By R. Rozhov. Morehouse College.
Intermediate-dose (25 mg/m2) intravenous melphalan for transplantation for multiple myeloma: a CIBMTR analysis buy flomax 0.2mg without a prescription. Crawley C cheap flomax 0.4mg free shipping, Iacobelli S, Bjo¨rkstrand B, Apperley JF, Niederwieser D, 28. Reduced-intensity conditioning for myeloma: lower nonre- of pegylated liposomal doxorubicin plus bortezomib compared with lapse mortality but higher relapse rates compared with myeloablative bortezomib alone in relapsed or refractory multiple myeloma: combina- conditioning. International Myeloma multiple myeloma: safety and efﬁcacy. New drugs and novel symptomatic multiple myeloma: updated Mayo Stratiﬁcation of My- mechanisms of action in multiple myeloma in 2013: a report from the eloma and Risk-Adapted Therapy (mSMART) consensus guidelines. The translation of the knowledge gained into routine clinical practice is an important challenge so that VTE is managed optimally and established and new anticoagulants are used effectively and safely. This chapter reviews issues of VTE treatment from acute management to treatment of long-term complications, addressing new data gained in the last 2 years and putting them into a clinical context, with the goal of improved everyday VTE management. I typically consult the ACCP 2012 Introduction 1,20,21 guidelines. A user-friendly summary of the ACCP 2012 guideline, referred to as a “Quick Reference Guide,” has been A variety of developments have occurred over the last 2 years that 22 published by the ACCP and is easily available online ; in addition, have had a signiﬁcant impact on our clinical management of venous 23 a succinct review has recently been published. The key developments are: (1) the best-practice advice has also been created regarding speciﬁc topics creation of several treatment guidelines and guidance documents 7 relevant to VTE, such as anticoagulation management, thrombo- that provide clinicians with evidence-based recommendations on 6,24,25 26,27 1-7 philia testing, management of thrombosis at unusual sites, state-of-the-art VTE management ; (2) publication of a study (the 1,6 21,28,29 inferior vena cava (IVC) ﬁlters, VTE in pregnancy, and PEITHO trial) that helps to deﬁne further the role of thrombolytic 1,30,31 8 VTE in patients with cancer. Easy and comprehensive internet therapy in patients with pulmonary embolism (PE) ; (3) the ongoing access to these guidelines is available through a guideline portal of ATTRACT trial, which will help to clarify which patients with deep 32 9 the web-based VTE information resource Clot Connect. Several scores have complex concentrate (Kcentra) for major bleeding on warfarin and been developed (and were recently reviewed33) to assess PE urgent warfarin reversal before surgery based on 2 recent stud- patients’ risk for poor outcome in the weeks after the PE diagnosis, ies11,12; (6) 2 studies (WARFASA and ASPIRE trials) suggesting but most were not developed for the determination of whom to treat that aspirin is mildly effective in decreasing the risk of recurrent on an outpatient or inpatient basis, but rather as tools to assess risk VTE in patients with unprovoked VTE who have been treated with a of good or poor outcomes from the PE. The HESTIA criteria, standard course of anticoagulation13-15; (7) publication of a clinical recently evaluated in a multicenter prospective cohort study, were trial (the SOX trial) showing that wearing compression stockings developed for inpatient/outpatient management decisions and use after an episode of acute DVT does not decrease the occurrence of common sense parameters to determine hospital admission need34 postthrombotic syndrome (PTS)16; (8) the further recognition that (Table 2). Noteworthy are the data suggesting that some patients progestin-releasing intrauterine devices (IUDs) appear to be contra- with right ventricular dysfunction can be safely treated as outpa- ceptive methods without thromboembolic risk and may thus be tients. A rough VTE17,18 and the recent approval by the FDA of a small, progestin- practical guide for deciding whether to admit a patient or not may be releasing IUD (Skyla) suitable for nulliparous women; and (9) the this: if the patient with DVT or PE can walk into the ofﬁce or creation of tools that help health care professionals educate patients emergency department, then he/she can walk out of it and be treated with VTE. Several common sense additional considerations chapter in a clinical-practical context. Guidelines Several good, recent guidelines and guidance statements for the Thrombolytic therapy treatment of VTE exist, providing solid, evidence-based recommen- DVT dations on the state-of-the art management of VTE. These include A recent study of 209 patients with proximal DVT showed that publications from the American College of Chest Physicians catheter-directed thrombolytic therapy decreases PTS, but at the Hematology 2014 297 Table 1. FDA approval status of non-vitamin K oral anticoagulants in the United States Dabigatran Rivaroxaban Apixaban Edoxaban (Pradaxa) (Xarelto) (Eliquis) (Savaysa) Atrial ﬁbrillation Approved Approved Approved Applied for approval 1/8/2014 VTE treatment Approved Approved Approved Applied for approval 1/8/2014 VTE prevention after orthopedic surgery* Not applied for approval Approved Approved Not applied for approval *Totalhipandtotalkneereplacementsurgery. However, normalized ratio (INR) is therapeutic or (2) one of the NOACs. It is typically one of The anatomical extent of PE on imaging studies and physiological convenience of drug therapy, not of superior efﬁcacy. An additional consequences (ie, right ventricular dysfunction or myocardial possible beneﬁt of apixaban and rivaroxaban is less major bleeding; injury) often do not correlate well; it is the latter that is the predictor furthermore, a lower composite of major bleeding and clinically of a poor outcome and is therefore used for risk stratiﬁcation. PE is relevant non major bleeding was seen with apixaban compared with categorized into 3 groups: (1) “massive PE,” PE with hemodynamic low-molecular-weight heparin (LMWH)/warfarin in the initial instability; (b) “submassive PE,” PE with right heart dysfunction treatment of VTE (AMPLIFY). However, it is unclear whether the based on imaging (cardiac echocardiography or CT angiography) or safety and efﬁcacy data from these controlled clinical trials translate elevated cardiac enzymes (troponin or brain natriuretic peptide; and to a similar beneﬁt (ie, effectiveness) in real world practice. In all others, the beneﬁt of thrombolytic therapy is The 6 acute VTE phase 3 trials (EINSTEIN-DVT and EINSTEIN-PE for questionable. The recent PEITHO trial of the sickest of patients with rivaroxaban; RECOVER I and II for dabigatran; AMPIFY for submassive PE (normotensive, yet with right ventricular dysfunc- apixaban; and Hokusai-VTE for edoxaban) have recently been tion plus myocardial injury by positivity of serum cardiac enzymes) discussed in detail elsewhere. Dabigatran and edoxaban, however, were used only after major bleeding. The cost of (CTEPH)] was included in the study report, so it is not known the drug therapy chosen depends on a patient’s insurance status and whether thrombolytics have a positive effect on that outcome. One should be clariﬁed before prescribing LMWH/warfarin or a NOAC. Therefore, at present, it seems fair to limit to and discussed with any patient on long-term warfarin for a history of VTE, but is a particularly attractive option in the patient with Table 2. HESTIA criteria34 widely ﬂuctuating INRs and one who reports a high “warfarin hate factor” (further discussed below in the section entitled “Patient Hemodynamic instability? There are 4 published phase Oxygen needed for 24 hours to keep O2 saturation 90%? EINSTEIN-EXTENSION for rivaroxaban; RESONATE for dabiga- Medical or social reason for admission? A comparison of Renal impairment (creatinine clearance 30 mL/min)? NOAC with warfarin (REMEDY for dabigatran) has recently been Severe liver impairment? A patient’s If at least one of the questions is answered with “yes,” then the patient should be renal function, preference of once daily (rivaroxaban) over twice admittedtohospital.
J Acquir Immune Defic Syndr 2009; 50(Suppl 2):126-36 buy cheap flomax 0.2 mg. TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments buy flomax 0.4mg otc. Resistance profile of etravirine: combined analysis of baseline geno- typic and phenotypic data from the randomized, controlled Phase III clinical studies. Leitlinien zur Tropismus-Testung Stand Dezember 2012: Empfehlungen zur Bestimmung des HIV-1- Korezeptor-Gebrauchs (Version Dezember 2012). An update of the list of NNRTI mutations associated with decreased viro- logic response to etravirine (ETR): multivariate analyses on the pooled DUET-1 and DUET-2 clinical trial data. HIV Resistance and Viral Tropism Testing 329 Walter H, Eberle J, Mueller H, et al. Empfehlungen zur Bestimmung des HIV-1-Korezeptor-Gebrauchs (Stand Mai 2014). Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation. Weinheimer S, Discotto L, Friborg J, Yang H, Colonno R. Atazanavir signature I50L resistance substitution accounts for unique phenotype of increased susceptibility to other protease inhibitors in a variety of HIV type 1 genetic backbones. Reduced maximal inhibition in phenotypic susceptibility assays indi- cates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry. Hypersusceptibility to non-nucleoside reverse transcriptase inhibitors in HIV-1: clinical, phenotypic and genotypic correlates. Longitudinal resistance analyses of the phase 3 EVG/COI/FTC/TDF studies. Antiviral Therapy & Infectious Diseases 2014, 2:15 (Abstract O_12). A combination of decreased NRTI incorporation and decreased excision deter- mines the resistance profile of HIV-1 K65R RT. Primary resistance mutations and polymorphisms in gp41-sequences of HIV- 1 B-and non-B subtypes from Fuzeon-naïve patients. The L76V mutation in HIV-1 protease is potentially associated with hyper- susceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? Update on antiretroviral drug resistance testing: Combining laboratory technology with patient care. Clonal analyses of HIV quasispecies in patients harbouring plasma genotype with K65R mutation associated with thymidine analogue mutations or L74V substitution. Effect of transmitted drug resistance on virological and immunologi- cal response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study. Emergence and evolution of enfuvirtide resistance following long-term therapy involves heptad repeat 2 mutations within gp41. Transmission of integrase strand-transfer inhibitor multi-drug resistant HIV: case report and natural history of response to raltegravir-containing antiretroviral therapy. Opportunistic Infections (OIs) CHRISTIAN HOFFMANN In Western industrialized countries, many opportunistic infections (OIs) that in pre- vious years were considered prevalent are now quite rare. This is particularly true for infections associated with severe immunodeficiency such as CMV and MAC. The incidence of these OIs has been reduced to less than one-tenth of their frequency in the pre-HAART era (Brooks 2009, Buchacz 2010). ART has not only decreased the incidence of OIs, but it has also changed the course of OIs considerably. In the early years of the AIDS epidemic, the life expectancy of individuals diagnosed with their first AIDS-defining illness was at most two to three years. Today, however, many patients live with AIDS for 15 years or longer. In our own clinical study of 144 patients with cerebral toxoplasmosis, data from 1990–1993 indicated a 5-year survival rate of 8%; it climbed to 30% by 1994–1996, and to 80% since 1997 (Hoffmann 2007). Up to 90% of patients who develop AIDS or severe opportunistic infections are unaware of their HIV status. Typically, these patients seek medical attention late, when their overall health condition is serious. Since AIDS remains life-threatening, every HIV clinician should be familiar with the diagnosis of OIs and their respective therapies. Even with recent improvements, many challenges still exist. First, there is still no adequate treatment available for diseases such as PML or cryptosporidio- sis.
Preventive Services Task Force recommendation trial of the German Chronic Lymphocytic Leukemia Study statement purchase flomax 0.4mg online. Adult Immunization Schedules proven flomax 0.2mg, Centers For Disease Control 68. CLLU1 expression results from the CLL8 trial [abstract]. Blood (ASH Annual analysis adds prognostic information to risk prediction in Meeting Abstracts). Minimal residual transplant: eradication of disease. Hematology Am Soc Hema- disease (MRD) regrowth kinetics are an independent predictor tol Educ Program. Indications for leukemia (CLL) and are related to biologically deﬁned allogeneic stem cell transplantation in chronic lymphocytic CLL-subgroups: results from the CLL8 trial of the German leukemia: the EBMT transplant consensus. Fludarabine compared follow-up of patients with advanced chronic lymphocytic with chlorambucil as primary therapy for chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplan- leukemia. Pentostatin, cyclophos- son of ﬂudarabine, CAP, and ChOP in 938 previously phamide, and rituximab regimen in older patients with chronic untreated stage B and C chronic lymphocytic leukemia lymphocytic leukemia. Multicentre prospective patients with chronic lymphocytic leukemia. Chronic lymphocytic stage chronic lymphocytic leukaemia: the French Cooperative leukemia in less ﬁt patients: “slow-go”. Optimal management of older patients prednisone versus chlorambucil with prednisone as ﬁrst-line with chronic lymphocytic leukemia: some facts and principles therapy in chronic lymphocytic leukemia: report of a prospec- guiding therapeutic choices. Phase III trial of phamide and intravenous rituximab (OFOCIR) as ﬁrst-line ﬂudarabine plus cyclophosphamide compared with ﬂudara- therapy of Flt patients with chronic lymphocytic leukaemia bine for patients with previously untreated chronic lympho- (CLL) aged 65 years: end of recruitment analysis of cytic leukemia: US Intergroup Trial E2997. Lymphoma Group (ALLG) and CLL AUstralian Research 63. Fludarabine plus COnsortium (CLLARC) CLL5 study [abstract]. Blood (ASH cyclophosphamide improves response and progression-free Annual Meeting Abstracts). Fludarabine plus chemoimmunotherapy regimens in patients with chronic lym- cyclophosphamide versus ﬂudarabine alone in ﬁrst-line therapy phocytic leukemia: results of sequential cancer and leukemia of younger patients with chronic lymphocytic leukemia. The addition of rituximab to analogues for the treatment of chronic lymphocytic leukae- ﬂudarabine may prolong progression-free survival and overall mia: a systematic review and meta-analysis. Cancer Treat survival in patients with previously untreated chronic lympho- Rev. Fludarabine in comparison of CALGB 9712 and CALGB 9011. Combination chemoimmu- lymphocytic leukemia: a systematic review and meta-analysis. Chlorambucil–still not toxicity in previously untreated B chronic lymphocytic leuke- bad: a reappraisal. Rituximab plus combination with rituximab for previously untreated patients chlorambucil in patients with CD20-positive B-cell chronic with chronic lymphocytic leukemia: a multicenter phase II lymphocytic leukemia (CLL): ﬁnal response analysis of an 166 American Society of Hematology open-label phase II study [abstract]. Blood (ASH Annual chronic lymphocytic leukemia recurrence. Lenalidomide as initial (GA101) plus chlorambucil (Clb) or tituximab (R) plus Clb therapy of elderly patients with chronic lymphocytic leuke- versus Clb alone in pateints with chronic lymphocytic mia. Phase II study of bidities): Final Stage 1 results of the CLL11 (BO21004) lenalidomide and rituximab as salvage therapy for patients phase III trial. Single-agent treatment with rituximab in symptomatic, untreated patients rituximab as ﬁrst-line and maintenance treatment for patients with B-cell chronic lymphocytic leukemia: results from Can- with chronic lymphocytic leukemia or small lymphocytic cer and Leukemia Group B 9712 (CALGB 9712). The combination of rituximab as initial therapy for chronic lymphocytic leukemia rituximab and GM-CSF as frontline treatment for elderly or small lymphocytic lymphoma: population-based experi- patients with chronic lymphocytic leukemia. Rituximab in therapy with low-dose ﬂudarabine and cyclophosphamide and combination with high-dose methylprednisolone for the treat- high dose rituximab in previously untreated patients with ment of chronic lymphocytic leukemia. Low-dose ﬂudara- biological and psychosocial function. The European cytic leukemia/small lymphocytic lymphoma (CLL/SLL): Organization for Research and Treatment of Cancer. QLQ- preliminary results of project Q-Lite by Czech CLL Study C30: a quality-of-life instrument for use in international Group [abstract]. Signaling the end of chronic lymphocytic leukemia: 103. Assessment of older people: self- new frontline treatment strategies. Hematology Am Soc Hema- maintaining and instrumental activities of daily living. A research and ibrutinib in relapsed chronic lymphocytic leukemia.
Natural metastasis to your national radiotherapy center buy flomax 0.2mg with amex. First line chemotherapy in low risk gestational trophoblastic neo- • In women with persistent blood loss after abor- plasia flomax 0.2mg with amex. Cochrane Database Syst Rev 2009;1:CD007102 tion and pregnancy, GTN should be excluded: 8. EMA/CO for and should be treated as soon as the diagnosis is high-risk gestational trophoblastic tumors: results from a made and staging is done. J Clin Oncol 1997;15:2636–43 • Single-agent chemotherapy include MTX and 10. The curative effect of a second curettage in persis- ing women with persistent low-risk molar tent trophoblastic disease: a retrospective cohort survey. Role of surgery in the • High-risk persistent GTN can still be cured by management of high-risk gestational trophoblastic neo- multiagent chemotherapy. J Reprod Med 2006;51:773–6 • In women who do not wish to conceive any- more, a hysterectomy can cure local disease, but Further reading is not effective against metastasis. Gestational trophoblastic tumours following initial diagnosis of partial ACKNOWLEDGEMENT hydatidiform mole. Lancet 1990;335:1074–6 We thank Dr Manivasan Moodley MBChB, MMed, FCOG for his comments and suggestions. The cancer registry in South cological malignancies, in both well- and under- Africa stopped collecting data in 1999 but the resourced parts of the world (Figure 11). Department of Health has recently started moves to The majority of women are diagnosed at an ad- recreate the South African Cancer Registry. In the vanced stage of disease due to the relative absence USA, there are approximately 21,550 new cases of of symptoms and signs during early stages of the ovarian cancer diagnosed per year, and more than disease. In addition, there are currently no cost- 14,600 women will die of the disease. It is the fifth effective screening tests with sufficient sensitivity most common cancer in women in the USA after or specificity for use in population screening to lung, breast, colon and uterus. In most underdeveloped countries, the most The difference in incidence between developed common causes of death in women are caused by countries and less-developed countries, could be communicable diseases such as HIV, tuberculosis, attributed to women having a shorter life expect- malaria and maternal mortality. Cancer is a less ancy in undeveloped countries [on average 45 years common cause of death but the incidence of cancer compared to 82 years (median age of patients with ovarian cancer is 56 years)]. In addition, women in poorer countries have some protection from life- style factors such as: • Late menarche • High parity. Survival Survival rates can be as high as 90% in early stages and decline in the late stages. Determinants of survival according to the SEER (Surveillance, Epi- demiology and End Results) database include race, Figure 1 Incidence of malignancies in women. Source: Global Cancer Statistics, 20022 Survival declines with age with 5-year survival rates 344 Ovarian Cancer of 77% in women aged <50 years compared with women with BRCA mutations tend to develop rates of 50% in women aged 50–69, and a reported ovarian cancer about 10 years earlier than non- 32% in women aged >70 years. There is also a higher risk of ovarian and endo- Borderline ovarian tumors as well as germ cell metrial cancer in women with the Lynch II syn- tumors are associated with a much better prognosis drome, which is also known as the hereditary while serous papillary cancers are associated with non-polyposis colorectal cancer (HNPCC) syn- poorer survival3,4. The mutations are autosomal dominant Varying inequalities in survival could exist be- and thus a complete family history is important to tween and within developing countries due to the document. General risk factors Risk factors General risk factors for ovarian cancer include low Genetic abnormalities: BRCA1 and BRCA2 and parity, infertility and endometriosis. Lynch syndrome About 10–14% of women with epithelial ovarian Protection against ovarian cancer cancer have a germ-line mutation in the BRCA1 The use of combined oral contraceptives (COC), or BRCA2 genes. BRCA1 is located on chromo- breastfeeding, tubal ligation and hysterectomy are some 17 and most genetic inherited ovarian cancers 5,6 protective. The lifetime risk of develop- ing ovarian cancer for women with BRCA1 muta- Staging for ovarian cancer according to the Inter- tion may be as high as 28–44% and for women national Federation of Gynecology and Obstetrics with the BRCA2 mutation around 27%. Table 1 Ovarian cancer staging by FIGO, 2009 Stage I Cancer limited to the ovaries IA Growth limited to one ovary, no ascites. No tumor on the external surfaces, capsule intact IB Growth limited to both ovaries, no ascites. No tumor on external surfaces, capsule intact IC Tumor either stage 1A or 1B, but with tumor on the surface of one or both ovaries, or with capsule ruptured, or with ascites containing malignant cells or with positive peritoneal washings Stage II Growth involving one or both ovaries with pelvic extension IIA Extension and/or metastases to the uterus and/or tubes IIB Extension to other pelvic tissue Stage III Tumor involving one or both ovaries with peritoneal implants outside the pelvis and/or positive retroperitoneal or inguinal node IIIA Tumor limited to the true pelvis with negative nodes but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces IIIB Tumor of one or both ovaries with histologically confirmed implants of abdominal peritoneal surfaces, none exceeding 2 cm in diameter. Nodes negative IIIC Abdominal implants >2 cm in diameter and/or positive retroperitoneal or inguinal nodes IV Growth involving one or both ovaries with distant metastasis. If pleural effusion present, there must be positive cytological test results to allot a case to stage IV. Parenchymal liver metastases equals stage IV 345 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS Classification/histological types CA-125 with ultrasound examination is dis- appointing even in high-risk groups (BRCA muta- Three main types of primary ovarian cancers exist.
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