Showing papers by "Guy's and St Thomas' NHS Foundation Trust published in 2010"

Sarcopenia: European consensus on definition and diagnosis Report of the European Working Group on Sarcopenia in Older People

Abstract: The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics-European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document. The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity? For the diagnosis of sarcopenia, EWGSOP recommends using the presence of both low muscle mass + low muscle function (strength or performance). EWGSOP variously applies these characteristics to further define conceptual stages as 'presarcopenia', 'sarcopenia' and 'severe sarcopenia'. EWGSOP reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research. Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment.

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

Abstract: We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

Functional impact of global rare copy number variation in autism spectrum disorders

Abstract: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.

The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis

Abstract: Objective The Surviving Sepsis Campaign (SSC or “the Campaign”) developed guidelines for management of severe sepsis and septic shock. A performance improvement initiative targeted changing clinical behavior (process improvement) via bundles based on key SSC guideline recommendations on process improvement and patient outcomes.

Association of Risk-Reducing Surgery in BRCA1 or BRCA2 Mutation Carriers With Cancer Risk and Mortality

Abstract: Context Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer. Objective To estimate risk and mortality reduction stratified by mutation and prior cancer status. Design, Setting, and Participants Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009. Main Outcomes Measures Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality. Results No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer–specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer–specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]). Conclusions Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer–specific mortality, and ovarian cancer–specific mortality.

European Society of Hypertension International Protocol revision 2010 for the validation of blood pressure measuring devices in adults

Abstract: The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland, dabl Ltd., Blackrock Co., Dublin, Ireland, Hypertension Center, Third University Department of Medicine, Sotiria Hospital, Athens, Greece, Istituto Scientifico Ospedale San Luca, IRCCS, Instituto Auxologico Italiano, Milan, Italy, Societe Francaise d’Hypertension Arterielle, Filiale de la Societe Francaise de Cardiolgie, Paris, France, The Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Science and Medicine, Sendai, Japan, Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, University Clinic Bonn, Department of Internal Medicine, Bonn, Germany and Guy’s and St Thomas’ Hospitals, London, UK

Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial

Abstract: Long-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis (LN). This investigator-initiated randomised trial tested whether mycophenolate mofetil (MMF) was superior to azathioprine (AZA) as maintenance treatment.

Mutation of the RAD51C gene in a Fanconi anemia-like disorder

Abstract: Fanconi anemia (FA) is a rare chromosomal-instability disorder associated with a variety of developmental abnormalities, bone marrow failure and predisposition to leukemia and other cancers. We have identified a homozygous missense mutation in the RAD51C gene in a consanguineous family with multiple severe congenital abnormalities characteristic of FA. RAD51C is a member of the RAD51-like gene family involved in homologous recombination-mediated DNA repair. The mutation results in loss of RAD51 focus formation in response to DNA damage and in increased cellular sensitivity to the DNA interstrand cross-linking agent mitomycin C and the topoisomerase-1 inhibitor camptothecin. Thus, biallelic germline mutations in a RAD51 paralog are associated with an FA-like syndrome.

Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma

Abstract: We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[ A], odds ratio (OR) = 1.36, P = 5.0 x 10(-10)). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG.

PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor–positive breast cancer

Abstract: PIK3CA mutations are reported to be present in approximately 25% of breast cancer (BC), particularly the estrogen receptor-positive (ER+) and HER2-overexpressing (HER2+) subtypes, making them one of the most common genetic aberrations in BC. In experimental models, these mutations have been shown to activate AKT and induce oncogenic transformation, and hence these lesions have been hypothesized to render tumors highly sensitive to therapeutic PI3K/mTOR inhibition. By analyzing gene expression and protein data from nearly 1,800 human BCs, we report that a PIK3CA mutation-associated gene signature (PIK3CA-GS) derived from exon 20 (kinase domain) mutations was able to predict PIK3CA mutation status in two independent datasets, strongly suggesting a characteristic set of gene expression-induced changes. However, in ER+/HER2- BC despite pathway activation, PIK3CA mutations were associated with a phenotype of relatively low mTORC1 signaling and a good prognosis with tamoxifen monotherapy. The relationship between clinical outcome and the PIK3CA-GS was also assessed. Although the PIK3CA-GS was not associated with prognosis in ER- and HER2+ BC, it could identify better clinical outcomes in ER+/HER2- disease. In ER+ BC cell lines, PIK3CA mutations were also associated with sensitivity to tamoxifen. These findings could have important implications for the treatment of PIK3CA-mutant BCs and the development of PI3K/mTOR inhibitors.

A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

Abstract: Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).

Genetic loci influencing kidney function and chronic kidney disease

Abstract: Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.

Guideline for investigation and management of adults and children presenting with a thrombocytosis

Abstract: Guy’s and St Thomas’ NHS Foundation Trust, London, Russells Hall Hospital, Dudley, West Midlands, Arrowe Park Hospital Arrowe Park Road Upton Wirral, Wellcome Trust Sanger Institute, Hinxton, Cambridge, St. James Hospital, James Street, Dublin, Gartnavel General Hospital 21 Shelley Road Glasgow, Addenbrooke’s Hospital, Cambridge, Salisbury Healthcare NHS Trust, Salisbury, Wiltshire, Cambridge Institute for Medical Research, Hills Road, Cambridge, John Radcliffe Hospital, Headley Way, Headington, Oxford, Royal Infirmary, Little France Crescent, Edinburgh, Sandwell and West Birmingham Hospitals, Dudley Road, Birmingham, Royal Hallamshire Hospital, Glossop Road, Sheffield, and Belfast City Hospital, Lisburn Road Belfast, UK

Outpatient pulmonary rehabilitation following acute exacerbations of COPD

Abstract: BACKGROUND Exacerbations of chronic obstructive pulmonary disease (COPD) are characterised by increased dyspnoea, reduced quality of life and muscle weakness. Re-exacerbation and hospital admission are common. Pulmonary rehabilitation (PR) administered after hospital admission for an exacerbation can improve quality of life and exercise capacity. OBJECTIVE To determine whether outpatient post-exacerbation PR (PEPR) could reduce subsequent hospital admission episodes. METHODS Patients admitted to hospital for an exacerbation of COPD were randomised to receive either usual follow-up care (UC) or PEPR after discharge. Hospital admission and emergency department attendances for COPD exacerbations were recorded over a 3-month period and analysed on an intention-to-treat basis. Secondary outcomes included exercise capacity and quadriceps strength. RESULTS 60 patients underwent concealed randomisation at the time of their hospital discharge (UC: n=30, mean (SD) age 65 (10) years, forced expiratory volume in 1 s (FEV(1)) 52 (22)% predicted; PEPR: n=30, 67(10) years, 52 (20)% predicted). The proportion of patients re-admitted to hospital with an exacerbation was 33% in the UC group compared with 7% in those receiving PEPR (OR 0.15, 95% CI 0.03 to 0.72, p=0.02). The proportion of patients that experienced an exacerbation resulting in an unplanned hospital attendance (either admission or review and discharge from the emergency department) was 57% in the UC group and 27% in those receiving PEPR (OR 0.28, 95% CI 0.10 to 0.82, p=0.02). CONCLUSIONS Post-exacerbation rehabilitation in COPD can reduce re-exacerbation events that require admission or hospital attendance over a 3-month period. Clinical Trials Registration Number NCT00557115.

Mephedrone use and associated adverse effects in school and college/university students before the UK legislation change.

Abstract: Background: Mephedrone is a synthetic cathinone that is commonly used as a recreational drug among those who attend nightclubs. There have been increasing reports of toxicity associated with its use and it was controlled as a Class B drug under the Misuse of Drugs Act (1971) in the UK on 16 April 2010. There has been a suggestion from media reports that mephedrone use is common in children/students but there is no data on the prevalence of its use among the general population. The aim of this study was to determine the prevalence and frequency of use of mephedrone among school and college/university aged individuals and to collect data on the sources of mephedrone and acute harm related to its use. Methods: Data was collected using a questionnaire survey in schools, colleges and universities in the Tayside area of Scotland, UK in February 2010. Results: A total of 1006 individuals completed the survey [501 (49.8%) males and 505 (50.2%) females], of whom 349 classified their educational institute as a school and 657 as a college/university. Among them 205 (20.3%) reported previous use of mephedrone; 23.4% reported using only using mephedrone on one occasion previously, although 4.4% reported daily use. A total of 56% of those who had used mephedrone, reported at least one unwanted effect associated with its use. A total of 17.6% of users reported ‘addiction or dependence’ symptoms associated with their mephedrone use. A total of 48.8% of users sourced mephedrone from street level dealers, 10.7% from the Internet. Conclusions: We have shown in this study that the use of mephedrone among school and college/university students is common and that users found it easy to obtain. There was a high prevalence of unwanted effects associated with its use. Further work is needed to determine the impact of the recent changes in the UK legislation relating to mephedrone and other related cathinones and whether this has been effective in reducing the prevalence of mephedrone use.

RYR1 mutations are a common cause of congenital myopathies with central nuclei

Abstract: Objective: Centronuclear myopathy (CNM) is a rare congenital myopathy characterized by prominence of central nuclei on muscle biopsy. CNM has been associated with mutations in MTM1, DNM2, and BIN1 but many cases remain genetically unresolved. RYR1 encodes the principal sarcoplasmic reticulum calcium release channel and has been implicated in various congenital myopathies. We investigated whether RYR1 mutations cause CNM. Methods: We sequenced the entire RYR1 coding sequence in 24 patients with a diagnosis of CNM from South Africa (n ¼ 14) and Europe (n ¼ 10) and identified mutations in 17 patients. The most common genotypes featured compound heterozygosity for RYR1 missense mutations and mutations resulting in reduced protein expression, including intronic splice site and frameshift mutations. Results: The high incidence in South African patients (n ¼ 12/14) in conjunction with recurrent RYR1 mutations associated with common haplotypes suggested the presence of founder effects. In addition to central nuclei, prominent histopathological findings included (often multiple) internalized nuclei and t ype 1f iber predominance and hypotrophy with relative type 2 hypertrophy. Although cores were not typically seen on oxidative stains, electron microscopy revealed subtle abnormalities in most cases. External ophthalmoplegia, proximal weakness, and bulbar involvement were prominent clinical findings. Interpretation: Our findings expand the range of RYR1-related phenotypes and suggest RYR1 mutations as a common cause of congenital myopathies with central nuclei. Corresponding to recent observations in X-linked CNM, these findings indicate disturbed assembly and/or malfunction of the excitation-contraction machinery as a key mechanism in CNM and related myopathies. ANN NEUROL 2010;68:717–726

Purchasing ‘legal highs’ on the Internet—is there consistency in what you get?

Abstract: Background: The supply of recreational drugs has changed and users increasingly buy ‘legal highs’ over the Internet. Use of these is common and there is a potential for significant toxicity associated with their use. Aim: To determine the content of legal highs available for purchase in the UK and whether the content of these remains consistent. Methods: Twenty-six legal highs were purchased monthly from five different Internet sites over 6 months. These were analysed to determine the drugs in the products and whether there were any changes in their content over this time period. Results: All products were supplied initially, but there was a decline in supply of products month by month. The following drug classes were detected: piperazines, cathinones, caffeine/ephedrine or products in which no psychoactive drugs were detected. Of the products supplied on more than one occasion, 15 (75%) contained the same compounds on each occasion. In three products there was a change in the piperazine detected, with 1-benzylpiperazine being substituted for 1-methyl-4-benzylpiperazine or vice versa. In two other products there was a cathinone [4-fluorophenylpiperazine (pFPP) or 3-fluromethcathinone (3FMC)] detected in products purchased in Month 1 that was not present in the products purchased in subsequent months. Conclusions: Whilst there was no variation in the composition of most legal highs supplied over 6 month, there was significant variation in the piperazine or cathinone content of one quarter of the products. This variation could be of clinical significance as the cathinone and piperazine products can be associated with significant toxicity.

Evolutionary Genetics of Human Enterovirus 71: Origin, Population Dynamics, Natural Selection, and Seasonal Periodicity of the VP1 Gene

Abstract: Human enterovirus 71 (EV-71) is one of the major etiologic causes of hand, foot, and mouth disease (HFMD) among young children worldwide, with fatal instances of neurological complications becoming increasingly common. Global VP1 capsid sequences (n 628) sampled over 4 decades were collected and subjected to comprehensive evolutionary analysis using a suite of phylogenetic and population genetic methods. We estimated that the common ancestor of human EV-71 likely emerged around 1941 (95% confidence interval [CI], 1929 to 1952), subsequently diverging into three genogroups: B, C, and the now extinct genogroup A. Genealogical analysis revealed that diverse lineages of genogroup B and C (subgenogroups B1 to B5 and C1 to C5) have each circulated cryptically in the human population for up to 5 years before causing large HFMD outbreaks, indicating the quiescent persistence of EV-71 in human populations. Estimated phylogenies showed a complex pattern of spatial structure within well-sampled subgenogroups, suggesting endemicity with occasional lineage migration among locations, such that past HFMD epidemics are unlikely to be linked to continuous transmission of a single strain of virus. In addition, rises in genetic diversity are correlated with the onset of epidemics, driven in part by the emergence of novel EV-71 subgenogroups. Using subgenogroup C1 as a model, we observe temporal strain replacement through time, and we investigate the evidence for positive selection at VP1 immunogenic sites. We discuss the consequences of the evolutionary dynamics of EV-71 for vaccine design and compare its phylodynamic behavior with that of influenza virus.

Genome Sequence of a Recently Emerged, Highly Transmissible, Multi-Antibiotic- and Antiseptic-Resistant Variant of Methicillin-Resistant Staphylococcus aureus, Sequence Type 239 (TW)

Abstract: The 3.1-Mb genome of an outbreak methicillin-resistant Staphylococcus aureus (MRSA) strain (TW20) contains evidence of recently acquired DNA, including two large regions (635 kb and 127 kb). The strain is resistant to a wide range of antibiotics, antiseptics, and heavy metals due to resistance genes encoded on mobile genetic elements and also mutations in housekeeping genes.

Case series of individuals with analytically confirmed acute mephedrone toxicity.

Abstract: Context. Previous reports of acute toxicity/harm associated with mephedrone use have been based on self-reported mephedrone use; toxicological screening has not been undertaken in these cases to determine whether mephedrone has been used. Objective. To report the first case series of analytically confirmed mephedrone-related acute toxicity. Materials and methods. Serum samples were collected from individuals presenting to an emergency department (ED) with acute toxicity related to self-reported mephedrone use. Toxicological analysis, by gas-chromatography coupled with mass-spectrometry and liquid chromatography with tandem mass-spectrometry was performed to qualitatively confirm mephedrone use. Symptoms/signs of acute mephedrone toxicity and basic physiological parameters were extracted from the routine ED records. Results. Acute mephedrone-related toxicity was analytically confirmed in seven male patients; the mean ± SD age was 24.6 ± 6.5 years (range 16–36 years). Agitation (four patients) was the most ...

Recreational use of mephedrone (4-methylmethcathinone, 4-MMC) with associated sympathomimetic toxicity

Abstract: Introduction Cathinone is a pharmacologically active alkaloid that can be extracted from the leaves of the khat plant (Catha edulis). There are synthetic derivatives of cathinone entering the recreational drug market, including mephedrone (4-methylmethcathinone, 4-MMC). There are discrepancies in the legal status of both the khat plant and its extracted alkaloids between the UK and the USA.

The added value of multislice SPECT/CT in patients with equivocal bony metastasis from carcinoma of the prostate

Abstract: The purpose of this study was to investigate the additional value of single photon emission computed tomography/computed tomography (SPECT/CT) over whole-body planar bone scintigraphy and SPECT in prostate cancer patients in terms of diagnostic confidence, inter-reviewer agreement and the possible impact on the clinical management. This was a retrospective review of 40 consecutive prostate cancer patients (mean age 71 years) who underwent 99mTc-methylene diphosphonate (MDP) whole-body planar bone scintigraphy, SPECT and SPECT/CT between April 2006 and April 2008. The images were evaluated by two independent reviewers; inter-reviewer agreement was evaluated using a weighted kappa score. Each focus of abnormal increased tracer uptake was recorded using a 4-point diagnostic confidence scale. Institutional Review Board approval was obtained. Fifty lesions on planar bone scintigraphy in the 40 patients were evaluated. On reporting the planar study and SPECT scans, reviewers rated 61% of lesions as equivocal. On reporting the SPECT/CT scans only 8% of lesions were rated as equivocal, 24% were rated as malignant and 68% as benign. Weighted kappa scores for inter-reviewer agreement were 0.43 for bone scintigraphy, 0.56 for SPECT and 0.87 for SPECT/CT. All were significant at p < 0.0001. Follow-up imaging confirmed the SPECT/CT diagnoses in 14 patients. The addition of SPECT/CT resulted in a significant reduction of equivocal reports; a definitive diagnosis was given in the majority of the patients due to the improved diagnostic confidence compared to planar or SPECT imaging alone in prostate cancer patients with suspected bone metastases.

Frontal fibrosing alopecia: a clinical review of 36 patients

Abstract: Summary Background Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia with a distinctive clinical pattern of progressive frontotemporal hairline recession. Currently, there are no evidence-based studies to guide treatment for patients with FFA; thus, treatment options vary among clinicians. Objectives We report clinical findings and treatment outcomes of 36 patients with FFA, the largest cohort to date. Further, we report the first evidence-based study of the efficacy of hydroxychloroquine in FFA using a quantitative clinical score, the Lichen Planopilaris Activity Index (LPPAI). Methods A retrospective case note review was performed of 36 adult patients with FFA. Data were collected on demographics and clinical findings. Treatment responses to hydroxychloroquine, doxycycline and mycophenolate mofetil were assessed using the LPPAI. Adverse events were monitored. Results Most patients in our cohort were female (97%), white (92%) and postmenopausal (83%). Apart from hairline recession, 75% also reported eyebrow loss. Scalp pruritus (67%) and perifollicular erythema (86%) were the most common presenting symptom and sign, respectively. A statistically significant reduction in signs and symptoms in subjects treated with hydroxychloroquine (P < 0·05) was found at both 6- and 12-month follow up. Conclusions In FFA, hairline recession, scalp pruritus, perifollicular erythema and eyebrow loss are common at presentation. Despite the limitations of a retrospective review, our data reveal that hydroxychloroquine is significantly effective in reducing signs and symptoms of FFA after both 6 and 12 months of treatment. However, the lack of a significant reduction in signs and symptoms between 6 and 12 months indicates that the maximal benefits of hydroxychloroquine are evident within the first 6 months of use.