Showing papers by "Royal Devon and Exeter Hospital published in 2014"

2014 European Thyroid Association Guidelines for the Management of Subclinical Hypothyroidism in Pregnancy and in Children

Abstract: This guideline has been produced as the official statement of the European Thyroid Association guideline committee. Subclinical hypothyroidism (SCH) in pregnancy is defined as a thyroid-stimulating hormone (TSH) level above the pregnancy-related reference range with a normal serum thyroxine concentration. Isolated hypothyroxinaemia (defined as a thyroxine level below the 2.5th centile of the pregnancy-related reference range with a normal TSH level) is also recognized in pregnancy. In the majority of SCH the cause is autoimmune thyroiditis but may also be due to iodine deficiency. The cause of isolated hypothyroxinaemia is usually not apparent, but iodine deficiency may be a factor. SCH and isolated hypothyroxinaemia are both associated with adverse obstetric outcomes. Levothyroxine therapy may ameliorate some of these with SCH but not in isolated hypothyroxinaemia. SCH and isolated hypothyroxinaemia are both associated with neuro-intellectual impairment of the child, but there is no evidence that maternal levothyroxine therapy improves this outcome. Targeted antenatal screening for thyroid function will miss a substantial percentage of women with thyroid dysfunction. In children SCH (serum TSH concentration >5.5-10 mU/l) normalizes in >70% and persists in the majority of the remaining patients over the subsequent 5 years, but rarely worsens. There is a lack of studies examining the impact of SCH on the neuropsychological development of children under the age of 3 years. In older children, the evidence for an association between SCH and impaired neuropsychological development is inconsistent. Good quality studies examining the effect of treatment of SCH in children are lacking.

Guidelines for the diagnosis and treatment of cobalamin and folate disorders

Abstract: The clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status because there is no 'gold standard' test to define deficiency. Serum cobalamin currently remains the first-line test, with additional second-line plasma methylmalonic acid to help clarify uncertainties of underlying biochemical/functional deficiencies. Serum holotranscobalamin has the potential as a first-line test, but an indeterminate 'grey area' may still exist. Plasma homocysteine may be helpful as a second-line test, but is less specific than methylmalonic acid. The availability of these second-line tests is currently limited. Definitive cut-off points to define clinical and subclinical deficiency states are not possible, given the variety of methodologies used and technical issues, and local reference ranges should be established. In the presence of discordance between the test result and strong clinical features of deficiency, treatment should not be delayed to avoid neurological impairment. Treatment of cobalamin deficiency is recommended in line with the British National Formulary. Oral therapy may be suitable and acceptable provided appropriate doses are taken and compliance is not an issue. Serum folate offers equivalent diagnostic capability to red cell folate and is the first-line test of choice to assess folate status.

Peritoneal Dialysis for Acute Kidney Injury

Abstract: Renal Unit,1 Greys Hospital, Pietermaritzburg, South Africa; Renal and Intensive Care Units,2 Royal Devon and Exeter Hospital, Exeter, United Kingdom; Pediatric Nephrology Unit,3 Soba University Hospital, University of Khartoum, Sudan; Pondicherry Institute of Medical Sciences and Madras Medical Mission,4 Chennai, India; Department of Medicine,5 Botucatu School of Medicine, Sao Paulo, Brazil; Division of Nephrology-Hypertension,6 University of California, San Diego, USA; Division of Pediatric Nephrology,7 Shaare Zedek Medical Center, Jerusalem, Israel; Pediatric Nephrology Unit,8 Instituto da Criança of the Hospital das Clinicas of the University of Sao Paulo Medical School, Sao Paulo, Brazil; Pediatric Nephrology Department,9 Red Cross War Memorial Children’s Hospital, University of Cape Town, Cape Town, South Africa; Department of Surgery,10 Red Cross War Memorial Children’s Hospital, University of Cape Town, Cape Town, South Africa; School of Medicine,11 Pontificia Universidade Catolica do Parana, Curitiba, Brazil; Division of Pediatric Nephrology,12 University of Missouri-Kansas City School of Medicine, Kansas City, USA; Division of Nephrology,13 Queen’s University, Kingston, Canada; and Yale University,14 New Haven, USA ispd guidelines/ReCOMMendATiOns

HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants

Abstract: Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 × 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the HLA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.

A Randomized Trial Comparing Treatments for Varicose Veins

Abstract: BACKGROUND Ultrasound-guided foam sclerotherapy and endovenous laser ablation are widely used alternatives to surgery for the treatment of varicose veins, but their comparative effectiveness and safety remain uncertain. METHODS In a randomized trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of foam, laser, and surgical treatments. Primary outcomes at 6 months were disease-specific quality of life and generic quality of life, as measured on several scales. Secondary outcomes included complications and measures of clinical success. RESULTS After adjustment for baseline scores and other covariates, the mean disease-specific quality of life was slightly worse after treatment with foam than after surgery (P = 0.006) but was similar in the laser and surgery groups. There were no significant differences between the surgery group and the foam or the laser group in measures of generic quality of life. The frequency of procedural complications was similar in the foam group (6%) and the surgery group (7%) but was lower in the laser group (1%) than in the surgery group (P<0.001); the frequency of serious adverse events (approximately 3%) was similar among the groups. Measures of clinical success were similar among the groups, but successful ablation of the main trunks of the saphenous vein was less common in the foam group than in the surgery group (P<0.001). CONCLUSIONS Quality-of-life measures were generally similar among the study groups, with the exception of a slightly worse disease-specific quality of life in the foam group than in the surgery group. All treatments had similar clinical efficacy, but complications were less frequent after laser treatment and ablation rates were lower after foam treatment. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN51995477.)

TSH Levels and Risk of Miscarriage in Women on Long-Term Levothyroxine: A Community-Based Study

Abstract: Context: Thyroid dysfunction is associated with adverse obstetric outcomes, but there is limited information on pregnancy outcomes in women established on levothyroxine. Objective: The objective of the study was to determine the relationship between TSH levels and pregnancy outcomes in levothyroxine-treated women in a large community-based database. Design: This was a historical cohort analysis. Patients: Individuals with a first prescription of levothyroxine from 2001 through 2009 (n = 55 501) were identified from the UK General Practice Research Database (population 5 million). Of these, we identified 7978 women of child-bearing age (18–45 y) and 1013 pregnancies in which levothyroxine had been initiated at least 6 months before conception. Main Outcome Measures: TSH, miscarriage/delivery status, and obstetric outcomes were measured. Results: Forty-six percent of levothyroxine-treated women aged 18–45 years had a TSH level greater than 2.5mU/L (recommended upper level in the first trimester). Among pregnant women who had their TSH measured in the first trimester, 62.8% had a TSH level greater than 2.5 mU/L, with 7.4% greater than 10 mU/L. Women with TSH greater than 2.5 mU/L in the first trimester had an increased risk of miscarriage compared with women with TSH 0.2–2.5 mU/L after adjusting for age, year of pregnancy, diabetes, and social class (P = .008). The risk of miscarriage was increased in women with TSH 4.51–10 mU/L [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.03, 3.14)] and TSH greater than 10 mU/L (OR 3.95, 95% CI 1.87, 8.37) but not with TSH 2.51–4.5 mU/L (OR 1.09, 95% CI 0.61, 1.93). Conclusions: The majority of levothyroxine-treated women have early gestational TSH levels above the recommended targets (>2.5 mU/L) with a strong risk of miscarriage at levels exceeding 4.5 mU/L. There is an urgent need to improve the adequacy of thyroid hormone replacement in early pregnancy.

Dietary interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood

Abstract: Background Between 4% and 25% of school-age children complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with daily activities. It is unclear whether the diagnosis includes children with different aetiologies for their pain. For the majority no organic cause for their pain can be found on physical examination or investigation. Although most children are likely managed by reassurance and simple measures, a large range of interventions have been recommended. Objectives To determine the effectiveness of dietary interventions for recurrent abdominal pain in school-age children. Search strategy The Cochrane Library (CENTRAL) 2006 (Issue 4), MEDLINE (1966 to Dec 2006), EMBASE (1980 to Dec 2006), CINAHL (1982 to Dec 2007), ERIC (1966 to Dec 2006), PsycINFO (1872 to Dec 2006), LILACS (1982 to Dec 2006), SIGLE (1980 to March 2005), and JICST (1985 to 06/2000) were searched . Where appropriate, search filters were employed. In addition, researchers working in this area were asked to identify relevant studies. Selection criteria Randomised or quasi-randomised studies of any dietary treatment versus placebo or no treatment in school-age children with a diagnosis of RAP or functional gastrointestinal disorder based on the Rome II criteria. Data collection and analysis Two authors independently assessed trials for inclusion, assessed quality and extracted data. Where appropriate studies were pooled using a random effects meta-analysis. Main results Seven trials were included in this review. Two trials, including 83 participants, compared fibre supplements with placebo (Christensen 1982, Feldman 1985), with data from one study reported in two papers (Christensen 1982, Christensen 1986). The pooled odds ratio for improvement in the frequency of abdominal pain was 1.16 (95% CI 0.45-2.87). Two trials, including 90 participants (Lebenthal 1981, Dearlove 1983) compared lactose-containing with lactose-free diets. Neither reported data in a form which could be used in the meta-analysis and the former trial had a loss to follow-up of 45%. We were not able to obtain further data for either trial. Three trials (Bausserman 2005, Gavronska 2007, Young 1997) comparing supplementation with Lactobacillus with placebo met the inclusion criteria but only two (Bausserman 2005, Gavronska 2007), including a total of 168 children, provided analysable data. The pooled odds ratio for improvement of symptoms was 1.17 (95% CI 0.62, 2.21). Authors' conclusions There is a lack of high quality evidence on the effectiveness of dietary interventions. This review provides no evidence that fibre supplements, lactose free diets or lactobacillus supplementation are effective in the management of children with RAP.

Whole exome sequencing in family trios reveals de novo mutations in PURA as a cause of severe neurodevelopmental delay and learning disability

Abstract: Background De novo mutations are emerging as an important cause of neurocognitive impairment, and whole exome sequencing of case-parent trios is a powerful way of detecting them. Here, we report the findings in four such trios. Methods The Deciphering Developmental Disorders study is using whole exome sequencing in family trios to investigate children with severe, sporadic, undiagnosed developmental delay. Three of our patients were ascertained from the first 1133 children to have been investigated through this large-scale study. Case 4 was a phenotypically isolated case recruited into an undiagnosed rare disorders sequencing study. Results Protein-altering de novo mutations in PURA were identified in four subjects. They include two different frameshifts, one inframe deletion and one missense mutation. PURA encodes Pur-α, a highly conserved multifunctional protein that has an important role in normal postnatal brain development in animal models. The associated human phenotype of de novo heterozygous mutations in this gene is variable, but moderate to severe neurodevelopmental delay and learning disability are common to all. Neonatal hypotonia, early feeding difficulties and seizures, or ‘seizure-like’ movements, were also common. Additionally, it is suspected that anterior pituitary dysregulation may be within the spectrum of this disorder. Psychomotor developmental outcomes appear variable between patients, and we propose a possible genotype–phenotype correlation, with disruption of Pur repeat III resulting in a more severe phenotype. Conclusions These findings provide definitive evidence for the role of PURA in causing a variable syndrome of neurodevelopmental delay, learning disability, neonatal hypotonia, feeding difficulties, abnormal movements and epilepsy in humans, and help clarify the role of PURA in the previously described 5q31.3 microdeletion phenotype.

A human mitochondrial poly(A) polymerase mutation reveals the complexities of post-transcriptional mitochondrial gene expression

Abstract: The p.N478D missense mutation in human mitochondrial poly(A) polymerase (mtPAP) has previously been implicated in a form of spastic ataxia with optic atrophy. In this study, we have investigated fibroblast cell lines established from family members. The homozygous mutation resulted in the loss of polyadenylation of all mitochondrial transcripts assessed; however, oligoadenylation was retained. Interestingly, this had differential effects on transcript stability that were dependent on the particular species of transcript. These changes were accompanied by a severe loss of oxidative phosphorylation complexes I and IV, and perturbation of de novo mitochondrial protein synthesis. Decreases in transcript polyadenylation and in respiratory chain complexes were effectively rescued by overexpression of wild-type mtPAP. Both mutated and wild-type mtPAP localized to the mitochondrial RNA-processing granules thereby eliminating mislocalization as a cause of defective polyadenylation. In vitro polyadenylation assays revealed severely compromised activity by the mutated protein, which generated only short oligo(A) extensions on RNA substrates, irrespective of RNA secondary structure. The addition of LRPPRC/SLIRP, a mitochondrial RNA-binding complex, enhanced activity of the wild-type mtPAP resulting in increased overall tail length. The LRPPRC/SLIRP effect although present was less marked with mutated mtPAP, independent of RNA secondary structure. We conclude that (i) the polymerase activity of mtPAP can be modulated by the presence of LRPPRC/SLIRP, (ii) N478D mtPAP mutation decreases polymerase activity and (iii) the alteration in poly(A) length is sufficient to cause dysregulation of post-transcriptional expression and the pathogenic lack of respiratory chain complexes.

The natural history of pain and neuropathic pain after knee replacement: a prospective cohort study of the point prevalence of pain and neuropathic pain to a minimum three-year follow-up

Abstract: A small proportion of patients have persistent pain after total knee replacement (TKR). The primary aim of this study was to record the prevalence of pain after TKR at specific intervals post-operatively and to ascertain the impact of neuropathic pain. The secondary aim was to establish any predictive factors that could be used to identify patients who were likely to have high levels of pain or neuropathic pain after TKR. A total of 96 patients were included in the study. Their mean age was 71 years (48 to 89); 54 (56%) were female. The mean follow-up was 46 months (39 to 51). Pre-operative demographic details were recorded including a Visual Analogue Score (VAS) for pain, the Hospital Anxiety and Depression score as well as the painDETECT score for neuropathic pain. Functional outcome was assessed using the Oxford Knee score. The mean pre-operative VAS was 5.8 (1 to 10); and it improved significantly at all time periods post-operatively (p < 0.001): (from 4.5 at day three to five (1 to 10), 3.2 at six weeks (0 to 9), 2.4 at three months (0 to 7), 2.0 at six months (0 to 9), 1.7 at nine months (0 to 9), 1.5 at one year (0 to 8) and 2.0 at mean 46 months (0 to 10)). There was a high correlation (r > 0.7; p < 0.001) between the mean VAS scores for pain and the mean painDETECT scores at three months, one year and three years post-operatively. There was no correlation between the pre-operative scores and any post-operative scores at any time point. We report the prevalence of pain and neuropathic pain at various intervals up to three years after TKR. Neuropathic pain is an underestimated problem in patients with pain after TKR. It peaks at between six weeks and three-months post-operatively. However, from these data we were unable to predict which patients are most likely to be affected. Cite this article: Bone Joint J 2014;96-B:1227–33.

Diagnosis and management of thyrotoxicosis

Abstract: #### Summary points Thyrotoxicosis is a common condition associated with excess circulating thyroid hormones that may present in myriad ways and thus will be encountered by practitioners in all medical disciplines In Europe, it affects around 1 in 2000 people annually1 Although thyrotoxicosis typically presents with weight loss, heat intolerance, and palpitations, there are a large variety of additional features, which manifest more variably with advancing age and in people with milder disease It is important to determine the cause of the thyrotoxicosis, as this determines treatment Some experts distinguish between thyrotoxicosis and hyperthyroidism by restricting the latter term to describe the conditions associated with excess synthesis and secretion of thyroid hormones from the thyroid gland This clinical review summarises the current evidence for the diagnosis and management of adults with thyrotoxicosis #### Sources and selection criteria We searched Medline, Clinical Evidence, and the Cochrane library using various combinations of terms: “thyrotoxicosis”, “hyperthyroidism”, “Graves’ disease”, “subclinical hyperthyroidism”, “thyroiditis”, “antithyroid drugs”, “carbimazole”, “methimazole”, “propylthiouracil”, “amiodarone”, “radioiodine”, and “thyroidectomy” We gave preference to high quality observational studies, randomised controlled trials, and systematic reviews published in the past 10 years Table 1⇓ lists the important causes of thyrotoxicosis and the underlying pathogeneses Graves’ disease is the …

Interarm Blood Pressure Difference in People With Diabetes: Measurement and Vascular and Mortality Implications: A Cohort Study

Abstract: OBJECTIVE Differences in blood pressure between arms are associated with vascular disease and increased mortality; this has not been reported in diabetes. We explored these associations, and assessed reference standard and pragmatic measurement techniques, in people with diabetes and in nondiabetic controls. RESEARCH DESIGN AND METHODS A prospective cohort study in Devon, England, recruited 727 people with type 1 or type 2 diabetes and 285 nondiabetic controls. Simultaneous repeated measurements of bilateral blood pressure were made at recruitment. Data were used to inform a pragmatic measurement strategy. Interarm differences were examined for cross-sectional associations with target organ disease and prospective mortality associations (median follow-up 52 months). RESULTS We found 8.6% of participants with diabetes and 2.9% of controls had systolic interarm differences ≥10 mmHg. Single pairs of blood pressure measurements had high negative predictive values (97–99%) for excluding interarm differences. Systolic interarm differences ≥10 mmHg in diabetes were associated with peripheral arterial disease (odds ratio [OR] 3.4 [95% CI 1.2–9.3]). Differences ≥15 mmHg were associated with diabetic retinopathy (OR 5.7 [1.5–21.6]) and chronic kidney disease (OR 7.0 [1.7–29.8]). Systolic interarm differences were associated prospectively with increased cardiovascular mortality: hazard ratios 3.5 (1.0–13.0) for ≥10 mmHg and 9.0 (2.0–41.0) for ≥15 mmHg. CONCLUSIONS Blood pressure should be measured in both arms during initial assessment in diabetes. Systolic interarm differences can be excluded with a single pair of measurements. In the population with diabetes, systolic differences may be associated with an increased risk of morbidity and mortality.

Evolution of the Southampton Enhanced Recovery Programme for radical cystectomy and the aggregation of marginal gains

Abstract: Objective To describe and assess the evolution of an enhanced recovery programme (ERP) for open radical cystectomy. Patients and Methods We introduced a mentored ERP for radical cystectomy in January 2011. The programme underwent service evaluation and multiple changes in August 2012 that we define as marginal gains. We present a retrospective review of 133 consecutive patients undergoing open radical cystectomy, grouped according to the three stages of the ERP from October 2008 to April 2013: (1) non-ERP group (October 2008 to December 2010): n = 69; (2) ERP-1 group (January 2011 to July 2012): n = 37; and (3) ERP-2 group (August 2012 to April 2013): n = 27. Primary outcomes were length of hospital stay (LOS), readmission, morbidity at 90 days using the Clavien classification system and mortality. Secondary outcomes were time to flatus, ileus rates, re-operation rates and oncological outcomes. Results There were no differences in patient demographics among any of the groups for: age, gender, BMI, American Society of Anesthesiologists score and the use of neoadjuvant chemotherapy. There were no differences in readmission, morbidity and mortality rates. The overall 90-day mortality was six patients (4.5%). There were significant differences in ileus rates between the non-ERP, the ERP-1 and the ERP-2 groups: 44.9% (31 patients), 29.7% (11 patients) and 14.8% (four patients), respectively (P = 0.017). There was a significant difference in the presence of pathological lymphadenopathy in the ERP-2 group: non-ERP group, 10.1%; ERP-1 group, 16.2%; and ERP-2 group, 44.4%; P = 0.002. There was also a difference in the mean (sd) lymph node yield in ERP-2: non-ERP group, 8.4 (5.4) nodes; ERP-1, 8.2 (6.4) nodes; and ERP-2, 16.7 (5.4) nodes (P < 0.001). The median (range) LOS was 14 (7–91) days, 10 (6–55) days and 7 (3–99) days in the non-ERP, ERP-1 and ERP-2 groups, respectively (P < 0.001). Conclusions Auditing an already successful ERP and implementing a number of marginal gains has led to a significant decrease in the median LOS for radical cystectomy. The LOS for open radical cystectomy at University Hospital Southampton has halved. In the second phase of our ERP, our median LOS is 7 days.

Training recruiters to randomized trials to facilitate recruitment and informed consent by exploring patients' treatment preferences

Abstract: Background Patients’ treatment preferences are often cited as barriers to recruitment in randomized controlled trials (RCTs). We investigated how RCT recruiters reacted to patients’ treatment preferences and identified key strategies to improve informed decision-making and trial recruitment.

Management of Periprosthetic Joint Infection After Total Hip Arthroplasty Using a Custom Made Articulating Spacer (CUMARS); the Exeter Experience

Abstract: Periprosthetic joint infection (PJI) after THA is a major complication with an incidence of 1%-3%. We report our experiences with a technique using a custom-made articulating spacer (CUMARS) at the first of two-stage treatment for PJI. This technique uses widely available all-polyethylene acetabular components and the Exeter Universal stem, fixed using antibiotic loaded acrylic cement. Seventy-six hips were treated for PJI using this technique. Performed as the first of a two-stage procedure, good functional results were commonly seen, leading to postponing second stage indefinitely with retention of the CUMARS prosthesis in 34 patients. The CUMARS technique presents an alternative to conventional spacers, using readily available components that are well tolerated, allowing weight bearing and mobility, and achieving comparable eradication rates.

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Abstract: Introduction More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers.

CD20+inflammatory T-cells are present in blood and brain of multiple sclerosis patients and can be selectively targeted for apoptotic elimination.

Abstract: Background A subset of T-cells expresses the B-cell marker CD20 and in rheumatoid arthritis secretes Interleukin (IL)-17. IL-17 secreting T-cells (Th17) have also been implicated in the inflammatory response in the central nervous system in multiple sclerosis (MS) and may be a potential target for elimination by biologic therapeutics. ScFvRit:sFasL comprises of a rituximab-derived antibody fragment scFvRit genetically fused to human soluble FasL that specifically eliminated T-cells. Objective To determine the presence and phenotype of CD20+T-cells in blood and brain of MS patients. Second, to determine whether scFvRit:sFasL can selectively eliminate CD20+T-cells. After CD20-selective binding, scFvRit:sFasL is designed to trigger FasL-mediated activation-induced cell death of T-cells, but not B-cells. Methods Flow cytometry and immunohistochemistry were used to screen for CD20+inflammatory T-cells in MS blood and brain tissue. ScFvRit:sFasL pro-apoptotic activity was evaluated by Annexin-V/PI staining followed by flow cytometry assessment. Results Peripheral blood ( n =11) and chronic but not active lesions of MS patient brains ( n =5) contained CD20+inflammatory T-cells. Activated CD20+T-cells were predominantly CD4+and secreted both IL-17 and INF-γ. ScFvRit:sFasL triggered CD20-restricted FasL-mediated activation-induced cell death in peripheral blood CD20+T-cells, but not CD20+B-cells. Conclusion CD20+inflammatory T-cells are present in blood and chronic brain lesions of MS patients. ScFvRit:sFasL selectively eliminated CD20+T-cells and may eliminate pathogenic T-cells without B-cell depletion.

The costs of late detection of developmental dysplasia of the hip

Abstract: Purpose Debate currently exists regarding the economic viability for screening for developmental dysplasia of the hip in infants. Methods A prospective study of infant hip dysplasia over the period of 1998–2008 (36,960 live births) was performed to determine treatment complexity and associated costs of disease detection and hospital treatment, related to the age at presentation and treatment modality. The involved screening programme utilised universal clinical screening of all infants and selective ultrasound screening of at-risk infants. Results One hundred and seventy-nine infants (4.8/1,000) presented with hip dysplasia. Thirty-four infants presented late (> 3 months of age) and required closed or open reduction. One hundred and forty-five infants presented at < 3 months of age, 14 of whom failed early Pavlik harness treatment. A detailed cost analysis revealed: 131 early presenters with successful management in a Pavlik harness at a cost of £601/child; 34 late presenters who required surgery...

Cost‐effectiveness of ultrasound‐guided foam sclerotherapy, endovenous laser ablation or surgery as treatment for primary varicose veins from the randomized CLASS trial

Abstract: This work was carried out as part of a project funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (project number 06/45/02).

Postconcussion syndrome (PCS) in the emergency department: predicting and pre-empting persistent symptoms following a mild traumatic brain injury

Abstract: Head injuries across all age groups represent an extremely common emergency department (ED) presentation. The main focus of initial assessment and management rightly concentrates on the need to exclude significant pathology, that may or may not require neurosurgical intervention. Relatively little focus, however, is given to the potential for development of post-concussion syndrome (PCS), a constellation of symptoms of varying severity, which may bear little correlation to the nature or magnitude of the precipitating insult. This review aims to clarify the aetiology and terminology surrounding PCS and to examine the mechanisms for diagnosing and treating.

Gluteal tendon repair augmented with a synthetic ligament: surgical technique and a case series

Abstract: We describe an augmented surgical repair technique for gluteus minimus and medius tears, along with a supportive case series. A consecutive series of 22 patients presenting with clinical and radiological findings consistent with hip abductor tears, who had undergone failed prior conservative treatments, were prospectively recruited. Patients underwent open bursectomy, Y-iliotibial release, debridement of the diseased tendon, decortication of the trochanteric foot-plate and reattachment augmented with a LARS ligament through a trans-osseous tunnel, together with suture anchors. All patients were assessed pre- and postoperatively to 12 months with the Oxford Hip Score (OHS), the Short-Form Health Survey (SF-36) and a Visual Analogue Pain Scale (VAS), while a satisfaction scale was employed at 12 months. A statistically significant improvement (p<0.05) was observed for all patient reported outcome measures, while all patients were at least 'satisfied' with the procedure at 12 months. One patient reported some lateral hip discomfort at 10 months, and removal of the LARS interference screw provided immediate relief. One patient had a urological catheter-related complication. With no other complications and no clinical failures of the repair, we believe the technique to be safe and reliable, whilst reducing the incidence of re-tears as reported in the existing literature.

Clinical and radiographic outcomes of acetabular impaction grafting without cage reinforcement for revision hip replacement: a minimum ten-year follow-up study

Abstract: Impaction bone grafting for the reconstitution of bone stock in revision hip surgery has been used for nearly 30 years. Between 1995 and 2001 we used this technique in acetabular reconstruction, in combination with a cemented component, in 304 hips in 292 patients revised for aseptic loosening. The only additional supports used were stainless steel meshes placed against the medial wall or laterally around the acetabular rim to contain the graft. All Paprosky grades of defect were included. Clinical and radiographic outcomes were collected in surviving patients at a minimum of ten years after the index operation. Mean follow-up was 12.4 years (sd 1.5) (10.0 to 16.0). Kaplan–Meier survival with revision for aseptic loosening as the endpoint was 85.9% (95% CI 81.0 to 90.8) at 13.5 years. Clinical scores for pain relief remained satisfactory, and there was no difference in clinical scores between cups that appeared stable and those that appeared radiologically loose. Cite this article: Bone Joint J 2014;96-B:188–94.

Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results.

Abstract: Bisphosphonates are recommended in patients with osteolytic lesions secondary to multiple myeloma. We report on the safety of bisphosphonate therapy with long-term follow-up in the Medical Research Council Myeloma IX study. Patients with newly diagnosed multiple myeloma were randomised to zoledronic acid (ZOL; 4 mg intravenously every 21-28 d) or clodronate (CLO; 1600 mg/d orally) plus chemotherapy. Among 1960 patients (5.9-year median follow-up), both bisphosphonates were well tolerated. Acute renal failure events were similar between groups (ZOL 5.2% vs. CLO 5.8% at 2 years; incidence plateaued thereafter). The overall incidence of confirmed osteonecrosis of the jaw (ONJ) was low, but higher with ZOL (ZOL 3.7% vs. CLO 0.5%; P < 0.0001). ONJ events were generally low grade and most occurred between 8 and 30 months (median time to ONJ, 23.7 months). Among 10 patients with ONJ recovery data, four patients in the ZOL group completely recovered, two patients improved, and three patients experienced no improvement; one CLO patient experienced no improvement. Dental surgery or trauma preceded ONJ in six ZOL patients. The incidence of renal adverse events was similar for ZOL and CLO. ONJ incidence remained low and was lower with CLO compared to ZOL. We have seen no further ONJ cases to date.

Factors determining penetrance in familial atypical haemolytic uraemic syndrome

Abstract: Background Inherited abnormalities of complement are found in ∼60% of patients with atypical haemolytic uraemic syndrome (aHUS). Such abnormalities are not fully penetrant. In this study, we have estimated the penetrance of the disease in three families with a CFH mutation (c.3643C>G; p. Arg1215Gly) in whom a common lineage is probable. 25 individuals have been affected with aHUS with three peaks of incidence—early childhood (n=6), early adulthood (n=11) and late adulthood (n=8). Eighteen individuals who have not developed aHUS carry the mutation. Methods We estimated penetrance at the ages of 4, 27, 60 and 70 years as both a binary and a survival trait using MLINK and Mendel. We genotyped susceptibility factors in CFH , CD46 and CFHR1 in affected and unaffected carriers. Results and Conclusions We found that the estimates of penetrance at the age of 4 years ranged from CFH haplotype on the allele not carrying the CFH mutation had a significant effect on disease penetrance. In this family, we did not find that the CD46 haplotypes had a significant effect on penetrance.

Block & replace regime versus titration regime of antithyroid drugs for the treatment of Graves' disease: a retrospective observational study.

Abstract: Context Two widely used antithyroid drug (ATD) regimes for Graves' disease (GD) include the 'block & replace' (BR adjusted mean difference = -0.4; 95% CI: -0.7 to -0.1; and P = 0.008) and the number of hospital clinic visits per year (mean (SD): 2.9 (1.0) vs 3.2 (1.3); adjusted mean difference = -0.4; 95% CI: -0.7 to -0.2; and P = 0.002) were lower in the BR adjusted mean difference = 0.05; 95%CI: -0.3 to 0.4; and P = 0.74). Conclusions In this retrospective study, there was little evidence that patients under B&R have more stable thyroid function. Further data from prospective studies, however, are needed to confirm this finding.