Evaluation of mobility recovery after hip fracture: a scoping review of randomized controlled studies.

Few older adults regain their pre-fracture mobility after a hip fracture. Intervention studies evaluating effects on gait typically use short clinical tests or in-lab parameters that are often limited to gait speed only. Measurements of mobility in daily life settings exist and should be considered to a greater extent than today. Less than half of hip fracture patients regain their pre-fracture mobility. Mobility recovery is closely linked to health status and quality of life, but there is no comprehensive overview of how gait has been evaluated in intervention studies on hip fracture patients. The purpose was to identify what gait parameters have been used in randomized controlled trials to assess intervention effects on older people's mobility recovery after hip fracture. This scoping review is a secondary paper that identified relevant peer-reviewed and grey literature from 11 databases. After abstract and full-text screening, 24 papers from the original review and 8 from an updated search and manual screening were included. Records were eligible if they included gait parameters in RCTs on hip fracture patients. We included 32 papers from 29 trials (2754 unique participants). Gait parameters were primary endpoint in six studies only. Gait was predominantly evaluated as short walking, with gait speed being most frequently studied. Only five studies reported gait parameters from wearable sensors. Evidence on mobility improvement after interventions in hip fracture patients is largely limited to gait speed as assessed in a controlled setting. The transition from traditional clinical and in-lab to out-of-lab gait assessment is needed to assess effects of interventions on mobility recovery after hip fracture at higher granularity in all aspects of patients' lives, so that optimal care pathways can be defined.

Mortality after hospital admission for trauma in Norway: A retrospective observational national cohort study.

BACKGROUND: National quality data for trauma care in Norway have not previously been reported. We have therefore assessed crude and risk-adjusted 30-day mortality in trauma cases after primary hospital admission on national and regional levels for 36 acute care hospitals and four regional trauma centres. METHODS: All patients in the Norwegian Trauma Registry in 2015-2018 were included. Crude and risk-adjusted 30-day mortality was assessed for the total cohort and for severe injuries (Injury Severity Score ≥16), and individual and combined effects of health region, hospital level, and hospital size were studied. RESULTS: 28,415 trauma cases were included. Crude mortality was 3.1% for the total cohort and 14.5% for severe injuries, with no statistically significant difference between regions. Risk-adjusted survival was lower in acute care hospitals than in trauma centres (0.48 fewer excess survivors per 100 patients, P<0.0001), amongst severely injured patients in the Northern health region (4.80 fewer excess survivors per 100 patients, P = 0.004), and in hospitals with <100 trauma admissions per year (0.65 fewer excess survivors than in hospitals with ≥100 admissions, P = 0.01). However, the only statistically significant effects in a multivariable logistic case mix-adjusted descriptive model were hospital level and health region. Case-mix adjusted odds ratio for survival for severely injured patients directly admitted to a trauma centre vs. an acute care hospital was 2.04 (95% CI 1.04-4.00, P = 0.04), and if admitted in the Northern health region vs. all other health regions was 0.47 (95% CI 0.27-0.84, P = 0.01). The proportion of cases admitted directly to the regional trauma centre in the sparsely populated Northern health region was half of that in the other regions (18.4% vs. 37.6%, P<0.0001). CONCLUSION: Differences in risk-adjusted survival for severe injuries can to a large extent be attributed to whether patients are directly admitted to a trauma centre. This should have implications for planning of transport capacity in remote areas.

Development of video tutorials to help parents manage children with acute illnesses using a modified Delphi method.

AIM: Children often fall sick, which causes concern among parents. Online health information can be confusing and difficult to understand. We aimed to produce simple, informative video tutorials on the symptoms ill children present. METHODS: We used a modified Delphi method to produce video tutorials on the symptoms of fever, vomiting and diarrhoea, abdominal pain, breathing difficulties, sore throat, red eyes, earache and rash. We identified the most common symptoms in acutely ill children. During the first consensus round, experts rated statements on out-of-hospital management from existing health information. Video tutorials were produced from statements rated to be included. The second consensus round involved video showings and editing. Two videos were evaluated in focus groups by parents. RESULTS: During the first round, experts rated a median of 79 (40-154) statements for each symptom. Panels consisted of a median of seven (6-11) experts, primarily. Panels reached a consensus on inclusion, neutrality or exclusion in 83% of statements. The second round led to adjustments to the videos and final approval by experts. Most parents evaluated the videos as 'informative, easy to understand and calming'. CONCLUSION: We produced video tutorials on the common symptoms ill children present using a modified Delphi method. Feedback from parents in focus groups was positive.

Evaluation of the EQ-5D-3L and 5L versions in low back pain patients.

BACKGROUND: The EuroQol EQ-5D is one of the most widely researched and applied patient-reported outcome measures worldwide. The original EQ-5D-3L and more recent EQ-5D-5L include three and five response categories respectively. Evidence from healthy and sick populations shows that the additional two response categories improve measurement properties but there has not been a concurrent comparison of the two versions in patients with low back pain (LBP). METHODS: LBP patients taking part in a multicenter randomized controlled trial of lumbar total disc replacement and conservative treatment completed the EQ-5D-3L and 5L in an eight-year follow-up questionnaire. The 3L and 5L were assessed for aspects of data quality including missing data, floor and ceiling effects, response consistency, and based on a priori hypotheses, associations with the Oswestry Disability Index (ODI), Pain-Visual Analogue Scales and Hopkins Symptom Checklist (HSCL-25). RESULTS: At the eight-year follow-up, 151 (87%) patients were available and 146 completed both the 3L and 5L. Levels of missing data were the same for the two versions. Compared to the EQ-5D-5L, the 3L had significantly higher floor (pain discomfort) and ceiling effects (mobility, self-care, pain/discomfort, anxiety/depression). For these patients the EQ-5D-5L described 73 health states compared to 28 for the 3L. Shannon's indices showed the 5L outperformed the 3L in tests of classification efficiency. Correlations with the ODI, Pain-VAS and HSCL-25 were largely as hypothesized, the 5L having slightly higher correlations than the 3L. CONCLUSION: The EQ-5D assesses important aspect of health in LBP patients and the 5L improves upon the 3L in this respect. The EQ-5D-5L is recommended in preference to the 3L version, however, further testing in other back pain populations together with additional measurement properties, including responsiveness to change, is recommended. TRIAL REGISTRATION: retrospectively registered: https://clinicaltrials.gov/ct2/show/NCT01704677 .

Prediction of radiation-induced mucositis of H&N cancer patients based on a large patient cohort.

PURPOSE/OBJECTIVE: Radiation-induced mucositis is a severe acute side effect, which can jeopardize treatment compliance and cause weight loss during treatment. The study aimed to develop robust models to predict the risk of severe mucositis. MATERIALS/METHODS: Mucosal toxicity scores were prospectively recorded for 802 consecutive Head and Neck (H&N) cancer patients and dichotomised into non-severe event (grade 0-2) and severe event (grade 3+) groups. Two different model approaches were utilised to evaluate the robustness of the models. These used LASSO and Best Subset selection combined with 10-fold cross-validation performed on two-thirds of the patient cohort using principal component analysis of DVHs. The remaining one-third of the patients were used for validation. Model performance was tested through calibration plot and model performance metrics. RESULTS: The main predicted risk factors were treatment acceleration and the first two principal dose components, which reflect the mean dose and the balance between high and low doses to the oral cavity. For the LASSO model, gender and current smoker status were also included in the model. The AUC values of the two models on the validation cohort were 0.797 (95%CI: 0.741-0.857) and 0.808 (95%CI: 0.749-0.859), respectively. The two models predicted very similar risk values with an internal Pearson coefficient of 0.954, indicating their robustness. CONCLUSIONS: Robust prediction models of the risk of severe mucositis have been developed based on information from the entire dose distribution for a large cohort of patients consisting of all patients treated H&N for within our institution over a five year period.

NTCP model validation method for DAHANCA patient selection of protons versus photons in head and neck cancer radiotherapy.

Introduction: Prediction models using logistic regression may perform poorly in external patient cohorts. However, there is a need to standardize and validate models for clinical use. The purpose of this project was to describe a method for validation of external NTCP models used for patient selection in the randomized trial of protons versus photons in head and neck cancer radiotherapy, DAHANCA 35. Material and methods: Organs at risk of 588 patients treated primarily with IMRT in the randomized controlled DAHANCA19 trial were retrospectively contoured according to recent international recommendations. Dose metrics were extracted using MatLab and all clinical parameters were retrieved from the DAHANCA database. The model proposed by Christianen et al. to predict physician-rated dysphagia was validated through the closed testing, where change of the model intercept, slope and individual beta's were tested for significant prediction improvements. Results: Six months prevalence of dysphagia in the validation cohort was 33%. The closed testing procedure for physician-rated dysphagia showed that the Christianen et al. model needed an intercept refitting for the best match for the Danish patients. The intercept update increased the risk of dysphagia for the validation cohort by 7.9 ± 2.5% point. For the raw model performance, the Brier score (mean squared residual) was 0.467, which improved significantly with a new intercept to 0.415. Conclusions: The previously published Dutch dysphagia model needed an intercept update to match the Danish patient cohort. The implementation of a closed testing procedure on the current validation cohort allows quick and efficient validation of external NTCP models for patient selection in the future.

Relationship between patient and physician-rated xerostomia and dose distribution to the oral cavity and salivary glands for head and neck cancer patients after radiotherapy.

Introduction: Xerostomia is a frequent complication after curative intended radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC). Assessment of xerostomia is commonly done by the physician. The aim of this study is to investigate the relation between patient and physician-rated xerostomia and to predict the degree of xerostomia from patients with self-reported xerostomia based on delivered doses to the oral cavity, parotid, and submandibular glands. Material and methods: During a 2-year period, consecutive HNSCC patients attending the follow-up clinic were included. All included patients had self-reported xerostomia, and completed the disease-specific EORTC QLQ-H&N35 questionnaire. The physician assessed the degree of xerostomia with the DAHANCA toxicity scale and was blinded for the EORTC score. Oral cavity, parotid, and submandibular glands (OAR) were delineated on the planning CT according to international guidelines. DVH were extracted from treatment plans. Logistic regression tested the relation between mean doses, patient characteristics, and xerostomia scores. Differences between DVH values and scoring of xerostomia were analyzed with a Kruskal-Wallis test. The relation between xerostomia and dose distributions was further investigated using principal component analysis (PCA). Results: In total, 109 patients were included in the study. A weak correlation was seen between patient and physician-rated toxicity (p = .001), however, in general patients reported more toxicity than physicians. For EORTC score ≥2, the multi-variable analysis was significant for doses to the oral cavity, tobacco status and use of xerogenic medication. Neither the DVH analysis nor the PCA found any clear distinction between xerostomia scores for EORTC or DAHANCA and investigated OARs. Conclusion: Patients tended to report higher scores of xerostomia than the physician. PCA indicated a complex relation between doses to the OAR and xerostomia scores, showing e.g., that reducing doses in one organ was on the expense of increased dose to another organ.

Olive oil quality classification and measurement of its organoleptic attributes by untargeted GC-MS and multivariate statistical-based approach.

The capabilities of dynamic headspace entrainment followed by thermal desorption in combination with gas chromatography (GC) coupled to single quadrupole mass spectrometry (MS) have been tested for the determination of volatile components of olive oil. This technique has shown a great potential for olive oil quality classification by using an untargeted approach. The data processing strategy consisted of three different steps: component detection from GC-MS data using novel data treatment software PARADISe, a multivariate analysis using EZ-Info, and the creation of the statistical models. The great number of compounds determined enabled not only the development of a quality classification method as a complementary tool to the official established method "PANEL TEST" but also a correlation between these compounds and different types of defect. Classification method was finally validated using blind samples. An accuracy of 85% in oil classification was obtained, with 100% of extra virgin samples correctly classified.

Fetal over- and undernutrition differentially program thyroid axis adaptability in adult sheep.

OBJECTIVE: We aimed to test, whether fetal under- or overnutrition differentially program the thyroid axis with lasting effects on energy metabolism, and if early-life postnatal overnutrition modulates implications of prenatal programming. DESIGN: Twin-pregnant sheep (n = 36) were either adequately (NORM), under- (LOW; 50% of NORM) or overnourished (HIGH; 150% of energy and 110% of protein requirements) in the last-trimester of gestation. From 3 days-of-age to 6 months-of-age, twin lambs received a conventional (CONV) or an obesogenic, high-carbohydrate high-fat (HCHF) diet. Subgroups were slaughtered at 6-months-of-age. Remaining lambs were fed a low-fat diet until 2½ years-of-age (adulthood). METHODS: Serum hormone levels were determined at 6 months- and 2½ years-of-age. At 2½ years-of-age, feed intake capacity (intake over 4-h following 72-h fasting) was determined, and an intravenous thyroxine tolerance test (iTTT) was performed, including measurements of heart rate, rectal temperature and energy expenditure (EE). RESULTS: In the iTTT, the LOW and nutritionally mismatched NORM:HCHF and HIGH:CONV sheep increased serum T3, T3:T4 and T3:TSH less than NORM:CONV, whereas TSH was decreased less in HIGH, NORM:HCHF and LOW:HCHF. Early postnatal exposure to the HCHF diet decreased basal adult EE in NORM and HIGH, but not LOW, and increased adult feed intake capacity in NORM and LOW, but not HIGH.Conclusions: The iTTT revealed a differential programming of central and peripheral HPT axis function in response to late fetal malnutrition and an early postnatal obesogenic diet, with long-term implications for adult HPT axis adaptability and associated consequences for adiposity risk.

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium.

BACKGROUND: Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. METHODS: This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). RESULTS: Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (ß std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. CONCLUSIONS: Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium.

OBJECTIVE: Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia. METHOD: This prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness. RESULTS: Positive symptom severity was negatively related to STG thickness in both hemispheres (left: ßstd = -0.052; P = 0.021; right: ßstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness. CONCLUSION: Our findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.

Brain volume change in first-episode psychosis: an effect of antipsychotic medication independent of BMI change.

OBJECTIVE: The effect of antipsychotic medication on brain structure remains unclear. Given the prevalence of weight gain as a side-effect, body mass index (BMI) change could be a confounder. METHOD: Patients with first-episode psychosis (n = 78) and healthy controls (n = 119) underwent two 1.5T MRI scans with a 1-year follow-up interval. siena (fsl 5.0) was used to measure whole-brain volume change. Weight and height were measured at both time points. Antipsychotic medication use at baseline and follow-up was converted into chlorpromazine equivalent dose and averaged. RESULTS: Patients did not show significantly larger brain volume loss compared with healthy controls. In the whole sample (n = 197), BMI change was negatively associated with brain volume change (ß = -0.19, P = 0.008); there was no interaction effect of group. Among patients, higher antipsychotic medication dosage was associated with greater brain volume loss (ß = -0.45, P < 0.001). This association was not affected by adjusting for BMI change. CONCLUSION: Weight gain was related to brain volume reductions to a similar degree among patients and controls. Antipsychotic dosage-related reductions of brain volume were not confounded by BMI change. Generalizability to contexts involving severe weight gain needs to be established. Furthermore, disentangling effects of medication from illness severity remains a challenge.

Alcohol use is associated with thinner cerebral cortex and larger ventricles in schizophrenia, bipolar disorder and healthy controls.

BACKGROUND: Excessive alcohol use is associated with brain damage but less is known about brain effects from moderate alcohol use. Previous findings indicate that patients with severe mental illness, particularly schizophrenia, are vulnerable to alcohol-related brain damage. We investigated the association between levels of alcohol consumption and cortical and subcortical brain structures in schizophrenia and bipolar disorder patients and healthy controls, and investigated for group differences for this association. METHOD: 1.5 T structural magnetic resonance images were acquired of 609 alcohol-using participants (165 schizophrenia patients, 172 bipolar disorder patients, 272 healthy controls), mean (s.d.) age 34.2 (9.9) years, 52% men. Past year alcohol use was assessed with the Alcohol Use Disorder Identification Test - Consumption part (AUDIT-C). General linear models were used to investigate associations between AUDIT-C score and cortical thickness, surface area, and total brain and subcortical volumes. RESULTS: Increasing AUDIT-C score was linearly associated with thinner cortex in medial and dorsolateral frontal and parieto-occipital regions, and with larger left lateral ventricle volume. There was no significant interaction between AUDIT-C score and diagnostic group. The findings remained significant after controlling for substance use disorders, antipsychotic medication and illness severity. CONCLUSION: The results show a dose-dependent relationship between alcohol use and thinner cortex and ventricular expansion. The findings are present also at lower levels of alcohol consumption and do not differ between schizophrenia or bipolar disorder patients compared to healthy controls. Our results do not support previous findings of increased vulnerability for alcohol-related brain damage in severe mental illness.

Acute exercise and motor memory consolidation: Does exercise type play a role?

A single bout of high-intensity exercise can augment off-line gains in skills acquired during motor practice. It is currently unknown if the type of physical exercise influences the effect on motor skill consolidation. This study investigated the effect of three types of high-intensity exercise following visuomotor skill acquisition on the retention of motor memory in 40 young (25.3 ±3.6 years), able-bodied male participants randomly assigned to one of four groups either performing strength training (STR), circuit training (CT), indoor hockey (HOC) or rest (CON). Retention tests of the motor skill were performed 1 (R1h) and 24 h (R1d) post acquisition. For all exercise groups, mean motor performance scores decreased at R1h compared to post acquisition (POST) level; STR (P = 0.018), CT (P = 0.02), HOC (P = 0.014) and performance scores decreased for CT compared to CON (P = 0.049). Mean performance scores increased from POST to R1d for all exercise groups; STR (P = 0.010), CT (P = 0.020), HOC (P = 0.007) while performance scores for CON decreased (P = 0.043). Changes in motor performance were thus greater for STR (P = 0.006), CT (P < 0.001) and HOC (P < 0.001) compared to CON from POST to R1d. The results demonstrate that high-intensity, acute exercise can lead to a decrease in motor performance assessed shortly after motor skill practice (R1h), but enhances offline effects promoting long-term retention (R1d). Given that different exercise modalities produced similar positive off-line effects on motor memory, we conclude that exercise-induced effects beneficial to consolidation appear to depend primarily on the physiological stimulus rather than type of exercise and movements employed.

Increased MRI-based cortical grey/white-matter contrast in sensory and motor regions in schizophrenia and bipolar disorder.

BACKGROUND: Schizophrenia and bipolar disorder share genetic risk factors and one possible illness mechanism is abnormal myelination. T1-weighted magnetic resonance imaging (MRI) tissue intensities are sensitive to myelin content. Therefore, the contrast between grey- and white-matter intensities may reflect myelination along the cortical surface. METHOD: MRI images were obtained from patients with schizophrenia (n = 214), bipolar disorder (n = 185), and healthy controls (n = 278) and processed in FreeSurfer. The grey/white-matter contrast was computed at each vertex as the difference between average grey-matter intensity (sampled 0-60% into the cortical ribbon) and average white-matter intensity (sampled 0-1.5 mm into subcortical white matter), normalized by their average. Group differences were tested using linear models covarying for age and sex. RESULTS: Patients with schizophrenia had increased contrast compared to controls bilaterally in the post- and precentral gyri, the transverse temporal gyri and posterior insulae, and in parieto-occipital regions. In bipolar disorder, increased contrast was primarily localized in the left precentral gyrus. There were no significant differences between schizophrenia and bipolar disorder. Findings of increased contrast remained after adjusting for cortical area, thickness, and gyrification. We found no association with antipsychotic medication dose. CONCLUSIONS: Increased contrast was found in highly myelinated low-level sensory and motor regions in schizophrenia, and to a lesser extent in bipolar disorder. We propose that these findings indicate reduced intracortical myelin. In accordance with the corollary discharge hypothesis, this could cause disinhibition of sensory input, resulting in distorted perceptual processing leading to the characteristic positive symptoms of schizophrenia.

Neuronal death in the dorsal root ganglion after sciatic nerve injury does not depend on sortilin.

Injury to the sciatic nerve induces loss of sensory neurons in the affected dorsal root ganglia (DRGs). Previous studies have suggested the involvement of the neurotrophin receptors p75 neurotrophin receptor (p75(NTR)) and sortilin, proposing that sensory neuron subpopulations undergo proneurotrophin-induced apoptosis in a similar manner to what can be observed in the CNS following injury. To further investigate this hypothesis we induced sciatic nerve injury in sortilin-deficient mice, thereby preventing apoptotic signaling of proneurotrophins via the sortilin-p75(NTR) receptor complex. Using an unbiased stereological approach we found that loss of sortilin did not prevent the injury-induced loss of DRG neurons. This result demonstrates that previous findings linking p75(NTR) and proneurotrophins to loss of sensory neurons need to involve sortilin-independent pathways and suggests that proneurotrophins may elicit different functions in the CNS and PNS.

The Neck Disability Index (NDI) and its correlation with quality of life and mental health measures among patients with single-level cervical disc disease scheduled for surgery.

BACKGROUND: The Neck Disability Index (NDI) is widely used as a self-rated disability score in patients with cervical radiculopathy. The purpose of this study was to evaluate whether the NDI score correlated with other assessments of quality of life and mental health in a specific group of patients with single-level cervical disc disease and corresponding radiculopathy. METHODS: One hundred thirty-six patients were included in a prospective, randomized controlled clinical multicenter study on one-level anterior cervical discectomy with arthroplasty (ACDA) versus one-level anterior cervical discectomy with fusion (ACDF). The preoperative data were obtained at hospital admission 1 to 3 days prior to surgery. The NDI score was used as the dependent variable and correlation as well as regression analyses were conducted to assess the relationship with the short form-36, EuroQol-5Dimension-3 level and Hospital Anxiety and Depression Scale. RESULTS: The mean age at inclusion was 44.1 years (SD ±7.0, range 26-59 years), of which 46.3 % were male. Mean NDI score was 48.6 (SD = 12.3, minimum 30 and maximum 88). Simple linear regression analysis demonstrated a significant correlation between NDI and the EuroQol-5Dimension-3 level [R = -0.64, 95 % confidence interval (CI) -30.1- -19.8, p < 0.001] and to a lesser extent between NDI and the short form-36 physical component summary [R = -0.49, 95 % CI (-1.10- -0.58), p < 0.001] and the short form-36 mental component summary [R = -0.25, 95 % CI (-0.47- -0-09), p = 0.004]. Regarding NDI and the Hospital Anxiety and Depression Scale, a significant correlation for depression was found [R = 0.26, 95 % CI (0.21-1.73), p = 0.01]. Multiple linear regression analysis showed a statistically significant and the strongest correlation between NDI and the independent variables in the following order: EuroQol-5Dimension-3 level [R = -0.64, 95 % CI (-23.5- -7.9), p <0.001], short form-36 physical component summary [R = -0.41, 95 % CI (-0.93- -0.23), p = 0.001] and short form-36 mental component summary [R = -0.36, 95 % CI (-0.53- -0.15), p = 0.001]. CONCLUSION: The results from the present study show that the NDI correlated significantly with a different quality of life and mental health measures among patients with single-level cervical disc disease and corresponding radiculopathy.

In vitro and in vivo dermal absorption assessment of acetyl aspartic acid: a compartmental study.

OBJECTIVE: The purpose of this study was to evaluate the dermal absorption of acetyl aspartic acid (A-A-A) through an in vitro and in vivo evaluation with human skin after 6 and 24 h of topical application of a cosmetic formulation containing A-A-A at 1%. METHODS: The in vitro experiment was carried out using the Franz diffusion cells system with ex vivo human skin samples. The profile of diffusion of A-A-A was evaluated after 6 and 24 h. The in vivo experiment was performed on human volunteers following a tape-stripping protocol after 6 h of topical application. A-A-A was quantified in the main skin compartments, that is the skin surface, the stratum corneum, the skin and the receptor fluid using LC-MS analysis. RESULTS: The 24-h in vitro experiment confirmed the great penetration potential of A-A-A in all skin compartments. After 6 h of topical application, the removed tape strips from both in vitro and in vivo experiments were analysed and the profile of diffusion of A-A-A was determined, allowing also an in vitro/in vivo comparison. The diffusion profile observed on the in vitro skin penetration test is highly representative of the in vivo situation evaluated on volunteers. CONCLUSION: The combination of in vitro with in vivo data confirmed that A-A-A has the capacity to diffuse through the skin after topical application and reach the dermis as the targeted skin layer for potential anti-ageing benefits.

The use of gene arrays and corresponding connectivity mapping (Cmap) to identify novel anti-ageing ingredients.

OBJECTIVE: The need for effective 'anti-ageing' treatments, in particular for the management of photodamaged skin, prompted us to develop a novel method to identify new active ingredients. The model utilized a gene profiling study with corresponding connectivity mapping (Cmap) to identify novel anti-ageing compounds using all-trans retinoic acid (RA) as the lead compound due to its beneficial effect on photodamaged skin and skin firmness. METHOD: A vehicle-controlled clinical study including nine healthy Caucasian female volunteers aged 57 ± 7 (mean ± SEM) exhibiting photodamage on their lower outer forearms was conducted. The volunteers applied RA once daily on photodamaged skin for 7 days, and biopsies were subjected to Affymetrix gene arrays. Connectivity mapping (Cmap), examining hundreds of gene expression profiles, was run on the gene signature of RA-treated photodamaged skin to identify small bioactive compounds. RESULTS: Affymetrix gene array identified 19 genes significantly differentially expressed after application of RA. Corresponding Cmap analysis revealed six natural bioactive compounds including N-acetyl aspartic acid (A-A-A) showing similar activity to RA on the differentially expressed genes identified. CONCLUSION: Based on RA mimicking gene array activity, potential use within skincare on molecular size, safety assessment and sourcing, we identified the natural amino acid, A-A-A as a potential candidate to treat ageing skin.