Validation, Deployment, and Real-World Implementation of a Modular Toolbox for Alzheimer's Disease Detection and Dementia Risk Reduction: The AD-RIDDLE Project.

The Real-World Implementation, Deployment, and Validation of Early Detection Tools and Lifestyle Enhancement (AD-RIDDLE) project, recently launched with the support of the EU Innovative Health Initiative (IHI) public-private partnership and UK Research and Innovation (UKRI), aims to develop, test, and deploy a modular toolbox platform that can reduce existing barriers to the timely detection, and therapeutic approaches in Alzheimer's disease (AD), thus accelerating AD innovation. By focusing on health system and health worker practices, AD-RIDDLE seeks to improve and smooth AD management at and between each key step of the clinical pathway and across the disease continuum, from at-risk asymptomatic stages to early symptomatic ones. This includes innovation and improvement in AD awareness, risk reduction and prevention, detection, diagnosis, and intervention. The 24 partners in the AD-RIDDLE interdisciplinary consortium will develop and test the AD-RIDDLE toolbox platform and its components individually and in combination in six European countries. Expected results from this cross-sectoral research collaboration include tools for earlier detection and accurate diagnosis; validated, novel digital cognitive and blood-based biomarkers; and improved access to individualized preventative interventions (including multimodal interventions and symptomatic/disease-modifying therapies) across diverse populations, within the framework of precision medicine. Overall, AD-RIDDLE toolbox platform will advance management of AD, improving outcomes for patients and their families, and reducing costs.

Novel insights into patient's thoughts about their body image in abdominal wall hernia.

BACKGROUND: Abdominal wall hernias (AWH) are frequently large and deforming. Despite this, little is known about how AWH impact upon body image. This study is the first study to qualitatively examine patients' subjective lived experiences of how AWH affects their body image. METHODS: Fifteen patients were interviewed from a purposive sample of AWH patients awaiting surgery until no new narrative themes emerged. Interviews explored patient thoughts and experiences of AWH and body image. Data were examined using interpretative phenomenological analysis (IPA). RESULTS: Two key themes pertaining to body image were identified: "Changes to perceptions of self" and "Fears concerning other's perceptions of them". Both themes were often interrelated and displayed detrimental effects AWH had on patients' body image. CONCLUSIONS: Our findings illustrate that AWH detrimentally affected patients' body image. This aspect of patient care can be treated and managed through better pre-operative information, including on body image as part of a holistic needs assessment (HNA), and ensuring the results are addressed in a patient care package. These development suggestions may positively affect the AWH patient's experience and outcomes in terms of Quality of Life (QoL) by preparing patients better for realistic results regarding what can be achieved in terms of form, function thus making a more holistic recovery from surgery.

A structured pathway for developing your complex abdominal hernia service: our York pathway.

PURPOSE: Clinical pathways are widely prevalent in health care and may be associated with increased clinical efficacy, improved patient care, streamlining of services, while providing clarity on patient management. Such pathways are well established in several branches of healthcare services but, to the authors' knowledge, not in complex abdominal wall reconstruction (CAWR). A stepwise, structured and comprehensive approach to managing complex abdominal wall hernia (CAWH) patients, which has been successfully implemented in our practice, is presented. METHODS: A literature search of common databases including Embase® and MEDLINE® for CAWH pathways identified no comprehensive pathway. We therefore undertook a reiterative process to develop the York Abdominal Wall Unit (YAWU) through examination of current evidence and logic to produce a pragmatic redesign of our own pathway. Having introduced our pathway, we then performed a retrospective analysis of the complexity and number of abdominal wall cases performed in our trust over time. RESULTS: We describe our pathway and demonstrate that the percentage of cases and their complexity, as defined by the VHWG classification, have increased over time in York Abdominal Wall Unit. CONCLUSION: A structured pathway for complex abdominal wall hernia service is one way to improve patient experience and streamline services. The relevance of pathways for the hernia surgeon is discussed alongside this pathway. This may provide a useful guide to those wishing to establish similar personalised pathways within their own units and allow them to expand their service.

A multistage process leading to the development of a structured consent form and patient information leaflet for complex abdominal wall reconstruction (CAWR).

PURPOSE: Informed consent is vital in surgery. The General Medical Council, UK and Royal College of Surgeons of England provide clear guidance on what constitutes the process of informed patient consent. Despite this, evidence suggests that the consent process may not be performed well in surgery. We utilised a staged patient-centred approach and rigorous methodology to develop a standardised patient information leaflet (PIL) and pre-written structured consent form for complex abdominal wall reconstruction (CAWR). METHODS: We utilised the principles of Deming's Plan-Do-Study-Act (PDSA) cycles to approach the process. Buzan's mind maps were used to identify the stakeholders and deficiencies in the consent process ('Plan' phase). The content of the PIL and pre-written consent form was then developed in collaboration with stakeholders ('Do' phase). Multidisciplinary and multidepartmental feedback was obtained on the proposed content and amendments were made ('Study' and 'Act' phases). RESULTS: We successfully produced a clear, focused PIL and structured consent form, in Plain English, presenting accurate, relevant and detailed information in a highly understandable way. The PIL had a Flesch Reading Ease score of > 80, demonstrating a high level of readability and comprehensibility, with positive implications for informed patient decision making and preparedness for surgery. CONCLUSION: Through sharing the process that we undertook, we aim to support other abdominal wall units who wish to develop and improve their own consent process.

Associations between patellofemoral joint cartilage T1ρ and T2 and knee flexion moment and impulse during gait in individuals with and without patellofemoral joint osteoarthritis.

OBJECTIVE: This study aimed to investigate the associations between patellofemoral cartilage T1ρ and T2 relaxation times and knee flexion moment (KFM) and KFM impulse during gait. METHOD: Knee magnetic resonance (MR) images were obtained from 99 subjects with and without patellofemoral joint (PFJ) osteoarthritis (OA), using fast spin-echo, T1ρ and T2 relaxation time sequences. Patellar and trochlear cartilage relaxation times were computed for the whole cartilage, and superficial and deep layers (laminar analysis). Subjects also underwent three-dimensional (3D) gait analysis. Peak KFM and KFM impulse were calculated during the stance phase. Linear regressions were used to examine whether cartilage relaxation times were associated with knee kinetics during walking while adjusting age, sex, body mass index (BMI) and walking speed. RESULTS: Higher peak KFM and KFM impulse were significantly related to higher T1ρ and T2 relaxation times of the trochlear and patellar cartilage, with standardized regression coefficients ranging from 0.21 to 0.28. Laminar analysis showed that overall the superficial layer of patellofemoral cartilage showed stronger associations with knee kinetics. Subgroup analysis revealed that in subjects with PFJ OA, every standard deviation change in knee kinetics was related to greater increases in PFJ cartilage T1ρ and T2 (standardized coefficients: 0.29 to 0.41). Conversely, in subjects without OA, weaker relationships were observed between knee kinetics and PFJ cartilage T1ρ and T2. CONCLUSIONS: Our findings suggest that increased peak KFM and KFM impulse were related to worse cartilage health at the PFJ. This association is more prominent in superficial layer cartilage and cartilage with morphological lesions.

Quadriceps intramuscular fat fraction rather than muscle size is associated with knee osteoarthritis.

OBJECTIVES: To compare thigh muscle intramuscular fat (intraMF) fractions and area between people with and without knee radiographic osteoarthritis (ROA); and to evaluate the relationships of quadriceps adiposity and area with strength, function and knee magnetic resonance imaging (MRI) lesions. METHODS: Ninety six subjects (ROA: Kellgren-Lawrence (KL) > 1; n = 30, control: KL = 0, 1; n = 66) underwent 3-T MRI of the thigh muscles using chemical shift-based water/fat MRI (fat fractions) and the knee (clinical grading). Subjects were assessed for isometric/isokinetic quadriceps/hamstrings strength, function Knee injury and Osteoarthritis Outcome Score (KOOS), stair climbing test (SCT), and 6-minute walk test (6MWT). Thigh muscle intraMF fractions, muscle area and strength, and function were compared between controls and ROA subjects, adjusting for age. Relationships between measures of muscle fat/area with strength, function, KL and lesion scores were assessed using regression and correlational analyses. RESULTS: The ROA group had worse KOOS scores but SCT and 6MWT were not different. The ROA group had greater quadriceps intraMF fraction but not for other muscles. Quadriceps strength was lower in ROA group but the area was not different. Quadriceps intraMF fraction but not area predicted self-reported disability. Aging, worse KL, and cartilage and meniscus lesions were associated with higher quadriceps intraMF fraction. CONCLUSION: Quadriceps intraMF is higher in people with knee OA and is related to symptomatic and structural severity of knee OA, whereas the quadriceps area is not. Quadriceps fat fraction from chemical shift-based water/fat MR imaging may have utility as a marker of structural and symptomatic severity of knee OA disease process.

Evaluation of Permacol as a cultured skin equivalent.

Skin loss following severe burn requires prompt wound closure to avoid such complications as fluid and electrolyte imbalance, infection, immune suppression, and pain. In clinical situations in which insufficient donor skin is available, the development of cultured skin equivalents (dermal matrices seeded with keratinocytes and fibroblasts) may provide a useful alternative. The aim of this study was to assess the suitability of a porcine-derived dermal collagen matrix (Permacol) to function as a cultured skin equivalent in supporting the growth of keratinocytes in vitro and providing cover to full thickness wounds in the BALB C/nude mouse model. A histological comparison was against Glycerol treated-Ethylene Oxide Sterilised Porcine Dermis (Gly-EO Dermis) which has successfully been used as a cultured skin equivalent in previous studies. Both Gly-EO Dermis and to a lesser extent Permacol were able to support the growth of cultured keratinocytes following a 16-day period of cell culture, however, this study was only able to demonstrate the presence of an epidermal layer on Gly-EO dermis 2 weeks after grafting onto full-thickness wounds in the BALB C/nude mouse model.

A technique for the orientation of endoscopically resected laryngeal lesions.

Endoscopic resection is a widely accepted method of treating early laryngeal malignancies. Accurate histological assessment of resected laryngeal specimens can be difficult due to their small size and potential damage and distortion caused by standard orientation and processing techniques. A new technique is described which employs dehydrated cucumber to mount laryngeal specimens for orientation and processing. This technique is quick, easy, cheap and reliable, allowing accurate histological assessment of potentially malignant lesions. Better orientating and processing of laryngeal specimens can optimise treatment decisions based on histological results.

Histological evaluation of Permacol as a subcutaneous implant over a 20-week period in the rat model.

This study assessed the suitability of Permacol (a porcine derived, isocyanate cross linked collagen based biomaterial) as an alternative to autologous tissue in soft tissue reconstruction. The Sprague-Dawley rat was used as a model for subcutaneous implantation over a 20 week period and comparison made with two other porcine biomaterials (small intestinal submucosa and glycerol treated-ethylene oxide sterilised porcine dermis). Implants were scored histometrically on the degree of acute inflammation, chronic inflammation, fibrosis and stromal response. The vascularity and percentage composition of collagen within Permacol were assessed by stereology and seescan image analysis, respectively. In general terms, Permacol was well tolerated as a subcutaneous implant, with only a minor chronic inflammatory response remaining after a 20 week period of implantation. There was evidence of collagen degradation during this period and vascular ingrowth into Permacol was limited. Permacol has the potential for a broad range of applications in plastic surgery, but may benefit from modification to promote a more rapid degree of vascularisation.

The diamond CO2 laser as a method of improving the vascularisation of a permanent collagen implant.

For a biomaterial to be considered as anything other than a simple filler material it must allow a certain degree of ingrowth from the surrounding host tissues. Permacol is a novel porcine derived biomaterial that is isocynate crosslinked to prevent its degradation in vivo, but while it appears to be biocompatible in terms of its histological tissue response, our early studies demonstrate only a limited degree of fibrovascular ingrowth. The aim of this study was to assess the effectiveness of both laser perforations and topically applied VEGF as methods of encouraging fibrovascular ingrowth. Treatment of Permacol with the diamond CO(2) laser significantly increased the porosity of the material as assessed by seescan image analysis. Fibrovascular ingrowth as assessed in the Sprague-dawley rat model was found to be limited to the pores themselves and not the surrounding native matrix. Pre-soaking of laser treated Permacol in vascular endothelial growth factor (VEGF) did not further increase fibrovascular ingrowth. Increasing the porosity of Permacol may allow its use as a dermal replacement in the support of an overlying skin graft or keratinocyte sheet; however using the laser may not be the optimal method of achieving this aim.

Evaluation of a porcine origin acellular dermal matrix and small intestinal submucosa as dermal replacements in preventing secondary skin graft contraction.

The degree to which a split thickness skin graft (STSG) contracts after application to its recipient bed is related in part to the proportion of the dermis harvested from the donor site. Harvesting thicker skin grafts may produce better cosmetic results in the recipient bed but result in increased donor site morbidity. The combination of an autologous ultra thin split thickness graft with an underlying non-autologous dermal component may reduce secondary skin graft contraction without further increasing donor site morbidity. This study was aimed at assessing the suitability of two porcine derived biomaterials (Permacol and small intestinal submucosa, SIS) for use in combination with skin grafts in a Sprague-Dawley rat model. Full thickness wounds (1 cm(2)) were created in Sprague-Dawley rats and grafted with skin in combination with Permacol or SIS either as a one-stage operation or following a 2-week-period of vascularisation of these dermal matrices before a second stage operation to cover with skin. Skin graft viability and wound area were assessed at weekly intervals until 4 weeks after graft application. Both Permacol and SIS were able to support an overlying skin graft but had no beneficial effect on skin graft contraction in this model compared to skin grafts alone.

An unusual complication of penile piercing: a report and literature review.

Body piercing has been practiced for many centuries and is thought to have its origins in the Hindu religion. As traditional ear piercings have given way to more adventurous anatomical sites, so too have the associated complications of these practices. We present the case of a 35 year old man who presented 12 months after a penile piercing with an extensive fistula of the glans penis resembling an acquired glanular hypospadius.

Prefabricated skin flaps in a rat model based on a dermal replacement matrix Permacol.

The reconstruction of three-dimensional structures is one of the most challenging problems in plastic surgery. While shaped frameworks incorporated within soft tissue envelopes often lose their fine detail, the integration of a blood supply to a stable biomaterial scaffold allows skin graft cover and emphasis of fine detail. The aim of this study was to evaluate whether a porcine derived isocyanate crosslinked collagen tissue matrix (Permacol) could be vascularised from an isolated vascular pedicle and subsequently sustain an overlying skin graft as a pedicled prefabricated flap. A vascular induction technique was employed using the epigastric pedicles in Sprague-Dawley rats to vascularise 2 x 2 cm(2) pieces of Permacol of standard 0.75 and 1.5 mm thickness Permacol and laser treated Permacol of 0.4 and 0.75 mm thickness. Flaps were able to support overlying skin grafts as early as 2 weeks following vessel implantation and laser treated Permacol had an increased vascularity compared to standard Permacol with no evidence of degradation. The study showed that Permacol could be a useful matrix for use in tissue engineered flaps.

New sunscreens confer improved protection for photosensitive patients in the blue light region.

BACKGROUND: Some patients with photosensitivity disorders are sensitive to visible radiation. As current commercial sunscreens do not significantly absorb in this region, there is a lack of effective topical photoprotection. To meet this need a new range of sunscreens has been developed incorporating zinc oxide and pigmentary grade titanium dioxide as active ingredients. OBJECTIVES: To determine the effectiveness of the new sunscreens in providing protection for patients with visible radiation photosensitivity. METHODS: In the first part of this study, an in vitro transmission spectrum was obtained. The properties of the new sunscreens, as well as a range of commercial agents, were compared, and a new parameter, photosensitivity protection factor (PPF), was developed. This was used to predict the likely degree of protection the various sunscreens would provide for patients with photosensitivity extending into the visible region. In the second in vivo part of the study, patients with known visible (blue) light photosensitivity were tested using light at 430 +/- 30 nm and the protection factor (PF) at this wavelength was determined. RESULTS: Mean +/- SD PPFs for the new sunscreens were between 5.4 +/- 0.3 and 9.6 +/- 0.3, compared with 4.1 +/- 0.1 for Sun E45 (sun protection factor, SPF 25) and 4.2 +/- 0.1 for RoC Total (SPF 25). The derived in vivo PF for Sun E45 ranged between 1 and 4 (median 2). For the new sunscreens the range was 3 to > 10 (median 8). CONCLUSIONS: This study demonstrates that the new sunscreens do provide protection for patients with sensitivity to visible light (blue light region).

Attitudes of the general public to the expanding role of community pharmacists: a pilot study.

BACKGROUND: The extension of the role of the community pharmacist in the UK has been under discussion for several years. Professional opinions have been reported. It is important to investigate consumer attitudes towards the acceptability of the proposed new role of the pharmacist. OBJECTIVES: This pilot study investigated the attitudes of consumers to the proposed extended role of the community pharmacist. METHODS: A total of 173 printed questionnaires were mailed to a random sample of patients stratified by age and sex, registered with an urban general practice in the north east of Scotland. The questionnaire asked subjects their views on ideas for new services to be provided by community pharmacists. RESULTS: A total of 96 questionnaires were returned (response rate 55%). Respondents were in favour of community pharmacist involvement in non-medicine-related roles such as 'healthy living' advice but less in favour of roles where the pharmacist would have access to selected information from medical records. CONCLUSION: This pilot study has indicated a range of attitudes towards the extended role of the community pharmacist. It is important to investigate fully consumer attitudes towards the acceptability of the new role of the pharmacist.

The accuracy of head and neck carcinoma sentinel lymph node biopsy in the clinically N0 neck.

BACKGROUND: Sentinel lymph node (SLN) biopsy originally was described as a means of identifying lymph node metastases in malignant melanoma and breast carcinoma. The use of SLN biopsy in patients with oral and oropharyngeal squamous cell carcinoma and clinically N0 necks was investigated to determine whether the pathology of the SLN reflected that of the neck. METHODS: Patients undergoing elective neck dissections for head and neck squamous cell carcinoma accessible to injection were enrolled into our study. Sentinel lymph node biopsy was performed after blue dye and radiocolloid injection. Preoperative lymphoscintigraphy and the perioperative use of a gamma probe identified radioactive SLNs; visualization of blue stained lymphatics identified blue SLNs. A neck dissection completed the surgical procedure, and the pathology of the SLN was compared with that of the remaining neck dissection. RESULTS: Sentinel lymph node biopsy was performed on 40 cases with clinically N0 necks. Twenty were pathologically clear of tumor and 20 contained subclinical metastases. SLNs were found in 17 necks with pathologic disease and contained metastases in 16. The sentinel lymph node was the only lymph node containing tumor in 12 of 16. CONCLUSIONS: The SLN, in head and neck carcinomas accessible to injection without anesthesia, is an accurate reflector of the status of the regional lymph nodes, when found in patients with early tumors. Sentinel lymph nodes may be found in clinically unpredictable sites, and SLN biopsy may aid in identifying the clinically N0 patient with early lymph node disease. If SLNs cannot be located in the neck, an elective lymph node dissection should be considered.

Transcripts of the MHM region on the chicken Z chromosome accumulate as non-coding RNA in the nucleus of female cells adjacent to the DMRT1 locus.

The male hypermethylated (MHM) region, located near the middle of the short arm of the Z chromosome of chickens, consists of approximately 210 tandem repeats of a BamHI 2.2-kb sequence unit. Cytosines of the CpG dinucleotides of this region are extensively methylated on the two Z chromosomes in the male but much less methylated on the single Z chromosome in the female. The state of methylation of the MHM region is established after fertilization by about the 1-day embryonic stage. The MHM region is transcribed only in the female from the particular strand into heterogeneous, high molecular-mass, non-coding RNA, which is accumulated at the site of transcription, adjacent to the DMRT1 locus, in the nucleus. The transcriptional silence of the MHM region in the male is most likely caused by the CpG methylation, since treatment of the male embryonic fibroblasts with 5-azacytidine results in hypo-methylation and active transcription of this region. In ZZW triploid chickens, MHM regions are hypomethylated and transcribed on the two Z chromosomes, whereas MHM regions are hypermethylated and transcriptionally inactive on the three Z chromosomes in ZZZ triploid chickens, suggesting a possible role of the W chromosome on the state of the MHM region.

Active and passive consent: a comparison of actual research with children.

Passive consent, which is ethically questionable, requires parents to sign and return a form if they refuse to allow their child to participate in research. Active consent requires parents to sign and return a form if they consent for their child to participate. To compare passive and active consent research projects, we evaluated 15 published examples (since 1995) of passive consent and the adjacent experimental article (active consent). Passive consent projects involved significantly higher response rates, more subjects, greater likelihood of being conducted in school rather than in clinical settings, but about the same age of participants as active consent projects. We recommend that: (a) Institutional Review Boards scrutinize all passive consent projects and consider whether the consent procedure is ethical for the research sample; (b) editors and reviewers examine all manuscripts for the consent procedure used; and (c) ethicists and researchers debate the appropriateness/ethics of passive consent.

Expression of a homeobox gene (SIX5) in borderline ovarian tumours.

AIMS: To assess the expression of SIX5 (a homeobox gene) mRNA in surface coelomic epithelium, endocervical epithelium, Fallopian tube epithelium, and benign, borderline, and malignant epithelial ovarian tumours. METHODS: 10 normal premenopausal ovaries, 10 normal Fallopian tubes, 10 normal cervices, 10 normal postmenopausal ovaries, 10 benign epithelial ovarian tumours, 10 malignant epithelial ovarian tumours, and 40 borderline epithelial ovarian tumours were studied retrospectively. The tissues had been fixed in formalin and embedded in paraffin wax. The tumours had previously been typed into mucinous, serous, or mixed tumours and assigned to the borderline category according to the FIGO/WHO criteria. Expression was assessed by in situ binding of SIX5 specific sense and antisense riboprobes. Hybridization of the riboprobes was detected using a standard immunohistochemical technique and the results correlated with expression in the normal epithelium of the endocervix, Fallopian tube, surface coelomic epithelium, and ovarian tumours. RESULTS: Expression of SIX5 mRNA was demonstrated in normal Fallopian tube epithelium and normal endocervical epithelium. SIX5 mRNA was not detected in normal ovarian epithelial tissue at any of the times studied during the menstrual cycle. Expression of SIX5 was not shown in benign epithelial ovarian tumours or in any of the malignant epithelial ovarian tumours. In 31 of 37 borderline epithelial ovarian tumours (84%), SIX5 expression was found in the epithelial cells. CONCLUSIONS: SIX5 expression is present in the normal epithelium throughout most of the female reproductive tract, suggesting it may have a role in maintaining epithelial differentiation in these tissues. SIX5 expression appears to be restricted to borderline epithelial ovarian tumours and may be a marker of epithelial differentiation in these tumours; thus borderline ovarian tumours may not be part of a continuum of disease between benign and malignant epithelial ovarian tumours. Further investigation of expression of SIX5 may clarify the molecular processes that promote differentiation of the ovarian surface epithelium.

Lithium monitoring before and after the distribution of clinical practice guidelines.

OBJECTIVE: To determine whether distribution of clinical practice guidelines improves lithium monitoring and whether standards of monitoring differed between patients in psychiatric contact and those seen only in primary care. METHOD: Standards of monitoring were assessed for patients on lithium in northeast Scotland throughout 1995 and/or throughout 1996. Guidelines were circulated in January 1996 to all local general practitioners and psychiatrists. Monitoring was compared between 1995 and 1996 and for patients with and without psychiatric contact. RESULTS: Both primary care and psychiatric records were scrutinized for 422 and 403 patients prescribed lithium throughout 1995 and 1996, respectively. While monitoring was poor on several parameters during both years, frequency of measurement of both thyroid and renal function improved in 1996. Standards of monitoring were better for patients in psychiatric care. CONCLUSION: Standards of lithium monitoring require further improvement. Locally agreed practice guidelines are helpful but patients on lithium should be in continuing contact with an experienced psychiatrist.