Evaluation of epigenetic methylation biomarkers for the detection of colorectal cancer using droplet digital PCR.

Colorectal cancer (CRC) is the third most common cancer worldwide. Screening programs allow early diagnosis and have improved the clinical management of this disease. Aberrant DNA methylation is increasingly being explored as potential biomarkers for many types of cancers. In this study we investigate the methylation of ten target genes in 105 CRC and paired normal adjacent colonic tissue samples using a MethylLight droplet digital PCR (ML-ddPCR) assay. Receiver operator characteristic (ROC) curves were used to determine the diagnostic performance of all target genes individually and in combination. All 515 different combinations of genes showed significantly higher levels of methylation in CRC tissue. The combination of multiple target genes into a single test generally resulted in greater diagnostic accuracy when compared to single target genes. Our data confirms that ML-ddPCR is able to reliably detect significant differences in DNA methylation between CRC tissue and normal adjacent colonic tissue in a specific selection of target genes.

Exploring what is important to patients with regards to quality of life after experiencing a lower limb reconstructive procedure: a qualitative evidence synthesis.

BACKGROUND: Patient reported outcome measures (PROMs) are used to understand the impact of lower limb reconstruction surgery on patients' quality of life (QOL). Existing measures have not been developed to specifically capture patient experiences amongst adults with lower limb conditions that require reconstruction surgery. This review aimed to synthesise qualitative evidence to identify what is important to patients requiring, undergoing, or following reconstructive surgery for lower limb conditions. METHODS: MEDLINE, Embase, PsychINFO and Cinahl were searched from inception until November 2020. Studies were included if they employed qualitative research methods, involved patients requiring, undergoing or following lower limb reconstruction and explored patients' experiences of care, treatment, recovery and QOL. Mixed methods studies that did not separately report qualitative findings, mixed population studies that were not separately reported and studies in languages other than English were excluded. Included studies were analysed using thematic synthesis. The Critical Appraisal Skills Programme qualitative studies checklist was used to undertake quality assessment. RESULTS: Nine studies met the inclusion criteria. The thematic synthesis identified two overarching themes: (1) areas of living key to QOL for lower limb reconstruction patients and (2) moving towards a new normal. The way in which lower limb reconstruction affects an individual's QOL and their recovery is complex and is influenced by a range of inter-related factors, which will affect patients to varying degrees depending on their individual circumstances. We identified these factors as: pain, daily functioning and lifestyle, identity, income, emotional wellbeing, support, the ability to adapt and adjust and the ability to move forwards. CONCLUSIONS: The way patients' QOL is affected after a lower limb reconstruction is complex, may change over time and is strongly linked to their recovery. These findings will aid us in developing a conceptual framework which identifies the outcomes important to patients and those that should be included in a PROM. Further research is then required to establish whether the range of factors we identified are captured by existing PROMs. Depending on the outcome of this work, a new PROM for patients following lower limb reconstruction may be required.

Arthropathy in hereditary haemochromatosis segregates with elevated erythrocyte mean corpuscular volume.

Objective: To evaluate the relationship between erythrocyte parameters and the presence or absence of arthritis in HFE C282Y homozygous hereditary haemochromatosis (HH) subjects compared to control groups of non-HH subjects with arthritis.Method: Erythrocyte and arthritis parameters [mean corpuscular volume (MCV) and mean cell haemoglobin (MCH)] were obtained from consecutive HH subjects (n = 119) who were referred for initial evaluation and management. For comparison, MCV and MCH values were collected from randomly selected non-HH subjects with rheumatoid arthritis (n = 100) and osteoarthritis (n = 100), consisting of equal numbers of men and women. Two other comparison groups comprised 16 men and women who were heterozygous for C282Y with arthritis, and 38 non-HH subjects with type 2 polyarticular osteoarthritis (T2POA).Results: MCV values were significantly higher in HH subjects with arthritis (95 ± 0.56 fL) than in HH subjects without arthritis (92.75 ± 0.50 fL, p = 0.037). HH subjects with or without arthritis demonstrated a higher mean MCV than the control groups of non-HH osteoarthritis (90.12 ± 0.46 fL, p < 0.001) and non-HH rheumatoid arthritis (90.94 ± 0.57 fL, p < 0.001). HH subjects with arthritis also demonstrated a higher MCV than heterozygous C282Y subjects with arthritis (93.18 ± 1.55 fL, p = 0.025) and non-HH subjects with a similar pattern of arthritis, notably T2POA (91.13 ± 0.50 fL, p < 0.01). An MCV of ≥ 97.85 fL provided a likelihood ratio of 2.2 for development of arthritis in HH subjects.Conclusion: This study demonstrated a relationship between elevated MCV and arthritis in incident cases of HH.

Design and testing of communication materials for a breastfeeding social media marketing campaign: Breastfeed4Ghana.

Breastfeed4Ghana was a social media-based campaign implemented to address identified gaps in the protection, promotion, and support of breastfeeding in Ghana. This paper describes the process of campaign materials development and testing to ensure their cultural and content appropriateness. The 60 campaign materials, each consisting of an image and text message, underwent a process of creation, testing, revision, and finalization. Existing research evidence and infant and young child feeding communication tools that were culturally relevant for Ghana were used to develop the materials. All materials were tested and finalized through an iterative process that incorporated input from six focus group discussions (FGDs) with mothers, and content and technical experts. The materials were revised to ensure scientific accuracy, understandability, and cultural appropriateness of the messages, as well as alignment of the messages with the images. Finalized materials were reviewed and approved by the Ghana Food and Drugs Authority. Analysis for this paper involved summarizing and categorizing the types and sources of input as well as the research team's responses to the input received. The 60 campaign materials received a total of 132 inputs. Most inputs came from FGDs (78.4%); and most inputs were on the campaign material images. The evidence-informed process of materials creation, use of multiple input sources, and a broad-based iterative process allowed the creation of 60 evidence-based and culturally appropriate materials for a breastfeeding social media campaign in Ghana. This paper could serve as a guide for other social media campaign efforts looking to develop culturally appropriate materials.

Identifying physiological measures of lifetime welfare status in pigs: exploring the usefulness of haptoglobin, C- reactive protein and hair cortisol sampled at the time of slaughter.

BACKGROUND: Physiological measures indicative of the welfare status of animals during rearing could form part of an abattoir-based animal health and welfare assessment tool. A total of 66 pigs were used in this study, the aim of which was to assess how serum concentrations of haptoglobin (Hp) and C-reactive protein (CRP) (assessed in 51 pigs), and hair concentrations of cortisol (assessed in 65 pigs), measured at or close to slaughter, reflected welfare-related indicators recorded from the animal during its lifetime. These indicators were recorded at intervals between 7 and 21 weeks of age and included assigning scores for levels of tail and skin lesions, recording the presence or absence of certain health issues, and conducting qualitative behavioural assessments (QBA). RESULTS: Pigs recorded as having tail lesions during their lifetime had higher hair cortisol levels than those with no tail lesions (tail lesions: 47.87 ± 3.34 pg/mg, no tail lesions: 42.20 ± 3.29 pg/mg, P = 0.023), and pigs recorded as having moderate or severe tail lesions had higher Hp levels than those with no or mild tail lesions (moderate/severe: 1.711 mg/ml ± 0.74, none/mild: 0.731 mg/ml ±0.10, P = 0.010). Pigs recorded as being lame during their lifetime tended to have higher hair cortisol levels than non-lame pigs (lame: 52.72 pg/mg ± 3.83, not lame: 43.07 pg/mg ± 2.69, P = 0.062). QBA scores were not associated with any of the physiological measures (P > 0.05). Receiver Operator Curve (ROC) analysis was also carried out to get a better understanding of the usefulness of the physiological measures in discriminating animals that had had welfare-related issues recorded during their lifetime from those that had not. Hair cortisol was determined as having 'moderate' accuracy in discriminating pigs that were tail bitten on-farm from unbitten pigs (AUC: 0.748) while Hp and CRP were determined to have no meaningful discriminatory ability (AUC < 0.600). CONCLUSION: This research should be repeated on a larger scale, but the results suggest that hair cortisol measured at slaughter could provide insight into the welfare status of pigs during their lifetime. Hp may be a useful indicator of tail lesions in pigs. However, further research utilising a greater proportion of severely bitten pigs is required before conclusions can be drawn.

The lack of analgesic use (oligoanalgesia) in small animal practice.

Oligoanalgesia is defined as failure to provide analgesia in patients with acute pain. Treatment of pain in emergencies, critical care and perioperatively may influence patient outcomes: the harmful practice of withholding analgesics occurs in teaching hospitals and private practices and results in severe physiological consequences. This article discusses the prevalence, primary causes, species and regional differences and ways to avoid oligoanalgesia in small animal practice. Oligoanalgesia may be addressed by improving education on pain management in the veterinary curriculum, providing continuing education to veterinarians and implementing pain scales.

Effects of scalding and dehairing of pig carcasses at abattoirs on the visibility of welfare-related lesions.

There is increasing interest in developing abattoir-based measures to assist in determining the welfare status of pigs. The primary aim of this study was to determine the most appropriate place on the slaughter line to conduct assessments of welfare-related lesions, namely apparent aggression-related skin lesions (hereafter referred to as 'skin lesions'), loin bruising and apparent tail biting damage. The study also lent itself to an assessment of the prevalence of these lesions, and the extent to which they were linked with production variables. Finishing pigs processed at two abattoirs on the Island of Ireland (n=1950 in abattoir A, and n=1939 in abattoir B) were used. Data were collected over 6 days in each abattoir in July 2014. Lesion scoring took place at two points on the slaughter line: (1) at exsanguination (slaughter stage 1 (SS1)), and (2) following scalding and dehairing of carcasses (slaughter stage 2 (SS2)). At both points, each carcass was assigned a skin and tail lesion score ranging from 0 (lesion absent) to 3 or 4 (severe lesions), respectively. Loin bruising was recorded as present or absent. Differences in the percentage of pigs with observable lesions of each type were compared between SS1 and SS2 using McNemar/McNemar-Bowker tests. The associations between each lesion type, and both cold carcass weight and condemnations, were examined at batch level using Pearson's correlations. Batch was defined as the group of animals with a particular farm identification code on a given day. The overall percentage of pigs with a visible skin lesion (i.e. score>0) decreased between SS1 and SS2 (P<0.001). However, the percentage of pigs with a severe skin lesion increased numerically from SS1 to SS2. The percentage of pigs with a visible tail lesion and with loin bruising also increased between SS1 and SS2 (P<0.001). There was a positive correlation between the percentage of carcasses that were partially condemned, and the percentage of pigs with skin lesions, tail lesions and loin bruising (P<0.05). In addition, as the batch-level frequency of each lesion type increased, average cold carcass weight decreased (P<0.001). These findings suggest that severe skin lesions, tail lesions and loin bruising are more visible on pig carcasses after they have been scalded and dehaired, and that this is when abattoir-based lesion scoring should take place. The high prevalence of all three lesion types, and the links with economically important production parameters, suggests that more research into identifying key risk factors is warranted.

A suspected case of intranasal inverted Schneiderian papilloma in an adult male from post-Medieval Holland.

During the routine assessment of skeletal material unearthed from Middenbeemster, a post-Medieval (AD 17-19th century) cemetery in Northern Holland, an adult male with an unidentified choanal lesion was discovered. The affected individual was analysed macroscopically and via computer tomography. Based on the phenotypic and radiographic characteristics of the lesion, and after a comprehensive review of clinical literature, it was determined that the lesion was likely caused by an inverted Schneiderian papilloma (ISP), a benign but locally aggressive endophytic neoplasm histopathologically characterized by the inversion of the epithelium into the lamina propria (Schneiderian membrane) of the respiratory nasal mucosa. This study presents a detailed description of the pathophysiology and aetiology of ISPs, using both bioarchaeological and biomedical frameworks. Several differential diagnoses are discussed, with emphasis on the reasons for their rejection as the primary pathogenic mechanism(s). To the best of the authors' knowledge, this research is the first reported case of ISP within palaeopathology, which highlights the need to consider ISPs whenever slow-growing sinonasal neoplasms are suspected, as well as in cases that exhibit focal rhinitis.

Can you die from obstructive sleep apnoea syndrome (OSAS)?

Studies suggest an independent association between Obstructive Sleep Apnoea Syndrome (OSAS) and cardiovascular death. The purpose of our study is to examine doctors' awareness of this association and to determine whether this correlates with recording of OSAS on death certificates. We contacted the Central Statistics Office (CSO) and obtained relevant mention of OSAS on death certificates. We surveyed doctors on their view of OSAS-related deaths, CSO data from 2008-2011 reveal two deaths with OSAS documented as a direct cause and 52 deaths with OSAS as a contributory cause. Seventy-five doctors' surveyed (41%) believe OSAS can be a direct cause of death and 177 (96%) believe OSAS can be an indirect cause of death. Only 22 (12%) had putdown OSAS as a cause of death. OSAS is seldom recorded on death certificates. This is at odds with epidemiological forecasts and contrary to an opinion poll from a selection of doctors.

The Appropriateness Evaluation Protocol is a poor predictor of in-hospital mortality.

BACKGROUND: The Appropriateness Evaluation Protocol (AEP) proposes admission criteria based only on physiological and laboratory parameters and has recently informed an Irish national bed utilisation review. Severity of illness tools can be poorly predictive of outcomes, particularly in older patients. AIMS: To assess the clinical utility of the AEP in moribund older and younger patients. METHODS: The study was conducted in four acute hospitals in South Munster, Ireland, and was of retrospective analytical cohort study design. The Hospital In-Patient Enquiry Scheme was used to ascertain patients who died within 10 days of hospital admission, over a 2-year period. Proximate death was used as a robust measure of validity of admission. Emergency department (ED) records were screened retrospectively to allocate the AEP criteria. RESULTS: There were 803 eligible in-hospital deaths. Establishment of AEP criteria was available in 72.9 % (585 patients, 50.8 % female). The median length of stay until death was 4 days. Just over 30 % (179/585) of patients did not meet AEP criteria, two-fifths (72/179) of whom had been coded as severely unwell on arrival to the ED. There was no significant difference in AEP identification rates between older and younger age groups. CONCLUSIONS: Our study illustrates that the AEP is a poor predictor of mortality in all age groups, having failed to identify approximately one-third of our cohort. Based on our findings, we feel that this tool should not be used to assess the appropriateness of admission.

On the potential of hydrated storage for naturally derived ECMs and associated effects on mechanical and cellular performance.

Tissue engineered acellular vascular grafts are an emerging concept in the development of vascular prostheses for the minimally invasive treatment of cardiovascular diseases. Extracellular matrix (ECM) scaffolds, such as small intestinal submucosa (SIS) and urinary bladder matrix (UBM), offer many advantages over currently available synthetic devices. However, storage of such biomaterials can unduly influence the scaffold properties. This study evaluated the effects of up to 16 weeks hydrated storage on the mechanical and cellular performance of stented and unstented tubular scaffolds. This study aimed to demonstrate the viability, mechanical integrity, and bioactive potential of xenogeneic ECMs as potential off-the-shelf vascular prosthetic devices. Rehydrated ECM samples versus the lyophilized controls showed an increase in UTS and stiffness. The mechanical strength of all samples evaluated was above the average reported aortic tissue failure strength and more compliant than current synthetic materials employed. Post-storage cellular bioactivity investigations indicated that both ECM scaffolds tested were unaffected by increased hydrated storage duration when compared with the controls. Overall, the results indicate that the biomechanical and biologic properties of ECMs are not negatively affected by long-term hydrated storage. Therefore, with further investigations, naturally derived ECM materials may offer potential as an off-the-shelf therapeutic treatment of cardiovascular diseases.

K/B×N serum transfer arthritis is delayed and less severe in leukaemia inhibitory factor (LIF)-deficient mice.

This study is investigating the role of leukaemia inhibitory factor (LIF) in the development of inflammation and joint damage in the mouse K/B×N serum transfer arthritis model. LIF knock-out (LIF(-/-)) mice were generated by mating heterozygote females (LIF(+/-)) with heterozygote males. Arthritis was induced in 8-20-week-old LIF knock-out mice (LIF(-/-)) by intraperitoneal injection of pooled K/B×N sera (50 µl) on days 0 and 2. Clinical disease was scored daily for 6 days. Safranin-O and haematoxylin-stained sections were scored for synovitis, joint space exudate, cartilage degradation and bone damage. RNA was extracted from ankle joints and used to investigate gene expression levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1, LIF, LIF receptor, oncostatin M (OSM), OSM receptor, IL-6 and their common receptor subunit gp130 by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results show that wild-type mice developed severe clinically overt polyarthritis. In contrast, LIF(-/-) mice showed a more than 50% reduction in clinical arthritis severity. Significantly lower histological scores were observed in LIF(-/-) mice compared to wild-type disease controls. LIF(-/-) mice had histopathological scores that were similar to normal healthy mice. IL-6 subfamily cytokine and receptor subunit expression remained unchanged. The expression levels for IL-6 were reduced significantly in all the diseased mice, whether wild-type or LIF(-/-) mice (P < 0·001), compared to healthy wild-type mice. We conclude that LIF contributes to the development of disease in the K/B×N serum transfer model of arthritis. These results provide further evidence for the role of LIF in inflammation and cartilage bone resorption and provide impetus to test the effects of LIF blockade as a therapeutic strategy in rheumatoid arthritis.

Perioperative management of chronic anticoagulation therapy in urological patients: a cross-sectional survey of practice.

BACKGROUND: There has been a significant increase in the volume of urological patients on daily anticoagulation therapy requiring invasive elective urological procedures. AIMS: We sought to assess whether urologists are familiar with appropriate perioperative management strategies in this patient cohort. METHODS: Urologists completed a questionnaire on their current management strategy for warfarin during the perioperative period in patients undergoing elective urological surgery. Eleven urological procedures graded as minor, endoscopic and major were assessed in the study. In addition, respondents were also asked whether they administered bridging therapy with heparin when warfarin was discontinued perioperatively. RESULTS: The response rate was 52.5% (210/400). Procedure grade did not influence the duration warfarin was discontinued preoperatively with respondents discontinuing the agent 4.71 ± 1.52 days (range 2-10 days) prior to minor procedures, 4.74 ± 1.43 days (range 2-10 days) prior to endoscopic procedures and 4.88 ± 1.34 days (range 2-10 days) prior to major procedures (p > 0.05). Postoperatively, procedure grade significantly affected the day to recommencement with respondents recommencing warfarin 2.41 ± 2.31 days (range 1-14 days) after minor procedures, 3.07 ± 3.52 days (range 1-28 days) after endoscopic procedures and 4.38 ± 3.53 days (range 1-14 days) after major procedures (p < 0.0001). In total, 60 ± 0.52% of the respondents who discontinued warfarin routinely administered bridging therapy with heparin perioperatively. CONCLUSIONS: Our study demonstrates variations in perioperative management practices for patients on chronic anticoagulation therapy undergoing urological procedures. Urologists should familiarise themselves with standardised guidelines if this patient subgroup are to receive optimal perioperative management.

Wall shear stresses remain elevated in mature arteriovenous fistulas: a case study.

Maintaining vascular access (VA) patency continues to be the greatest challenge for dialysis patients. VA dysfunction, primarily due to venous neointimal hyperplasia development and stenotic lesion formation, is mainly attributed to complex hemodynamics within the arteriovenous fistula (AVF). The effect of VA creation and the subsequent geometrical remodeling on the hemodynamics and shear forces within a mature patient-specific AVF is investigated. A 3D reconstructed geometry of a healthy vein and a fully mature patient-specific AVF was developed from a series of 2D magnetic resonance image scans. A previously validated thresholding technique for region segmentation and lumen cross section contour creation was conducted in MIMICS 10.01, allowing for the creation of a 3D reconstructed geometry. The healthy vein and AVF computational models were built, subdivided, and meshed in GAMBIT 2.3. The computational fluid dynamic (CFD) code FLUENT 6.3.2 (Fluent Inc., Lebanon, NH) was employed as the finite volume solver to determine the hemodynamics and shear forces within the healthy vein and patient-specific AVF. Geometrical alterations were evaluated and a CFD analysis was conducted. Substantial geometrical remodeling was observed, following VA creation with an increase in cross-sectional area, out of plane curvature (maximum angle of curvature in AVF=30 deg), and angle of blood flow entry. The mean flow velocity entering the vein of the AVF is dramatically increased. These factors result in complex three-dimensional hemodynamics within VA junction (VAJ) and efferent vein of the AVF. Complex flow patterns were observed and the maximum and mean wall shear stress (WSS) magnitudes are significantly elevated. Flow reversal was found within the VAJ and efferent vein. Extensive geometrical remodeling during AVF maturation does not restore physiological hemodynamics to the VAJ and venous conduit of the AVF, and high WSS and WSS gradients, and flow reversal persist. It is theorized that the vessel remodelling and the continued non-physiological hemodynamics within the AVF compound to result in stenotic lesion development.

Hereditary hemochromatosis is characterized by a clinically definable arthropathy that correlates with iron load.

OBJECTIVE: To determine the frequency and character of arthropathy in hereditary hemochromatosis (HH) and to investigate the relationship between this arthropathy, nodal interphalangeal osteoarthritis, and iron load. METHODS: Participants were recruited from the community by newspaper advertisement and assigned to diagnostic confidence categories for HH (definite/probable or possible/unlikely). Arthropathy was determined by use of a predetermined clinical protocol, radiographs of the hands of all participants, and radiographs of other joints in which clinical criteria were met. RESULTS: An arthropathy considered typical for HH, involving metacarpophalangeal joints 2-5 and bilateral specified large joints, was observed in 10 of 41 patients with definite or probable HH (24%), all of whom were homozygous for the C282Y mutation in the HFE gene, while only 2 of 62 patients with possible/unlikely HH had such an arthropathy (P=0.0024). Arthropathy in definite/probable HH was more common with increasing age and was associated with ferritin concentrations>1,000 µg/liter at the time of diagnosis (odds ratio 14.0 [95% confidence interval 1.30-150.89], P=0.03). A trend toward more episodes requiring phlebotomy was also observed among those with arthropathy, but this was not statistically significant (odds ratio 1.03 [95% confidence interval 0.99-1.06], P=0.097). There was no significant association between arthropathy in definite/probable HH and a history of intensive physical labor (P=0.12). CONCLUSION: An arthropathy consistent with that commonly attributed to HH was found to occur in 24% of patients with definite/probable HH. The association observed between this arthropathy, homozygosity for C282Y, and serum ferritin concentrations at the time of diagnosis suggests that iron load is likely to be a major determinant of arthropathy in HH and to be more important than occupational factors.

Ferritin concentrations in synovial fluid are higher in osteoarthritis patients with HFE gene mutations (C282Y or H63D).

OBJECTIVES: In view of the clinical similarities between polyarticular osteoarthritis (POA) with metacarpophalangeal (MCP) joint involvement and the arthropathy that occurs in hereditary haemochromatosis (HH), it was hypothesized that osteochondral damage in both disorders may be due to localized iron overload. Accordingly, it was predicted that the concentration of ferritin in synovial fluid (SF) would be higher in OA patients with HFE gene mutations than in HFE wild-type (wt) OA patients. The aim of this study was to test this proposition. METHODS: Sequential patients with physician-diagnosed OA and, for comparison, diverse inflammatory diseases of the joints, who required diagnostic or therapeutic arthrocentesis, were studied. Participants underwent HFE genotyping. SF samples were assayed for ferritin and also for selected cytokines and matrix metalloproteinases (MMPs). RESULTS: Seventy-three patients with diverse rheumatic disorders were recruited. Of the 29 patients who had knee OA, 15 were wt and 14 were heterozygous for HFE mutations (C282Y or H63D). Mean SF ferritin concentrations in the wt and heterozygous OA groups were 273 and 655 ng/mL, respectively (p = 0.0146). CONCLUSIONS: A predicted difference in SF ferritin concentrations in patients with knee OA was confirmed. Concentrations of ferritin in the SF were found to be two- to threefold higher in knee OA patients with HFE gene mutations compared to wt patients. This finding is consistent with the possibility that, in OA patients with HFE gene mutations, localized iron overload may contribute either directly or indirectly to osteochondral damage, possibly in a similar way to that which occurs in the arthropathy that complicates HH.

Demand management in plastic surgery for low priority procedures: the Welsh experience.

INTRODUCTION: Health Commission Wales (Specialist Services) [HCW] are responsible for resource allocation and demand management in plastic surgery for the population of Wales (2.9 M). Since 2004, all low priority plastic surgery referrals have been screened by a single HCW Case Officer against clinical inclusion criteria before the referral is passed to the provider. Only patients fulfilling these criteria proceed to an outpatient appointment, although there is an appeals procedure. Revised guidelines were introduced in 2006. Our aim was to investigate the effectiveness of the process and the impact of the revised criteria. METHODS: The Case Officer's database was used to determine numbers of index procedures referred and those disallowed before and after the policy change. RESULTS: Since 2004 9,654 referrals have been screened. In 2005-6, 32.5% failed to meet the inclusion criteria and were disallowed. In the year after the policy revision fewer low priority patients were referred (1720 vs. 2013) and more (46.6%) were declined. Body contouring / abdominoplasty were particularly affected with 73.2% not compliant with funding criteria. CONCLUSION: The Welsh model is an efficient, effective and equitable system for demand management, which amounts to thousands of requests per year. After 2006, tighter guidelines have resulted in a higher proportion of patients not meeting the criteria for funding, particularly for body contouring / abdominoplasty procedures. Difficulties remain however in determining reproducible and clinically appropriate criteria for patients seeking plastic surgery following massive weight-loss. Whilst this process streamlines the provision of NHS plastic surgery for the people of Wales, there is a potential impact on specialist training.

Confirmation of two major polyarticular osteoarthritis (POA) phenotypes--differentiation on the basis of joint topography.

OBJECTIVES: Previous studies of patients with primary hand and ankle osteoarthritis (OA) have suggested the presence of two major polyarticular OA (POA) phenotypes, designated Type 1 and Type 2. The former, characterised by sentinel distal interphalangeal (IP) (DIP) or proximal IP (PIP) joint OA resembles generalised OA (GOA), whereas the latter characterised by sentinel metacarpophalangeal (MCP)2,3 OA, resembles the arthropathy associated with hereditary haemochromatosis (HH). The aim of this study was to validate these putative phenotypes and to further investigate their clinical and genetic characteristics. METHODS: Newly referred patients had X-rays if pre-determined clinical criteria for OA in hand and other joints were met. Subjects were assigned to the putative Type 1 POA (T1POA) or Type 2 POA (T2POA) phenotypes if radiological criteria were satisfied. Human haemochromatosis (HFE) gene mutations were determined in buffy-coat DNA by polymerase chain reaction amplification, followed by restriction enzyme cleavage and analysis on a 3% agarose gel. The significance of differences was determined by Chi-square test or by Fisher's exact test. RESULTS: Sixty-seven patients fulfilled criteria for inclusion in this study; 39 (6M, 33F) for T1POA and 28 (18M, 10F) for T2POA. A statistically significant difference in gender was observed (64% male in the T2POA subset, P<0.0001). Heberden's nodes (HNs) were found in 34 of the 39 Type 1 subjects, but in only nine of the 28 Type 2 subjects (P<0.0001). HFE gene mutations were found in nine of the 39 Type 1 subjects (23%), whereas 21 of the 28 Type 2 subjects had a single HFE gene mutation (75%, P<0.0001). CONCLUSIONS: These findings confirm the hitherto hypothetical proposition of a T1POA phenotype conforming to nodal GOA (NGOA) and a T2POA phenotype closely resembling the arthropathy described in haemochromatosis (HH).