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K-ras surrogate for immunoglobulin-variable-region mutations in mutations and beneﬁt from cetuximab in advanced colorectal chronic lymphocytic leukemia buy benicar mastercard blood pressure urination. Relation of gene mutant IDH1 delays growth and promotes differentiation of expression phenotype to immunoglobulin mutation genotype in glioma cells buy discount benicar line hypertension herbal remedies. Neunert2 1Hematology Service cheap generic benicar canada hypertension clinic, Texas Children’s Cancer Center, Houston, TX; and 2Cancer Center, Georgia Regents University, Augusta, GA A 5-year-old boy presents with platelet count of 2 109/L and clinical and laboratory evidence of immune thrombocytopenia. Complete blood count reveals isolated thrombocyto- penia without any decline in hemoglobin and he is Rh. You are asked if anti-D immunoglobulin is an appropriate initial therapy for this child given the 2010 Food and Drug Administration “black-box” warning. Immune thrombocytopenia (ITP) in children is usually self-limited highlighting the risks of intravascular hemolyis, acute renal failure, and and can often be managed by cautious observation. However, the DIC after IV administration of anti-D for ITP. Monitoring recommen- presence of “wet” bleeding, such as the oral mucosal bleeding dations were provided. Corticosteroids, IVIG, and anti-D preparation, have been comprehensively reviewed in a recent anti-D immunoglobulin (anti-D) are all considered appropriate publication and the data are summarized in Table 2. The risk of speciﬁc warning was issued by the Food and Drug Administration development of acute hemolytic reactions appears to be highest in (FDA) highlighting the risk of intravascular hemolysis, acute renal adults 65 years of age, patients with baseline hemolysis or renal failure, and disseminated intravascular coagulation (DIC) after function abnormalities, and those with current or recent signiﬁcant administration of anti-D to patients with ITP. In patients with increased risk based on the followed, anecdotal evidence suggests that providers are less above factors, an alternative therapy for ITP is recommended. During the To examine the current best evidence for anti-D as frontline postinfusion period, clinicians should monitor for any evidence treatment of newly diagnosed ITP in adults and children, we of severe hemolysis by obtaining a complete blood count and urinalysis and should perform further testing as necessary. Future studies should identify any additional publications. Of the 33 results that were address possible alternative administration strategies (including categorized as clinical trials, 22 were excluded because they did subcutaneous administration), the application of monitoring not involve anti-D (n 5), were not a therapeutic trial (n 5), recommendations in routine clinical practice, the effect that the recommended monitoring has had on reducing the number of used nonstandard administration (n 1), primarily evaluated serious hemolytic reactions, and the role of routine premedica- response in patients with chronic ITP (n 9), or duplicated tion strategies (eg, corticosteroids, diphenhydramine, acetamino- patients reported in another study (n 2). Three additional trials phen) to decrease infusion reactions. The included studies reporting efﬁcacy data are found in Table 1. In summary, multiple clinical trials in both adults and children have shown that anti-D effectively raises the Disclosures platelet count in the majority of treated patients and is associated Conﬂict-of-interest disclosure: The authors declare no competing with an acceptable safety proﬁle (Table 1). Studies reporting anti-D efﬁcacy in adults and children including patients with newly diagnosed ITP Reference Study type Patient groups (n) Treatment (n) Outcome Rodeghiero et al11 Retrospective Adults (49) HD IVIG (45); anti-D (12); 8 patients No difference in efﬁcacy received both between groups Blanchette et al12 Prospective, randomized Children (146) IVIG 1 g/kg 2 (34) Response at 72 h (platelets 20) highest in IVIG ( 90%), followed by anti-D (82%) and prednisone (79%) Acute* (146) IVIG 0. Reported acute hemolytic reactions and total infusions purpura treated with high dose immunoglobulins and anti-D per year since licensure immunoglobulins. Bussel JB, Graziano JN, Kimberly RP, Pahwa S, Aledort LM. Efﬁcacy, safety and dose response of intravenous anti-D immune globulin (WinRho SDF) for the treatment of idiopathic thrombocytopenic purpura in children. A dose of 75 report on the investigation and management of primary immune microg/kg/d of i. Single dose of adults with immune thrombocytopenic purpura. Initial management of count in newly diagnosed immune thrombocytopenic purpura immune thrombocytopenic purpura in adults: a randomized in children. The American Society of nous immunoglobulin in newly diagnosed immune thrombocy- Hematology 2011 evidence-based practice guideline for im- topenic purpura in Korean children. Intravenous immune globulin intravenous (human): risk of intravascular hemo- immune globulin versus intravenous anti-D immune globulin lysis. Naithani R, Kumar R, Mahapatra M, Tyagi S, Saxena R. Trends in anti-D Efﬁcacy and safety of anti-D for the treatment of adults with immune globulin for childhood immune thrombocytopenia: immune thrombocytopenia. Kane I, Ragucci D, Shatat IF, Bussel J, Kalpatthi R. Anti-D immune globulin as initial therapy for childhood immune immunoglobulin therapy for pediatric ITP: before and after the thrombocytopenic purpura. Intravenous anti-D immunoglobulin in the treatment of newly diagnosed childhood treatment of immune thrombocytopenic purpura: experience in primary immune thrombocytopenia. Comparison of anti-D uria and sequelae following Rh(o)(D) immune globulin intrave- immunoglobulin, methylprednisolone, or intravenous immuno- nous administration in immune thrombocytopenic purpura globulin therapy in newly diagnosed pediatric immune thrombo- patients. A comparison of intravenous Rh(0)(D) immune globulin intravenous administration for immunoglobulin (2g/kg totally) and single doses of anti-D immune thrombocytopenic purpura. Senter1 1Seattle Genetics Inc, Bothell, WA For more than a century, the concept of a “magic bullet” to deliver cytotoxic therapy to the site of disease has been envisioned but only recently have technological advances enabled antibody-drug conjugates to fulﬁll that dream. The recent approvals of brentuximab vedotin and ado-trastuzumab emtansine and emerging data for many molecules in clinical trials highlight the potential for antibody-drug conjugates to offer new therapeutic options for patients. This chapter reviews the evolution, state of the art, and potential future improvements that are enabling rapid development of this important class of cancer therapeutics. Introduction based on 2 single-arm open-label trials demonstrating unprec- The term “magic bullet,” attributed to the German physician Paul edented antitumor activity in patients with relapsed or refractory Ehrlich more than a century ago, captures the deceptively simple Hodgkin lymphoma (75% objective response rate, 34% complete concept that a targeting agent could be harnessed to deliver response) and systemic anaplastic large cell lymphoma (86% cytotoxic therapy directly to the source of disease. It was not until the advent of trastuzumab and a taxane. Approval was based on a randomized monoclonal antibody technology in the mid-1970s that therapeutic trial of Kadcyla versus lapatinib plus capecitabine, demonstrating an antibodies against relevant cancer targets were developed and began increase in progression-free survival (hazard ratio 0. However, it promising molecules in clinical testing and a signiﬁcant investment would require decades of additional experimentation through trial in trying to reﬁne the science and technology that underlies this and error before the right elements were combined to create the ﬁrst powerful therapeutic modality. Traditional chemotherapy employs potent small molecules to kill GO received accelerated approval based on 3 uncontrolled phase 2 rapidly dividing cells, often through antimitotic or DNA-damaging trials demonstrating antitumor activity in patients with relapsed mechanisms. Systemic administration of these drugs results in both AML (13% complete responses and 13% complete remission with tumor killing and damage to healthy tissues. As a result, most cancer regimens consist of withdrawn in June 2010. Despite these shortcomings, learning how to best In contrast, monoclonal antibodies, are large molecules (150 kDa) use GO as part of a frontline combination regimen has rekindled that are retained in the vasculature for several weeks and slowly interest in making this early ADC available again for patients. The complementarity-determin- ing regions can provide high-afﬁnity binding directed against ADCs come of age cell-surface antigens on tumor cells. The combination of a long The current technology has evolved signiﬁcantly, resulting in the half-life, speciﬁcity for tumor cells, and high afﬁnity results in the recent clinical success of 2 next-generation ADCs: brentuximab accumulation of antibody at the tumor over time. The lack of direct vedotin (ADCETRIS), targeting CD30 on relapsed Hodgkin lym- cytotoxicity often allows prolonged treatment that is well tolerated. Despite decades of active development, only 9 306 American Society of Hematology Table 1.
For immediate-release quetiapine discount benicar 10mg on line hypertension management, data on weight gain outcomes was only reported in 1 440 of 4 trials (N=58) purchase benicar 20 mg line blood pressure medication grapefruit. Weight gain data was not reported in the other trials 40mg benicar free shipping blood pressure upon waking, but differences between immediate-release quetiapine and placebo were described as not statistically significant. We could not verify whether the pattern of higher mean weight gain for olanzapine was apparent with regard to incidence of weight gain of 7% or more, as this outcome was not reported consistently across these trials (Table 20). Weight gain in adults with major depressive disorder for atypical antipsychotics compared with placebo Weighted mean Atypical difference (95% CI) for Pooled incidence of weight gain > 7%, antipsychotic (AAP) mean weight gain (kg) Relative risk (95% CI) Adjunctive treatment, history of inadequate response to antidepressants a 5% vs 1% 1. For CN138-165, standard deviation was estimated based on the averaging across CN138-139 and CN138-163. Atypical antipsychotic drugs Page 111 of 230 Final Report Update 3 Drug Effectiveness Review Project Extrapyramidal symptoms Compared with placebo, aripiprazole was the only atypical antipsychotic for which statistically significant increases for any extrapyramidal symptoms-related adverse event were consistently 432, 433, 439 found. When used to augment standard antidepressant therapy in adults who showed prior inadequate treatment response, pooled akathisia rates were significantly greater for aripiprazole than placebo (23% compared with 4%; rate difference +20. Using data from trials that were conducted in similarly-aged samples of patients (range of mean ages, 40. Based on our analyses, the difference between extended-release quetiapine monotherapy and placebo reached statistical significance only in the unpublished trial of older 451 adults with a mean age of 73. There was also no significant difference between monotherapy with extended-release quetiapine or placebo when taken for up to 52 weeks as maintenance treatment in adults without a history of inadequate 451 response. There were no significant differences between risperidone and placebo in changes 442 438 on the SAS and AIMS or in incidence of akathisia (0. There were also no significant differences between ziprasidone and placebo in changes on the Barnes 435 Akathisia Scale, the SAS, or the AIMS. Subgroups Age The difference between adjunctive risperidone and placebo in median time to relapse was similar in a subgroup of older patients with a mean age of 63. Compared with placebo, rate of MADRS response (64% compared with 30%; P≤0. When mean change in MADRS Total Scores was examined in the subgroup of patients above 50 years of age and in the subgroup aged 50 years and below, there was no treatment-by- 460 subgroup interaction between age and the comparison of adjunctive aripiprazole to placebo. Atypical antipsychotic drugs Page 112 of 230 Final Report Update 3 Drug Effectiveness Review Project Behavioral and Psychological Symptoms of Dementia Summary of Evidence Effectiveness • Seven head-to-head trials compared an atypical antipsychotic to another in patients with behavioral and psychological symptoms of dementia. The 1 fair-quality study found no difference between olanzapine and risperidone or between drug and placebo on the Neuropsychiatric Inventory (NPI), Clinical Global Impression (CGI) scale, BPRS, and the Cohen- Mansfield Agitation Inventory (CMAI) after 10 weeks. These studies did not provide comparative evidence due to differences in outcome measures used and other factors. They did not show consistent evidence that any atypical antipsychotic is superior to haloperidol for treating behavioral and psychological symptoms of dementia. Adverse Events • The CATIE-AD trial found no difference between active treatment groups or between any treatment group and placebo in overall withdrawals. All treatment groups had higher rates of withdrawals due to intolerability, adverse events, or death compared with placebo but there was no difference between treatment groups for this outcome. Atypical antipsychotic drugs Page 113 of 230 Final Report Update 3 Drug Effectiveness Review Project Subgroups • No conclusions about comparative effectiveness or safety based on age, gender, or comorbidities could be made from this body of evidence. Detailed Assessment for Behavioral and Psychological Symptoms of Dementia: Comparative Effectiveness, Efficacy, and Harms Effectiveness and Efficacy We included 25 trials on the efficacy of atypical antipsychotics in patients with behavioral and psychological symptoms of dementia. Seven of these were head-to-head trials (Evidence Table 13), 8 were active-control (Evidence Table 15), and 10 were placebo-controlled (Evidence Table 16). Details of the quality assessment of all trials are shown in Evidence Table 14. Four head- to-head trials were rated poor quality and 3 were fair. Seven active-control trials were rated fair quality and 1 was rated poor. One placebo-controlled trial was rated good quality and the rest were fair. To measure efficacy in trials of patients with dementia, a variety of outcome scales was used. The most frequently used were the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD), the NPI, the CMAI, the Clinical Global Impression-Severity of Illness scale (CGI-S), and the Clinical Global Impression of Change (CGI-C). Other systematic reviews We identified 7 systematic reviews of the evidence for efficacy or safety of atypical antipsychotics in patients with behavioral and psychological symptoms of dementia (Evidence 461-467 462, 464, 466, 467 Table 12). Of the 3 that reported efficacy outcomes, 2 performed pooled analyses of placebo-controlled trials and their results are shown in 461, 463 Table 21, below (statistically significant results are in boldface). These data show that different outcome scales were used in trials assessing different drugs, making indirect comparisons about comparative efficacy difficult. The BPRS total score was reported for all 4 drugs and was significantly better than placebo only for aripiprazole. Aripiprazole and risperidone, but not immediate-release quetiapine, were superior to placebo on the CMAI total score (not measured for olanzapine). The Neuropsychiatric Inventory-Nursing Home (NPI-NH) total score was superior to placebo for aripiprazole but not olanzapine or risperidone. Atypical antipsychotic drugs Page 114 of 230 Final Report Update 3 Drug Effectiveness Review Project Table 21. Pooled efficacy results reported in systematic reviews of atypical antipsychotics in patients with behavioral and psychological symptoms of dementia Mean difference compared with placebo (95% CI) Outcome scale Aripiprazole Olanzapine Immediate-release Risperidone quetiapine BEHAVE-AD Total -1. Direct evidence Head-to-head trials of effectiveness and efficacy Seven head-to-head trials compared an atypical antipsychotic to another in patients with behavioral and psychological symptoms of dementia. Their main results are summarized in Tables 22 and 23, and details of the trials are shown in Evidence Tables 13 (data) and 14 (quality). The best evidence for comparative effectiveness of atypical antipsychotics in patients 468, 469 with behavioral and psychological symptoms of dementia came from CATIE-AD. Patients with Alzheimer’s disease were randomized to treatment with olanzapine, immediate-release quetiapine, risperidone, or placebo and were followed up to 36 weeks. The protocol allowed medication dose adjustments or a switch to a different treatment on the basis of the judgment of a clinician. The main outcomes were time to discontinuation for any reason and percentage of group with at least minimal improvement on the CGI-C at 12 weeks. Results showed few differences among the active treatment groups. Time to discontinuation for any reason did not differ between treatment groups. Overall Atypical antipsychotic drugs Page 115 of 230 Final Report Update 3 Drug Effectiveness Review Project withdrawal rates were similar for olanzapine (80%), risperidone (82%), immediate-release quetiapine (77%), and placebo (85%; P=0. Discontinuations for lack of efficacy favored olanzapine over immediate-release quetiapine (hazard ratio, 0. The percentage of patients who responded did not significantly differ for olanzapine (32%), immediate-release quetiapine (26%), risperidone (29%), and placebo (21%; overall P=0. Results of clinical symptom outcome measures in CATIE-AD have been published more 469 recently. Differences between treatment groups on change in clinical symptoms at the last observation during the initially assigned treatment were analyzed. Additional analyses examined clinical symptom changes in patients who continued treatment for up to 12 weeks.
Yan-Li L benicar 10 mg fast delivery arteria music, Kang-Sheng G benicar 10 mg cheap heart attack grill menu, Yue-Yin P buy benicar with visa arteria publicidad, Yang J, Zhi-Min Z. The lower imaging for treated diffuse large B-cell lymphoma: ﬁndings from a large peripheral blood lymphocyte/monocyte ratio assessed during routine national database. The role of predicting relapse in patients with diffuse large B-cell lymphoma. Leuk surveillance CT scans in patients with diffuse large B-cell non- Res. Value of follow-up dehydrogenase beyond initial diagnosis: a retrospective analysis of procedures in patients with large-cell lymphoma who achieve a patients with diffuse large B cell lymphoma. Elevated lactate dehydroge- tomography in the follow-up of diffuse large B-cell and follicular nase levels detected during routine follow-up do not predict relapse in lymphomas. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and remission after primary treatment with rituximab, cyclophosphamide, non-Hodgkin lymphoma: The Lugano Classiﬁcation. Revised response criteria for dehydrogenase in the follow up of patients with diffuse large B-cell malignant lymphoma. Positron emission tomography/computed positron emission tomography scan in the follow-up of lymphoma. ACR Appropriateness Criteria: surveillance scans in DLBCL. Trent Spencer1 1Aﬂac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia Hemophilia A and B are bleeding disorders that result from functional deﬁciencies in speciﬁc circulating blood clotting factors termed factor VIII (FVIII) and factor IX (FIX), respectively, and collectively display an incidence of 1 in 4000 male births. Stem cell transplantation therapies hold the promise of providing a cure for hemophilia, but currently available transplantable stem cell products do not confer endogenous FIX or FVIII biosynthesis. For this reason, stem cell–based approaches for hemophilia have focused primarily on genetic engineering of pluripotent or multipotent stem cells. While pluripotent stem cells have been branded with high expectation and promise, they remain poorly characterized in terms of clinical utility and safety. In contrast, adult-lineage-restricted stem cells are established agents in the clinical armamentarium. Of the clinically established stem cell types, hematopoietic stem cells (HSCs) are the most utilized and represent the standard of care for several genetic and acquired diseases. Furthermore, HSCs are ideal cellular vehicles for gene therapy applications because they self-renew, repopulate the entire blood lineage while concurrently amplifying the transgene copy number 106 fold, and also have direct access to the bloodstream. Current research on HSC transplantation gene therapy approaches for hemophilia A and B is focused on the following: (1) identiﬁcation of safe and efﬁcient methods of nucleic acid transfer, (2) optimization of transgene product expression, (3) minimization of conditioning-regimen-related toxicity while maintaining HSC engraftment, and (4) overcoming preexisting immunity. Based on the existing data and current rate of progress, clinical trials of HSC transplantation gene therapy for hemophilia are predicted to begin in the coming years. Therefore, even though tremendous progress has been made in the treatment of Current state of hemophilia care hemophilia through research and development, the pursuit of novel An ongoing revolution in the care of persons with hemophilia A and and transformative therapeutic approaches remains an active area of B has been taking place over the past half century. Recent transfer-based therapy of hemophilia and prominent examples of continued therapeutic advancement are Several characteristics of hemophilia A and B make them amenable the bioengineered “long-acting” FIX and FVIII products, as well as to stem cell- and gene transfer–based therapeutic strategies. First, activated recombinant FVII and bispeciﬁc-antibody-based FVIII small increases in circulating FVIII or FIX levels can render mimetics, for the treatment of FVIII inhibitors. For example, increasing the baseline these treatments is curative and signiﬁcant deﬁciencies exist in FVIII level to 1% of normal, which represents a minimal plasma global hemophilia care. For example, there remains polarizing concentration of 10 pM (or 1 ng/mL), can eradicate spontaneous disparity in the range of care available throughout the world, with bleeding episodes, and achieving levels in the range of 500 pM (or 70% of persons with hemophilia not receiving any treatment and 50 ng/mL) could completely cure the disease. Second, gene therapy often not being speciﬁcally diagnosed. In the untreated state, severe should be more economical and less invasive than factor replace- hemophilia is a lethal disease with median mortality in the ment therapy because it would consist of a single treatment event. The limited treatment availability is a depend on gamma-carboxylation for function, which is a cell consequence of factor product costs, which frequently exceed type–speciﬁc activity and is most prevalent in hepatocytes. There- $250 000 per patient per year in the United States and are a lifelong fore, FVIII can be biosynthesized and secreted into the bloodstream expense. Although signiﬁcant efforts are being directed toward by most cell types with vascular access without loss of speciﬁc economic treatment strategy optimization, it does not seem feasible activity. For those who do receive trials of various gene therapies for hemophilia. Late preclinical, clinical, and commercial activities in cell and gene therapy for hemophilia Hemophilia Sponsor Vector Approval status A BioMarin rAAV-HLP-codop-h-FVIII-V3 Late preclinical A Blood Center of Wisconsin/Medical College of 2BF8-BDD-h-FVIII; SIN HIV-1 Lentivector Late preclinical Wisconsin A Expression Therapeutics LLC/ Lentigen EF1alpha-HP-FVIII; SIN HIV-1 Lentivector Late preclinical Corporation/Emory University A and B Bayer Healthcare/Dimension AAV Candidate selection (A)/ Therapeutics/REGENIX Biosciences IND-enabling (B) B Baxter International/Chatham rAAV-codop-h-FIX-Padua (BAX 335) Phase 1/2 Biosciences/Asklepios Biopharmaceutical B Spark, LLC AAV8-hFIX19 Phase 1, recruiting B St. Jude Children’s Research Hospital scAAV2/8-LP1-hFIXco Phase 1, recruiting B uniQure AAV5-h-FIX Phase 1/2 trials was halted due to either immune responses to the vector or remain elusive. Furthermore, HSCs have proven to be excellent lack of evidence for therapeutic efﬁcacy. Despite these setbacks, targets for genetic manipulation and ongoing clinical trials continue clinical gene therapy of hemophilia continues with 3 ongoing, to demonstrate the utility of targeting this cell population as a means independent trials (St. Jude Children’s Research Center/University of delivering nucleic acid therapeutics for the treatment and cure of College London; Spark, LLC; and Baxter International/Chatham several previously intractable diseases. Therapeutics) all testing liver-directed adeno-associated viral (AAV) vectors encoding FIX for the treatment of hemophilia B. Of these Origins and limitations of FVIII and FIX biosynthesis trials, only initial results from the St. However, a prerequisite of this approach is the which is the 5-fold more prevalent form of the disease. Most endogenous expression of the deﬁcient protein by the donor cells. It recently, in June 2014, Bayer HealthCare agreed to a collaboration has been known for decades that orthotopic liver transplantation with Dimension Therapeutics to commercialize another indepen- cures hemophilia in dogs and humans. This is not unexpected given dent AAV gene therapy product for hemophilia A. As these that vitamin K–dependent coagulation factors such as FIX require activities clearly indicate, gene therapy of hemophilia is being the activities of 2 proteins highly expressed in hepatocytes, gamma- aggressively pursued and multiple commercial entities have active glutamyl carboxylase and vitamin K epoxide reductase. However, preclinical and clinical hemophilia gene therapy pipeline programs several paradoxical observations surrounding FVIII biology made (Table 1). First, it was known that FVIII levels increase during fulminant hepatic failure, whereas Stem cells as therapeutics the levels of all other coagulation factors decrease. Second, it was One anticipated shortcoming of AAV-based gene therapy ap- observed clinically that FVIII levels did not decrease in the recipient proaches is limited therapeutic duration due to the turnover of the of a liver from a donor with mild hemophilia. In contrast, targeting stem cells has been widely speculated that both hepatic and extrahepatic for genetic modiﬁcation and delivery of FVIII or FIX theoretically sources of FVIII exist, a role likely held by endothelial cells of both presents as the most durable approach. In the simplest sense, stem the liver sinusoids and elsewhere. However, it was not until early cells can be deﬁned as undifferentiated cells that possess 2 key 2014 that endothelial cells clearly were identiﬁed as the primary properties, self-renewal and potency (ie, cellular differentiation endogenous source of FVIII by the Montgomery and Ginsburg potential).
It takes about ing an IUD expulsion and it is good if she checks the 3 months of supervised observation of their own threads monthly with IUDs buy cheap benicar 40mg line blood pressure medication diabetes. Hence benicar 20 mg cheap blood pressure medication starting with z, there is little cycle to become proficient in the method 10 mg benicar fast delivery arteria pudenda interna, while difference between typical use and perfect use of RCC-controlled courses are often only offered to LARCs (Table 1). This difference is sometimes the married, making it difficult for couples to post- enormous for other non-permanent methods, espe- pone their first pregnancy. Moreover, there are cially if used by those not yet in a stable relationship 152 Contraception Box 4 When to start and when does protection start If according to Box 3 the client is unlikely to be nant. They are immediately effective, even pregnant then (modern) methods can be started any retrospectively, if used as EC (see under Emer- day but not all are effective at once. Consult not breastfeeding, a COC can be started from Box 3 and for extra considerations, the section day 21 post-partum (if there are no extra throm- on female sterilization. If she could be pregnant botic risk factors) and COCs are then effective but it is too early to tell and she has succeeded directly. If there are these extra risk factors [such in getting on the operation list only after a lot of as high body mass index (BMI), post-cesarean], trouble, perform the operation anyway: it does then – after post-partum day 42 – being post- not cause a miscarriage, there is maximum 25% partum is not a risk factor anymore and COC chance she became pregnant this cycle and if eligibility is decided as per Box 2. By this time she is pregnant she will at least be protected in when non-breastfeeding CSAOUCFAW future. There are no known side-effects to EC could be repeated or, better, a Cu IUD the pregnancy if COC or progestogen-based could be inserted. Continue previous reliable method (unless • PBC are effective directly if given in the first 5 partner is pregnant) or – less reliable – days of the cycle (LNG-IUD up to 7 days), or CSAOUCF 3 months. In all • After proper COC, CHC ring or CHC patch other cases except during lactation amenorrhea use, the stop week (real stop or use of placebo method (LAM): CSAOUCFAW. If on POP, give LARC/ nancy can’t be completely excluded and even if DMPA/COC or TO during POP use, stop CSAOUCFAW is unrealistic. Cu IUD and TO are effective not harm the pregnancy and a pregnancy test (or directly. Also on day of: miscarriage; first- to DMPA, LARC or TO. There are theoretical and second-trimester abortion; ectopic opera- concerns of possible virilization of a female fetus tion; removal of LNG-IUD; removal of with use of DMPA and implants, but they are previous implant; post-partum discharge. If, while waiting LARC on the day next injection was due with for the results, CSAOUCFAW is unrealistic, 14 days ‘grace period’ to have direct effect. This happened in the because of their age, unlikely to get pregnant. Make it known that the side-effects reversibility of LARCs, unlike TOs, makes LARC a can be a nuisance but are not dangerous and mostly good option for women who want to postpone hav- the advantages overshadow them. After removal ing children, who want to space, or who are not yet there is a quick return to fertility. All LARCs are The method can be used by nearly every woman suitable for women who have a high BMI, a history (Box 2) whether she has a completed family or of ectopic, of DVT or migraine with aura, HIV, are wants to space, or postpone her first pregnancy. This is WHO teaching, but studies Dedicated staff can make an enormous contribu- show that an implant inserted just before post-par- tion to reproductive health if there is access to tum discharge is also fine: a US study showed that LARCs6. LARCs are, if used their whole lifespan, placing an implant just before discharge from hospi- in general more cost-effective than COC, POP or tal after delivery does not affect breastfeeding7. This DMPA, certainly when the costs of unintended is a good idea if there are transport problems. Prices under different circum- and they make the cervical mucus impenetrable stances in different countries differ enormously for for sperms. They protect from PID but not from STI LARCs, up to a factor of 50 more in some instanc- urethritis/cervicitis/syphilis. All progestogen-based contracep- most economical, good for at least 10 years. A recent study TOs when a laparotomy/laparoscopy has to be showed that the use of hormonal contraceptives, es- performed anyway or under local analgesia is pecially injectables, just like pregnancy itself, prob- cheaper per couple-years protection, and often so is ably facilitates HIV-1 acquisition and transmission vasectomy. In circumstances where supply systems in HIV-discordant couples by increased viral shed- are not optimal or where there are upheavals (war, ding in the vagina and perhaps an immunological revolutions, earthquakes, tornados, strikes) it can effect8. Other studies give different results, and be very advantageous to be on LARC. Jadelle (labelled for 5 years) and Sino-implant (4 A study in Kenya estimated that if 100,000 years) both consist of two rods with 75mg LNG COC/POP users switched to implants, then an each, and Implanon (3 years) consists of one rod estimated 26,000 unintended pregnancies could be with 68 mg etonorgestrel. They are inserted far from a possible geni- The only real setback is the unpredictable bleed- tal STI. They are the best hope for the unmet need ing pattern seen with implants. This is also the case of 45 million sub-Saharan women4. Training is with POP, DMPA and LNG IUD, but with the last easy, there are even fewer risks than with IUDs, two methods amenorrhea is more likely. Amenor- and, because the private parts are not involved, rhea is not unpleasant for most, but is sometimes a there are fewer understandable cultural/religious/ problem for Muslim women, although DMPA (and psychological sensitivities. Inserting them costs implants) are popular in Bangladesh and Indonesia, 2 min, removing them 5 min. Placing them just the most populous Muslim countries. Beside under the skin is the knack; this facilitates easy re- amenorrhea (10–15% first year), implants frequently moval. Providers need a good training course, give irregular bleedings, sometimes long light bleed- however, (five insertions under supervision; prac- ings or sometimes the cycle continues (around 25%) tice on a dummy also helps) because a few, placed often with fewer bleeding days. Some women much too deeply, very-difficult-to-remove im- complain of weight gain (not proven), acne (but can plants can, via the press (tabloids) or rumors, ruin a also improve), mood changes and headaches. The RCC limited IUD access stage, bleeding becomes irritating the best approach because IUDs were suspected of causing abortions. Recent The USA and UK Colleges of Obstetrics and Gyne- studies showed that 50mg of mifepristone (used for cology became very positive about the use of IUDs, 1 day) during an irritating stretch of bleeding will also in nullipara, and so too became the WHO. It (Cu IUDs) countries and China kept on using IUDs is very important to counsel the client about prob- with success. In the Western world there is much able changes in bleeding patterns. If she knows she more use for IUDs in nullipara than elsewhere, be- can expect that, it will not frighten/irritate her that cause adolescents are not all too seriously embar- much and she is more likely to continue. She should rassed to go to a general practitioner (GP) or FP be informed that amenorrhea is very unlikely to clinic before they are married for contraception, indicate a pregnancy because the method is so reli- and they are seldom chased away. Counseling might able and that amenorrhea does not mean that she result in either type of IUD being chosen. If inserted Concerns exist about gonorrhea and chlamydia after day 5 of the cycle, after 6 months LAM or and IUD insertion/use.
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