DNA content and clinicopathological features aid in distinguishing ameloblastic carcinoma from ameloblastoma.

BACKGROUND: Ameloblastoma and ameloblastic carcinoma are epithelial odontogenic tumors that can be morphologically similar. In the present study, we evaluated the DNA content and Ki-67 index in the two tumors. METHODS: The paraffin blocks of the tumors were selected to obtain sections for the immunohistochemical reactions and preparation of the cell suspension for acquisition in a flow cytometer. The Random Forest package of the R software was used to verify the contribution of each variable to classify lesions into ameloblastoma or ameloblastic carcinoma. RESULTS: Thirty-two ameloblastoma and five ameloblastic carcinoma were included in the study. In our sample, we did not find statistically significant differences in Ki-67 labeling rates. A higher fraction of cells in 2c (G1) was correlated with the diagnosis of ameloblastoma, whereas higher rates of 5c-exceeding rate (5cER) were correlated with ameloblastic carcinoma. The Random Forest model highlighted histopathological findings and parameters of DNA ploidy study as important features for distinguishing ameloblastoma from ameloblastic carcinoma. CONCLUSION: Our findings suggest that the parameters of the DNA ploidy study can be ancillary tools in the classification of ameloblastoma and ameloblastic carcinoma.

Using a mobile application to reduce potentially inappropriate prescribing for older Brazilian adults in primary care: a triple-blind randomised clinical trial.

BACKGOUND: Potentially inappropriate prescribing (PIP) has been evaluated in several countries, and several strategies have been devised for deprescribing drugs in older adults. The aim of this study was to evaluate the efficacy of a mobile application in reducing PIP for older adults in primary care facilities in Brazil. METHODS: This randomised, triple-blind, parallel-group trial was conducted in 22 public primary care facilities in Brazil. During the intervention phase, the general practitioners (GPs) were randomly allocated to the intervention (MPI Brasil app provides information about PIP, therapeutic alternatives and deprescribing) or control (MedSUS app provides general information about medications) group. All GPs were trained on the Clinical Decision-Making Process and how to access an Evidence-Based Health website. The GPs received an Android tablet with an installed mobile application depending on their allocated group, which they used when caring for older patients over at least 3 months. At the end of this period, a sample of older patients aged ≥ 60 years who had been awaiting medical consultation by the participating GPs were interviewed and their prescriptions analysed. The primary outcome was the frequency of PIP in and between the groups. RESULTS: Among 53 GPs who were administered the baseline survey, 14 were included in the clinical trial. At baseline, 146 prescriptions were analysed: the PIP overall was 37.7% (55/146), in the intervention group was 40.6% (28/69), and in the control group was 35.1% (27/77). After the intervention, 284 prescriptions were analysed: the PIP overall was 31.7% (90/284), in the intervention group was 32.2% (46/143), and in the control group was 31.2% (44/141) (RR: 1.16; 95% CI, 0.76-1.76). In the within-group analysis, the PIP reduced from before to after the intervention in both groups-more significantly in the intervention than in the control group (p < 0.001). In the stratified analysis of PIP frequency by GPs, there was a relative risk reduction in 86% (6/7) of GPs in the intervention group compared to 71% (5/7) in the control group. CONCLUSION: We found that the MPI Brasil app effectively reduced PIP, suggesting that it may be useful to incorporate this tool into clinical practice. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02918643). First registration on 22/09/2016.

Effects of amino acid supplementation on muscle mass, muscle performance and functional capacity in subjects undergoing total knee arthroplasty: a systematic review of randomized clinical trials.

The aim of the present study was to summarize the effectiveness of amino acid supplementation on muscle strength, muscle volume, and functional capacity in patients undergoing total knee arthroplasty. For this, in November 2022, a search was carried out in the PubMed, Cochrane Library, and EMBASE databases, identifying a total of 2182 documents, of which only 4 were included in the present review. The included studies had 148 participants (47 men and 101 women), with a minimum age of 53 and a maximum of 92 years, and supplementation times of 13 to 30 days (1 to 3 times a day). For the results, in relation to muscle performance, when comparing the control and experimental groups, greater muscle atrophy was observed in the pre- and post-moments of the control group, in relation to the experimental group. In addition, studies suggest a good tendency for muscle mass gain, and improvement in the functional capacities of patients who used supplementation. Therefore, the use of amino acids after TKA surgery reduces muscle atrophy, which preserves muscle mass and leads to better performance in tests of strength and functional capacity, when compared to the use of a placebo.

Benefits of high-intensity interval training compared to continuous training to reduce apoptotic markers in female rats with cisplatin nephrotoxicity - possible modulatory role of IL-11.

Apoptotic signaling pathways are involved in acute kidney injury (AKI) induced by the antineoplastic drug cisplatin (Cis). Mechanical stress is known to increase interleukin (IL) -11, a pleiotropic cytokine with antiapoptotic and antinecrotic effects. We compared the impact of high-intensity interval training (HIIT) with low-intensity continuous training (LICT) and moderate-intensity continuous training (MICT) on renal levels of IL-11 and the expression of apoptotic markers in female rats with nephrotoxicity induced by Cis. For that, the animals were divided into five groups (n = 7): control and sedentary (C + S); Cis and sedentary (Cis + S); Cis and LICT (Cis + LICT); Cis and MICT (Cis + MICT) and Cis and HIIT (Cis + HIIT). At the end of 8 weeks of treadmill running, the rats received a single injection of Cis (5 mg/kg), and 7 days later they were euthanized. Serum and kidney samples were collected to assess the blood urea nitrogen (BUN), gene expression of TNF receptor 1 (TNFR1) and 2 (TNFR2), caspase-3, (p38) MAPK (MAPK14), p53, Bax, Bak, Bcl-2, and Bcl-xL, renal levels of IL-11, IL-8, and p53, and immunolocalization of cleaved caspase-3, Bax, Bcl-2, and (p38) MAPK in renal tissue. Our data indicate that all trained groups showed a significant intensity-dependent increase in renal levels of IL-11 associated with reduced local expression of proapoptotic and increased antiapoptotic markers, but these effects were more pronounced with HIIT. So, HIIT appears to provide superior renoprotection than traditional continuous training by modulating apoptotic signaling pathways, and this effect can be related to the increase in renal levels of IL-11.

Performance evaluate of different chemometrics formalisms used for prostate cancer diagnosis by NMR-based metabolomics.

INTRODUCTION: In general, two characteristics are ever present in NMR-based metabolomics studies: (1) they are assays aiming to classify the samples in different groups, and (2) the number of samples is smaller than the feature (chemical shift) number. It is also common to observe imbalanced datasets due to the sampling method and/or inclusion criteria. These situations can cause overfitting. However, appropriate feature selection and classification methods can be useful to solve this issue. OBJECTIVES: Investigate the performance of metabolomics models built from the association between feature selectors, the absence of feature selection, and classification algorithms, as well as use the best performance model as an NMR-based metabolomic method for prostate cancer diagnosis. METHODS: We evaluated the performance of NMR-based metabolomics models for prostate cancer diagnosis using seven feature selectors and five classification formalisms. We also obtained metabolomics models without feature selection. In this study, thirty-eight volunteers with a positive diagnosis of prostate cancer and twenty-three healthy volunteers were enrolled. RESULTS: Thirty-eight models obtained were evaluated using AUROC, accuracy, sensitivity, specificity, and kappa's index values. The best result was obtained when Genetic Algorithm was used with Linear Discriminant Analysis with 0.92 sensitivity, 0.83 specificity, and 0.88 accuracy. CONCLUSION: The results show that the pick of a proper feature selection method and classification model, and a resampling method can avoid overfitting in a small metabolomic dataset. Furthermore, this approach would decrease the number of biopsies and optimize patient follow-up. 1H NMR-based metabolomics promises to be a non-invasive tool in prostate cancer diagnosis.

Deep learning applied to the histopathological diagnosis of ameloblastomas and ameloblastic carcinomas.

BACKGROUND: Odontogenic tumors (OT) are composed of heterogeneous lesions, which can be benign or malignant, with different behavior and histology. Within this classification, ameloblastoma and ameloblastic carcinoma (AC) represent a diagnostic challenge in daily histopathological practice due to their similar characteristics and the limitations that incisional biopsies represent. From these premises, we wanted to test the usefulness of models based on artificial intelligence (AI) in the field of oral and maxillofacial pathology for differential diagnosis. The main advantages of integrating Machine Learning (ML) with microscopic and radiographic imaging is the ability to significantly reduce intra-and inter observer variability and improve diagnostic objectivity and reproducibility. METHODS: Thirty Digitized slides were collected from different diagnostic centers of oral pathology in Brazil. After performing manual annotation in the region of interest, the images were segmented and fragmented into small patches. In the supervised learning methodology for image classification, three models (ResNet50, DenseNet, and VGG16) were focus of investigation to provide the probability of an image being classified as class0 (i.e., ameloblastoma) or class1 (i.e., Ameloblastic carcinoma). RESULTS: The training and validation metrics did not show convergence, characterizing overfitting. However, the test results were satisfactory, with an average for ResNet50 of 0.75, 0.71, 0.84, 0.65, and 0.77 for accuracy, precision, sensitivity, specificity, and F1-score, respectively. CONCLUSIONS: The models demonstrated a strong potential of learning, but lack of generalization ability. The models learn fast, reaching a training accuracy of 98%. The evaluation process showed instability in validation; however, acceptable performance in the testing process, which may be due to the small data set. This first investigation opens an opportunity for expanding collaboration to incorporate more complementary data; as well as, developing and evaluating new alternative models.

Physicians' and nurses' perspective on chronic disease care practices in Primary Health Care in Brazil: a qualitative study.

BACKGROUND: Primary health care-oriented systems provide better healthcare, especially for chronic diseases. This study analyzed the perspectives of physicians and nurses performing care for patients with chronic diseases in Primary Health Care in a Brazilian city. METHODS: A qualitative study was conducted in Vitória da Conquista, Bahia, Brazil, using semi-structured interviews with five physicians and 18 nurses. The interview included questions from an analytical matrix based on three dimensions of healthcare practices: organizational, technical care, and biopsychosocial, following a deductive approach. The interviews were fully transcribed and analyzed using a thematic categorical approach. RESULTS: The results indicated that the provision of chronic care occurs in a comprehensive way. Potentialities were identified in the diversification of access, offer of care actions and technologies, integration of teamwork, and bringing together social networks to foster autonomy and self-care. Weaknesses were mostly related to the high number of people in the teams, follow-up of several cases, high turnover of support teams, low integration of Primary Health Care with other levels, difficulties in intersectoral articulation and family participation in care. CONCLUSION: The multidimensional assessment of health care practices aimed at individuals with chronic noncommunicable diseases was useful to portray the strengths and weaknesses of the services. It also ratifies the need to consider the importance of and investment in primary health care by offering the necessary technical, political, logistical and financial support to the units, to ensure the sustainability of the actions by nurses, doctors and entire team.

Challenges to reducing post-consumer plastic rejects from the MSW selective collection at two MRFs in São Paulo city, Brazil.

​The present study is concerned with an overview of the main aspects of the selective collection from the municipal solid waste in São Paulo City and the limitations of its two automated Material Recovery Facilities (MRFs) to tackle the problem of reducing recyclable plastic waste sent to landfills as rejects. The research aimed to characterize the composition of screened mass flows of as-received mixes from the selective collection at the two MRFs through in situ random collection campaigns. The results of the gravimetric analysis have shown that both MRFs provided higher recovery yields (> 40%) for paper, cardboard, Tetrapack®, ferrous and non-ferrous metals (aluminium), akin to some post-consumer plastics (PET, HDPE/LDPE and PP) that ranged from 38% for PP up to 89% for HDPE, Losses in recovery yields of recyclable plastics after the screening process resulted from lack of clear resin label identification, inefficient materials sortation by households and poor recognition capabilities of the MRFs screening devices to target and segregate specific types of plastics such as PS and vinylic. Packaging design complexity, multi-layered material diversity, and food contaminated post-consumer packaging pose further challenges to improve the plastics recovery capabilities of the two MRFs.

Epidemiology, clinical aspects, outcomes and prognostic factors associated with Trichosporon fungaemia: results of an international multicentre study carried out at 23 medical centres.

BACKGROUND: Trichosporon fungaemia (TF) episodes have increased in recent years and mortality rates remain high despite the advances in the management of sepsis. New concepts about its clinical course, treatment and microbiology need to be investigated for the better management of this infection. OBJECTIVES: To describe the aetiology, natural history, clinical management and prognostic factors of TF. METHODS: TF episodes documented between 2005 and 2018 in 23 South American centres were retrospectively investigated by using a standard clinical form. Molecular identification, antifungal susceptibility testing and biofilm production were also performed. RESULTS: Eighty-eight TF episodes were studied. Patients had several underlying conditions, including haematological diseases (47.7%), post-operative status (34%), solid organ transplants (n = 7, 7.9%), among others. Seventy-three (82.9%) patients had a central venous catheter (CVC) at TF diagnosis. The 30 day mortality rate was 51.1%. Voriconazole-based therapy was given to 34 patients (38.6%), with a 30 day mortality rate of 38.2%. Multivariate predictors of 30 day mortality were age (OR 1.036), mechanical ventilation (OR 8.25) and persistent neutropenia (OR 9.299). CVC removal was associated with over 75% decreased risk of 30 day mortality (OR 0.241). Microbiological analyses revealed that 77.7% of the strains were identified as Trichosporon asahii, and voriconazole showed the strongest in vitro activity against Trichosporon spp. Most of the strains (63%) were considered medium or high biofilm producers. CONCLUSIONS: Older age, mechanical ventilation and persistent neutropenia were associated with poor prognosis. CVC may play a role in the pathogenicity of TF and its removal was associated with a better prognosis.

Low-Back Pain and Knee Position-Related Differences on Postural Control Measures During a One-Legged Stance in Athletes.

CONTEXT: Chronic low-back pain (CLBP) may be associated with changes in postural balance in athletes as poor postural control during sports practice. OBJECTIVE: To compare the postural control of athletes with and without CLBP during 2 one-legged stance tasks and identify the center of pressure (COP) cutoff values to determine the main differences. Designed: A cross-sectional study. SETTING: Laboratory of functional evaluation and human motor performance. PARTICIPANTS: A total of 56 male athletes, 28 with and 28 without CLBP (mean age = 26 y). INTERVENTION: The one-legged stance with knee extension and with the knee at 30° flexion tasks were measured and analyzed on a force platform. The participants completed three 30-second trials (30 s of rest between each trial). MAIN OUTCOME MEASURES: The COP parameters: the area of COP, mean COP sway velocity in both the anteroposterior and mediolateral directions, and total COP displacement were computed, and a receiver operating characteristics curve analysis was applied to determine the group differences. RESULTS: Athletes with CLBP had poorer postural control (P < .01) in both tasks. The 30° knee flexion reported more postural instability than the knee extension for all COP parameters (a large effect size d = 0.80).The knee extension cutoffs identified were >7.1 cm2 for the COP area, >2.6 cm/s for the COP sway velocity in the anterior-posterior direction, and >3.2 cm/s for the mediolateral direction. Whereas, the 30° knee flexion cutoffs were >10.9 cm2 for the COP area, >2.9 cm/s for the COP sway velocity in the anterior-posterior direction, and >4.1 cm/s for the mediolateral direction. Both measures showed enough sensitivity and specificity (ie, area under the curve = 0.88 in and 0.80, respectively) to discriminate both groups. CONCLUSIONS: The athletes with CLBP had poorer postural control than the healthy athletes and obtained specific cutoff scores from the COP values.

Association between increased mortality rate and antibiotic dose adjustment in intensive care unit patients with renal impairment.

PURPOSE: Adjusting the antibiotic dose based on an estimation of the glomerular filtration rate (eGFR) may result in subdosing, which may actually be significantly more problematic for intensive care unit (ICU) patients than not adjusting the dose. The aim of this study was to assess the outcomes of antibiotic dose adjustment in ICU patients with renal impairment. METHODS: A retrospective cohort study was conducted in adult patients admitted to an ICU of a Brazilian hospital from January 2014 to December 2015. The eGFR was determined using Cockcroft-Gault and Modified Diet in Renal Disease equations for each day of hospitalization. Treatment failure was defined based on the clinical, laboratory, and radiological criteria. RESULTS: A total of 126 patients were assessed to meet the inclusion criteria and subsequently enrolled in the study (19.9% of patients admitted to the ICU during the study period). Of the 168 opportunities for dose adjustment, 99 (58.9%) adjustments were made. The mean eGFR in the group with dose adjustment was lower than that in the group without dose adjustment (38.5 vs. 40.7 mL/min/1.73 m2, respectively). The treatment failure rate among patients with dose adjustment and those treated with the usual dose was 59.3 and 38.9%, respectively (p = 0.023), and the mortality rates in the respective groups were 74.1 and 55.5% (p = 0.033). An association between dose adjustment and treatment failure/mortality rates was also observed in the multivariate analysis including the prognostic score. CONCLUSIONS: In ICU patients with renal impairment, adjustments in antibiotic dose based on eGFR, significantly increased the risk of treatment failure and death.

Biochemical changes in injured sciatic nerve of rats after low-level laser therapy (660 nm and 808 nm) evaluated by Raman spectroscopy.

The aim of this study was to identify biochemical changes in sciatic nerve (SN) after crush injury and low-level laser therapy (LLLT) with 660 nm and 808 nm by Raman spectroscopy (RS) analysis. A number of 32 Wistar rats were used, divided into four groups (control 1, control 2, LASER 660 nm, and LASER 808 nm). All animals underwent surgical procedure of the SN and groups control 2, LASER 660 nm, and LASER 808 nm were submitted to SN crush damage (axonotmesis). The LLLT in the groups LASER 660 nm and LASER 808 nm was applied daily for 21 consecutive days (100 mW, 30 s, 133 J/cm2 fluence). The hind paw was removed and the SN was dissected and positioned on an aluminum support to collect dispersive Raman spectra (830 nm excitation, 30 s accumulation). To estimate the biochemical changes in the SN associated with LLLT, the principal component analysis (PCA) was applied. The Raman spectra of the sciatic nerve fragments showed peaks of the major biochemical components of the nerve, especially sphingolipids, phospholipids, glycoproteins, and collagen. The spectral features identified in some of the principal component loading vectors are referred to the biochemical elements present on the SN and were increased in the groups treated with LLLT, mainly lipids (sphingo and phospholipids) and proteins (collagen)-constituents of the myelin sheath. The RS was effective in identifying the biochemical differences in the SN after the crush injury, and LASER 660 nm was more efficient than the LASER 808 nm in cell proliferation and repair of the injured SN.

Anti-inflammatory activity of ß-caryophyllene combined with docosahexaenoic acid in a model of sepsis induced by Staphylococcus aureus in mice.

BACKGROUND: Sepsis is a set of serious organic manifestations caused by an infection, whose progression culminates in exacerbated inflammation and oxidative stress, poor prognosis, and high hospital costs. Antioxidants used against sepsis have been evaluated, including essential oils such as ß-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The aim of this study was to evaluate the anti-inflammatory activity of the association of these two compounds. RESULTS: Treatment with BCP-DHA, at a dose of 200 µL/animal, significantly inhibited the migration of neutrophils in a Cg-induced peritonitis model. After Staphylococcus aureus infection, in the groups treated with BCP-DHA there was a significant decrease in the total and differential count of leukocytes, increased expression of cytokines TNF-α and IFN-γ in treated groups, an increase of IL-4 and IL-5 in B/D and B/D + SA groups, and an augmentation of IL-6 and IL-12 groups in B/D + SA groups. Histological and bacterial analysis revealed lower neutrophil migration and lower bacterial load in the infected and treated groups. CONCLUSION: In general, the BCP-DHA association presented anti-inflammatory activity against two different models of acute inflammation and infection, showing promising potential as a therapeutic adjuvant in sepsis. © 2019 Society of Chemical Industry.

Effect of body mass index and fat mass on balance force platform measurements during a one-legged stance in older adults.

The purpose of this study was to evaluate the impact of body mass index (BMI) and fat mass on balance force platform measurements in older adults. The sample consisted of 257 participants who were stratified into four groups by BMI: low weight, normal weight, pre-obesity and obesity. For fat mass variables, older individuals were classified into low and high-fat mass. All groups investigated performed three trials of one-legged stance balance on a force platform. Center of pressure (COP) domain parameters were computed from the mean across trials. Analysis of variance results revealed no significant interactions for groups and sexes for all COP parameters. Comparable balance results were found for BMI and fat groups for all COP parameters. A statistical effect (P < 0.05) was only reported for sex differences for COP parameters, regardless of BMI and fat mass variables. Overall, women presented better balance than men. In conclusion, BMI and fat mass do not seem to influence the balance of older adults during a one-leg stance task.

Benzodiazepines for restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common disease affecting about 5% to 15% of the population. Symptoms of RLS can be severe in a minority of and can have a major impact on sleep, mostly sleep initiation, and quality of life. Benzodiazepines are drugs that can induce and maintain sleep and, hence, intuitively are thought to be beneficial to people with RLS. Altough benzodiazepines, particularly clonazepam, are used to treat RLS symptoms, a systematic review done by the American Academy of Sleep Medicine stated that benzodiazepines should not be used as a first-line treatment, although could be used as a coadjuvant therapy. OBJECTIVES: To evaluate the efficacy and safety of benzodiazepine compared to placebo or other treatment for idiopathic RLS, including unconfounded trials comparing benzodiazepines versus open control. SEARCH METHODS: In March 2016 we searched CENTRAL, MEDLINE, Embase and LILACS We checked the references of each study and contacted study authors to identify any additional studies. We considered studies published in any language. SELECTION CRITERIA: Randomised clinical trials of benzodiazepine treatment in idiopathic RLS. DATA COLLECTION AND ANALYSIS: We did not perform data collection and analysis, since we did not include any studies, MAIN RESULTS: We did not identify any studies that met the inclusion criteria of the review. Two cross-over studies are awaiting classification because the cross-over trials did not give data at the end of the first cross-over period. AUTHORS' CONCLUSIONS: The effectiveness of benzodiazepines for RLS treatment is currently unknown.

Changes on Walking During Street Crossing Situations and on Dorsiflexion Strength of Older Caribbean Americans After an Exercise Program: A Pilot Study.

The objective of this pilot study was to evaluate a 6-month exercise program completed by 10 older Caribbean Americans. Assessments were done at baseline and 3 and 6 months, and included walks on an instrumented mat at preferred speed, and during street crossing simulations with regular (10 s) and reduced time (5 s). There were no significant differences on preferred walking speed over time. Differences between the street crossing conditions were found only at 6 months. Significant changes over time among the assessments were found only during street crossing with reduced time. Street crossing with reduced time was the only walking condition sensitive to capture changes associated with participating in the exercise program. There was a significant increase in dorsiflexion strength overtime. At 6 months it was significantly higher than at baseline and 3 months. The program was feasible, acceptable, and had some positive effects on walking, knee flexion, and dorsiflexion strength.

Fatal hepatocellular carcinoma presenting with oral metastasis in a patient with synchronic primary malignancies of prostate and liver.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent type of liver cancer and its occurrence in the oral cavity as a metastatic neoplasm is a rare event. We describe a fatal case of HCC with oral metastasis in a patient firstly diagnosed with prostatic and hepatic carcinomas. The histopathological examination revealed a hepatocyte-like tumour cells arranged in organoid structures as well as positivity to cytokeratin 8 and Hep Par 1. The present findings highlight the importance of a complete medical evaluation of the patient to identify possible oral repercussions of primary diseases.

Effects of Holding an External Load on the Standing Balance of Older and Younger Adults With and Without Chronic Low Back Pain.

OBJECTIVE: The purpose of this study was to assess the effect of holding an external load on the standing balance of younger and older adults with and without chronic low back pain (CLBP). METHODS: Twenty participants with and 20 without CLBP participated in the study. Each group contained 10 younger (50% men) and 10 older adults (50% men). Participants were instructed to look straight ahead while standing on a force platform during two 120-second trials with and without holding an external load (10% of body mass). The center of pressure area, mean velocity, and mean frequency in the anteroposterior and mediolateral directions were measured. RESULTS: Older adults had worse standing balance than younger adults did (P < .001, d = 0.20). There were no significant balance differences between participants with and without CLBP within age groups during standing balance condition. However, holding the external load significantly increased postural instability for both age groups and CLBP status, with mean effect size across center of pressure variables of d = 0.82 for older participants without CLBP and d = 2.65 for younger participants without CLBP. These effects for people with CLBP were d = 1.65 for subgroup of older and d = 1.60 for subgroup of younger participants. CONCLUSION: Holding an external load of 10% of body mass increased postural instability of both younger and older adults with and without CLBP.

Pharmacological treatment for Kleine-Levin syndrome.

BACKGROUND: This is an updated version of the original Cochrane review, published in 2009, Issue 2.Kleine-Levin syndrome (KLS) is a rare disorder that mainly affects adolescent men. It is characterised by recurrent episodes of hypersomnia, usually accompanied by hyperphagia, cognitive and mood disturbances, abnormal behaviour, such as hypersexuality, and signs of dysautonomia.In 1990, the diagnostic criteria for Kleine-Levin syndrome were modified in the International Classification of Sleep Disorders, where KLS was defined as a syndrome comprised of recurring episodes of undue sleepiness lasting some days, which may or may not be associated with hyperphagia and abnormal behaviour. According to the International Classification of Sleepiness Disorders, 3rd version (ICSD-3), revised in 2014, the Kleine-Levin syndrome is a disorder characterized by recurrent episodes of hypersomnia that last from two days to four weeks, with at least annual recurrence, and hyperphagia (rapid consumption of a large amount of food), usually with onset in early adolescence in males but occasionally in later life and in women. A monosymptomatic form of the disorder with hypersomnia only can occur without binge eating or hypersexuality.The cause of Kleine-Levin syndrome remains unknown, and several treatment strategies have been used. Some medications have been reported to provide benefit in the treatment of patients with KLS, but because of the rarity of the condition, no long-term follow-up therapies have yet been described. OBJECTIVES: This review aimed to evaluate:1. whether pharmacological treatment for Kleine Levin syndrome was effective and safe.2. which drug or category of drugs was effective and safe. SEARCH METHODS: For the latest update, we searched the following sources: the Cochrane Epilepsy Group Specialized Register (7 April 2016); the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online CRSO (7 April 2016); MEDLINE (1946 to April 2016); LILACS (7 April 2016); ClinicalTrials.gov (7 April 2016); WHO International Clinical Trials Registry Platform ICTRP (7 April 2016); reference lists of sleep medicine textbooks; review articles and reference lists of articles identified by the search strategies. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-randomised controlled trials looking at pharmacological interventions for Kleine-Levin syndrome were eligible. We had planned to include both parallel-group and cross-over studies. DATA COLLECTION AND ANALYSIS: Two review authors (MMO and CC) had planned to extract the data reported in the original articles. MAIN RESULTS: No studies met the inclusion criteria for this systematic review. AUTHORS' CONCLUSIONS: Therapeutic trials of pharmacological treatment for Kleine-Levin syndrome with a double-blind, placebo-controlled design are needed.

Opioids for restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a distressing and common neurological disorder that may have a huge impact in the quality of life of those with frequent and intense symptoms. Patients complain of unpleasant sensations in the legs, at or before bedtime, and feel an urge to move the legs, which improves with movement, such as walking. Symptoms start with the patient at rest (e.g. sitting or lying down), and follow a circadian pattern, increasing during the evening or at night. Many pharmacological intervention are available for RLS, including drugs used to treat Parkinson's disease (L-Dopa and dopaminergic agonists), epilepsy (anticonvulsants), anxiety (benzodiazepines), and pain (opioids). Dopaminergic drugs are those most frequently used for treatment of RLS, but some patients do not respond effectively and require other medication. Opioids, a class of medications used to treat severe pain, seem to be effective in treating RLS symptoms, and are recommended for patients with severe symptoms, because RLS and pain appear to share the same mechanism in the central nervous system. All available drugs are associated to some degree with side effects, which can impede treatment. Opioids are associated with adverse events such as constipation, tolerance, and dependence. This justifies the conduct of a systematic review to ascertain whether opioids are safe and effective for treatment of RLS. OBJECTIVES: To asses the effects of opioids compared to placebo treatment for restless legs syndrome in adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled trials, CENTRAL 2016, issue 4 and MEDLINE, EMBASE, and LILACS up to April 2016, using a search strategy adapted by Cochraneto identify randomised clinical trials. We checked the references of each study and established personal communication with other authors to identify any additional studies. We considered publications in all languages. SELECTION CRITERIA: Randomised controlled clinical trials of opioid treatment in adults with idiopathic RLS. DATA COLLECTION AND ANALYSIS: Two review authors independently screened articles, independently extracted data into a standard form, and assessed for risk of bias. If necessary, they discussed discrepancies with a third researcher to resolve any doubts. MAIN RESULTS: We included one randomised clinical trial (N = 304 randomised; 204 completed; 276 analysed) that evaluated opioids (prolonged release oxycodone/naloxone) versus placebo. After 12 weeks, RSL symptoms had improved more in the drug group than in the placebo group (using the IRLSSS: MD -7.0; 95% CI -9.69 to -4.31 and the CGI: MD -1.11; 95% CI -1.49 to -0.73). More patients in the drug group than in the placebo group were drug responders (using the IRLSSS: RR 1.82; 95% CI 1.37 to 2.42 and the CGI: RR1.92; 95% ICI 1.49 to 2.48). The proportion of remitters was greater in the drug group than in the placebo group (using the IRLSSS: RR 2.14; 95% CI 1.45 to 3.16). Quality of life scores also improved more in the drug group than in the placebo group (MD -0.73; 95% CI -1.1 to -0.36). Quality of sleep was improved more in the drug group measured by sleep adequacy (MD -0.74; 95% CI -1.15 to -0.33), and sleep quantity (MD 0.89; 95% CI 0.52 to 1.26).There was no difference between groups for daytime somnolence, trouble staying awake during the day, or naps during the day. More adverse events were reported in the drug group (RR 1.22; 95% CI 1.07 to 1.39). The major adverse events were gastrointestinal problems, fatigue, and headache. AUTHORS' CONCLUSIONS: Opioids seem to be effective for treating RLS symptoms, but there are no definitive data regarding the important problem of safety. This conclusion is based on only one study with a high dropout rate (moderate quality evidence).