93 research outputs found

    Leg Ulceration in Sickle Cell Disease: An Early and Visible Sign of End‐Organ Disease

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    Introduction: Leg ulcers are a frequent and debilitating complication of sickle cell disease (SCD), particularly of the SS genotype. The prevalence of leg ulcers in patients with sickle cell disease (SCD) varies geographically ranging widely from 75% in Jamaica to as low as 1% in Saudi Arabia. The prevalence of leg ulcers in the Cooperative Study of Sickle Cell Disease (CSSCD) in the United States was 5% in SS genotype with the incidence increasing with age. As patients with SCD have increasingly improved survival, the prevalence of leg ulcers is likely to be higher. These ulcers are slow to heal, have a high rate of recurrence, and are associated with severe unremitting pain and depression, thus leading to high healthcare costs. Despite being a well‐recognized complication of SCD, there are no specifically designed evidence‐based guidelines to help clinicians manage these patients

    Leg ulcers in sickle cell disease.

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    Sickle cell disease is a single amino acid molecular disorder of hemoglobin leading to its pathological polymerization, red cell rigidity that causes poor microvascular blood flow, with consequent tissue ischemia and infarction. The manifestations of this disease are protean.Among them, leg ulcers represent a particularly disabling and chronic complication, often associated with a more severe clinical course.Despite the fact that this complication has been recognized since the early times of SCD, there has been little improvement in the efficacy of its management and clinical outcome over the past 100 years. Recently, vasculopathic abnormalities involving abnormal vascular tone and activated, adhesive endothelium have been recognized as another pathway to end organ damage in sickle cell disease. Vasculopathy of sickle cell disease has been implicated in the development of pulmonary hypertension, stroke, leg ulceration and priapism, particularly associated with hemolytic severity, and reported in other severe hemolytic disorders. The authors present the proceedings from the Educational Session on Chronic leg ulcers in Sickle cell disease, held during the 4th Annual Sickle Cell Disease Research and Educational Symposium, on February 17, 2010 in Fort Lauderdale, Fla

    Sleep disturbance, depression and pain in adults with sickle cell disease

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    Background Sleep disturbance and depression are commonly encountered in primary care. In sickle cell disease, depression is associated with pain, poor treatment compliance, and lower quality of life. The prevalence of sleep disturbance and its effect upon quality of life in adults with sickle cell disease is unknown. The goal of this study was to determine the prevalence of sleep disturbance and if it is associated with pain and depression in sickle cell disease. Methods Three hundred twenty eight adults with sickle cell disease enrolled on the Bethesda Sickle Cell Cohort Study were assessed using the Pittsburgh Sleep Quality Index and Beck Depression Inventory II screening measures as a cross-sectional survey. Scores greater than 5 (Pittsburgh Sleep Quality Index) and 16 (Beck Depression Inventory II) defined sleep disturbance and depression, respectively. Clinical and laboratory parameters were also assessed. Results The mean Pittsburgh Sleep Quality Index score was 8.4 (SD ± 4.2) indicating a 71.2% prevalence of sleep disturbance. The mean Beck Depression Inventory II score was 8.0 (SD ± 8.9). Sixty five (20.6%) participants had a score indicating depression, and half of these (10.0%) had thoughts of suicide. Both Pittsburgh Sleep Quality Index and Beck Depression Inventory II scores were significantly correlated (p \u3c .001). The number of days with mild/moderate pain (p = .001) and a history of headaches (p = .005) were independently associated with depression by multivariate regression analysis. Patients with sleep disturbance were older (p = .002), had higher body mass index (p = .011), had more days of pain (p = .003) and more frequent severe acute painful events (emergency room visits and hospitalizations) during the previous 12 months (p \u3c .001). Conclusions More than 70 percent of adults with sickle cell disease had sleep disturbance, while 21 percent showed evidence of clinical depression. Sleep disturbance and depression were correlated, and were most common among those with more frequent pain. Providers caring for adults with sickle cell disease and frequent pain should consider screening for these common co-morbidities. Additional study is needed to confirm these findings and to determine if treatments for pain, depression or sleep disturbances will improve quality of life measures in this patient population

    RV dysfunction by MRI is associated with elevated transpulmonary gradient and poor prognosis in patients with sickle cell associated pulmonary hypertension

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    Patients with sickle cell disease (SCD) and pulmonary hypertension (PH) have increased mortality. SCD-PH is often complicated by high cardiac output (CO) related to anemia. The transpulmonary gradient (TPG) reflects a pressure differential across the pulmonary vascular bed without the confounding effect of CO (PVR=TPG/CO). Based on the cardiac transplant literature, a TPG ≥ 12 mmHg indicates significant pulmonary arterial hypertension (PAH). With PH, there is often morphologic adaptation by the right ventricle (RV). In idiopathic PAH, RV dilation and decreased function have been correlated with poor prognosis. We hypothesize that patients with SCD and a TPG ≥ 12 mmHg would have lower functional capacity, increased mortality, and evidence of RV dysfunction on cardiac MRI (CMR)

    Association of G6PD 202A,376G with lower haemoglobin concentration but not increased haemolysis in patients with sickle cell anaemia

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    The genetic bases of the highly variable degrees of anaemia and haemolysis in persons with Hb SS are not fully known, but several studies have indicated that G6PD deficiency is not a factor. The G6PD 202A and G6PD 376G alleles and α-thalassaemia were determined by molecular genetic testing in 261 children and adolescents with Hb SS in a multicentre study. G6PD 202A,376G (G6PD A−) was defined as hemizygosity for both alleles in males and homozygosity in females. Among the participants 41% were receiving hydroxycarbamide. The prevalence of G6PD 202A,376G was 13·6% in males and 3·3% in females with an overall prevalence of 8·7%. G6PD 202A,376G was associated with a 10 g/l decrease in haemoglobin concentration ( P  = 0·008) but not with increased haemolysis as measured by lactate dehydrogenase, bilirubin, aspartate-aminotransferase, reticulocyte count or a haemolytic component derived from these markers ( P  > 0·09). Similar results were found within a sub-group of children who were not receiving hydroxycarbamide. By comparison, single and double α-globin deletions were associated with progressively higher haemoglobin concentrations ( P  = 0·005 for trend), progressively lower values for haemolytic component ( P  = 0·007), and increased severe pain episodes ( P  < 0·001). In conclusion, G6PD 202A,376G may be associated with lower haemoglobin concentration in sickle cell anaemia by a mechanism other than increased haemolysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79250/1/j.1365-2141.2010.08215.x.pd

    Angiogenic and Inflammatory Markers of Cardiopulmonary Changes in Children and Adolescents with Sickle Cell Disease

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    Background: Pulmonary hypertension and left ventricular diastolic dysfunction are complications of sickle cell disease. Pulmonary hypertension is associated with hemolysis and hypoxia, but other unidentified factors are likely involved in pathogenesis as well. Design and Methods: Plasma concentrations of three angiogenic markers (fibroblast growth factor, platelet derived growth factor-BB [PDGF-BB], vascular endothelial growth factor [VEGF]) and seven inflammatory markers implicated in pulmonary hypertension in other settings were determined by Bio-Plex suspension array in 237 children and adolescents with sickle cell disease at steady state and 43 controls. Tricuspid regurgitation velocity (which reflects systolic pulmonary artery pressure), mitral valve E/Edti ratio (which reflects left ventricular diastolic dysfunction), and a hemolytic component derived from four markers of hemolysis and hemoglobin oxygen saturation were also determined. Results: Plasma concentrations of interleukin-8, interleukin-10 and VEGF were elevated in the patients with sickle cell disease compared to controls (P≤0.003). By logistic regression, greater values for PDGF-BB (P = 0.009), interleukin-6 (P = 0.019) and the hemolytic component (P = 0.026) were independently associated with increased odds of elevated tricuspid regurgitation velocity while higher VEGF concentrations were associated with decreased odds (P = 0.005) among the patients with sickle cell disease. These findings, which are consistent with reports that PDGF-BB stimulates and VEGF inhibits vascular smooth muscle cell proliferation, did not apply to E/Etdi. Conclusions: Circulating concentrations of angiogenic and pro-Inflammatory markers are altered in sickle cell disease children and adolescents with elevated tricuspid regurgitation velocity, a subgroup that may be at risk for developing worsening pulmonary hypertension. Further studies to understand the molecular changes in these children are indicated

    Tricuspid regurgitation velocity and other biomarkers of mortality in children, adolescents and young adults with sickle cell disease in the United States: The PUSH study

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    In the US, mortality in sickle cell disease (SCD) increases after age 18- 20- years. Biomarkers of mortality risk can identify patients who need intensive follow- up and early or novel interventions. We prospectively enrolled 510 SCD patients aged 3- 20- years into an observational study in 2006- 2010 and followed 497 patients for a median of 88- months (range 1- 105). We hypothesized that elevated pulmonary artery systolic pressure as reflected in tricuspid regurgitation velocity (TRV) would be associated with mortality. Estimated survival to 18- years was 99% and to 25- years, 94%. Causes of death were known in seven of 10 patients: stroke in four (hemorrhagic two, infarctive one, unspecified one), multiorgan failure one, parvovirus B19 infection one, sudden death one. Baseline TRV - ¥2.7 m/second (>2 SD above the mean in age- matched and gender- matched non- SCD controls) was observed in 20.0% of patients who died vs 4.6% of those who survived (P =- .012 by the log rank test for equality of survival). The baseline variable most strongly associated with an elevated TRV was a high hemolytic rate. Additional biomarkers associated with mortality were ferritin - ¥2000- μg/L (observed in 60% of patients who died vs 7.8% of survivors, P <- .001), forced expiratory volume in 1 minute to forced vital capacity ratio (FEV1/FVC) <0.80 (71.4% of patients who died vs 18.8% of survivors, P <- .001), and neutrophil count - ¥10x109/L (30.0% of patients who died vs 7.9% of survivors, P =- .018). In SCD children, adolescents and young adults, steady- state elevations of TRV, ferritin and neutrophils and a low FEV1/FVC ratio may be biomarkers associated with increased risk of death.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155951/1/ajh25799_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155951/2/ajh25799.pd

    STATO DI SALUTE DELLE POPOLAZIONI RESIDENTI NELLE AREE GEOTERMICHE DELLA TOSCANA

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    Objective The limited scientific knowledge on relationship between exposure and health effects in relation to geothermal activity motivated an epidemiologic investigation in Tuscan geothermal area. The study aims to describe the health status of populations living in Tuscany municipalities where concessions for exploitation of geothermal resources were granted. Design This is an ecological study, so it is not useful to produce evidence to sustain a judgment on the cause-effect link. The major limits of this type of study are the use of the residence at municipal level as a proxy of exposure to both environmental and socioeconomic factors and the use of aggregated data of health outcomes that can lead to the well-known ecological fallacy. Setting and participants Sixteen municipalities were included in the study area: eight are part of the so-called "traditional" geothermal area, defined as Northern Geothermal Area (NGA) and eight located in the Amiata Mountain defined as Southern Geothermal Area (SGA). In 2000-2006, the average resident population in the overall area was approximately 43,000 inhabitants. Thirty-one geothermal power plants were active, with a production capacity of 811 MW, 5 of them with 88 MW located in the SGA. Statistical analyses on the entire geothermal area, NGA and SGA subareas, and the sixteen municipalities were performed. Main outcome measures Mortality data were obtained from Tuscany Regional Mortality Registry for the 1971-2006 period, analysing 60 causes of death, of interest for population health status or consistent with "Project SENTIERI" criteria. Hospital discharge records of residents in Tuscany Region in 2004-2006, anywhere admitted to hospital, were analyzed considering only the main diagnosis, excluding repeated admissions for the same cause. The causes taken into account are the same analysed for mortality were considered. Age-standardized mortality rates (TSDM) and the temporal trends of TSDM for four periods (1971-1979, 1980- 1989, 1990-1999, 2000-2006) were computed. Age-standardized mortality/hospitalization ratios (SMR/SHR), with and without adjustment for the deprivation index based on 2001 census data, were calculated: mortality in the years 2000-2006 and hospitalization in 2004-2006. The expected number of events were computed using rates of residents in neighbouring municipalities (municipalities included in 50 km radius circle centred on the study area). Bayesian estimates of mortality/hospitalization ratios (BMR/BHR) at municipal level only and relating maps of the Bayesian risk estimators were elaborated. Congenital malformations (MC) were analysed using data from Tuscan Registry of Birth Defect in 1992-2006 period, relative to outcomes of pregnancies in women resident in the municipalities of study area, wherever the birth or termination of pregnancy occurred. The ratio between observed and expected cases (O/A), with expected defined according to regional rate, were calculated and O/A Bayesian estimates (BMR) are showed only at municipal level . The low weight and the males/females ratio at birth were analysed using data from Tuscany Birth Certificates, covering period 2001-2007, excluding biths occurred in facilities outside Tuscany Region. For Low birth weight (<2,500 grams), very low birth weight (<1,500 grams), low birth weight in women with normal gestational age or greater than 36 weeks, gestational age less than 36 weeks, and the frequency of males, the observed/expected ratio was calculated, with the expected number defined according to regional rate. Results Environmental background High levels of arsenic in drinking water distribution emerges as a critical element, so that several municipalities resorted to granting exemptions for the parameters laid down by the Legislative Decree in force (DLgs 31/01). However, during the final phase of the study, new blast systems activated in the SGA decreased the arsenic levels in the water supply, reaching values not requiring derogations, which, instead, are still effective in some NGA municipalities. Air quality data, from Tuscany Regional Agency for Environmental Protection-ARPAT, show that geothermal activities are able to affect air quality, especially with hydrogen sulphide in NGA, and hydrogen sulphide and mercury in SGA. A significant contribution to the presence of mercury in air is due to previous metallurgical sites. Although mercury levels are belowWHO guideline values, in SGA nearby Siena, values were significantly higher than in other geothermal areas, because of power plant PC2 (turned off in July 2011) in Piancastagnaio municipality. The hydrogen sulphide concentration levels were generally lower than WHO reference values, with occasional excesses over guideline value for health protection (150 &#956;g/m3 as average of the 24 hours). Olfactory pollution was more critic with values exceeding 7-10 &#956;g/m3 range even in areas without geothermal plants.Obiettivo Le limitate conoscenze scientifiche sui rapporti tra esposizione a fattori ambientali correlati all\u27attivit? geotermica e lo stato di salute della popolazione esposta hanno motivato la conduzione di una indagine epidemiologica nell\u27area geotermica toscana basata sull\u27analisi dei dati ambientali e sanitari disponibili negli archivi regionali. Lo studio ha lo scopo di descrivere lo stato di salute delle popolazioni residenti nelle aree geotermiche toscane, identificate con i territori comunali per i quali sono state rilasciate concessioni di sfruttamento della risorsa geotermica. Disegno Lo studio ? di tipo ecologico e quindi non adatto a produrre evidenze che permettano di esprimere un giudizio sul nesso causa-effetto. I maggiori limiti degli studi ecologici derivano dall\u27assunzione che la residenza anagrafica a livello comunale rappresenti una valida misura di esposizione a fattori sia ambientali sia socioeconomici e dall\u27utilizzo di dati aggregati degli esiti sanitari che possono portare a risultati affetti da fallacia ecologica. Setting e partecipanti I comuni inclusi nell\u27area geotermica dello studio sono 16, di cui 8 compresi nell\u27area geotermica cosiddetta ?tradizionale?, che include le localit? di Larderello, Val di Cornia e Radicondoli-Travale (area geotermica Nord) e gli altri 8 situati nella zona dell\u27Amiata senese e grossetana (area geotemica Sud). Nel periodo 2000-2006 la popolazione media residente nell\u27area geotermica complessiva era di oltre 43.000 abitanti. Al momento dello studio erano attive 31 centrali geotermoelettriche con capacit? di produzione di 811 MW, di cui 5 con 88 MW totali nell\u27area geotermica Sud. Le analisi statistiche sono state effettuate a livello di intera area geotermica, delle due subaree geotermiche (Nord e Sud) e dei 16 comuni. Principali misure di outcome La mortalit? ? stata analizzata utilizzando i dati del Registro di mortalit? regionale della Toscana per l\u27intero periodo disponibile (1971-2006), con dettaglio per 60 cause, scelte in quanto di interesse generale per il profilo di salute della popolazione o perch? coerenti con i criteri adottati dal Progetto SENTIERI. L\u27ospedalizzazione ? stata valutata analizzando i dati delle schede di dimissione ospedaliera (SDO) della Re-gione Toscana nel periodo 2004-2006, includendo i ricoverati residenti in Toscana ovunque abbiano effettuato un ricovero, considerando solo la diagnosi principale di ricovero, escludendo i ricoveri ripetuti degli stessi soggetti per la stessa causa. Le cause di ospedalizzazione selezionate per l\u27analisi dei ricoveri sono le stesse utilizzate per l\u27analisi della mortalit?. Per la mortalit? sono stati calcolati i tassi di mortalit? standardizzati per et? (TSDM) e i trend temporali dei TSDM in quattro periodi (1971- 1979, 1980-1989, 1990-1999, 2000-2006). Sia per la mortalit? del periodo 2000-2006, sia per l\u27ospedalizzazione del periodo 2004-2006,sono stati calcolati: &#61692; i rapporti di mortalit?/ospedalizzazione standardizzati per et? (SMR/SHR), con e senza aggiustamento per l\u27indice di deprivazione (ID), utilizzando per il calcolo dell\u27ID i dati del censimento 2001, con gli attesi calcolati usando il tasso di mortalit?/ospedalizzazione della popolazione residente nei comuni limitrofi (comuni con la coordinata geografica del municipio compresa in un cerchio con raggio di 50 km centrato sull\u27area in studio); &#61692; le stime bayesiane dei rapporti di mortalit? (BMR) e di ospedalizzazione (BHR) a livello esclusivamente comunale; &#61692; le mappe (disease mapping) dei rischi bayesiani di mortalit?/ospedalizzazione comunali. Le malformazioni congenite (MC) sono state analizzate utilizzando i dati del Registro toscano dei difetti congeniti (RTDC) nel periodo 1992-2006, relativi a esiti di gravidanze di donne residenti nei comuni dell\u27area in studio, ovunque sia avvenuto il parto o l\u27interruzione di gravidanza. Per le MC ? stato calcolato il rapporto tra casi osservati e casi attesi (O/A), con gli attesi definiti in base al tasso regionale e vengono fornite le stime bayesiane del rapporto O/A (BMR) a livello esclusivamente comunale. Per valutare il basso peso e il rapporto tra maschi e femmine alla nascita sono stati utilizzati i dati dei certificati di assistenza al parto della Regione Toscana, relativi al periodo 2001-2007, con esclusione degli eventi occorsi in presidi di altre regioni. L\u27analisi ? stata condotta considerando i nati con: basso peso alla nascita (LW: peso <2.500 grammi), bassissimo peso alla nascita (VLW: peso <1.500 grammi), basso peso alla nascita nelle donne con et? gestazionale normale e maggiore di 36 settimane (LW36), et? gestazionale inferiore a 36 settimane, e il numero di maschi osservato. Per tutti gli indicatori ? stato calcolato il rapporto osservato/atteso, con l\u27atteso definito in base al tasso regionale. Risultati Il contesto ambientale Dalla descrizione del contesto ambientale, per quanto riguarda l\u27acqua, emerge come elemento di criticit? il riscontro talvolta di elevati livelli di arsenico nelle acque della rete di distribuzione degli acquedotti, tanto che in diverse realt? comunali si ? dovuto far ricorso alla concessione di deroghe ai parametri previsti dal decreto legislativo vigente (DLgs 31/01). Comunque, durante la fase conclusiva dello studio, nell\u27area geotermica Sud i nuovi sistemi abbattitori hanno ridotto i livelli di arsenico nella rete idrica fino a valori tali da non dover pi? ricorrere alle deroghe, ancora attive, invece, in alcuni comuni dell\u27area geotermica Nord. Le informazioni dell\u27ARPAT sui dati dell\u27aria evidenziano che l\u27attivit? geotermica ? in grado di modificare la qualit? dell\u27aria, soprattutto per l\u27acido solfidrico nell\u27area geotermica Nord, e per l\u27acido solfidrico e il mercurio nell\u27area geotermica Sud, in particolare nel versante senese dell\u27Amiata. Per il mercurio nell\u27aria, un contributo rilevante ? legato anche alle emissioni dagli ex siti metallurgici. Sebbene i livelli di mercurio nelle postazioni di monitoraggio rientrino sempre al di sotto dei valori guida raccomandati dall\u27OMS, le concentrazioni riscontrate nell\u27aria dell\u27Amiata senese, e perlopi? legate alla centrale PC2 di Piancastagnaio (spenta nel luglio 2011), sono significativamente superiori a quelle rilevate nelle altre aree geotermiche che, al contrario, sono assestate sugli stessi livelli registrati nei territori non geotermici. I livelli di concentrazione di acido solfidrico sono inferiori ai valori di riferimento, con occasionali superamenti del valore guida di tutela sanitaria OMS (150 &#956;g/m3 come media delle 24 ore). Pi? critici sono i dati di inquinamento olfattivo, che si verifica con il superamento del valore di 7-10 g/m3 di acido solfidrico nell\u27aria, riscontrato con vario grado di intensit? in tutte le postazioni di monitoraggio, anche in aree dove non sono presenti impianti geotermici. In alcune aree con insediamenti produttivi geotermici la frequenza, la persistenza e l\u27intensit? dei cattivi odori sono tali da comportare condizioni di qualit? dell\u27aria scadente
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