C om parative clinicaltrials A uth or order online clomipramine, A dverse effects assessed? O xybutyninIR D avila Invalidatedquestionnairetoevaluatetitrationforpresenceandseverityof 10sym ptom sassessedat2 buy clomipramine 10 mg online,4 2001 and6wks buy clomipramine with american express. R CT = R andom ControlledTrial,U TI = U rinaryTractInfection,N S = N ostatisticaldifference Overactive bladder 97 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 1. C om parative clinicaltrials A uth or, Y ear W ith drawals due to adverse events C om m ents Transderm alvs. O xybutyninIR D avila O x yIR :1(drym outh) 2001 O x yTD :1contactderm atitisduetopatch *Padtest= patientfillsbladderto300m l,thenperform saseriesof m aneuvers,i. R CT = R andom ControlledTrial,U TI = U rinaryTractInfection,N S = N ostatisticaldifference Overactive bladder 98 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 1. C om parative clinicaltrials A uth or, Study Design Y ear Setting Eligibility criteria Exclusioncriteria Transderm alvs. Tolterodine SR D m ochowski R CT M enandwom en,aged>18,taking current Historyof urinarytractsurgeryinprevious6m onths,diagnosisof interstitial 2003 M ulticenter pharm acologic treatm entforoveractivebladder cystitis,urethralsyndrom e,painfulbladdersyndrom e,oroverflow urinary U SA with beneficialresponse(bypatientresponse). Post-washout:>/= 4urgeurinaryincontinent episodes,with eitherpureurgeorpredom inant urge,24orm orevoids,andanaverageurinary voidvolum eof 350m lorlessover3days. R CT Patients≥18with O ABsym ptom s(including Patientswith clinicallysignificantBO O ,apostvoidresidualvolum eof 2004 M ulticenter urgency,urgeincontinence,orfrequency)for≥3 >200m l,stressincontinence,presenceof aneurologicalcausefordetrusor International m onths;post-run-ineligibilityincludedan m uscleoveractivity,evidenceof U TI orof bladderstones,previouspelvic averagefrequencyof ≥8voids/24h and3 irradiation,previousorcurrentm alignantdiseaseof thepelvic organs,any episodesof urgencyand/or3episodesof m edicalconditioncontraindicating theuseof antim uscaric m edication incontinenceduring 3-dayvoiding period. R CT = R andom ControlledTrial,U TI = U rinaryTractInfection,N S = N ostatisticaldifference Overactive bladder 99 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 1. C om parative clinicaltrials A uth or, Interventions (drug,regim en, O th erinterventions/ M eth od ofO utcom e A ssessm entand Tim ing of Y ear duration) m edications A ssessm ent Transderm alvs. Tolterodine SR D m ochowski O x ybutynintransderm al(O x yTD )3. Q O L instrum entandVAS Tolterodinesustainedrelease(TolSR )4 incontinencem anagem ent "periodically. PlaceboBID ; Patient-reportedvoiding diary(episodesof urgencyand 2004 Tolterodine2m g BID (Tol); incontinence,tim esof voiding,volum evoided/void,pad Solifenacin5m g Q D (Sol5); use,andepisodesof sleep disturbance)atwks0,4,8,& Solifenacin10m g Q D (Sol10) 12 *Padtest= patientfillsbladderto300m l,thenperform saseriesof m aneuvers,i. R CT = R andom ControlledTrial,U TI = U rinaryTractInfection,N S = N ostatisticaldifference Overactive bladder 100 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 1. C om parative clinicaltrials N um berscreened/ A ge O th erpopulation A uth or, eligible/ G ender ch aracteristics N um berwith drawn/ Y ear enrolled Eth nicity (diagnosis,etc) lostto fu/analyz ed Transderm alvs. R CT = R andom ControlledTrial,U TI = U rinaryTractInfection,N S = N ostatisticaldifference Overactive bladder 101 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 1. C om parative clinicaltrials A uth or, Y ear O utcom es Transderm alvs. Tolterodine SR D m ochowski M eanchangeinincontinenceepisodesperdayat12wks: 2003 O x y-2. Changeinm eannum berof urgencyepisodes/24h: 2004 Tolterodine:-38%,p= 0. R CT = R andom ControlledTrial,U TI = U rinaryTractInfection,N S = N ostatisticaldifference Overactive bladder 102 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 1. C om parative clinicaltrials A uth or, A dverse effects assessed? Tolterodine SR D m ochowski M ethodof assessm entnotreported 2003 Applicationsitereactions: O x y32/121(25. R CT = R andom ControlledTrial,U TI = U rinaryTractInfection,N S = N ostatisticaldifference Overactive bladder 103 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 1. C om parative clinicaltrials A uth or, Y ear W ith drawals due to adverse events C om m ents Transderm alvs. R CT = R andom ControlledTrial,U TI = U rinaryTractInfection,N S = N ostatisticaldifference Overactive bladder 104 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 1. C om parative clinicaltrials A uth or, Study Design Y ear Setting Eligibility criteria Exclusioncriteria Chapple,etal. R CT, M enandwom enaged≥18y,O ABSym ptom sfor StressIncontinence(SI)orM ix edIncontinencewhereSI waspredom inant 2005 E urope ≥ 3m ,outpatient,dem onstratedU I (≥1 andneurogenic D O STAR episode/24h)andurinaryfrequency(≥8 (datafrom m icturitions/d)and ≥1U rgencyepisodes/24h uncorrectedproof) during 3-dayvoiding diaryperiod Chappleetal R CT M enandwom enaged≥18y,O ABSym ptom sfor StressIncontinence(SI)orM ix edIncontinencewhereSI waspredom inant 2007 E urope ≥ 3m ,outpatient,dem onstratedU I (≥1 andneurogenic D O STAR post-hoc episode/24h)andurinaryfrequency(≥8 m icturitions/d)and ≥1U rgencyepisodes/24h during 3-dayvoiding diaryperiod Darifenacinvs. O xybutinin *Padtest= patientfillsbladderto300m l,thenperform saseriesof m aneuvers,i. R CT = R andom ControlledTrial,U TI = U rinaryTractInfection,N S = N ostatisticaldifference Overactive bladder 105 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 1. C om parative clinicaltrials A uth or, Interventions (drug,regim en, O th erinterventions/ M eth od ofO utcom e A ssessm entand Tim ing of Y ear duration) m edications A ssessm ent Chapple,etal. Stabledosing phase:(W eeks0-4) nonereported 3-daym icturitiondiarypresentedatscheduledvisitsat 2005 Solifenacin5m g once/d wks4,8and12. Sym ptom sassessedinclude: STAR TolterodineE R 4m g once/d m icturitionfrequency(prim aryendpoint),episodesof (datafrom F lex ible-dosing phase:(W eeks5-12) urgency,incontinencewith andwithouturgency, uncorrectedproof) Solifenacin5m g once/d(Sol5) nocturia,padusage/24h,volum evoidedperm icturition. Solefenacin10m g once/d (Sol10) Health relatedQ oL :validated6-pointcategoricalscaleto TolterodineE R 4m g once/d(Tol4) assessPerceptionof BladderCondition. Chappleetal Stabledosing phase:(W eeks0-4) nonereported 3-daym icturitiondiarypresentedatscheduledvisitsat 2007 Solifenacin5m g once/d wks4,8and12. Sym ptom sassessedinclude: STAR post-hoc TolterodineE R 4m g once/d m icturitionfrequency(prim aryendpoint),episodesof N odoseincrease(N D I)phase:(W eeks5- urgency,incontinencewith andwithouturgency, 12) nocturia,padusage/24h,volum evoidedperm icturition.
We excluded these trials because all had follow-up duration of less than 4 weeks purchase clomipramine 25 mg otc. Efficacy: Comparisons between oral and topical drugs 74 buy cheap clomipramine 10mg on line, We included 2 randomized controlled trials that compared an oral NSAID to a topical NSAID order clomipramine with paypal. In both trials, regardless of whether participants had bilateral knee osteoarthritis, only one knee was treated with the topical solution. Thus, efficacy assessments related to only the single treated knee. The first trial (N=622) evaluated equivalence between treatment with 50 drops (1. The second trial (N=755) was Nonsteroidal antiinflammatory drugs (NSAIDs) 21 of 72 Final Report Update 4 Drug Effectiveness Review Project designed to evaluate superiority of treatment with 40 drops (1. In the first trial, oral diclofenac showed greater mean changes in pain (−134 mm compared with −118 mm; P=0. In the second trial, there was no significant difference between topical and oral diclofenac in either than change in WOMAC pain (−6. Are there clinically important differences in short-term (< 6 months) or long-term (≥ 6 months) harms between NSAIDs, with or without antiulcer medication, when used in adults with chronic pain from osteoarthritis, rheumatoid arthritis, soft-tissue pain, back pain, or ankylosing spondylitis? Summary of Evidence Comparisons between oral drugs • Celecoxib compared with nonselective NSAIDs o With regard to upper gastrointestinal adverse events, celecoxib may offer a short- term advantage over nonselective NSAIDs, but this has not been conclusively demonstrated in longer-term (>6 months) studies o Short-term risk of clinically significant upper plus lower gastrointestinal events was significantly lower for celecoxib compared with diclofenac slow release plus omeprazole, primarily due to a lower risk of clinically significant decrease in hemoglobin due to presumed occult bleeding of gastrointestinal origin, including possible blood loss from the small bowel o Based on findings from 3 meta-analyses of randomized controlled trials that were primarily 12 weeks in duration, as well as in 1 large case-control study, risk of myocardial infarction for celecoxib was not significantly different compared with NSAIDs o No significant increase in risk of other cardiovascular events or cerebrovascular events was found for celecoxib as compared with nonselective NSAIDs in 6 meta- analyses of randomized controlled trials and 5 observational studies o With regard to cardiorenal harms, results from the longest-term CLASS trial and meta-analyses of shorter-term trials found no increased risk of hypertension or heart failure with celecoxib compared with nonselective NSAIDs o Celecoxib was not associated with an increased fracture risk in a fair-quality, large-scale, Danish population-based study • Partially selective NSAIDs o Meloxicam has not been conclusively demonstrated to offer an advantage over nonselective NSAIDs with regard to gastrointestinal adverse events; limited Nonsteroidal antiinflammatory drugs (NSAIDs) 22 of 72 Final Report Update 4 Drug Effectiveness Review Project evidence from observational studies has not suggested any increased risk for meloxicam in myocardial infarction, hepatotoxicity, or fracture o Compared with nonselective NSAIDs, nabumetone had a lower short-term risk of gastrointestinal perforation, symptomatic ulcer, or bleeding events, but long-term comparative risks are unknown; nabumetone was not associated with an increased fracture risk in a fair-quality, large-scale, Danish population-based study o Comparative short-term and long-term gastrointestinal risk for etodolac relative to nonselective NSAIDs has not been evaluated; a small increase in risk of fracture was found to be associated with recent use of etodolac (within 1 year) in a fair- quality, large-scale, Danish population-based study (adjusted relative risk, 1. Several older observational studies of salsalate were identified, but could not be used to contribute evidence about specific serious gastrointestinal and cardiovascular events due to limitations in outcome definition and methodology • No specific data was found on the comparative risks of serious cardiovascular or serious gastrointestinal effects for either tenoxicam or tiaprofenic acid compared with other NSAIDs; three observational studies reported cases of potentially serious cystitis in patients using tiaprofenic acid, particularly in patients >70 years old. Comparisons between topical drugs • We found no trials that directly compared harms between different topical drugs • Indirect evidence was only available from 1 placebo-controlled trial of diclofenac 1. Comparisons between oral and topical drugs • In 2 trials that directly compared diclofenac 1. Detailed Assessment Comparisons between oral drugs Adverse events evaluated included serious gastrointestinal events, cardiovascular risk, mortality, hypertension, congestive heart failure, edema, renal function, hepatotoxicity, and general tolerability. The majority of NSAID-related adverse effects have not appeared to be dependent upon long (>6 months) duration of exposure. The exception was cardiovascular risk, which was 27, 76-81 only been observed in trials with exposure periods that exceeded 8 months in duration. A continued important weakness of the available evidence was that long-term studies which simultaneously assess gastrointestinal, cardiac, and other serious adverse events were lacking, particularly for the nonselective NSAIDs, thus seriously limiting our ability to accurately determine the true balance of overall benefits and harms. Celecoxib compared with nonselective NSAIDs (with and without antiulcer medication) Celecoxib is currently the only COX-2 inhibitor available in the United States. The Agency for Healthcare Research and Quality Effective Health Care Comparative Effectiveness Review is the most comprehensive review to date of the comparative safety of celecoxib relative to other 31 NSAIDs, placebo, or nonuse. Conclusions of the review were based on numerous meta- 27, 32, 33, 79, 81-91 analyses of primarily short-term randomized controlled trials (7 months or less) 92-102 and population based observational studies. Nonsteroidal antiinflammatory drugs (NSAIDs) 24 of 72 Final Report Update 4 Drug Effectiveness Review Project With regard to upper gastrointestinal adverse events celecoxib seemed to offer a short- term advantage over nonselective NSAIDs, when neither were taken with antiulcer medication, but this has not been conclusively demonstrated in longer-term (>6 months) studies. CLASS 27 remains the longest-term trial to date of patients with osteoarthritis/rheumatoid arthritis. Results from an interim, 6-month analysis from the CLASS trial (32/3987 compared with 51/3981, 27 annualized incidence rates 2. In a meta-analysis of 14 randomized controlled trials from 2000, annual rates of upper gastrointestinal ulcer complications were 2 per 1000 yearly for celecoxib 83 and about 17 per 1000 yearly for NSAIDs (P=0. Celecoxib was also associated with lower rates of clinical ulcers and bleeds relative to nonselective NSAIDs in a recent meta-analysis of 33 data from Pfizer records of 18 primarily short-term randomized controlled trials. Observational 103 98, 104 studies evaluating exposure to celecoxib of unknown or short-term duration are consistent with the randomized controlled trial results. Regarding longer-term gastrointestinal safety, however, celecoxib, diclofenac, and ibuprofen were associated with similar rates of complicated or symptomatic ulcers after 12 months in the CLASS trials, as reported by US Food 84, 90 and Drug Administration documents, and gastrointestinal safety outcomes associated with long-term use were not clearly reported in any observational study. Additionally, 3 short-term randomized controlled trials found celecoxib was as effective as co-therapy with a nonselective NSAID and an antiulcer medication in preventing ulcer 105-107 complications in high-risk patients. In very high-risk patients with a recent gastrointestinal bleed, there were no statistically significant differences between either celecoxib 400 mg and 105 diclofenac 150 mg plus omeprazole 20 mg or celecoxib 200 mg and naproxen 750 mg plus lansoprazole 30 mg in recurrent ulcer bleeding after 6 months (mean rate: 4. Likewise, in patients receiving aspirin (81 mg in 89% of the patients and 325 mg in 11% of patients ) and who required ongoing NSAID therapy for osteoarthritis (N=1045), rates of endoscopically confirmed gastroduodenal ulcers at 12 weeks were similar in patients given celecoxib 200 mg and those given naproxen 100 mg plus lansoprazole 30 mg (20. However, the most recent evidence suggested that the best protection of the upper gastrointestinal tract in higher-risk patients may come from taking celecoxib in combination with 108, 109 a proton pump inhibitor. In a good-quality randomized controlled trial of very high risk patients with a recent gastrointestinal bleed (N=273), the 13-month cumulative incidence of recurrent ulcer bleeding was significantly lower for celecoxib 200 mg plus esomeprazole 20 mg (0%) compared with celecoxib 200 mg alone (8. Additionally, in a subgroup analysis from a fair-quality, population- based retrospective cohort study in elderly patients which used data from the government of Quebec health services administrative databases, there were significantly fewer gastrointestinal hospitalizations when a proton pump inhibitor was added to celecoxib compared with celecoxib alone when age was above 75 years (adjusted hazard ratio, 0.
The leading causes of death It was estimated that 208 million pregnancies are hemorrhage best purchase for clomipramine, infection and poisoning from sub- occurred worldwide in 2008 buy clomipramine 75mg with mastercard, approximately 16% stances used for induced abortion purchase cheap clomipramine line. Gas gangrene (33 million) of them resulted in unintended births 25 from Clostridium perfringens is commonly reported and 20% (41 million) ended as induced abortions. These also in- While consistent use of contraceptives will reduce crease the risk of tetanus infection in women who the number of unintended pregnancies, induced are not immunized. Commonly used materials for abortions will be performed safely in countries 28 unsafe abortions are presented in Table 4 ; possible where it is legal, and largely ‘unsafely’ in countries complications associated with the use of these sub- where it is illegal. Up to 50% of women who either by persons lacking the necessary skills or in 6 have an unsafe abortion will require medical care. Worldwide, 48% of term health consequences of unsafe abortion, all induced abortions are unsafe; 95% of these are WHO estimates that about 20–30% of unsafe abor- performed under unsafe circumstances in Africa tions result in reproductive tract infections and that and Latin America. An estimated 5 million women about 20–40% of these result in upper genital tract are hospitalized each year for treatment of abortion- 6 25 infection and infertility. Long-term risk of ectopic Table 4 Part inventory of unsafe abortion methods, by route of administration28 Treatments taken by mouth Toxic solutions Turpentine; laundry bleach; detergent solutions; acid; laundry bluing; cottonseed oil; arak (a strong liquor) Teas and herbal remedies Strong tea; tea made of livestock manure; boiled and ground avocado or basil leaves; wine boiled with raisins and cinnamon; black beer boiled with soap, oregano and parsley; boiled apio (celery plant) water with aspirin; tea with apio, avocado bark, ginger, etc; ‘bitter concoction’; assorted herbal medications Drugs Uterine stimulants, such as misoprostol or oxytocin (used in obstetrics); quinine and chloroquine (used for treating malaria); oral contraceptive pills (ineffective in causing abortion) Treatments placed in the vagina or cervix Potassium permanganate tablets; herbal preparations; misoprostol Intramuscular injections Two cholera immunizations Foreign bodies placed into the uterus through the cervix Stick, sometimes dipped in oil; lump of sugar; hard green bean; root or leaf of plant; wire; knitting needle; rubber catheter; bougie (large rubber catheter); intrauterine contraceptive device; coat hanger; ballpoint pen; chicken bone; bicycle spoke; air blown in by a syringe or turkey baster; sharp curette Enemas Soap; Shih tea (wormwood) Trauma Abdominal or back massage; lifting heavy weights; jumping from top of stairs or roof 128 Abortion pregnancy, premature delivery and spontaneous advocate to increase contraceptive use and prevent abortion in subsequent pregnancies are known to unwanted pregnancy, space births and reduce un- be associated with unsafe abortion. The participation by community Women who have had complications arising members in decisions about availability, accessibil- from spontaneous or induced abortions require ity and cost of services is crucial to sustaining post- post-abortion care. The community also has an important role in improving health-seeking behav- POST-ABORTION CARE ior through education on recognition and response to obstetric and reproductive health emergencies. In addition to treatment for complications incom- Even if women and their families decide to seek plete and unsafe abortions, there is an opportunity care early, they will need to travel to the healthcare to provide other reproductive health services such facility. Communities can mobilize the resources as family planning, cervical cancer screening, HIV needed to ensure that transportation is readily avail- counseling and testing etc. Post-abortion care has five main com- Lastly community advocacy for holistic, human ponents: community and service provider partner- rights-based reproductive health policies and serv- ships, treatment, counseling, family planning and ices that cater for women from disadvantaged contraceptive services and linkage with other re- groups such as adolescents, women with HIV or productive health services. Box 2 has details of each AIDS, women who have experienced violence or component. Community and service provider partnerships Women who have lost a pregnancy need both • Prevent unwanted pregnancies and unsafe psychological/mental support; immediate counsel- abortion ing is often of great value. Adequate resuscitation (support for respira- • Ensure that health services reflect and meet tory and cardiovascular systems) may be necessary community expectations and needs in severe cases (for management of severe cases see 2. Simple laboratory investigations like • Identify and respond to women’s emotional hemoglobin level/packed cell volume, full blood and physical health needs and other concerns count and differentials are useful and may be avail- 3. In district hospitals • Treat incomplete and unsafe abortion and or larger referral hospitals, in addition to these potentially life-threatening complications blood urea and electrolytes tests, blood, urine and 4. Family planning and contraceptive services genital tract swab cultures may be available. Paren- • Help women practice birth spacing or pre- teral antibiotics with broad-spectrum antibiotics vent an unwanted pregnancy based on local protocols and availability should be 5. Reproductive and other health services started as soon as possible prior to any uterine evac- • Preferably provide on-site, or via referrals to uation or laparotomy. Blood should also be cross- other accessible facilities in provider’s network matched and transfused as soon as possible if indicated. There are several approaches of managing re- COMMUNITY SERVICE PROVIDER tained uterine products. Expectant management PARTNERSHIPS (allowing the miscarriage to complete on its own), The community plays a very important role work- medical management (use of drugs) or surgical ing with health service providers to educate and management (MVA or D&C) are options to ensure 129 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS that the miscarriage is complete and that the risk of • Fever/chills: These are transient; if they persist complications is minimized. Expectant manage- beyond 24 h rule out any uterine/pelvic infec- ment is likely to result in a higher risk of incom- tion. Also bear in mind other causes of fever in plete miscarriage, bleeding and a need for surgical that setting. Paracetamol or NSAIDs can be used uterine evacuation compared to surgical manage- for the management. It is not suitable for complicated abor- • Nausea and vomiting: These are likely to occur tions, such as septic abortion. However surgical and resolve within 2–6 h of administration of evacuation is associated with significantly higher misoprostol. An antiemetic such as hyoscine risk of infection than expectant management in un- hydrochloride may be necessary. This usu- formed consent, appropriate pain management, ally resolves within 24 h. The woman surgical evacuation the cervix needs to be dilated in should be instructed to contact a provider if she cases of missed abortion (this will be associated with soaks more than two extra-large sanitary pads an more pain), but with incomplete abortion (sponta- hour for more than two consecutive hours, or has neous or induced) the cervix is dilated and no bled continuously for more than 2 weeks and or/ further cervical dilation is required. With the medi- cal method for uterine evacuation, if there is infec- tion or heavy bleeding prior to complete evacuation Medical treatment of spontaneous miscarriages (failed medical evacuation), surgical evacuation and missed abortions may be indicated. However if the women remains A recent Cochrane review concluded that medical clinically stable after 10–14 days without complete treatment with misoprostol and expectant care are evacuation and she is willing to continue with this both acceptable alternatives to routine surgical method, the dose of misoprostol can be repeated9. Surgical treatment of spontaneous miscarriages Hospitalization is not necessary if hemodynamic- and missed abortion ally stable.
Other factors that predict thrombosis appear to be persistence of aPLs and a high aPL titer purchase clomipramine without prescription, which resulted in the inclusion of these criteria in the Sydney Criteria clomipramine 50 mg online. Similarly buy cheap clomipramine 25 mg on line, there appears to be no There have been 2 randomized trials comparing standard-intensity association between thrombosis or pregnancy loss in patients only 24 (INR 2. In contrast, LA appears to be more 34,35 17 patients with APS meeting the current criteria. The majority of strongly associated with thrombosis and pregnancy complications, the patients in these studies had a ﬁrst episode venous thrombosis, although there are conﬂicting data that suggest isolated LA may not 22,25 and the study results have since been interpreted as being applicable be associated with elevated thrombotic risk. The ELISA assays to this speciﬁc subset of patients with APS. These studies found no for aCLs and anti- 2GPI have been plagued by poor standardization 26 difference in the rates of recurrent thrombosis or major bleeding, and unreliable results. In contrast, assays for LA have better supporting the use of standard-intensity anticoagulation. Further, patients whose initial event occurred been speciﬁcally studied in these patients to date. Although anticoagulation is the mainstay of APS treatment, non- anticoagulant treatments have been evaluated. In patients with SLE, Patients with aPLs and arterial thromboembolism hydroxychloroquine has been shown to reduce the risk of an initial Recurrent arterial thrombosis appears to be more common than thrombotic event in patients with or without aPL40 and is frequently venous recurrence in patients with APS. The Warfarin versus The use of hydroxychloroquine in patients without SLE is uncertain, Aspirin Recurrent Stroke Study (WARSS) compared warfarin although hydroxychloroquine has been shown to protect the annexin (target INR 1. A subgroup analysis of this study, the Antiphospholipid Antibodies and Stroke Study (APASS)38 found Statins have anti-inﬂammatory, anticoagulant, and immunoregula- that aPL positivity at presentation was not predictive of recurrent tory effects and may potentially have a role as a novel treatment stroke and no difference between warfarin and aspirin for secondary option for patients with APS. In a small study of 41 aPL-positive stroke prevention was observed. Patients in this study did not meet patients who had inﬂammatory and prothrombotic markers mea- the current deﬁnition of APS, because only one measurement of LA sured at baseline and after treatment with ﬂuvastatin 40 mg daily for or aCL was measured at baseline and low-titer aCL patients were 3 months, 50% of the measured biomarkers were signiﬁcantly included. Many of these patients were older with cardiovascular risk reduced compared with control subjects. Rituximab was found in a cardiovascular risk factors. This study is interpreted by many small phase 2 pilot study of 19 patients to reduce some of the experts as having enrolled patients with stroke who had an aPL, but non-criteria manifestations of APS. This has resulted in uncertainty as to whether the results can be generalized to patients Treatment of CAPS with APS and ischemic stroke. Early recognition and aggressive initiation of anticoagulant therapy is critically important in the treatment of CAPS. A treatment A systematic review of mainly retrospective studies found that 7 algorithm has been proposed by the CAPS Registry Project Group. These investigators recommended high- combination therapy with anticoagulants, corticosteroids, and plasma intensity warfarin (INR 3. Patients with arterial events comprised almost 44 those diagnosed between 2001 and 2005. Decreased mortality was observed in sions cannot be drawn due to the limited numbers. A small patients who received anticoagulation compared with patients who randomized trial compared aspirin versus aspirin and warfarin in 45 were not anticoagulated (37% vs 78%, P. There was no patients with APS for secondary stroke prevention and found lower 39 difference between unfractionated and low-molecular-weight hepa- rates of recurrent stroke in patients receiving combination therapy. Corticosteroids are also used as a Congress on Antiphospholipid Antibodies recommended that pa- ﬁrst-line therapy in CAPS. Expert recommendations suggest meth- tients with deﬁnite APS and arterial thrombosis receive warfarin ylprednisolone 1000 mg daily for 3 days, but longer duration of (INR 3. In general, patients with arterial thrombosis and aPLs registry, but is empirically used based on the presumed pathophysi- receive indeﬁnite duration therapy. Plasma exchange (PLEX) using fresh frozen plasma has been shown in observational studies and in the CAPS Patients with recurrent thrombosis while receiving registry to improve mortality. Recurrence must be carefully established, and patients with administered alone did not appear to improve mortality, but may be a subtherapeutic INR, recurrence in the setting of other thrombotic of beneﬁt in patients with immune-mediated thrombocytopenia risk factors and postphlebitic syndrome must be excluded before when used in combination with PLEX. Treatment options range from increasing the administered after completion of PLEX. The dose of IVIg typically 678 American Society of Hematology used has been 0. APS is a prothrombotic disorder with various manifestations, most 8. Catastrophic commonly venous and arterial thromboembolism and recurrent antiphospholipid syndrome (CAPS): descriptive analysis of a pregnancy loss.