Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro.

Mechanotransduction is defined as the ability of cells to sense mechanical stimuli from their surroundings and translate them into biochemical signals. Epidermal keratinocytes respond to mechanical cues by altering their proliferation, migration, and differentiation. In vitro cell culture, however, utilises tissue culture plastic, which is significantly stiffer than the in vivo environment. Current epidermal models fail to consider the effects of culturing keratinocytes on plastic prior to setting up three-dimensional cultures, so the impact of this non-physiological exposure on epidermal assembly is largely overlooked. In this study, primary keratinocytes cultured on plastic were compared with those grown on 4, 8, and 50 kPa stiff biomimetic hydrogels that have similar mechanical properties to skin. Our data show that keratinocytes cultured on biomimetic hydrogels exhibited major changes in cellular architecture, cell density, nuclear biomechanics, and mechanoprotein expression, such as specific Linker of Nucleoskeleton and Cytoskeleton (LINC) complex constituents. Mechanical conditioning of keratinocytes on 50 kPa biomimetic hydrogels improved the thickness and organisation of 3D epidermal models. In summary, the current study demonstrates that the effects of extracellular mechanics on keratinocyte cell biology are significant and therefore should be harnessed in skin research to ensure the successful production of physiologically relevant skin models.

Follow-up of Metal-on-Metal Hip Replacements at a Large District Hospital and the Implementation of Medicines and Healthcare Products Regulatory Agency Guidelines: A Review of 297 Patients.

BACKGROUND: Medicines and Healthcare products Regulatory Agency (MHRA) guidance for patients with metal-on-metal (MoM) hip replacements was provided in 2012 and updated in 2017 to assist in the early detection of soft-tissue reactions due to metal wear debris. A large number of MoM hip replacements were undertaken at our hospital trust. A program of recall for all patients with MoM hip replacements was undertaken and MHRA guidelines were implemented. In this study, we aimed to investigate the effectiveness of the revised MHRA guidelines in the detection of early adverse reactions to metal debris and to re-evaluate the indications for metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) and revision surgery. METHODS: Identification and recall of all patients with MoM hip replacements from 2001 were conducted by using theatre logs, patient records, clinical coding information, and consultant logbooks. Two senior arthroplasty consultants reviewed X-rays and patient records. Postal questionnaires were forwarded to patients, together with requests for general practitioners to complete cobalt and chromium blood tests. The two consultant-led review of MOM replacements was undertaken with further radiological investigations (X-rays, MARS-MRI) performed according to the 2017 guidance with support of consultant radiologists. RESULTS: Of 674 identified patients, 297 were available for review: 26 patients did not have MoM implants, 36 were untraceable, 59 refused follow-up, 87 moved out of area, 147 had died, and 22 already had revision. Of 297 patients, 126 were women and 171 were men; age range was 39 to 95 years (mean age, 69 years); 126 had resurfacing and 171 had MoM replacements. Twenty-six patients had elevated metal ions. Thirty-three patients underwent MARS-MRI: MARS-MRI results were positive in 17 and negative in 16. Of 17 patients with positive MARS-MRI, 10 patients were asymptomatic and seven were waiting revision. CONCLUSIONS: Positive MARS-MRI can often occur in the absence of elevated metal ion levels; elevated blood metal ion levels do not mean MARS-MRI will be positive. All patients with MoM replacements were at risk. It is imperative to assess patients regularly for symptoms that may raise clinical suspicion and maintain a low threshold to performing MARS-MRI.

A Parent Treatment Program for Preschoolers With Obesity: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Early obesity treatment seems to be the most effective, but few treatments exist. In this study, we examine the effectiveness of a parent-only treatment program with and without booster sessions (Booster or No Booster) focusing on parenting practices and standard treatment (ST). METHODS: Families of children 4 to 6 years of age with obesity were recruited from 68 child care centers in Stockholm County and randomly assigned to a parent-only program (10 weeks) with or without boosters (9 months) or to ST. Treatment effects on primary outcomes (BMI z score) and secondary outcomes (BMI and waist circumference) during a 12-month period were examined with linear mixed models. The influence of sociodemographic factors was examined by 3-way interactions. The clinically significant change in BMI z score (-0.5) was assessed with risk ratios. RESULTS: A total of 174 children (mean age: 5.3 years [SD = 0.8]; BMI z score: 3.0 [SD = 0.6], 56% girls) and their parents (60% foreign background; 39% university degree) were included in the analysis (Booster, n = 44; No Booster, n = 43; ST, n = 87). After 12 months, children in the parent-only treatment had a greater reduction in their BMI z score (0.30; 95% confidence interval [CI]: -0.45 to -0.15) compared with ST (0.07; 95% CI: -0.19 to 0.05). Comparing all 3 groups, improvements in weight status were only seen for the Booster group (-0.54; 95% CI: -0.77 to -0.30). The Booster group was 4.8 times (95% CI: 2.4 to 9.6) more likely to reach a clinically significant reduction of ≥0.5 of the BMI z score compared with ST. CONCLUSION: A parent-only treatment with boosters outperformed standard care for obesity in preschoolers.

Wear properties of poly-ether-ether-ketone bearing combinations under zero and cross shear kinematics in total knee arthroplasty.

Poly-ether-ether-ketone (PEEK), having shown favorable biocompatibility in spinal applications is being considered as an alternative biomaterial in orthopaedics, either as part of an all-polymer bearing couple, or a replacement for the metallic component in hard-on-soft bearings. Throughout the literature ultra-high molecular weight polyethylene exhibits a range of wear behavior dependent upon the amount of cross shear (CS) present in the bearing motion; in comparison, the behavior of PEEK bearing combinations subject to cross shear conditions is less understood. The aim of this study was to investigate the effect of cross shear on PEEK-on-PEEK and PEEK-on-Metal bearing couples. Wear tests were conducted using a four station pin-on-plate rig capable of uni-directional motion (zero cross shear) and multidirectional motion (cross shear); reciprocation (1 Hz), rotation (0 or 1 Hz), with gravimetric wear analysis used to determine the wear factors. The combined wear factors from the PEEK pins articulating on either PEEK or metal plates in this study suggest that it is preferable to use PEEK-on-Metal bearing couples under zero cross shear kinematic conditions and PEEK-on-PEEK for high cross shear applications. PEEK appears to demonstrate a CS dependency when articulating on hard surfaces. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 445-453, 2019.

A combined physical activity and fall prevention intervention improved mobility-related goal attainment but not physical activity in older adults: a randomised trial.

QUESTIONS: In people aged ≥ 60 years, does a combined physical activity and fall prevention intervention affect physical activity and mobility-related goal attainment? Does the combined intervention also improve fall rates, daily steps, the proportion of people meeting the physical activity guidelines, quality of life, mood, fear of falling, and mobility limitation? DESIGN: Randomised trial with concealed allocation, intention-to-treat analysis and assessor blinding. PARTICIPANTS: One hundred and thirty-one people living in the community and aged ≥ 60 years. INTERVENTIONS: The experimental group received one physiotherapist visit, fortnightly telephone-based health coaching, a pedometer, tailored fall prevention advice, and a fall prevention brochure. The control group received the same fall prevention brochure. OUTCOME MEASURES: Primary outcomes were mobility goal attainment (Goal Attainment Scale) and objectively measured physical activity (accelerometer counts per minute) at 6 and 12 months. Secondary outcomes were falls, other physical activity measures, quality of life, fear of falling, mood, and mobility. RESULTS: Participants had a mean age of 71 years (SD 6.5) and 31 (24%) had fallen in the past year. The experimental group reported significantly better mobility goal attainment at 6 months compared to controls (OR 2.0, 95% CI 1.1 to 3.7) but this was not maintained at 12 months (OR 1.1, 95% CI 0.6 to 2.1). Physical activity counts were not significantly different between groups at 6 months (MD 13 counts/minute, 95% CI -98 to 124) or 12 months (MD 56 counts/minute, 95% CI -14 to 125). There were no significant between-group differences in the secondary outcomes. CONCLUSION: A combined physical activity and fall prevention intervention was associated with significantly higher mobility goal attainment at 6 months. There was no significant impact on physical activity but future investigation in a larger trial is warranted. TRIAL REGISTRATION: ACTRN12614000016639.

The More and Less Study: a randomized controlled trial testing different approaches to treat obesity in preschoolers.

BACKGROUND: While obesity has been shown to be difficult to treat in school aged children and in adolescence, promising results have been detected for children who started treatment in early childhood. Yet knowledge on the effectiveness of structured early childhood obesity treatment programs is limited, preventing the widespread implementation of such programs. The main objective of this study is to evaluate the effectiveness of early treatment of childhood obesity with respect to treatment focus (parenting practices or lifestyle), length and intensity. The study will also examine the influence of gender, age, parental weight status, parenting practices, child behavior as well as parents' socioeconomic status and child and parental psychosocial health on children's weight status. METHODS/DESIGN: This is a parallel open label randomized controlled trial assessing two different behavioral treatment approaches offered in three conditions to families with children aged 4-6 years in Stockholm County, Sweden. Children (n = 180) identified as obese will be referred from primary child health care, school health care, and from outpatient pediatric clinics, and randomized to: 1) a standard treatment with focus on lifestyle, provided within the current healthcare system (n = 90); 2) a 10-session, 1.5 h/week group treatment with focus on parenting (n = 45); or 3) the same group treatment as 2) with additional follow-up sessions (n = 45). The primary study outcome is change in children's body mass index standard deviation score (BMI SDS) one year post-baseline. Secondary outcomes include changes in children's waist circumference, metabolic health, lifestyle patterns (Food Frequency Questionnaire), obesity-related child behaviors (Child Eating Behavior Questionnaire and Lifestyle Behavior Checklist, Problem Scale), parents' general and feeding parenting practices (Communicating with Children and Child Feeding Questionnaire) and lifestyle-specific self-efficacy (Lifestyle Behavior Checklist, Confidence Scale), family functioning (Family Assessment Device), child and parental psychosocial health (Child Behavior Checklist and Beck's Depression Inventory II). DISCUSSION: This study will facilitate a close examination of key components of treatment for obesity during early childhood and mechanisms of change. Results from this study will lead to better healthcare options for obesity treatment during early childhood and ultimately to the prevention of obesity later in life. TRIAL REGISTRATION: ClinicalTrials.gov NCT01792531 Registered February 14, 2013.

What is the effect of a combined physical activity and fall prevention intervention enhanced with health coaching and pedometers on older adults' physical activity levels and mobility-related goals? Study protocol for a randomised controlled trial.

BACKGROUND: Physical inactivity and falls in older people are important public health problems. Health conditions that could be ameliorated with physical activity are particularly common in older people. One in three people aged 65 years and over fall at least once annually, often resulting in significant injuries and ongoing disability. These problems need to be urgently addressed as the population proportion of older people is rapidly rising. This trial aims to establish the impact of a combined physical activity and fall prevention intervention compared to an advice brochure on objectively measured physical activity participation and mobility-related goal attainment among people aged 60+. METHODS/DESIGN: A randomised controlled trial involving 130 consenting community-dwelling older people will be conducted. Participants will be individually randomised to a control group (n = 65) and receive a fall prevention brochure, or to an intervention group (n = 65) and receive the brochure plus physical activity promotion and fall prevention intervention enhanced with health coaching and a pedometer. Primary outcomes will be objectively measured physical activity and mobility-related goal attainment, measured at both six and 12 months post randomisation. Secondary outcomes will include: falls, the proportion of people meeting the physical activity guidelines, quality of life, fear of falling, mood, and mobility limitation. Barriers and enablers to physical activity participation will be measured 6 months after randomisation. General linear models will be used to assess the effect of group allocation on the continuously-scored primary and secondary outcome measures, after adjusting for baseline scores. Between-group differences in goal attainment (primary outcome) will be analysed with ordinal regression. The number of falls per person-year will be analysed using negative binomial regression models to estimate the between-group difference in fall rates after one year (secondary outcome). Modified Poisson regression models will compare groups on dichotomous outcome measures. Analyses will be pre-planned, conducted while masked to group allocation and will use an intention-to-treat approach. DISCUSSION: This trial will address a key gap in evidence regarding physical activity and fall prevention for older people and will evaluate a program that could be directly implemented within Australian health services. TRIAL REGISTRATION: ACTRN12614000016639, 7/01/2014.

Introducing GRADE across the NICE clinical guideline program.

OBJECTIVES: Grading of Recommendations Assessment, Development and Evaluation (GRADE) is a system for rating the confidence in estimates of effect and grading guideline recommendations. It promotes evaluation of the quality of the evidence for each outcome and an assessment of balance between desirable and undesirable outcomes leading to a judgment about the strength of the recommendation. In 2007, the National Institute for Health and Clinical Excellence began introducing GRADE across its clinical guideline program to enable separation of judgments about the evidence quality from judgments about the strength of the recommendation. STUDY DESIGN AND SETTING: We describe the process of implementing GRADE across guidelines. RESULTS: Use of GRADE has been positively received by both technical staff and guideline development group members. CONCLUSION: A shift in thinking about confidence in the evidence was required leading to a more structured and transparent approach to decision making. Practical problems were also encountered; these have largely been resolved, but some areas require further work, including the application of imprecision and presenting results from analyses considering more than two alternative interventions. The use of GRADE for nonrandomized and diagnostic accuracy studies needs to be refined.

Do occupational health assessments match guidelines for low back pain?

BACKGROUND: Audit is an important facet of clinical governance and good occupational health practice. There are well-established clinical guidelines for the management of low back pain. Occupational Health Guidelines for the Management of Low Back Pain at Work were launched by the Faculty of Occupational Medicine in March 2000, based on an extensive, systematic review of the scientific literature predominantly from occupational settings or concerning occupational outcomes. AIM: To determine whether documented National Health Service occupational health assessment of low back pain in the North West region of England conforms to the published guidelines. METHODS: A retrospective audit of case notes was conducted. Six performance indicators were derived from the Occupational Health Guidelines for the Management of Low Back Pain at Work in order to evaluate the performance by occupational physicians. Two hundred and seventy-seven case notes were identified from eight different occupational health departments. RESULTS: Low rates of compliance with national standards were observed for recording of some performance indicators, notably for the assessment and documentation of 'red' and 'yellow flags'. Our findings suggest that the quality of documentation of key information in the notes leaves significant room for improvement. CONCLUSIONS: For future audits, we recommend having two external auditors and seek to demonstrate a high degree of agreement between observers by conducting a reproducibility exercise. Future Faculty guidelines should emphasize documentation of the assessment and perhaps consider assessment tools to improve documentation.