Need For Secondary Prophylaxis Research Articles

Management of Deep Vein Thrombosis: An Update Based on the Revised AWMF S2k Guideline.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are the most common manifestations of venous thromboembolism (VTE). Most DVTs affect the lower-extremity veins. Since the symptoms of DVT are non-specific, a prompt and standardised diagnostic work-up is essential to minimise the risk of PE in the acute phase and to prevent thrombosis progression, post-thrombotic syndrome and VTE recurrence in the long-term. Only recently, the AWMF S2k guidelines on Diagnostics and Therapy of Venous Thrombosis and Pulmonary Embolism have been revised. In the present article, we summarize current evidence and guideline recommendations focusing on lower-extremity DVT (LEDVT). Depending on whether the diagnostic work-up is performed by a specialist in vascular medicine or by a primary care physician, different diagnostic algorithms are presented that combine clinical probability, D-dimer testing and diagnostic imaging. The diagnosis of ipsilateral recurrent DVT poses a particular challenge and is presented in a separate algorithm. Anticoagulant therapy is an essential part of therapy, with current guidelines clearly favouring regimens based on direct oral anticoagulants over the traditional sequential therapy of parenteral anticoagulants and vitamin K antagonists. For most DVTs, a duration of therapeutic-dose anticoagulation of at least 3 to 6 months is considered sufficient, and this raises the question of the risk of VTE recurrence after discontinuation of anticoagulation and the need for secondary prophylaxis in the long-term. Depending on the circumstances and trigger factors that have contributed to the occurrence of DVT, management strategies are presented that allow decision-making taking into account the individual bleeding risk and patient's preferences.

Update on therapeutic approaches for invasive fungal infections in adults.

Invasive fungal infections are increasingly encountered with the expansion of iatrogenic immunosuppression, including not only solid organ and hematopoietic stem cell transplant recipients but also patients with malignancies or autoimmune diseases receiving immunomodulatory therapies, such as Bruton Tyrosine Kinase (BTK) inhibitor. Their attributable mortality remains elevated, part of which is a contribution from globally emerging resistance in both molds and yeasts. Because antifungal susceptibility test results are often unavailable or delayed, empiric and tailored antifungal approaches including choice of agent(s) and use of combination therapy are heterogeneous and often based on clinician experience with knowledge of host's net state of immunosuppression, prior antifungal exposure, antifungal side effects and interaction profile, clinical severity of disease including site(s) of infection and local resistance data. In this review, we aim to summarize previous recommendations and most recent literature on treatment of invasive mold and yeast infections in adults to guide optimal evidence-based therapeutic approaches. We review the recent data that support use of available antifungal agents, including the different triazoles that have now been studied in comparison to previously preferred agents. We discuss management of complex infections with specific emerging fungi such as Scedosporium spp., Fusarium spp., Trichosporon asahii, and Candida auris. We briefly explore newer antifungal agents or formulations that are now being investigated to overcome therapeutic pitfalls, including but not limited to olorofim, rezafungin, fosmanogepix, and encochleated Amphotericin B. We discuss the role of surgical resection or debridement, duration of treatment, follow-up modalities, and need for secondary prophylaxis, all of which remain challenging, especially in patients chronically immunocompromised or awaiting more immunosuppressive therapies.

215a. Use of Viracor Cytomegalovirus T-Cell Immunity Panel (TCIP) to Predict the Risk of Recurrent Cytomegalovirus Infection in Solid Transplant Patients and Guide Appropriate Management

Abstract Background Cytomegalovirus infection (CMV) is the most common opportunistic infection in solid organ transplant recipients (SOTR). Predicting recurrent disease and appropriate use of secondary antiviral prophylaxis is currently poorly defined. CMV-specific T-cell assays have been shown to be promising tools in determining presence of CMV immunity and helping guide primary and secondary antiviral prophylaxis. The goal of this study was to evaluate the ability of commercially available CMV-TCIP in predicting the risk of CMV relapse. Methods After IRB approval, clinical and laboratory data was retrospectively collected from our Enterprise Data Warehouse and primary chart review on 74 SOTR. As part of routine clinical care, the CMV T-Cell Immunity Panel (CMV-TCIP, Viracor Eurofins, Lenexa, KS) were collected by the TID provider managing the infection; generally this was done around the time of first negative test to inform choice of 2° prophylaxis. Analysis was completed for the total patient population and a subgroup of patients with CMV-TCIP tests completed ± 21 days of the first negative CMV VL. Descriptive statistics and Cohen’s Kappa statistics were used to assess association of relapse with assay results. Results Patient demographics are shown in Table 1. 2° prophylaxis was given to 60 (81.1%) of total patients for a mean of 86 days (0-614 days) after the first negative CMV VL. 26 (35.1%) SOTRs had relapse – 9 with positive CD4 and 20 with positive CD8 CMV-TCIP values. There was no association between specific test results and risk of relapse in the overall study population (see table 2). Similarly, no significance was found in the subgroup analysis of patients with CMV-TCIP results ± 21 days after first negative CMV VL. Conclusion In this study, CMV-TCIP did not predict CMV relapse after initial infection and treatment. While prior studies have shown a potential role for assessment of CMV-specific immunity to guide need for secondary prophylaxis, more studies of the CMV-TCIP are needed to assess the utility of this assay for this indication. Disclosures Michael P. Angarone, DO, Abbvie: Advisor/Consultant Valentina Stosor, MD, DiaSorin: Advisor/Consultant|Eli Lilly and Company: Grant/Research Support|Med Learning Group: Honoraria Michael G. Ison, MD MS, GlaxoSmithKlein: Grant/Research Support|Pulmocide: Grant/Research Support|Viracor Eurfins: Advisor/Consultant.

Invasive Group A Streptococcal Infections: Benefit of Clindamycin, Intravenous Immunoglobulins and Secondary Prophylaxis.

Introduction: Mortality associated with invasive group A streptococcal infections (iGAS) remains high among adults, with lower mortality in children. The added value of both clindamycin and immunoglobulins in such treatment is still controversial, as is the need for antibiotic secondary prophylaxis. It is unlikely that conclusive randomized clinical studies will ever definitively end these controversies.Materials and Methods: A clinical and experimental literature review was conducted in Pubmed, Cochrane, and lay literature to determine the benefit of adding clindamycin and immunoglobulins to β-lactams in the management of iGAS, as well as the need for secondary prophylaxis measures in close contacts.Results: This review includes two meta-analyses, two randomized controlled trials, four prospective studies, five retrospective studies, and microbiological studies. To reduce mortality and morbidity, it appears useful to add clindamycin to β-lactams in severe clinical presentations, including necrotizing fasciitis or streptococcal toxic shock syndrome, and immunoglobulins for the latter two presentations. The high risk of secondary infection in household contacts justifies the need of taking preventive measures.Conclusions: Both clinical studies and available experimental evidence suggest that adding clindamycin and immunoglobulins as adjunctive therapies in the management of invasive group A streptococcal infections may reduce mortality. Household contacts should be warned about the increased risk of secondary infection, and chemoprophylaxis may be considered in certain situations.

One-Year Experience of Cytomegalovirus T Cell Immunity Monitoring in Heart Transplant Recipients

<h3>Purpose</h3> Guidelines suggest optional use of Cytomegalovirus (CMV) T Cell immunity monitoring (TCell) to guide primary prophylaxis duration or need for secondary prophylaxis after infection. This may help balance the negative implications of CMV (rejection, coronary artery vasculopathy) against those of valganciclovir (expense, leukopenia/neutropenia). We present one year of experience to evaluate the potential utility of this test. <h3>Methods</h3> CMV TCell was implemented at our center to assess immunity at end of primary prophylaxis (R+ serostatus) and need for secondary prophylaxis after treatment of CMV. Heart transplant recipients with CMV TCell September 2019 to 2020 were retrospectively reviewed. Primary prophylaxis tests were excluded if R- serostatus or within 6 months of rATG. Tests at time of CMV detection prior to treatment were also excluded. <h3>Results</h3> Table 1 describes requirements for implementation. 24 patients had CMV TCell during study period; 1 never processed. Patients were excluded for: R- serostatus (6), rATG (1), and at time of CMV detection (2). 14 patients were included for analysis; 5 CMV R+ to guide primary prophylaxis discontinuation, 8 for secondary prophylaxis after infection treatment, 1 early for neutropenia. The early test for neutropenia was inconclusive after G-CSF administration. Immunity was noted at first test in 2/5 (40%) of the primary prophylaxis and 4/8 (50%) of the secondary group. Of non-immune in primary prophylaxis group, 2 had inconclusive tests concurrent to non-CMV infection and other in setting of neutropenia. After repeat tests, 9/14 (64%) patients were noted to have immunity. Of those with immunity, 5/9 (55%) had recurrence of low level viremia; 2 treated at detection, 3 self-cleared without treatment. <h3>Conclusion</h3> Early review of our data suggests CMV TCell may serve a role to identify patients who would benefit from secondary prophylaxis after treatment of CMV infection. Additional data over future years will help better define optimal utilization of this test.

Outcomes of Pediatric Patients With Defibrillators Following Initial Presentation With Sudden Cardiac Arrest.

Implantable cardioverter defibrillators (ICD) are recommended for secondary prevention after sudden cardiac arrest (SCA). The outcomes of pediatric patients receiving an ICD after SCA remain unclear. The objective of this study is to evaluate outcomes, future risk for appropriate shocks, and identify characteristics associated with appropriate ICD therapy during follow-up. Multicenter retrospective analysis of patients (age ≤21 years) without prior cardiac disease who received an ICD following SCA. Patient/device characteristics, cardiac function, and underlying diagnoses were collected, along with SCA event characteristics. Patient outcomes including complications and device therapies were analyzed. In total, 106 patients were included, median age 14.7 years. Twenty (19%) received appropriate shocks and 16 (15%) received inappropriate shocks (median follow-up 3 years). First-degree relative with SCA was associated with appropriate shocks (P<0.05). In total, 40% patients were considered idiopathic. Channelopathy was the most frequent late diagnosis not made at time of presentation. Neither underlying diagnosis nor idiopathic status was associated with increased incidence of appropriate shock. Monomorphic ventricular tachycardia (hazard ratio, 4.6 [1.2-17.3]) and family history of sudden death (hazard ratio, 6.5 [1.4-29.8]) were associated with freedom from appropriate shock in a multivariable model (area under the receiver operating characteristic curve, 0.8). Time from diagnoses to evaluation demonstrated a nonlinear association with freedom from appropriate shock (P=0.015). In patients >2 years from implantation, younger age (P=0.02) and positive exercise test (P=0.04) were associated with appropriate shock. The risk of future device therapy is high in pediatric patients receiving an ICD after SCA, irrelevant of underlying disease. Lack of a definitive diagnosis after SCA was not associated with lower risk of subsequent events and does not obviate the need for secondary prophylaxis.

Cryptococcal Infections in Kidney Transplant Recipients. A Single Center Experience

Introduction Cryptococcal infections are reported to be an infrequent but important cause of morbidity and mortality in solid organ transplant recipients. Best treatment and the need for secondary prophylaxis are still debated. The aim of this research was to describe incidence, clinical presentation, treatment and outcomes of kidney transplant recipients with cryptococcal infections observed at our institution. Materials and Methods Retrospective analysis of cryptococcal infections observed in patients (Pts) transplanted from January 1st 2008 to October 1st 2017. Data on demography, immunosuppression, clinical presentation, treatment and outcome was recollected. Results and Discussion 1413 transplants were performed in the period 2008-2017. A total of 12 cases of cryptococcal infection was observed (incidence:0.85%). Pts were 3 males/9 females. Age: Median 53.87 (range 20-72) years. Donors were: Deceased: 7 (58.3%); Living related 3 (25 %) Living non-related 2(16.7%.%). Immunosuppression: 10 received induction with timoglobulin. Maintenance immunosuppression: Tacrolimus (FK)- mycophenolic acid (MPA)- prednisone (P): 8 (67%), MPA-P/FK-MPA-P- belatacept/Belatacept MPA-P/and;, sirolimus-FK-MPA-P: 1 each.Four Pts suffered rejections previous to cryptococcal infection (Median time before cryptococcosis: 344.5 (Range: 83-1022) days). Time to infection after transplantation: Median 27.37 (range 3.2-84.3) months. Clinical forms: Meningeal: 6 (50%); Disseminated: 4 (33.3%); Pulmonary: 1 (8.3%); Pleural: 1 (8.3%). Median CD4 count at diagnosis: 88/mm3 (range 47-172). One Pt had a post-mortem diagnosis. Treatment: (Induction): Liposomal Amphotericin B (L-AmB) 9 Pts; L-AmB+Fluconazole: 2 pt. Immunosuppression was temporarily minimized on all Pts until infection was controlled. Consolidation: Fluconazole 11 Pts. (2 pt. still on treatment), 9 pt. completed treatment (median: 12 (range 8,5-20) months,). Outcomes All treated Pts (11/11) cured. 9 Pts maintained a functioning graft. Of these, 7 completed treatment (with no secondary prophylaxis) with no relapse of follow-up (FU). Median FU: 13,17 (range 3,44-72,33) months. 2 Pts lost the graft on FU (unrelated to cryptococcosis), and 1 Pt died of unrelated cause. Conclusion Treatment with induction with L-AmB (with or without fluconazole), combined with appropriate immunosuppression management was successful in all clinical forms of cryptococcal infection. No relapses were observed in Pts with treatment completed and no secondary prophylaxis.

Long-term mortality after poisoning with antipsychotics

Introduction: The objective of this study was to investigate the long-term mortality and cause of death after deliberate self-poisoning with antipsychotics. Furthermore, we investigated the risk of repeated self-poisoning after a first episode of poisoning with antipsychotics.Methods: We identified patients with antipsychotic poisoning from the Danish Poison Information Centre Database and correlated their personal identification number with four Danish national registries related to health aspects.Results: From August 2006 to December 2013 we identified 2289 patients poisoned with antipsychotic agents. The average age of the patients was 35.6 years (SD 14.3) and 68.5% were women. Eleven patients died during the first 30 days, and at the end of follow-up in March 2014, 150 patients were deceased, leading to a mortality rate of 2.1 per 100 person-years and a standardized mortality ratio of 9.0. The most common causes of death were poisoning (29%) and violent suicide (18%) – however half of the patients died from natural reasons. 643 patients (28%) repeated the poisoning once or more.Conclusions: Poisoning with antipsychotics was associated with an increased risk of death. Most of these deaths were preventable, and this highlights the need for secondary prophylaxis following a suicide attempt.

Prophylaxis with beta blockers as a performance measure of quality health care in cirrhosis

Prophylaxis with beta blockers as a performance measure of quality health care in cirrhosis

High Prvalence of Thrombophilia in Perinatal Thrombosis. Reaffirmation of the Recommendations for Routine Testing.

Background: Comprehensive laboratory testing for genetic and acquired thrombophilia traits is recommended for the evaluation of children with thrombosis by the Perinatal and Pediatric Subcommittee of the International Society on Thrombosis and Haemostasis (ISTH), and is becoming a standard of care. Evidence to date suggests that the incidence, etiology, and pathophysiology of thrombosis in the perinatal period exhibit important differences from those of older infants and children. The frequency with which thrombophilia laboratory evaluation reveals clinically useful information in perinatal thrombosis has not been well established.Objective: To determine the prevalence and nature of thrombophilia in perinatal thrombosis.Methods: All children had been referred to the Thrombosis/Thrombophilia Program at The Children's Hospital, Denver, and were consecutively recruited for participation in collection of laboratory and clinical data for this research. Perinatal thrombosis was defined as a venous and/or arterial thrombotic event diagnosed at birth or within the first month of life. The ISTH-recommended thrombophilia laboratory panel was performed clinically, and consisted of the following: a complete blood count; detection of the factor V Leiden (FVL) and prothrombin 20210 (PT20210) polymorphisms by PCR; functional assays of antithrombin (AT), protein C (PC), factor VIII (FVIII), and the lupus anticoagulant (LA); immunologic assays of lipoprotein(a) [Lp(a)], free protein S (PS), and anticardiolipin antibody (ACA); and detection of plasma homocysteine (Hcy) concentration by gas chromatograph mass spectroscopy. Antiphospholipid antibody testing was performed in the neonate and/or mother. Age-related abnormal values for non-genetic tests were defined as PC and PS < 20%, AT < 25%, FVIII > 150%, Lp(a) > 30 mg/dL, and homocysteine > 13.9 mM.Results: Forty neonates with thrombosis were referred for evaluation during an 8-year period, of which data were available in 37. Sixteen (43%) had venous thrombosis (including cerebral sinovenous, inferior vena caval, renal vein thrombosis, and isolated pulmonary embolism), an equal number had isolated ischemic arterial stroke in the distribution of the middle cerebral artery, and the remaining 5 (14%) had both arterial and venous thrombosis. Twenty-one (57%) of the 37 neonates with thrombosis exhibited thrombophilia upon comprehensive testing. Among these children, two had three-trait thrombophilia (low PC + low PS + high FVIII), four had two-trait thrombophilia (PT20210 + FVL; PT20210 + high Lp(a); low PC + low AT; and LA + ACA), and fifteen had single thrombophilia traits (low PC in 4; high Lp(a) or high FVIII in 3 each; LA, ACA, low AT, or polycythemia in 1 each).Conclusions: Upon comprehensive standardized laboratory assessment, thrombophilia was detected in greater than half of all children with perinatal thrombosis. Given that in many cases the identified abnormalities impact upon antithrombotic management and call for follow-up testing to guide duration of antithrombotic therapy and the need for secondary prophylaxis as well as consideration of future pregnancy management, comprehensive thrombophilia testing is warranted in perinatal thrombosis.

PATIENT VIEWS ON THE MANAGEMENT OF RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE IN THE KIMBERLEY: A QUALITATIVE STUDY

ABSTRACT Objective: To describe, from a patient perspective, factors leading to suboptimal management of individuals with rheumatic fever (RF) and rheumatic heart disease (RHD) among members of the Kimberley population. Method: Qualitative in‐depth semistructured and repeated interviews of seven Kimberley patients, or parents of children, with rheumatic fever and/or rheumatic heart disease, during 1998. Results: Participants showed variable levels of understanding about RF/RHD, often relating to the need for secondary prophylaxis. Compliance with medication was closely linked with positive patient–staff interactions. From the perspective of health care, living in a remote location was frequently described as a negative influence. Participants desire more accessible and culturally appropriate opportunities for learning about their disease. Conclusions: Participants focused on issues closely related to effective and ineffective management of RF/RHD. The lessons learned are indicators for health staff attempting to improve the quality of management that people receive.

Patient views on the management of rheumatic fever and rheumatic heart disease in the Kimberley: a qualitative study.

To describe, from a patient perspective, factors leading to suboptimal management of individuals with rheumatic fever (RF) and rheumatic heart disease (RHD) among members of the Kimberley population. Qualitative in-depth semistructured and repeated interviews of seven Kimberley patients, or parents of children, with rheumatic fever and/or rheumatic heart disease, during 1998. Participants showed variable levels of understanding about RF/RHD, often relating to the need for secondary prophylaxis. Compliance with medication was closely linked with positive patient-staff interactions. From the perspective of health care, living in a remote location was frequently described as a negative influence. Participants desire more accessible and culturally appropriate opportunities for learning about their disease. Participants focused on issues closely related to effective and ineffective management of RF/RHD. The lessons learned are indicators for health staff attempting to improve the quality of management that people receive.

Toxoplasma gondii pneumonia in liver transplantation: survival after a severe case of reactivation

Toxoplasmosis is an infrequent infection in solid organ transplantation, except in heart transplantation, where the grafting of a positive organ in a negative recipient transmits the infection in a high percentage of cases, in the absence of prophylaxis. We report a case of pneumonia by Toxoplasma gondii in a woman who received a liver transplant and had pre-transplant positive serology. Diagnosis was made by cytologic examination of bronchoalveolar lavage fluid, where the parasite was observed with hematoxylin-eosin and Giemsa staining. That finding was confirmed by direct immunofluorescence and positive polymerase chain reaction. The patient had a favorable outcome, although she had not initially received first-choice drugs. This was a case of severe illness secondary to reactivation of Toxoplasma infection, diagnosed pre-mortem and with a favorable outcome. Duration of treatment and need for secondary prophylaxis in these patients are discussed in the literature. Although infrequent, toxoplasmosis must be considered among the differential diagnoses of pulmonary infiltrates in solid organ transplantation.