Does Cryotherapy Improve Outcomes With Soft Tissue Injury?

Reference:

Bleakley C, McDonough S, MacAuley D. The use of ice in the treatment of acute soft-tissue injury: a systematic review of randomized controlled trials. Am J Sport Med. 2004; 32:251–261.

Clinical Question:

What is the clinical evidence base for cryotherapy use?

Data Sources:

Studies were identified by using a computer-based literature search on a total of 8 databases: MEDLINE, Proquest, ISI Web of Science, Cumulative Index to Nursing and Allied Health (CINAHL) on Ovid, Allied and Complementary Medicine Database (AMED) on Ovid, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effectiveness, and Cochrane Controlled Trials Register (Central). This was supplemented with citation tracking of relevant primary and review articles. Search terms included surgery,orthopaedics,sports injury,soft tissue injury,sprains and strains,contusions,athletic injury,acute,compression, cryotherapy,ice,RICE, andcold.

Study Selection:

To be included in the review, each study had to fulfill the following conditions: be a randomized, controlled trial of human subjects; be published in English as a full paper; include patients recovering from acute soft tissue or orthopaedic surgical interventions who received cryotherapy in inpatient, outpatient, or home-based treatment, in isolation or in combination with placebo or other therapies; provide comparisons with no treatment, placebo, a different mode or protocol of cryotherapy, or other physiotherapeutic interventions; and have outcome measures that included function (subjective or objective), pain, swelling, or range of motion.

Data Extraction:

The study population, interventions, outcomes, follow-up, and reported results of the assessed trials were extracted and tabulated. The primary outcome measures were pain, swelling, and range of motion. Only 2 groups reported adequate data for return to normal function. All eligible articles were rated for methodologic quality using the PEDro scale. The PEDro scale is a checklist that examines the believability (internal validity) and the interpretability of trial quality. The 11-item checklist yields a maximum score of 10 if all criteria are satisfied. The intraclass correlation coefficient and kappa values are similar to those reported for 3 other frequently used quality scales (Chalmers Scale, Jadad Scale, and Maastricht List). Two reviewers graded the articles, a method that has been reported to be more reliable than one evaluator.

Main Results:

Specific search criteria identified 55 articles for review, of which 22 were eligible randomized, controlled clinical trials. The articles'' scores on the PEDro scale were low, ranging from 1 to 5, with an average score of 3.4. Five studies provided adequate information on the subjects'' baseline data, and only 3 studies concealed allocation during subject recruitment. No studies blinded their therapist''s administration of therapy, and just 1 study blinded subjects. Only 1 study included an intention-to-treat analysis. The average number of subjects in the studies was 66.7; however, only 1 group undertook a power analysis. The types of injuries varied widely (eg, acute or surgical). No authors investigated subjects with muscle contusions or strains, and only 5 groups studied subjects with acute ligament sprains. The remaining 17 groups examined patients recovering from operative procedures (anterior cruciate ligament repair, knee arthroscopy, lateral retinacular release, total knee and hip arthroplasties, and carpal tunnel release). Additionally, the mode of cryotherapy varied widely, as did the duration and frequency of cryotherapy application. The time period when cryotherapy was applied after injury ranged from immediately after injury to 1 to 3 days postinjury. Adequate information on the actual surface temperature of the cooling device was not provided in the selected studies. Most authors recorded outcome variables over short periods (1 week), with the longest reporting follow-ups of pain, swelling, and range of motion recorded at 4 weeks postinjury. Data in that study were insufficient to calculate effect size. Nine studies did not provide data of the key outcome measures, so individual study effect estimates could not be calculated. A total of 12 treatment comparisons were made. Ice submersion with simultaneous exercises was significantly more effective than heat and contrast therapy plus simultaneous exercises at reducing swelling. Ice was reported to be no different from ice and low-frequency or high-frequency electric stimulation in effect on swelling, pain, and range of motion. Ice alone seemed to be more effective than applying no form of cryotherapy after minor knee surgery in terms of pain, but no differences were reported for range of motion and girth. Continuous cryotherapy was associated with a significantly greater decrease in pain and wrist circumference after surgery than intermittent cryotherapy. Evidence was marginal that a single simultaneous treatment with ice and compression is no more effective than no cryotherapy after an ankle sprain. The authors reported ice to be no more effective than rehabilitation only with regard to pain, swelling, and range of motion. Ice and compression seemed to be significantly more effective than ice alone in terms of decreasing pain. Additionally, ice, compression, and a placebo injection reduced pain more than a placebo injection alone. Lastly, in 8 studies, there seemed to be little difference in the effectiveness of ice and compression compared with compression alone. Only 2 of the 8 groups reported significant differences in favor of ice and compression.

Conclusions:

Based on the available evidence, cryotherapy seems to be effective in decreasing pain. In comparison with other rehabilitation techniques, the efficacy of cryotherapy has been questioned. The exact effect of cryotherapy on more frequently treated acute injuries (eg, muscle strains and contusions) has not been fully elucidated. Additionally, the low methodologic quality of the available evidence is of concern. Many more high-quality studies are required to create evidence-based guidelines on the use of cryotherapy. These must focus on developing modes, durations, and frequencies of ice application that will optimize outcomes after injury.     

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

Critical stages of tumor growth regulation in transgenic mice harboring a hepatocellular carcinoma revealed by distinct patterns of tumor necrosis factor-alpha and transforming growth factor-beta mRNA production

There is now good evidence that cytokines contribute to the regulation of tumor growth. The cytokine-driven modulation of tumor growth was investigated during the progression of a hepatocellular carcinoma (HCC) in SV40 large T tumor antigen transgenic mice. In vivo, an increased rate of liver growth correlated with increased transforming growth factor (TGF)-beta 1 mRNA expression, while the greatest amounts of tumor necrosis factor (TNF)-alpha mRNA were detected earlier during tumor development. Conversely, no particular alteration of IL-1 alpha, IL-1 beta, IL-6, IL-2, IL-4 and IFN-gamma mRNA production could be reported. In vitro, hepatocyte-like tumor cell lines established at two stages, either before or after HCC differentiation, were characterized. The early-stage-derived cell line produced TNF-alpha mRNA, but had barely detectable expression of TGF-beta 1 mRNA, while later-stage- derived cell lines showed the reciprocal pattern. All cell lines displayed a lack of sensitivity to TNF-alpha, although some degree of sensitivity to TNF-alpha could be observed in the presence of actinomycin-D or after treatment with IFN-gamma. The early-stage- derived cell line was sensitive to the growth inhibitory effects of TGF- beta 1, but late-stage-derived tumor cell lines displayed a loss of sensitivity to TGF-beta 1 which correlated with the increased expression of TGF-beta 1 mRNA. Altogether, this suggests that tumor cells contribute to the discrete TNF-alpha and TGF-beta 1 expression patterns during HCC progression. This model of HCC could be of valuable interest to assess the impact of various immunotherapeutic strategies on modulation of tumor growth.      

<Emphasis Type="Italic">TCF7L2</Emphasis>variant genotypes and type 2 diabetes risk in Brazil: significant association,but not a significant tool for risk stratification in the general population

Background  

Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population.     

An experimental COVID-19 messaging study in a representative sample of the Scottish population: Increasing physical distancing intentions through self-efficacy

Objectives

Self-efficacy is important for adherence to transmission-reducing behaviours (e.g., physical distancing) as also shown in the CHARIS project. We aimed to show that a theory-based short message can increase physical distancing self-efficacy and intentions to keep physical distance.

Design

Structured telephone surveys with a randomly selected nationally representative sample of adults in Scotland (N = 497).

Methods

Participants were randomly assigned to one of two experimental conditions: message condition (short message to increase self-efficacy via vicarious experiences, verbal persuasion and emotional arousal) or control condition (no message). Followed by measures for self-efficacy and intention for physical distancing on 4-point scales. Adherence to physical distancing was assessed on a 5-point frequency scale (never – always).

Results

Using mediation analyses with bootstrapping procedures, we first confirmed that self-efficacy was associated indirectly with adherence, via higher intentions in a partial mediation (unstandardized indirect effect .21, 95% CI .18–.25). The message increased self-efficacy; participants receiving the message reported higher self-efficacy (M = 4.23, SD = .80) compared to participants in the control condition (M = 4.08, SD = .77; standardized regression coefficient = .19, p < .05) and self-efficacy affected intention (.48, p < .001). There was a small significant indirect effect of the message on intention via self-efficacy (unstandardized indirect effect .07, CI .01–.14).

Conclusions

Increasing self-efficacy for physical distancing with a short message can successfully increase intention to physical distance via increased self-efficacy. As both self-efficacy and intentions are important predictors of adherence to transmission-reducing behaviours short messages have potential to limit the spread of COVID-19.     

Alpha-synuclein pathology in the olfactory pathways of dementia patients

Lewy-type pathology is a characteristic of a number of neurodegenerative disorders, including Parkinson's disease and dementia with Lewy bodies. Thus far, the definitive diagnosis of these dementias can only be confirmed at post-mortem. However, it is known that the loss of smell (anosmia) is an early symptom in patients who develop dementia, and the use of the smell test has been proposed as an early diagnostic procedure. The aim of this study was to understand further the extent of Lewy pathology in the olfactory system of patients with neurodegenerative disorders. Post-mortem tissue from 250 subjects was obtained from the OPTIMA brain bank. Five areas of the olfactory pathway were examined by immunolabelling for alpha-synuclein - a major component of Lewy pathology: the olfactory tract/bulb (n = 79), the anterior olfactory nucleus in the lateral olfactory gyrus (n = 193), the region of olfactory projection to the orbito-frontal cortex (n = 225), the hippocampus (n = 236) and the amygdala (n = 201). Results show that Lewy pathology affects different parts of the olfactory pathways differentially, suggesting a specific pattern of development of pathology. Clinical Parkinson's disease is most likely to be identified if the orbito-frontal cortex is affected, while the diagnosis is less likely if the pathology is restricted to the olfactory bulb or tract. These results suggest that pathology in the olfactory bulb and tract occurs prior to clinical signs of Parkinson's disease. Furthermore, the results presented here provide further evidence supporting the possible value of a smell test to aid the clinical diagnosis of neurodegenerative diseases.     

Comparative evaluation of three JAK2V617F mutation detection methods

The correlation of JAK2V617F with a proportion of chronic myeloproliferative disorders has generated numerous studies focused on the development of molecular-based assays for JAK2V617F detection. The current parallel study comparatively evaluated 3 JAK2V617F molecular detection methods. Genomic DNA from blood or bone marrow was assayed by 3 laboratories using allele-specific polymerase chain reaction (AS-PCR) or kit-based restriction fragment length polymorphism methods, which used polyacrylamide gel or capillary electrophoresis analysis. In addition, samples were sequenced in 2 of the laboratories. Results found 100% concordance among the 3 methods, with analytic sensitivities of 5% for both kit methods and 0.01% for AS-PCR. The kitbased assays detect JAK2V617F with equal sensitivity regardless of analysis method, and, despite greater sensitivity of AS-PCR, all 3 methods yielded 100% concordant results for this 36-sample set. Consistent with other reports, direct sequencing was insufficiently sensitive to serve as an initial diagnostic tool for JAK2V617F detection.     

Age-related progression of tau pathology in brains of baboons

Recently, cytoskeletal changes associated with abnormally phosphorylated tau protein were demonstrated in neurons and glial cells of two aged baboons (Papio). The present study examines the effects of age on the development of tau pathology in baboons. Brains of 50 baboons ranging in age from 1 to 30 years were categorized into four age groups: Group I: 1–10 years [n = 9], group II: 11–20 years [n = 13], group III: 21–25 years [n = 17], group IV: 26–30 years [n = 11]). Whole hemisphere sections (100 μm) were examined using phosphorylation-dependent anti-tau antibodies. Cytoskeletal changes were completely absent in animals of group I. In group II four animals (31%) exhibited cytoskeletal changes which were rated as mild or moderate. In group III abnormal tau was found in 12 brains (71%) ranging in severity from mild to severe. Finally, in group IV 10 out of 11 animals (91%) exhibited some degree of tau pathology which was rated as severe in 4 animals (36%). A statistically significant relationship was found between advancing age and progression of tau pathology in baboons. In conclusion, the present findings underline the value of the baboon as a potential nonhuman primate model for age-related tau pathology afflicting the human brain.