agonists that bind to different opioid receptor types, may prove successful.^ We discovered that subcutaneous co-administration of a moderately analgesic dose of the mu-opioid receptor (MOR) selective agonist fentanyl (20μg/kg) with subanalgesic doses of the less MOR-specific agonist morphine (100ng/kg-100μg/kg), augmented acute fentanyl analgesia in rats. Parallel [35S]GTPγS binding studies using naïve rat substantia gelatinosa membrane treated with fentanyl (4μM) and morphine (1nM-1pM) demonstrated a 2-fold increase in total G-protein activation. This correlation between morphine-induced augmentation of fentanyl analgesia and G-protein activation led to our proposal that interactions between MORs and DORs underlie opioid-induced augmentation. We discovered that morphine-induced augmentation of fentanyl analgesia and G-protein activity was mediated by DORs. Adding the DOR-selective antagonist naltrindole (200ng/kg, 40nM) at doses that did not alter the analgesic or G-protein activation of fentanyl, blocked increases in analgesia and G-protein activation induced by fentanyl/morphine combinations. Equivalent doses of the MOR-selective antagonist cyprodime (20ng/kg, 4nM) did not block augmentation. Substitution of the DOR-selective agonist SNC80 for morphine yielded similar results, further supporting our conclusion that interactions between MORs and DORs are responsible for morphine-induced augmentation of fentanyl analgesia and G-protein activation. Confocal microscopy of rat substantia gelatinosa showed that changes in the rate of opioid receptor internalization did not account for these effects.^ In conclusion, fentanyl analgesia augmentation by subanalgesic morphine is mediated by increased G-protein activation resulting from functional interactions between MORs and DORs, not changes in MOR internalization. Additional animal and clinical studies are needed to determine whether side effect incidence changes following opioid co-administration. If side effect incidence decreases or remains unchanged, these findings could have important implications for clinical pain treatment. ^

Advanced Protein Modeling Method: Benchmarking and Applications in Computer-Aided Drug Discovery

Development of homology modeling methods will remain an area of active research. These methods aim to develop and model increasingly accurate three-dimensional structures of yet uncrystallized therapeutically relevant proteins e.g. Class A G-Protein Coupled Receptors. Incorporating protein flexibility is one way to achieve this goal. Here, I will discuss the enhancement and validation of the ligand-steered modeling, originally developed by Dr. Claudio Cavasotto, via cross modeling of the newly crystallized GPCR structures. This method uses known ligands and known experimental information to optimize relevant protein binding sites by incorporating protein flexibility. The ligand-steered models were able to model, reasonably reproduce binding sites and the co-crystallized native ligand poses of the β2 adrenergic and Adenosine 2A receptors using a single template structure. They also performed better than the choice of template, and crude models in a small scale high-throughput docking experiments and compound selectivity studies. Next, the application of this method to develop high-quality homology models of Cannabinoid Receptor 2, an emerging non-psychotic pain management target, is discussed. These models were validated by their ability to rationalize structure activity relationship data of two, inverse agonist and agonist, series of compounds. The method was also applied to improve the virtual screening performance of the β2 adrenergic crystal structure by optimizing the binding site using β2 specific compounds. These results show the feasibility of optimizing only the pharmacologically relevant protein binding sites and applicability to structure-based drug design projects.

Impacto no sistema imunológico da utilização prolongada de morfina para tratamento da dor

Introdução. Apesar das evidências dos efeitos imunomodulatórios da morfina, não há na literatura estudos que tenham comparado a interação entre citocinas, imunidade celular (linfócitos T, B e NK) e a administração prolongada de morfina administrada pelas vias oral ou intratecal em doentes com dor crônica neuropática não relacionada ao câncer. Foram avaliados de forma transversal e comparativa 50 doentes com diagnóstico de dor lombar crônica e com presença de radiculopatia (dor neuropática) previamente operados para tratar hérnia discal lombar (Síndrome Dolorosa Pós- Laminectomia), sendo 18 doentes tratados prolongadamente com infusão de morfina pela via intratecal com uso de sistema implantável no compartimento subaracnóideo (grupo intratecal); 17 doentes tratados prolongadamente com morfina pela via oral (n=17) e 15 doentes tratados com fármacos mas sem opióides (grupo sem opioide). Foram analisadas as concentração das citocinas IL-2, IL-4, IL-8, TNFalfa, IFNy, IL-5, GM-CSF, IL-6, IL-10 e IL-1beta no plasma e no líquido cefalorraquidiano; imunofenotipagem de linfócitos T, B e células NK e avaliados os Índice de Escalonamento de Opióide (em percentagem de opióide utilizada e em mg), dose cumulativa de morfina (mg), duração do tratamento em meses, dose final de morfina utilizada (em mg), e equivalente de morfina por via oral (em mg). Resultados. Não houve diferença estatisticamente significativa entre o número de linfócitos T, B e NK nos doentes com morfina administrada pelas vias IT, VO e os não usuários de morfina. Houve correlação positiva entre as concentrações de linfócitos T CD4 e o Índice de Escalonamento de Opióide (em % e mg) nos doentes tratados com morfina por via intratecal. Houve correlação negativa entre as concentrações de células NK (CD56+) e o Índice de Escalonamento de Opióide (em % e mg) nos doentes tratados com morfina por via intratecal. Houve correlação positiva entre o número de células NK (CD56+) e a dose cumulativa de morfina (em mg) administrada pelas vias intratecal e oral. Houve correlação positiva entre as concentrações de linfócitos T CD8 e a duração do tratamento em meses nos doentes tratados com morfina pela via oral. As concentrações de IL-8 e IL-1beta foram maiores no LCR do que no plasma em todos os doentes da amostra analisada. As concentrações de IFNy no LCR foram maiores nos doentes que utilizavam morfina pela via oral e nos não usuários de morfina do que nos que a utilizavam pela via intratecal. As concentrações de plasmáticas de IL-5 foram maiores nos doentes utilizavam morfina pela via oral ou intratecal do que nos que não a utilizavam. A concentração de IL-5 no LCR correlacionou-se negativamente com a magnitude da dor de acordo com a EVA nos doentes tratados com morfina pelas via oral ou intratecal. Nos doentes tratados com morfina pelas via oral ou intratecal, a concentração de IL-2 no LCR correlacionou-se positivamente com a magnitude da dor de acordo com a EVA e negativamente com o Índice de Escalonamento de Opióide (em % e mg) e a dose cumulativa de morfina (em mg). As concentrações plasmáticas de GMCSF foram maiores nos doentes utilizavam morfina pela via oral ou intratecal do que nos não a utilizavam. A concentração de TNFalfa no LCR nos doentes tratados com morfina pela via intratecal correlacionou-se negativamente com o Índice de Escalonamento de Opióide (em % e mg), a dose cumulativa de morfina (em mg) e dose equivalente por via oral (em mg) de morfina. A concentração plasmática das citocinas IL-6 e IL-10 correlacionou-se negativamente com a duração do tratamento (em meses) nos doentes tratados com morfina administrada pela via oral. O Índice de Escalonamento de Opióide (em mg e %) correlacionou-se negativamente com as concentrações no LCR de IL-2 e TNFalfa nos doentes tratados com morfina administrada pela via intratecal. O Índice de Escalonamento de Opióide (em mg e %) correlacionou-se negativamente com as concentrações no LCR de IL-2 e IL-5 nos doentes tratados com morfina administrada pela via oral. Houve correlação negativa entre a intensidade da dor de acordo com a EVA e as concentrações de IL-5 e IL-2 no LCR nos doentes tratados com morfina administrada pelas vias oral e intratecal. Houve correlação negativa entre a intensidade da dor de acordo com a EVA e as concentrações plasmáticas de IL-4 nos doentes tratados com morfina administrada pela via intratecal. Houve correlação negativa entre a intensidade da dor de acordo com a EVA e as concentrações plasmáticas de IL-1beta nos doentes tratados com morfina administrada pela via intratecal. Conclusões: Os resultados sugerem associações entre citocinas e imunidade celular (células T , B e NK) e o tratamento prolongado com morfina administrada pela via oral ou intratecal. Estes resultados podem contribuir para a compreensão da imunomodulação da morfina administrada por diferentes vias em doentes com dor neuropática crônica não oncológica . São necessários mais estudos sobre os efeitos da morfina sobre o sistema imunológico

Patients' and professionals' views on managing fibromyalgia

BACKGROUND: Managing fibromyalgia is a challenge for both health care systems and the professionals caring for these patients, due, in part, to the fact that the etiology of this disease is unknown, its symptoms are not specific and there is no standardized treatment. OBJECTIVE: The present study examines three aspects of fibromyalgia management, namely diagnostic approach, therapeutic management and the health professional-patient relationship, to explore specific areas of the health care process that professionals and patients may consider unsatisfactory. METHODS: A qualitative study involving semistructured interviews with 12 fibromyalgia patients and nine health professionals was performed. RESULTS: The most commonly recurring theme was the dissatisfaction of both patients and professionals with the management process as a whole. Both groups expressed dissatisfaction with the delay in reaching a diagnosis and obtaining effective treatment. Patients reported the need for greater moral support from professionals, whereas the latter often felt frustrated and of little help to patients. Patients and professionals agreed on one point: the uncertainty surrounding the management of fibromyalgia and, especially, its etiology. CONCLUSION: The present study contributes to a better understanding regarding why current management of fibromyalgia is neither effective nor satisfactory. It also provides insight into how health professionals can support fibromyalgia patients to achieve beneficial results. Health care services should offer greater support for these patients in the form of specific resources such as fibromyalgia clinics and health professionals with increased awareness of the disease.

Life Experiences of People Affected by Crohn’s Disease and Their Support Networks Scoping Review

This scoping review identifies and describes relevant studies related to the evidence published on life experiences and perceived social support of people affected by Crohn’s disease. Twenty-three studies were definitely selected and analyzed for the topics explored. The overall findings show patients’ needs and perceptions. There is a lack of evidence about patients’ perceived needs as well as the understanding of social support that has contributed to improve their life experiences with that chronic illness. Lack of energy, loss of body control, body image damaged due to different treatments and surgeries, symptoms related to fear of disease, feeling burdened loss related to independence, and so on are some of the concerns with having to live with those affected by the Crohn. To underline those experiences through this scoping review provides valuable data for health care teams, especially for the nursing profession, considered by those affected as one of the main roles along the whole pathological process. This review provides the basis for developing broader research on the relatively underexplored topics and consequently improves specific programs that could address patients’ needs.

Sexualidade nos adolescentes : intervenção formativa

Enquadramento – Os adolescentes com acesso a conhecimentos, informação e motivação, para adotarem comportamentos sexuais seguros, serão capazes de alterar as suas atitudes e os seus comportamentos. Objetivos – Caraterizar os adolescentes relativamente às variáveis de contexto sexual; identificar os conhecimentos dos adolescentes sobre IST e planeamento familiar; identificar as atitudes dos adolescentes face à sexualidade, pílula e preservativos; identificar a motivação dos adolescentes para terem ou não relações sexuais; determinar a eficácia de uma intervenção formativa no âmbito da sexualidade nos conhecimentos sobre IST, Planeamento Familiar, bem como nas suas atitudes face à sexualidade. Métodos - Investigação experimental de campo. O instrumento de recolha de dados é um questionário, elaborado pela equipa de investigadores do Projeto Monitorização de Indicadores de Saúde Infanto-Juvenil (MISIJ) no domínio temático da “Sexualidade Adolescente”. Este permite caracterizar sociodemograficamente e sexualmente os adolescentes, inclui ainda a Escala de atitudes face à sexualidade em adolescentes (AFSA) (Nelas et al., 2010), Escala de conhecimentos sobre infeções de transmissão sexual (Nelas et al., 2010), Escala de atitudes face ao preservativo (Ramos et al., 2009), Escala de atitudes face à pílula (Ramos et al., 2009), Escala de conhecimentos sobre planeamento familiar (Nelas et al., 2010), Escala de motivação para fazer e para não fazer sexo (Alferes, 1997). Resultados - A amostra é constituída por 56 estudantes do 9º ano de escolaridade (28 do grupo de controlo e 28 do grupo experimental). A maioria dos adolescentes do grupo de controlo é do sexo feminino (71,4%), contrariamente ao grupo de controlo onde 64,3% é do sexo masculino. As raparigas do grupo de controlo revelaram mais conhecimentos sobre infeções transmissíveis sexualmente, em ambos os momentos da avaliação, os adolescentes do sexo masculino, em ambos os momentos, revelam mais conhecimentos sobre o planeamento familiar, comparativamente às adolescentes do género feminino. Aos índices positivos antes da intervenção formativa corresponderam melhores índices após a intervenção formativa. Conclusão - Os profissionais de saúde devem, através da educação para a saúde, promover atitudes que promovam a saúde sexual e reprodutiva e promover o desenvolvimento de competências indispensáveis para adoção de comportamentos saudáveis. Palavras-chave - Adolescentes; Sexualidade; Educação sexual; Intervenção formativa.