What Is the Evidence for Rest,Ice, Compression,and Elevation Therapy in the Treatment of Ankle Sprains in Adults?

Context:

Ankle sprains are common problems in acute medical care. The variation in treatment observed for the acutely injured lateral ankle ligament complex in the first week after the injury suggests a lack of evidence-based management strategies for this problem.

Objective:

To analyze the effectiveness of applying rest, ice, compression, and elevation (RICE) therapy begun within 72 hours after trauma for patients in the initial period after ankle sprain.

Study Selection:

Eligible studies were published original randomized or quasi-randomized controlled trials concerning at least 1 of the 4 subtreatments of RICE therapy in the treatment of acute ankle sprains in adults.

Data Sources:

MEDLINE, Cochrane Clinical Trial Register, CINAHL, and EMBASE. The lists of references of retrieved publications also were checked manually.

Data Extraction:

We extracted relevant data on treatment outcome (pain, swelling, ankle mobility or range of motion, return to sports, return to work, complications, and patient satisfaction) and assessed the quality of included studies. If feasible, the results of comparable studies were pooled using fixed- or random-effects models.

Data Synthesis:

After deduction of the overlaps among the different databases, evaluation of the abstracts, and contact with some authors, 24 potentially eligible trials remained. The full texts of these articles were retrieved and thoroughly assessed as described. This resulted in the inclusion of 11 trials involving 868 patients. The main reason for exclusion was that the authors did not describe a well-defined control group without the intervention of interest.

Conclusions:

Insufficient evidence is available from randomized controlled trials to determine the relative effectiveness of RICE therapy for acute ankle sprains in adults. Treatment decisions must be made on an individual basis, carefully weighing the relative benefits and risks of each option, and must be based on expert opinions and national guidelines.Key Words: ankle ligament injury, cryotherapy, bandages

Key Points

• Randomized controlled trials provide insufficient evidence to determine the effectiveness of rest, ice, compression, and elevation (RICE) therapy for acute ankle sprains in adults.
• Treatment decisions must be made on an individual basis, carefully weighing the relative risks and benefits of each option, and must be based on expert opinions and guidelines.
• Sufficiently powered, high-quality, and appropriately reported randomized trials of the different elements of RICE therapy for acute ankle sprains are needed.

Ankle sprains are one of the most prevalent injuries of the musculoskeletal system. Researchers have estimated that 1 ankle sprain occurs per 10 000 people each day.¹ The most common mechanism of injury is inversion of the plantar-flexed foot. Inversion injuries involve about 25% of all injuries of the musculoskeletal system, which affect more than 20 000 patients in the United States each day.^2,3 About 50% of these injuries are sport related^4,5; some sports (basketball, soccer, and volleyball) have a particularly high incidence of ankle injuries.^6,7 If not treated properly, inversion injuries of the ankle can result in persistent problems in 30% to 40% of patients.^4,8The treatment of inversion ankle injuries is provided by emergency and primary health care physicians, athletic trainers, physiotherapists, and orthopaedic and trauma surgeons. Each year, approximately 1 million patients with acute lateral ankle ligament injuries are examined by primary care physicians in the United States.⁹ The annual cost to society for ankle injuries has been estimated to be approximately €40 million (US $30.4 million) per 1 million people.¹⁰ Most authors use the term sprain to describe a morphologic condition representing a diversity of pathologic conditions, ranging from overstretching of the ligament to complete rupture with gross instability of the joint.¹¹The ankle ligaments are the anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL), and posterior talofibular ligament (PTFL), and together they form the lateral ligament complex of the ankle.¹² The ATFL is the first or only ligament to sustain injury in 97% of the cases.^13,14 Broström⁵ found that combined ruptures of the ATFL and the CFL occurred in 20% of the cases and that isolated rupture of the CFL occurred in only 3%. The PTFL usually is not injured unless a true dislocation of the ankle occurs.⁵ Rest, ice, compression, and elevation (RICE) are generally accepted methods for treating inflammation after trauma, such as acute ankle sprain.^15,16 Inflammation causes pain, edema, hyperalgesia, and erythema, all of which can limit the patient''s ability to perform the rehabilitation required for proper healing.¹⁷ Gentle tension and stretching at the joint promote proper ligament fiber growth into tight, parallel strands. Accumulation of fluid and edema around an injury site also increases tissue damage, delays healing, and can result in some degree of chronic disability.¹⁸According to the Dutch Quality Institute for Healthcare CBO consensus guidelines,¹⁹ RICE therapy is the preferred treatment for the first 4 to 5 days. After this period, the physical examination provides a high-quality assessment.^19–21 The inconsistent outcome of physical examination within 48 hours of trauma is caused by the diffuse character of the pain, the swelling that gives no information about whether it is due to hematoma or edema formation, and the unreliability of the anterior drawer test due to pain and swelling.^19–21Rest, ice, compression, and elevation therapy is an accessible and popular modality in the treatment of acute ankle sprains. Therefore, the objective of our study was to analyze the effectiveness of applying RICE therapy begun within 72 hours after trauma for patients in the initial period of ankle sprain. The specific null hypotheses included the following: (1) No differences existed in outcome measurements between using rest, immobilization, or no movement or mobilization and using early mobilization or movement for acute treatment of ankle sprains; (2) No differences existed in outcome measurements between using ice, cold, cold therapy, cryotherapy, or cooling and using no ice, no cold, or heat for acute treatment of ankle sprains; (3) No differences existed in outcome measurements between using compression and using no compression for acute treatment of ankle sprains; and (4) No differences existed in outcome measurements between using elevation and using no elevation for acute treatment of ankle sprains. In addition to other reviews concerning the treatment of acute lateral ankle sprains^22–28 (also G.M.M.J.K., unpublished data, January 2011), our systematic review will be helpful in the further development of evidence-based treatment recommendations and protocols.     

Defensins: key players or bystanders in infection, injury, and repair in the lung?

Antimicrobial peptides have been identified as key elements in the innate host defense against infection. Recent studies have indicated that the activity of antimicrobial peptides may be decreased in cystic fibrosis, suggesting a major role for these peptides in host defense against infection. One of the most intensively studied classes of antimicrobial peptides are defensins. Defensins comprise a family of cationic peptides that in human subjects can be divided into the alpha- and beta-defensin subfamilies. The alpha-defensins are produced by neutrophils and intestinal Paneth's cells, whereas beta-defensins are mainly produced by epithelial cells. Although studies on beta-defensins have so far focused on their antimicrobial activity, studies on alpha-defensins have suggested a role of these peptides in inflammation, wound repair, and specific immune responses. alpha-Defensins, which accumulate in airway secretions of patients with various chronic inflammatory lung disorders, were shown to be cytotoxic toward airway epithelial cells and to induce chemokine secretion in several cell types. Furthermore, the capacity of alpha-defensins to promote bacterial adherence to epithelial cells in vitro further supports a role for these peptides in the pathogenesis of chronic obstructive pulmonary disease and cystic fibrosis. Increased numbers of neutrophils are also present in the airways of patients with asthma, suggesting that neutrophils are involved in the pathogenesis of this disease. Because defensins are able to induce histamine release by mast cells and increase the airway hyperresponsiveness to histamine, it is tempting to speculate that defensins may also contribute to the inflammatory processes in asthma. Besides these proinflammatory effects, alpha-defensins may also display anti-inflammatory activities, including regulation of complement activation and proteinase inhibitor secretion. Finally, defensins may be involved in wound repair because defensins increase epithelial cell proliferation. Thus recent defensin research has revealed potential links between the innate and acquired immune system.     

Expression and regulation of αB-crystallin in the kidney in vivo and in vitro

αB-crystallin, a major component of the mammalian eye lens, is a small heat shock protein and molecular chaperone that is also abundant in the mammalian kidney. The present study aimed to characterize more closely the intrarenal expression and regulation of αB-crystallin in vivo and in vitro. In normal rat kidney, the expression of αB-crystallin mRNA and protein were both close to the detection limit in cortex, but increased steeply from the outer to the inner medulla where αB-crystallin constitutes approximately 2% of total tissue protein. Immunohistochemistry disclosed papillary collecting duct cells and thin limbs as the major sites for intrapapillary αB-crystallin immunoreactivity. In rats subjected to sucrose diuresis for 3 days, αB-crystallin mRNA expression was reduced by 27 and 46% in outer and inner medulla, respectively. In agreement with the results obtained in vivo, in Madine–Darby canine kidney cells, αB-crystallin mRNA and protein were induced significantly by elevating the medium osmolality to 500 mosm/kg H₂O by the addition of NaCl and raffinose, and also by urea. The NaCl-induced increase in αB-crystallin expression was concentration-dependently blunted by SP600125, a specific JNK inhibitor. Overexpression of αB-crystallin in 293 cells resulted in increased tolerance to acute osmotic stress. These results indicate that αB-crystallin may be regulated by papillary interstitial tonicity in a JNK-dependent process. Moreover, the high abundance of αB-crystallin in the renal medulla may be important for cell survival in an environment characterized by extreme interstitial solute concentrations as present during antidiuresis.     

Travelling Knowledge and Forensic Medicine: Infanticide,Body and Mind in the Netherlands, 1811–1911

This article aims to explain why the notion of mania puerperalis, or puerperal insanity, was not used in the Netherlands to exonerate women accused of infanticide, in contrast to other countries. It applies the concept of ‘travelling knowledge’ as an approach to the history of forensic medicine, pointing to the fields of medicine and law as contact zones inviting, promoting or barring the transmission of knowledge. Although the notion of mania puerperalis was known in the Netherlands from 1822 on, psychiatric expertise was not requested in actual court cases of infanticide for several reasons. First, physicians and legal scholars continued to doubt the existence of this form of mania. Moreover, it was not always directly connected to infanticide. Also, the specific formulation of the law strongly determined what medical evidence was needed in court cases. Not only did the Code Pénal generally emphasise material evidence, the laws on infanticide specifically mentioned fear and therefore an additional reference to the mental condition of the accused was not needed. Most importantly, the article argues that the existing vocabulary on emotion, both vernacular and medical, already allowed for an analysis of psychic components. Keywords : Forensic Medicine, Infanticide, Knowledge, Psychiatry, Emotions     

Are cognitive processes manifested in event-related gamma, alpha, theta and delta oscillations in the EEG?

The restricted capacity of the nervous system to regenerate calls for novel therapeutic concepts. We have tested biocompatible polylactide fibers as potential nerve guides that could bridge proximal nerve stumps and synaptic target regions after nerve lesion. Polylactides have the great advantage that they degrade and resorb after completion of regeneration. Material surface properties were optimized three-fold by oxygen plasma treatment, polyanion coating and the seeding of Schwann cells from rat sciatic nerve. Immunocytochemistry and scanning electron microscopy revealed that in vitro axonal outgrowth of dorsal root ganglia on two specifically synthesized lactide polymers can be greatly improved by these surface treatments. The approach aims to develop an 'intelligent neuroprosthesis' that in vivo facilitates directed axonal regrowth in the first place and disappears thereafter.     

Differences in the modulation of reactive species,lipid bodies,cyclooxygenase-2, 5-lipoxygenase and PPAR-γ in cerebral malaria-susceptible and resistant mice

Proinflammatory responses are associated with the severity of cerebral malaria. NO, H₂O₂, eicosanoid and PPAR-γ are involved in proinflammatory responses, but regulation of these factors is unclear in malaria. This work aimed to compare the expression of eicosanoid-forming-enzymes in cerebral malaria-susceptible CBA and C57BL/6 and −resistant BALB/c mice. Mice were infected with Plasmodium berghei ANKA, and the survival rates and parasitemia curves were assessed. On the sixth day post-infection, cyclooxygenase-2 and 5-lipoxygenase in brain sections were assessed by immunohistochemistry, and, NO, H₂O₂, lipid bodies, and PPAR-γ expression were assessed in peritoneal macrophages. The C57BL/6 had more severe disease with a lower survival time, higher parasitemia and lower production of plasmodicidal NO and H₂O₂ molecules than BALB/c. Enhanced COX-2 and 5-LOX expression were observed in brain tissue cells and vessels from C57BL/6 mice, and these mice expressed higher constitutive PPAR-γ levels. There was no translocation of PPAR-γ from cytoplasm to nucleus in macrophages from these mice. CBA mice had enhanced COX-2 expression in brain tissue cells and vessels and also lacked PPAR-γ cytoplasm-to-nucleus translocation. The resistant BALB/c mice presented higher survival time, lower parasitemia and higher NO and H₂O₂ production on the sixth day post-infection. These mice did not express either COX-2 or 5-LOX in brain tissue cells and vessels. Our data showed that besides the high parasite burden and lack of microbicidal molecules, an imbalance with high COX-2 and 5-LOX eicosanoid expression and a lack of regulatory PPAR-γ cytoplasm-to-nucleus translocation in macrophages were observed in mice that develop cerebral malaria.     

Do multifilament alloplastic meshes increase the infection rate? Analysis of the polymeric surface,the bacteria adherence,and the in vivo consequences in a rat model

Within the last decade hernia surgery has changed from suture repair to mesh repair. Biomaterials, and multifilaments in particular, are thought to increase the risk of infection. Therefore, the aim of this study was to study the influence of the presence of either a monofilament or a multifilament mesh material on the bacterial infection risk. The filament surface of a monofilament and a multifilament mesh were calculated on the basis of a theoretical model. The adherence of Staphylococcus aureus was measured in vitro by fluorescence analysis. Additionally, the two mesh materials (8-mm platelets) were implanted subcutaneously in Sprague-Dawley rats with daily surveillance for clinical signs of infection. After 7 days the meshes were explanted for histological and microbiological analysis. Calculations of the mesh surface area revealed a higher level for the multifilament mesh. The extent of adherent bacteria corresponded to the estimated filament surface in vitro. In vivo, the implantation of meshes in the presence of 5 x 10(6) S. aureus did not show an increased infection rate in rats with either monofilament or multifilament material, compared to the control groups (mesh implantation without S. aureus contamination). However, after 7 days bacteria were still detectable in the majority of the implantation sites, and a clinically inapparent intensification of local inflammation and fibrosis was induced. The increased surface area of a multifilament meshes promotes the persistence of bacteria in the implant bed, though this alone is not sufficient to create a clinically apparent infection. This might explain the development of mesh-related infections after a delay of several months or even years. In vivo, the adherence of bacteria to the implant material depends on the surface area, which favors the use of monofilament materials.     

Anxiety-like behavior in the elevated-plus maze tests and enhanced IL-1β, IL-6, NADPH oxidase-1, and iNOS mRNAs in the hippocampus during early stage of adjuvant arthritis in rats

We studied anxiety-like behavior in the elevated plus-maze (EPM) tests in male Lewis rats on days 2 and 4 of adjuvant arthritis (AA). In plasma we analyzed C-reactive protein (CRP), albumin, ACTH, corticosterone, in the hippocampus the mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), corticotrophin releasing factor (CRH), NADPH oxidases NOX1 and NOX2, and inducible NO-synthase (iNOS). EPM tests showed a higher anxiety index in AA rats on days 2 and 4 and reduction of total entries. On days 2 and 4 we found reduced plasma albumin, enhanced CRP, ACTH and corticosterone, and in the hippocampus enhanced mRNA for NOX1 and IL-1β in AA rats, on day 4 we found enhanced mRNAs for iNOS and IL-6, and reduced mRNA for CRH. The mRNA for NOX2 did not change on any experimental day. These results suggest enhanced anxiety, as well as locomotor impairment during the early phase of AA that correlate with enhanced mRNA expressions of parameters of oxidative stress NOX1, iNOS, and inflammatory cytokines IL-1β and IL-6 in the hippocampus.     

Placentophagia in naïve adults, new fathers, and new mothers in the biparental dwarf hamster, Phodopus campbelli

Placentophagia in mammals typically occurs only in females during the birth. Male hamsters, Phodopus campbelli, with an extensive paternal behavior repertoire eat placenta during the birth and as alloparental juveniles. Two fresh placentae were presented to sexually naïve males and females covering the developmental range from puberty through reproductive maturity and into senescence. Expectant parents and new mothers were also tested. Placentophagia occurred in both sexes at all developmental stages and was higher in reproductive than in naïve hamsters. Placentophagia declined with increasing age in females, but not males. Liver was readily accepted, but acceptance did not decline with age in females, and was not low in juvenile males, confirming that animals distinguished between the two tissues. Senescent females consumed both tissues willingly. In these paternal males, which do not experience pregnancy or parturition, and in naïve females that selectively refuse placenta, the stimuli influencing placentophagia remain unknown. © 2005 Wiley Periodicals, Inc. Dev Psychobiol 47: 179–188, 2005.     

Exosomes in the Immune Response and Tolerance

Exosomes are small vesicles with endocytic origin secretedby many live cells. They are flattened or round sphere se-questered by a lipid bi-layer visualized by under electronmicroscopy (EM), with sizes from 30 run to 100 nm. Ex-osomes were first described…     

Daily variations of epinephrine, norepinephrine, and β-adrenoceptors in the blood and lymphoid organs of intact rats

Daily variations of catecholamine concentrations in the blood and lymphoid organs in Wistar rats were revealed. Daily fluctuations of epinephrine and norepinephrine levels in the spleen and blood were synchronous. Circadian variations of epinephrine in the thymus, lymph nodes, and plasma were synphasic. A relationship between neurotransmitter concentrations and expression of β-adrenoceptors on thymic and splenic lymphocytes was noted. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 9, pp. 344–346, September, 1999     

Secular trend in the menopausal age in Finland 1997–2007 and correlation with socioeconomic,reproductive and lifestyle factors

Background and aims

Only few studies have studied secular trend of menopausal age during last decade. The aim of our study is to analyze secular trend of menopausal age and to evaluate the role of socioeconomic, reproductive and lifestyle factors.

Material and methods

National FINRISK Study sample from years 1997 and 2007 was utilized. The sample size for 1997 was 4193 and during 2007 was 4253 women. Covariance analysis included menopausal age as dependent variable and covariates (age, study year, education, occupation, parity, age at first birth, smoking, use of alcohol, physical activity, body mass index, waist circumference and waist–hip ratio) as independent variables.

Results

Median of menopausal age was 50 years in 1997 and 51 years in 2007. Differences in menopausal age by covariate were largest in smoking, education and occupation. Difference in mean menopausal age between smokers and non-smokers was larger in 2007 than in 1997 (p < 0.001). Lowest educated women had lower average menopausal age during 2007 than higher educated women (p < 0.001), but not in 1997. When including sociodemographic, reproductive and lifestyle factors in a model, smoking was significantly related to earlier and physical activity to later menopausal age. Study year was not significant in any model.

Conclusion

Education, smoking and physical activity have an important role in menopausal age determination when comparing 10-year differences in menopausal age.     

Performance of the Genotype® MTBDRPlus assay in the diagnosis of tuberculosis and drug resistance in Samara, Russian Federation

Background

Russia is a high tuberculosis (TB) burden country with a high prevalence of multidrug resistant tuberculosis (MDRTB). Molecular assays for detection of MDRTB on clinical specimens are not widely available in Russia.

Results

We performed an evaluation of the GenoType^® MTBDRplus assay (HAIN Lifescience GmbH, Germany) on a total of 168 sputum specimens from individual patients at a public health laboratory in Central Russia, as a model of a middle income site in a region with high levels of drug resistance. Phenotypic drug resistance tests (DST) were performed on cultures derived from the same sputum specimens using the BACTEC 960 liquid media system. Interpretable GenoType^® MTBDRplus results were obtained for 154(91.7%) specimens with readability rates significantly higher in sputum specimens graded 2+ and 3+ compared to 1+ (RR = 1.17 95%CI 1.04–1.32). The sensitivity and specificity of the assay for the detection of rifampicin (RIF) and isoniazid (INH) resistance and MDR was 96.2%, 97.4%, 97.1% and 90.7%, 83.3%, 88.9% respectively. Mutations in codon 531 of the rpoB gene and codon 315 of the katG gene dominated in RIF and INH resistant strains respectively. Disagreements between phenotypical and molecular tests results (12 samples) could be explained by the presence of rare mutations in strains circulating in Russia and simultaneous presence of resistant and sensitive bacilli in sputum specimens (heteroresistance).

Conclusion

High sensitivity, short turnaround times and the potential for screening large numbers of specimens rapidly, make the GenoType^® MTBDRplus assay suitable as a first-line screening assay for drug resistant TB.