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Objectives: Our goal was to optimize infection control of paired environmental control interventions within hospitals to reduce methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), and vancomycin-resistant Enterococci (VRE). Background: The most widely used infection control interventions are deployment of handwashing (HW) stations, control of relative humidity (RH), and negative pressure (NP) treatment rooms. Direct costs of multidrug-resistant organism (MDRO) infections are typically not included in the design of such interventions. Methods: We examined the effectiveness of pairing HW with RH and HW with NP. We used the following three data sets: A meta-analysis of progression rates from uncolonized to colonized to infected, 6 years of MDRO treatment costs from 400 hospitals, and 8 years of MDRO incidence rates at nine army hospitals. We used these data as inputs into an Infection De-Escalation Model with varying budgets to obtain optimal intervention designs. We then computed the infection and prevention rates and cost savings resulting from these designs. Results: The average direct cost of an MDRO infection was $3,289, $1,535, and $1,067 for MRSA, CRE, and VRE. The mean annual incidence rates per facility were 0.39%, 0.034%, and 0.011% for MRSA, CRE, and VRE. After applying the cost-minimizing intervention pair to each scenario, the percentage reductions in infections (and annual direct cost savings) in large, community, and small acute care hospitals were 69% ($1.5 million), 73% ($631K), 60% ($118K) for MRSA, 52% ($460.5K), 58% ($203K), 50% ($37K) for CRE, and 0%, 0%, and 50% ($12.8K) for VRE. Conclusion: The application of this Infection De-Escalation Model can guide cost-effective decision making in hospital built environment design to improve control of MDRO infections.

We conducted an observational descriptive study evaluating the effectiveness of therapeutic modification of lifestyle with adding of 1000 mg of myo-inositol and 200 mg of D-chiro inositol combination (ratio 5:1) for nutritional support in 104 women of reproductive age with polycystic ovary syndrome (classic phenotype and nonclassical phenotypes in the presence of hyperandrogenism) for 6 months. Revealed changes in anthropometric parameters (decrease in body mass index by 0.89 kg/m 2 ; p

OBJECTIVE: To explore practice variations in the care of patients with Kawasaki disease (KD) among pediatric hospitalist physicians (PHPs). METHODS: A 13-item questionnaire was developed by a multi-institutional group of KD experts. The survey was administered via live-audience polling by using smartphone technology during a KD plenary session at the 2017 Pediatric Hospital Medicine National Meeting, and simple descriptive statistics were calculated. RESULTS: Of the 297 session attendees, 90% responded to at least 1 survey question. Approximately three-quarters of respondents identified as PHPs practicing in the United States. The reported length of inpatient monitoring after initial intravenous immunoglobulin (IVIG) therapy demonstrated a wide time distribution (30% 24 hours, 36% 36 hours, and 31% 48 hours). Similarly, PHP identification of the treatment failure interval, indicated by recrudescent fever after IVIG, demonstrated a broad distribution (56% 24 hours, 27% 36 hours, and 16% 48 hours). Furthermore, there was variation in routine consultation with non-PHP subspecialists. In contrast, PHPs reported little variation in their choice of initial and refractory treatment of patients with KD. CONCLUSIONS: In a convenience sample at a national hospitalist meeting, there was variation in reported KD practice patterns, including observation time after initial treatment, time when the recurrence of fever after initial therapy was indicative of nonresponse to IVIG, and routine consultation of non-PHP subspecialists. These results may guide future study of KD practice patterns and inform efforts to improve evidence-based practices in the care of patients with KD.

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a rare autoinflammatory disorder. Cutaneous manifestations of CANDLE syndrome include characteristic recurring violaceous annular plaques comprised of an immature dermal mononuclear cell infiltrate. In CANDLE syndrome, deleterious genetic mutations inhibit proteasome-immunoproteasome function, resulting in cellular accumulation of ubiquitinated waste proteins that activate type I interferon signaling to drive inflammation. We describe a report of successful treatment of a 12-year-old girl with CANDLE syndrome with tofacitinib.

Vaccination against communicable diseases is crucial for disease prevention, but this practice poses challenges to healthcare professionals in patients with haemophilia. Poor knowledge of the vaccination requirements for these patients and safety concerns often result in vaccination delay or avoidance. In order to address this issue, a panel of 11 Italian haemophilia and immunization experts conducted a Delphi consensus process to identify the main concerns regarding the safe use of vaccines in patients with haemophilia. The consensus was based on a literature search of the available evidence, which was used by the experts to design 27 consensus statements. A group of clinicians then rated these statements using the 5‐point Likert‐type scale (1 = strongly disagree; 5 = strongly agree). The main issues identified by the expert panel included vaccination schedule for haemophilic patients; protocol and optimal route of vaccine administration; vaccination of haemophilic patients with antibodies inhibiting coagulation factor VIII (inhibitors); and vaccination and risk of inhibitor development. This manuscript discusses these controversial areas in detail supported by the available literature evidence and provides evidence‐ and consensus‐based recommendations. Overall, participants agreed on most statements, except those addressing the potential role of vaccination in inhibitor formation. Participants agreed that patients with haemophilia should receive vaccinations according to the institutional schedule for individuals without bleeding disorders; however, vaccination of patients with haemophilia requires comprehensive planning, taking into account disease severity, type and route of vaccination, and bleeding risk. Data also suggest vaccination timing does not need to take into consideration when the patient received factor VIII replacement.

The objective of this study was to assess the energy demand and economic cost of two hospital-based COVID-19 infection control interventions. The intervention control measures evaluated include use of negative pressure (NP) treatment rooms and xenon pulsed ultraviolet (XP-UV) infection control equipment. After projecting COVID-19 hospitalizations, a Hospital Energy Model and Infection De-escalation Models are applied to quantify increases in energy demand and reductions in secondary infections. The scope of the interventions consisted of implementing NP in 11, 22, and 44 rooms (at small, medium, and large hospitals) while the XP-UV equipment was used eight, nine, and ten hours a day, respectively. The annum kilowatt-hours (kWh) for NP (and costs were at $0.1015 per kWh) were 116,700 ($11,845), 332,530 ($33,752), 795,675 ($80,761) for small, medium, and large hospitals ($1,077, $1,534 $1,836 added annum energy cost per NP room). For XP-UV, the annum kilowatt-hours and costs were 438 ($45), 493 ($50), 548 ($56) for small, medium, and large hospitals. There are other initial costs associated with the purchase and installation of the equipment, with XP-UV having a higher initial cost. XP-UV had a greater reduction in secondary COVID-19 infections in large and medium hospitals. NP rooms had a greater reduction in secondary SARS-CoV-2 transmission in small hospitals. Early implementation of interventions can result in realized cost savings through reduced hospital-acquired infections.

Objectives To assess whether high doses of Low Molecular Weight Heparin (LMWH) (i.e. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (i.e., Enoxaparin 4000 IU once day), in hospitalized patients with COVID19 not requiring Invasive Mechanical Ventilation [IMV], are: more effective in preventing clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: DeathAcute Myocardial Infarction [AMI]Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]Need of either: Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orIMV in patients who at randomisation were receiving standard oxygen therapyIMV in patients who at randomisation were receiving non-invasive mechanical ventilationSimilar in terms of major bleeding risk Trial design Multicentre, randomised controlled, superiority, open label, parallel group, two arms (1:1 ratio), in-hospital study. Participants Inpatients will be recruited from 7 Italian Academic and non-Academic Internal Medicine Units, 2 Infectious Disease Units and 1 Respiratory Disease Unit. Inclusion Criteria (all required) Age > 18 and < 80 years Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) Severe pneumonia defined by the presence of at least one of the following criteria: Respiratory Rate ≥25 breaths /minArterial oxygen saturation≤93% at rest on ambient airPaO2/FiO2 ≤300 mmHg Coagulopathy, defined by the presence of at least one of the following criteria: D-dimer >4 times the upper level of normal reference rangeSepsis-Induced Coagulopathy (SIC) score >4 No need of IMV Exclusion Criteria Age 80 years IMV Thrombocytopenia (platelet count < 80.000 mm3) Coagulopathy: INR >1.5, aPTT ratio > 1.4 Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min) Known hypersensitivity to enoxaparin History of heparin induced thrombocytopenia Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular aneurysms, arteriovenous malformations) Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, venous thromboembolism, prosthetic heart valves) Concomitant double antiplatelet therapy Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization; prophylactic doses are allowed Pregnancy or breastfeeding or positive pregnancy test Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) Lack or withdrawal of informed consent Intervention and comparator Control Group (Low-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at standard prophylactic dose (i.e., 4000 UI subcutaneously once day). Intervention Group (High-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at dose of 70 IU/kg every 12 hours, as reported in the following table. This dose is commonly used in Italy when a bridging strategy is required for the management of surgery or invasive procedures in patients taking anti-vitamin K oral anticoagulants Body Weight (kg)Enoxaparin dose every 12 hours (IU)200050-69400070-89600090-1108000>11010000 The treatment with Enoxaparin will be initiated soon after randomization (maximum allowed starting time 12h after randomization). The treatment will be administered every 12 hours in the intervention group and every 24 hours in the control group. Treatments will be administered in the two arms until hospital discharge or the primary outcomes detailed below occur. Main outcomes Primary Efficacy Endpoint: Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: DeathAcute Myocardial Infarction [AMI]Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]Need of either: Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orIMV in patients who at randomisation were in standard oxygen therapy by delivery interfacesNeed for IMV, in patients who at randomisation were in Cpap or NIV Time to the occurrence of each of these events will be recorded. Clinical worsening will be analysed as a binary outcome as well as a time-to-event one. Secondary Efficacy Endpoints: Any of the following events occurring within the hospital stay DeathAcute Myocardial Infarction [AMI]Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]Need of either: Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orIMV in patients who at randomisation were in standard oxygen therapy by delivery interfacesNeed for IMV in patients who at randomisation were in Cpap or NIVImprovement of laboratory parameters of disease severity, including: o D-dimer levelo Plasma fibrinogen levelso Mean Platelet Volumeo Lymphocyte/Neutrophil ratioo IL-6 plasma levels Mortality at 30 days Information about patients’ status will be sought in those who are discharged before 30 days on Day 30 from randomisation. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Primary safety endpoint: Major bleeding, defined as an acute clinically overt bleeding associated with one or more of the following: Decrease in haemoglobin of 2 g/dl or more;Transfusion of 2 or more units of packed red blood cells;Bleeding that occurs in at least one of the following critical sites [intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal];Bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death);Bleeding that necessitates surgical intervention Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Secondary safety endpoint: Clinically Relevant non-major bleeding, defined as an acute clinically overt bleeding that does not meet the criteria for major and consists of: Any bleeding compromising hemodynamicSpontaneous hematoma larger than 25 cm2, or 100 cm2 if there was a traumatic causeIntramuscular hematoma documented by ultrasonographyEpistaxis or gingival bleeding requiring tamponade or other medical interventionBleeding from venipuncture for >5 minutesHaematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive proceduresHaemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical interventionAny other bleeding requiring temporary cessation of a study drug. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Randomisation Randomisation (with a 1:1 randomisation ratio) will be centrally performed by using a secure, web-based system, which will be developed by the Methodological and Statistical Unit at the Azienda Ospedaliero-Universitaria of Modena. Randomisation stratified by 4 factors: 1) Gender (M/F); 2) Age (2) with random variable block sizes will be generated by STATA software. The web-based system will guarantee the allocation concealment. Blinding (masking) The study is conceived as open-label: patients and all health-care personnel involved in the study will be aware of the assigned group. Numbers to be randomised (sample size) The target sample size is based on the hypothesis that LMWH administered at high doses versus low doses will significantly reduce the risk of clinical worsening. The overall sample size in this study is expected to be 300 with 150 in the Low-Dose LMWH control group and 150 in the High-Dose LMWH intervention group, recruited over 10-11 months. Assuming an alpha of 5% (two tailed) and a percentage of patients who experience clinical worsening in the control group being between 25% and 30%, the study will have 80% power to detect at least 50% relative reduction in the risk of death between low and high doses of heparin. Trial Status Protocol version 1.2 of 11/05/2020. Recruitment start (expected): 08/06/2020 Recruitment finish (expected): 30/04/2021 Trial registration EudraCT 2020-001972-13, registered on April 17th, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Summary Background Within 4 months of COVID-19 first being reported in the USA, it spread to every state and to more than 90% of all counties. During this period, the US COVID-19 response was highly decentralised, with stay-at-home directives issued by state and local officials, subject to varying levels of enforcement. The absence of a centralised policy and timeline combined with the complex dynamics of human mobility and the variable intensity of local outbreaks makes assessing the effect of large-scale social distancing on COVID-19 transmission in the USA a challenge. Methods We used daily mobility data derived from aggregated and anonymised cell (mobile) phone data, provided by Teralytics (Zurich, Switzerland) from Jan 1 to April 20, 2020, to capture real-time trends in movement patterns for each US county, and used these data to generate a social distancing metric. We used epidemiological data to compute the COVID-19 growth rate ratio for a given county on a given day. Using these metrics, we evaluated how social distancing, measured by the relative change in mobility, affected the rate of new infections in the 25 counties in the USA with the highest number of confirmed cases on April 16, 2020, by fitting a statistical model for each county. Findings Our analysis revealed that mobility patterns are strongly correlated with decreased COVID-19 case growth rates for the most affected counties in the USA, with Pearson correlation coefficients above 0·7 for 20 of the 25 counties evaluated. Additionally, the effect of changes in mobility patterns, which dropped by 35–63% relative to the normal conditions, on COVID-19 transmission are not likely to be perceptible for 9–12 days, and potentially up to 3 weeks, which is consistent with the incubation time of severe acute respiratory syndrome coronavirus 2 plus additional time for reporting. We also show evidence that behavioural changes were already underway in many US counties days to weeks before state-level or local-level stay-at-home policies were implemented, implying that individuals anticipated public health directives where social distancing was adopted, despite a mixed political message. Interpretation This study strongly supports a role of social distancing as an effective way to mitigate COVID-19 transmission in the USA. Until a COVID-19 vaccine is widely available, social distancing will remain one of the primary measures to combat disease spread, and these findings should serve to support more timely policy making around social distancing in the USA in the future. Funding None.

Introduction Ureteric injuries are among the most serious complications of pelvic surgery. The incidence in low-resource settings is not well documented. Methods This retrospective review analyzes a cohort of 365 ureteric injuries with ureterovaginal fistulas in 353 women following obstetric and gynecologic operations in 11 countries in Africa and Asia, all low-resource settings. The patients with ureteric injury were stratified into three groups according to the initial surgery: (a) obstetric operations, (b) gynecologic operations, and (c) vesicovaginal fistula (VVF) repairs. Results The 365 ureteric injuries in this series comprise 246 (67.4%) after obstetric procedures, 65 (17.8%) after gynecologic procedures, and 54 (14.8%) after repair of obstetric fistulas. Demographic characteristics show clear differences between women with iatrogenic injuries and women with obstetric fistulas. The study describes abdominal ureter reimplantation and other treatment procedures. Overall surgical results were good: 92.9% of women were cured (326/351), 5.4% were healed with some residual incontinence (19/351), and six failed (1.7%). Conclusions Ureteric injuries after obstetric and gynecologic operations are not uncommon. Unlike in high-resource contexts, in low-resource settings obstetric procedures are most often associated with urogenital fistula. Despite resource limitations, diagnosis and treatment of ureteric injuries is possible, with good success rates. Training must emphasize optimal surgical techniques and different approaches to assisted vaginal delivery.

The present study is a quantitative synthesis of the available literature to investigate the efficacy of psychotherapy for children's mental health outcomes. In particular, this study focuses on potential moderating variables-study design, treatment, client, and therapist characteristics-that may influence therapeutic outcomes for youth but have not been thoroughly accounted for in prior meta-analytic studies. An electronic search of relevant databases resulted in 190 unpublished and published studies that met criteria for inclusion in the analysis. Effect sizes differed by study design. Pre-post-test designs resulted in absolute magnitudes of treatment effects ranging from |-0.02| to |-0.76| while treatment versus control group comparison designs resulted in absolute magnitudes of treatment effects ranging from |-0.14| to |-2.39|. Changes in youth outcomes larger than 20% were found, irrespective of study design, for outcomes focused on psychosomatization (29% reduction), school attendance (25% increase), and stress (48% reduction). The magnitude of changes after psychotherapy ranged from 6% (externalizing problems) to 48% (stress). Several moderator variables significantly influenced psychotherapy treatment effect sizes, including frequency and length of treatment as well as treatment format. However, results did not support the superiority of a single type of intervention for most outcomes. Implications for therapy with school-aged youth and future research are discussed.Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved. Language: en

Summary. Background: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding. Although data on several AHA cohorts have been collected, limited information is available on the optimal management of AHA. Objectives: The European Acquired Hemophilia Registry (EACH2) was established to generate a prospective, large-scale, pan-European database on demographics, diagnosis, underlying disorders, bleeding characteristics, treatment and outcome of AHA patients. Results: Five hundred and one (266 male, 235 female) patients from 117 centers and 13 European countries were included in the registry between 2003 and 2008. In 467 cases, hemostasis investigations and AHA diagnosis were triggered by a bleeding event. At diagnosis, patients were a median of 73.9 years. AHA was idiopathic in 51.9%; malignancy or autoimmune diseases were associated with 11.8% and 11.6% of cases. Fifty-seven per cent of the non-pregnancy-related cases were male. Four hundred and seventy-four bleeding episodes were reported at presentation, and hemostatic therapy initiated in 70.5% of patients. Delayed diagnosis significantly impacted treatment initiation in 33.5%. Four hundred and seventy-seven patients underwent immunosuppression, and 72.6% achieved complete remission. Conclusions: Representing the largest collection of consecutive AHA cases to date, EACH2 facilitates the analysis of a variety of open questions in AHA.

Traditional administration of rituximab requires careful titration and may involve many hours to minimize the risk of reactions. The objective of this study was to evaluate the safety of rapid infusions of rituximab in a pilot group of children with hematologic, oncologic, and rheumatologic disorders, and to determine the incidence of rate-related infusion reactions. Twenty patients enrolled in the study. All patients tolerated the rapid infusion of rituximab and no patient had an infusion-related reaction. We conclude that rapid infusions of rituximab are well tolerated and safe in our pilot group of patients.

START-Register - Survey on anTicoagulated pAtients RegisTer - is an independent, inception-cohort, observational, collaborative database aimed at recording prospectively the clinical history of adult patients starting anticoagulant treatment for any reason and using whatever drug. In this article we present the START-Register and give cross section baseline data focusing on non valvular atrial fibrillation (NVAF). Participants are asked to insert prospectively consecutive patients recorded as electronic file on the web-site of the registry. Required data are: demographic and clinical characteristics of patients, associated risk factors for stroke and bleeding, laboratory routine data, clinical indication for treatment, expected therapeutic range (in cases of treatment with vitamin K antagonists -VKAs). The follow-up is carried out to record: quality of treatment (for patients on VKAs), bleeding complications, thrombotic events, and the onset of any type of associated disease. To date 5252 patients have been enrolled; 97.6% were on VKAs because direct oral anticoagulants (DOAC) have been available in Italy only recently. The median age was 74 years [interquartile range (IQR) 64-80]; males 53.7%. This analysis is focused on the 3209 (61.1%) NVAF patients. Mean CHADS2 score was 2.1±1.1, CHADSVASc score was 3.1±1.3;median age was 76 years (IQR 70-81); 168 patients (5.3%) had severe renal failure [Creatinine clearance (CrCl) 80 years with high prevalence of renal failure.

Summary Despite great advances in haemophilia care in the last 20 years, a number of questions on haemophilia therapy remain unanswered. These debated issues primarily involve the choice of the product type (plasma-derived vs. recombinant) for patients with different characteristics: specifically, if they were infected by blood-borne virus infections, and if they bear high or low risk of inhibitor development. In addition, the most appropriate treatment regimen in non-inhibitor and inhibitor patients compel physicians operating at the haemophilia treatment centres (HTCs) to take important therapeutic decisions, which are often based on their personal clinical experience rather than on evidence-based recommendations from published literature data. To know the opinion on the most controversial aspects in haemophilia care of Italian expert physicians, who are responsible for common clinical practice and therapeutic decisions, we have conducted a survey among the Directors of HTCs affiliated to the Italian Association of Haemophilia Centres (AICE). A questionnaire, consisting of 19 questions covering the most important topics related to haemophilia treatment, was sent to the Directors of all 52 Italian HTCs. Forty Directors out of 52 (76.9%) responded, accounting for the large majority of HTCs affiliated to the AICE throughout Italy. The results of this survey provide for the first time a picture of the attitudes towards clotting factor concentrate use and product selection of clinicians working at Italian HTCs.

We present the case of an 8-year-old girl who presented with distal extremity necrosis of the hands, feet, nose, and ears as an acute manifestation of cutaneous polyarteritis nodosa (CPAN). She was emergently managed with intravenous steroids, nifedipine, sildenafil, pentoxifylline, nitroglycerin paste, aspirin, low-molecular-weight heparin, and intravenous gamma globulin. The necrosis was controlled, and reperfusion was attained to salvage the extremities. It is important for clinicians to be aware that acute distal extremity necrosis can be a manifestation of CPAN in children. Etiology is often not clear on presentation, but once infection is excluded, acute management with systemic steroids and systemic vasodilators is indicated regardless of the cause. Iloprost and bosentan may represent options for adjunctive vasodilators. More studies are needed to create guidelines for the acute and long-term management of these children. Close follow-up of children with CPAN, especially with a history of vaso-occlusive symptoms, is important to allow prompt intervention in the event of distal extremity infarction.

Objective.Cerebral atrophy is a prominent feature in adults with systemic lupus erythematosus (SLE). We assessed cerebral and cerebellar volume loss on clinically acquired brain magnetic resonance imaging (MRI) scans of children and adolescents with SLE.Methods.We abstracted information on disease course for patients who underwent clinical brain MRI during the period 2002–2008. We completed qualitative assessments of volume loss and measured corpus callosum thickness and ventricular enlargement for patients with lupus and controls.Results.Forty-nine children underwent brain MRI during the review period due to clinical indications. The lupus cohort was predominantly female and ethnically diverse. Mean age at imaging was 15.3 ± 2.6 years and mean disease duration was 30.6 ± 33.3 months. Findings suggestive of cerebral and cerebellar volume loss were seen respectively in 89.8% and 91.8% of lupus patients. Cerebral volume loss was moderate or severe in 26.5% of children. Cerebellar volume loss was moderate in 20.4% of these patients. Linear measurement means reflected corpus callosum thinning and ventricular enlargement in lupus patients. Volume loss was observed in newly diagnosed patients prior to corticosteroid use. Disease duration and corticosteroid use did not predict the severity of volume loss. There were statistically significant differences in linear imaging measurements comparing lupus patients to 14 similar-age controls.Conclusion.Regional volume loss was observed in most adolescents with lupus undergoing clinical brain MRI scans. As in other pediatric conditions with inflammatory or vascular etiologies, these findings may be reflecting disease-associated neuronal loss and not solely the effects of corticosteroid.

Endothelial damage, hypertension and cytotoxic medications may serve as risk factors for the posterior reversible encephalopathy syndrome (PRES) in systemic lupus erythematosus. There have been few case reports of these findings in pediatric lupus patients.We describe clinical and neuroimaging findings in children and adolescents with lupus and a PRES diagnosis.We identified all clinically acquired brain MRIs of lupus patients at a tertiary care pediatric hospital (2002-2008). We reviewed clinical features, conventional MRI and diffusion-weighted imaging (DWI) findings of patients with gray- and white-matter changes suggestive of vasogenic edema and PRES.Six pediatric lupus patients presenting with seizures and altered mental status had MRI findings suggestive of PRES. In five children clinical and imaging changes were seen in conjunction with hypertension and active renal disease. MRI abnormalities were diffuse and involved frontal regions in five children. DWI changes reflected increased apparent diffusivity coefficient (unrestricted diffusion in all patients). Clinical and imaging changes significantly improved with antihypertensive and fluid management.MRI changes suggestive of vasogenic edema and PRES may be seen in children with active lupus and hypertension. The differential diagnosis of seizures and altered mental status should include PRES in children, as it does in adults.

Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level.

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).

background The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial. methods We enrolled 518 patients with polycythemia vera, no clear indication for aspirin treatment, and no contraindication to such treatment in a double-blind, placebo-controlled, randomized trial to assess the safety and efficacy of prophylaxis with low-dose aspirin (100 mg daily). The two primary end points were the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. The mean duration of follow-up was about three years. results Treatment with aspirin, as compared with placebo, reduced the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.03). Overall mortality and cardiovascular mortality were not reduced significantly. The incidence of major bleeding episodes was not significantly increased in the aspirin group (relative risk, 1.62; 95 percent confidence interval, 0.27 to 9.71). conclusions Low-dose aspirin can safely prevent thrombotic complications in patients with polycythemia vera who have no contraindications to such treatment.

Dear Sir, Treatment of haemophilia is costly, and it must be carefully monitored by physicians and health authorities, so as to improve the planning of the supply of factor concentrates obtained from the fractionation of human plasma or by recombinant technology. Therapy with coagulation factors can be used either prophylactically to prevent bleeding, which entails multiple weekly infusions, or on-demand, through infusion of the amount of factors determined by the severity of the disease and patient’s weight, to stop ongoing bleeding. According to a recent study, factor VIII (FVIII) consumption among persons with haemophilia A (HA) has increased in countries with high-income economies (Stonebraker et al., 2010). In Italy, haemophiliacs and other persons with congenital coagulation disorders are monitored by the National Registry of Congenital Coagulopathies (NRCC) established at the Istituto Superi=

(2002). Risperidone in Children and Adolescents with Autistic Disorder and Aggressive Behaviour. The British Journal of Development Disabilities: Vol. 48, No. 95, pp. 113-122.

National haemophilia registries are powerful instruments to support health care and research. A national registry was established in Italy by the Ministry of Health until 1999. Since 2003 the Italian Association of Haemophilia Centres (AICE) started a new programme aiming at building up the Italian Registry of Haemophilia and Allied Disorders. The AICE identified an expert panel to steer the registry. A computer software to assist patient management was developed and all the AICE-affiliated haemophilia treatment centres (HTC) were prompted to adopt it. Twice a year a predefined set of anonymized data is centralized and merged into a national database. Duplicated entries are managed through a confidentiality sparing mechanism. The database covers sociodemographic, clinical, laboratory and treatment data. A subset of data are shared with the Ministry of Health (Istituto Superiore di Sanita,ISS).Overall, data were collected six times by 43 of 49 HTC; 41 centres updated their patients' records up to December 2006. The database contains 6632 unique records, 442 of them referring to dead patients. Database growth and missing data clearance showed a constantly positive trend over time. The database has collected records of the following alive patients - haemophilia A: 1364 severe, 398 moderate and 935 mild; haemophilia B: 231 severe, 138 moderate and 204 mild; von Willebrand's disease: 1208 type 1, 346 type 2 and 96 type 3. Inhibitor patients were 296 (of which 194 high responders and 65 low responders).The Italian registry run by AICE adds to the list of the available national haemophilia registries and is intended to establish treatment guidelines and foster research projects in Italy.

Diffuse alveolar hemorrhage most commonly refers to bleeding from the low-pressure pulmonary vascular bed and is a rare cause of chronic interstitial lung disease in children. Patients can present acutely with respiratory failure or more indolently with a history of worsening exercise intolerance and cough. Diffuse alveolar hemorrhage is divided into two broad categories: immune mediated and nonimmune mediated with immune-mediated hemorrhage being more common. The most common causes of immune-mediated diffuse alveolar hemorrhage are the ANCA-associated vasculitidies and idiopathic pulmonary capillaritis. It is important to distinguish between immune and nonimmune causes of hemorrhage, such as idiopathic pulmonary hemosiderosis, as treatment is significantly different.Regardless of the cause of alveolar hemorrhage patients most often present with diffuse infiltrates on chest x-ray and anemia. Chest CT scan is very useful in establishing a diagnosis and most often reveals diffuse ground glass opacities and septal thickening or nodules. Bronchoscopy and bronchoalveolar lavage are used to establish pulmonary hemorrhage. A lung biopsy is necessary in any patient with diffuse hemorrhage and negative ANCA to help distinguish between immune- and nonimmune-mediated hemorrhage.Treatment of diffuse alveolar hemorrhage is dependent on the type of hemorrhage. Immune-mediated hemorrhage requires aggressive immune suppression to halt progression of the disease. Nonimmune-mediated hemorrhage is managed with much less immune suppression.

Summary. The treatment of haemophilia in developed countries is based on home self-infusion of concentrates. Improving communication between haemophilia centres (HC) and patients is very important. The Hub Centre (Parma) designed a new outpatient clinical record, ‘xl’Emofilia®’, as part of a project ‘Web Connections of the Region’s HC’ funded by Emilia-Romagna Health Authority. It is a web-based application suited to the needs of HC, which shares the databases of the region’s HC, integrated with regional and national registries that can be accessed from anywhere. Data are managed with the ‘https’ protocol. Significant innovations are ‘pathways’ that help with the entry of data and ‘problem list’, which is a summary (updated automatically) of the patient’s clinically significant data that can be consulted at a glance. With a ‘web identity’ (a personal USB key for secure web access), patients can record bleeds and home infusions, consult their own data and allow access to their general practitioners or in emergency departments anywhere in the world (also in English language). In December 2006, the HC started to use ‘xl’Emofilia®’ and 673 clinical records are now active. Since April 2007, 50 pilot patients have been trained and are successfully using the system. A questionnaire administered to these patients on their level of satisfaction with the system and its ease of use gave excellent results. Our web-based system facilitates communication between patients and HC, improves the quality of care and enables patients to use these information at any time and from anywhere in the world.

Erratum to: Int Urogynecol J DOI 10.1007/s00192-014-2445-3 The version of Table 2 in the original publication was potentially misleading. The corrected table is presented here. aVesico-cervico-vaginal fistulas and vault fistulas correspond to Waaldijk type I, and ureteric injury fistulas to Waaldijk type III

Introduction and hypothesis Genitourinary fistula poses a public health challenge in areas where women have inadequate access to quality emergency obstetric care. Fistulas typically develop during prolonged, obstructed labor, but providers can also inadvertently cause a fistula when performing obstetric or gynecological surgery. Methods This retrospective study analyzes 805 iatrogenic fistulas from a series of 5,959 women undergoing genitourinary fistula repair in 11 countries between 1994 and 2012. Injuries fall into three categories: ureteric, vault, and vesico-[utero]/-cervico-vaginal. This analysis considers the frequency and characteristics of each type of fistula and the risk factors associated with iatrogenic fistula development. Results In this large series, 13.2 % of genitourinary fistula repairs were for injuries caused by provider error. A range of cadres conducted procedures resulting in iatrogenic fistula. Four out of five iatrogenic fistulas developed following surgery for obstetric complications: cesarean section, ruptured uterus repair, or hysterectomy for ruptured uterus. Others developed during gynecological procedures, most commonly hysterectomy. Vesico-[utero]/-cervico-vaginal fistulas were the most common (43.6 %), followed by ureteric injuries (33.9 %) and vault fistulas (22.5 %). One quarter of women with iatrogenic fistulas had previously undergone a laparotomy, nearly always a cesarean section. Among these women, one quarter had undergone more than one previous cesarean section. Conclusions Women with previous cesarean sections are at an increased risk of iatrogenic injury. Work environments must be adequate to reduce surgical error. Training must emphasize the importance of optimal surgical techniques, obstetric decision-making, and alternative ways to deliver dead babies. Iatrogenic fistulas should be recognized as a distinct genitourinary fistula category.

Normal resting human breast tissue was obtained from immediate autopsies performed on six women who had died from head injuries sustained in accidents. Tissue samples containing epithelium were dissected asceptically and either fixed immediately or placed into culture. Samples in culture for 2 or 3 days were exposed to radioiodide for 4 hr in order to establish whether or not the isotope became incorporated into proteins. Light and electron microscope autoradiographs were prepared and evaluated. Radiolabeled secretory material was observed in both the terminal ductules and intralobular terminal ducts, but not within the larger ducts. Therefore the products in these separate compartments of the mammary epithelial tree differ in composition. Extensive gap junctions were discovered between adjacent myoepithelial cells in the terminal ductules and intralobular terminal ducts. These junctions probably serve to coordinate contractions which facilitate the movement of material from the most distal parts of the gland into larger ducts.

In any group of people, the pattern of disease and injury mirrors their environment and culture. With this tenet in mind, Dr. Wells describes the hybrid discipline of paleopathology, presenting his fascinating investigations and the methods used therein. A paleopathologist bases his findings on two kinds of evidence: primary material, consisting of actual remains of a body, and secondary sources, such as descriptions or artifacts depicting disease. Making suitable inferences from a bone or mummified remains can be exciting, although the incomplete evidence available to paleopathologists may be misleading. The author well expresses the delicate balance between informed intuition and an overenthusiastic guess. With thoroughness Dr. Wells discusses ancient illnesses, including injuries, infections, growths, congenital abnormalities, and metabolic and deficiency diseases. Related topics discussed are the practices of trephination, cannibalism, and artificial interference with the body in mutilation or binding of the head. An appendix of photographs and drawings illustrates

Objective Anti-prothrombin (aPT) antibodies have been found in Lupus Anticoagulant (LA) positive patients. Their prevalence and relative contribution to thromboembolic risk in LA-positive patients is not well defined. The aim of this study was to determine their presence and association with thromboembolic events in a large series of patients with confirmed LA. Methods Plasma from LA-positive patients was collected at Thrombosis Centers and sent to a reference central laboratory for confirmation. Positive plasma was tested using home-made ELISA for the presence of aPT and anti-β2GPI antibodies. Results LA was confirmed in 231 patients. Sixty-one of 231 (26%, 95%CI 22-33) LA positive subjects were positive for IgG aPT and 62 (27%, 95% CI 21-33) were positive for IgM aPT antibodies. Clinical features of Antiphospholipid Syndrome (APS) were not associated with the presence of IgG aPT [43 APS in 61 (70%) positive and 109 APS in 170 (64%) negative IgG aPT subjects, p = ns] or IgM aPT. Rate of positivity of IgG and IgM aβ2GPI was significantly higher than that of IgG and IgM aPT. Clinical events accounting for APS occurred in 97 of 130 (75%) IgG aβ2GPI positive and in 55 of 101 (54%) IgG aβ2GPI negative patients (OR 2.4, 95% CI 1.4 to 4.3, p = 0.002). No significant association with clinical events in patients positive for both IgG aPT and IgG aβ2GPI as compared to those positive for one or another test was found. When patients negative for both IgG aPT and IgG aβ2GPI (LA positive only) were compared with remaining patients, a significantly lower association with clinical events was found (OR = 0.4, 95% CI: 0.2 to 0.7, p = 0.004). Conclusions As compared to IgG aβ2GPI, the prevalence of IgG aPT in patients with LA is significantly lower and not associated with the clinical features of APS.

Chromosome analysis has progressed swiftly from the 1960s to the present time. Banding techniques allow more and more precise localization of defects. Concomitantly, case reports of affected persons have mushroomed. The need for an atlas combining clinical descriptions and photographs with chromosomal findings is evident. Other atlases are available but are less oriented to cytogenetics. Organized by chromosome number, the book may be initially confusing to those not well oriented to cytogenetics. But the book is small enough to thumb through quickly when looking for a clinical photograph or list of characteristics to match with the patient. Six appendixes add further information. These cover current cytogenetic techniques, dermatoglyphics, clinical descriptive terms, chromosome nomenclature, genetic markers, and an abbreviated listing of syndromes. Pediatricians, cytogeneticists, and genetic counselors will find this book useful. Pediatricians, especially, need to recognize syndromes, interpret cytogenetic analyses, and improve communication with the laboratory. This atlas will facilitate

Modern immunology has come a long way from Jenner and his milkmaids. Now we have "nude" mice in the laboratory and a plethora of eponyms and classifications of the many components of the immunological system. Read this book to review the basic knowledge now available, particularly the important portion relevant to human health and disease. The intricacies of immunology confound many physicians, particularly since much of its growth has come in the past 15 years. Writing with both the specialist and the generalist in mind, the contributors to this book have combined a presentation of laboratory investigations with clinical descriptions of immunologic disorders. The information is presented with admirable brevity and the illustrations serve to convey the sense of order of nature's plan. Key references to summary and review articles are provided; however, most chapters are followed by at least a page of references. The terminology employed is that recommended

Normal children fare poorly in this day of enzyme chemistry and exotic syndromes. But they cannot be ignored. Mothers' questions about normal children and about child-rearing must still be answered by their physicians. This English book, very worthwhile, is indeed a treasury of practical answers to common pediatric problems. Breast feeding, rarely taught in current medical education, finds a welcome place here, and in several chapters, the author discusses the problems and mechanics of successful breast feeding. He presents the developmental milestones of infancy and childhood in thorough form, dwelling upon the individual variation so often found. His chapters concerning personality development and discipline contain wit and humor and also provide a firm philosophy of child-rearing. Preparation and selection of formulas are oriented toward English brand names, but that chapter is a minor bit of provincialism in an otherwise universally applicable book.

Review books tend to be passive in nature, reciting the obvious and adding few new thoughts.The Pediatric Patient, 1968is no exception. In the pattern of earlier editions, it contains a general discussion rooted in the basic sciences, followed by selected, specialty-oriented topics. This year the text includes a technical presentation of enzymology, including the historical background of medical interest in enzymes. The section on orthopedic problems offers little but a review of physical diagnosis. The most interesting and useful chapter concerns neurology, with sections discussing the "at risk" infant, the minimal brain damage syndrome, intracranial tumors, and Wilson's disease. The last chapter in the book is a collection of short, wellreferenced statements of opinion on diverse subjects such as sports for children and the estimation of gestational age of an infant. The book suffers from the differing levels of quality of chapters and is not, in general, easily

Medical personnel may be initially uninterested in population studies of moths, rodents, and bees. But through other population studies, the mysteries of sickle cell anemia and bacterial drug resistance vanished. It is essential that we understand why a population should be considered as more than a sum of the characteristics of its members. In preparing this book, the authors compiled a series of lectures. The four areas of study are ecology, genetics, behavior, and disease. The book introduces some of the methods used in population research and adds as examples certain advances in this field. Although the book is primarily a textbook, needing a lecturer's interpretation, it is clearly written and supplemented with pertinent graphs and illustrations. There is a need for those in private practice to understand population dynamics and control. Public health officers, also, may profit from a consideration of basic research methods. I recommend it to everyone

Direct oral anticoagulants (DOAC) are mostly prescribed to prevent cardioembolic stroke in patients with non-valvular atrial fibrillation (AF). An increasing number of guidelines recommend DOAC in AF patients with preserved renal function for the prevention of thromboembolism and an increased use of DOAC in daily practice is recorded also in elderly patients. Aging is associated with a reduction of glomerular filtration rate and impaired renal function, regardless of the cause, increases the risk of bleeding. Multiple medication use (polypharmacy) for treating superimposed co-morbidities is common in both elderly and chronic kidney disease (CKD) patients and drug-drug interaction may cause accumulation of DOAC, thereby increasing the risk of bleeding. There is uncertainty on the safety profile of DOAC in patients with CKD, particularly in those with severely impaired renal function or end stage renal disease, due to the heterogeneity of studies and the relative paucity of data. This document reports the position of three Italian scientific societies engaged in the management of patients with atrial fibrillation who are treated with DOAC and present with CKD.

© 2018 European Federation of Internal Medicine Despite recent advances in the treatment of Deep Vein Thrombosis (DVT) provided by Direct Oral Anticoagulants (DOAC), a substantial proportion of lower limb DVT patients will develop some degree of post-thrombotic syndrome (PTS) within 2 years. Systemic thrombolysis, although effective in reducing the risk of PTS and leg ulceration, is associated with a high risk of major bleeding, making it unsuitable for the vast majority of patients. A local approach, aimed at delivering the fibrinolytic drug directly into, or near to, the thrombus surface, is attractive because of the possibility of lowering of the administered drug dose, thus reducing the bleeding risks. However, even after the recent publication of the ATTRACT trial, only weak evidence is available about the efficacy and safety of Catheter Directed Thrombolysis (CDT), either alone (pharmacological technique) or in combination with additional endovascular approaches (pharmacomechanical technique, PMT) including percutaneous mechanical thrombectomy, angioplasty with or without stenting and ultrasound-assisted CDT. The present review is aimed at providing the physicians with a comprehensive evaluation of the current evidence about this relevant topic, in order to build a reliable conceptual framework for a more appropriate use of this resource.

Patients with cirrhosis present with hemostatic alterations secondary to reduced availability of pro-coagulant and anti-coagulant factors. The net effect of these changes is a rebalanced hemostatic system. The Italian Association of the Study of the Liver (AISF) and the Italian Society of Internal Medicine (SIMI) promoted a consensus conference on the hemostatic balance in patients with cirrhosis. The consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Rome in December 2014. The statements were graded according to quality of evidence and strength of recommendations, and approved by an independent jury. The statements presented here highlight strengths and weaknesses of current laboratory tests to assess bleeding and thrombotic risk in cirrhotic patients, the pathophysiology of hemostatic perturbations in this condition, and outline the optimal management of bleeding and thrombosis in patients with liver cirrhosis.

Hemophilia B is a congenital recessive disorder caused by deficiency of coagulation factor IX (FIX). Surgical procedures can be performed in patients with hemophilia using high-purity and/or recombinant FIX, which has been shown to be safe and effective in surgical hemostasis. Liver transplantation is the only potentially curative treatment available for these patients, providing a long-term phenotypic cure for hemophilia. End-stage liver disease together with hemophilia exposes patients to greater risks of bleeding complications during the perioperative period with consequent difficulties in managing coagulopathy. The limited experiences reported by different investigators and the various strategies for clotting factor replacement make it difficult to define a single approach with respect to the optimal dose and method of administering FIX to achieve perioperative hemostasis. The limits of plasma-based coagulation tests--prothrombin time, activated partial thromboplastin time--have made thromboelastography a valid alternative in this kind of surgery. It has been demonstrated to be a useful tool for real-time analysis of clot formation using a whole-blood assay format. Further, it accurately illustrates the clinical effects of procoagulant or anticoagulant interventions. In this article, we have described the usefulness of thromboelastography to monitor the ability of high-purity FIX supplementation to restore a normal coagulation state and to guide the perioperative administration of blood products in a successful orthotopic liver transplantation in a hemophilic patient with deficiencies of factors IX and X, presenting with hepatitis C virus-related cirrhosis and hepatocellular carcinoma.

Summary. Background: Little information is available on the long-term clinical outcome of cerebral vein thrombosis (CVT). Objectives and methods: In an international, retrospective cohort study, we assessed the long-term rates of mortality, residual disability and recurrent venous thromboembolism (VTE) in a cohort of patients with a first CVT episode. Results: Seven hundred and six patients (73.7% females) with CVT were included. Patients were followed for a total of 3171 patient-years. Median follow-up was 40 months (range 6, 297 months). At the end of follow-up, 20 patients had died (2.8%). The outcome was generally good: 89.1% of patients had a complete recovery (modified Rankin Score [mRS] 0–1) and 3.8% had a partial recovery and were independent (mRS 2). Eighty-four per cent of patients were treated with oral anticoagulants and the mean treatment duration was 12 months. CVT recurred in 31 patients (4.4%), and 46 patients (6.5%) had a VTE in a different site, for an overall incidence of recurrence of 23.6 events per 1000 patient-years (95% confidence Interval [CI] 17.8, 28.7) and of 35.1 events/1000 patient-years (95% CI, 27.7, 44.4) after anticoagulant therapy withdrawal. A previous VTE was the only significant predictor of recurrence at multivariate analysis (hazard ratio [HR] 2.70; 95% CI 1.25, 5.83). Conclusions: The long-term risk of mortality and recurrent VTE appears to be low in patients who survived the acute phase of CVT. A previous VTE history independently predicts recurrent events.

SYNOPSIS OF RECOMMENDATIONS: The Italian Society for Thrombosis and Haemostasis (SISET: Società Italiana per lo Studio dell' Emostasi e della Trombosi) promoted the development of a series of guidelines which would adopt evidence-based medicine methodology on clinically relevant problems in the field of haemostasis and thrombosis. The objective of the present guidelines is to provide recommendations for the pre-operative and pre-procedural assessment of the bleeding risk with the aim of reducing the incidence of preventable bleeding complications and limiting laboratory tests to the those necessary. The predictive value of haemostatic tests for bleeding complications after surgery or invasive procedures has been evaluated in prospective or retrospective cohort studies only. All retrieved studies were of low methodological quality with a high potential for bias because none conducted a blinded outcome assessment. In addition, different criteria for the severity of bleeding events and different reference values of the laboratory tests were adopted. The low methodological quality limits the validity of the results of these studies. Some of the clinical queries proposed by the working group were not addressed by the studies available in the literature. The areas with evidence, although of low quality, are the following: general surgery in adults (for history, PT, APTT, platelet count and bleeding time), neurosurgery in adults (for history, PT, APTT, platelet count), adenotonsillectomy in children (for history, PT, APTT, platelet count and bleeding time), invasive procedures in adults (for PT, APTT, platelet count), dental extractions (for the bleeding time only), cataract extraction (for platelet count). No studies are available in children for major surgery other than adenotonsillectomy, neurosurgery and invasive procedures.

BACKGROUND & AIMS: We performed a randomized controlled trial to evaluate the safety and efficacy of enoxaparin, a low-molecular-weight heparin, in preventing portal vein thrombosis (PVT) in patients with advanced cirrhosis. METHODS: In a nonblinded, single-center study, 70 outpatients with cirrhosis (Child-Pugh classes B7-C10) with demonstrated patent portal veins and without hepatocellular carcinoma were assigned randomly to groups that were given enoxaparin (4000 IU/day, subcutaneously for 48 weeks; n = 34) or no treatment (controls, n = 36). Ultrasonography (every 3 months) and computed tomography (every 6 months) were performed to check the portal vein axis. The primary outcome was prevention of PVT. Radiologists and hepatologists that assessed outcomes were blinded to group assignments. Analysis was by intention to treat. RESULTS: At 48 weeks, none of the patients in the enoxaparin group had developed PVT, compared with 6 of 36 (16.6%) controls (P = .025). At 96 weeks, no patient developed PVT in the enoxaparin group, compared with 10 of 36 (27.7%) controls (P = .001). At the end of the follow-up period, 8.8% of patients in the enoxaparin group and 27.7% of controls developed PVT (P = .048). The actuarial probability of PVT was lower in the enoxaparin group (P = .006). Liver decompensation was less frequent among patients given enoxaparin (11.7%) than controls (59.4%) (P < .0001); overall values were 38.2% vs 83.0%, respectively (P < .0001). The actuarial probability of liver decompensation was lower in the enoxaparin group (P < .0001). Eight patients in the enoxaparin group and 13 controls died. The actuarial probability of survival was higher in the enoxaparin group (P = .020). No relevant side effects or hemorrhagic events were reported. CONCLUSIONS: In a small randomized controlled trial, a 12-month course of enoxaparin was safe and effective in preventing PVT in patients with cirrhosis and a Child-Pugh score of 7-10. Enoxaparin appeared to delay the occurrence of hepatic decompensation and to improve survival.