By C. Mitch. Houston Baptist University. 2018.
There were fewer discontinuations because of adverse events purchase caverta 50 mg. However order 50 mg caverta, resistance as well as virological failure were observed more frequently with rilpivirine discount 100 mg caverta visa. In ECHO and THRIVE the rates were 9% vs 5% caverta 100mg lowest price, in STaR 4% vs discount caverta 100 mg online. Resistance mutations were mainly seen in the NNRTI loci (mainly E138K or K101E) but also in the NNRTI region (Rimsky 2012). Compared to efavirenz, the risk of resistance-associated virologic failure was significantly elevated in highly viremic patients. Thus, the approval of rilpivirine is restricted to patients with a baseline viral load of less than 100,000 copies/ml. CNS side effects may occur but are less inten- sive than seen with efavirenz. The QT prolongation observed earlier (at a higher dose), seems to occur less frequently at 25 mg (Vanveggel 2009) and the teratogenic risk is small (Desmidt 2009). A parenteral nano-suspension is being investigated, in which ripilvirine levels are achieved via monthly injections, corresponding to a daily dose of 25 mg (Verloes 2008). Rilpivirine currently plays an important role in long- acting strategies. In 2013, rilpivirine was also approved for treatment-experienced patients. In the SPIRIT trial, 476 patients with viral suppression have been randomized to remain on their PI-based regimen or to switch to rilpivirine. The switch was safe and improved lipid changes seen with PIs (Palella 2012). In conclusion, rilpivirine has become an important option in antiretroviral therapy. A certain disadvantage in everyday practice is the requirement that the substance must be taken with food (a fatty meal of at least 500 kcal is necessary) to guarantee 6. Overview of antiretroviral agents 87 sufficient resorption (Crauwels 2013). This can be a problem if patients have irregular daily habits. TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1. Rilpivirine Resistance Mutations in HIV-1+ Patients Failing NNRTI Therapy: Drug- resistance Database, the Spanish AIDS Research Network. Twenty-four-week efficacy and safety of switching virologically suppressed HIV-1-infected patients from nevirapine immediate release 200 mg twice daily to nevirapine extended release 400 mg once daily (TRANxITION). Rilpivirine versus efavirenz with emtricitabine/tenofovir disoproxil fumarate in treatment-naïve HIV-1-infected patients with HIV-1 RNA 100,000 copies/mL: week 96 pooled ECHO/THRIVE subanalysis. The Risk of Virologic Failure Associated with Low Frequency Nevirapine-resis- tant Variants in Women Initiating Nevirapine-containing ART Varies Depending on the History of Exposure to sd-Nevirapine: OCTANE/ACTG 5208. Role of low-frequency HIV-1 variants in failure of nevirapine-containing antiviral therapy in women previously exposed to single-dose nevirapine. Nevirapine versus efavirenz for patients co-infected with HIV and tubercu- losis: a randomised non-inferiority trial. Nevirapine-associated early hepatotoxicity: incidence, risk factors, and asso- ciated mortality in a primary care ART programme in South Africa. First-line ART with Lopinavir/ritonavir vs Nevirapine with Tenofovir/ Emtricitibine or Zidovudine/Lamivudine in a Developing Country: Week 96 of a Prospective Randomized Trial. Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treat- ment-naïve, HIV-1-infected patients: Pooled results from the phase 3 double-blind, randomized ECHO and THRIVE trials. Week 48 results from a randomized clinical trial of rilpivirine/emtricitabine/ tenofovir disoproxil fumarate vs. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Efficacy and safety of etravirine (TMC125) in treatment-experienced HIV-1- infected patients: 48-week results of a phase IIb trial. The rate of accumulation of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in patients kept on a virologically failing regimen containing an NNRTI. Cozzi-Lepri A, Phillips AN, d’Arminio Monforte A, et al.
A related study demonstrated that children with SCD who experienced comprehensive care had lower Although there is increasing prioritization of molecular and transla- rates of ER encounters and hospitalizations compared with those tional research to address SCD-related pain cheap caverta 50mg online, strategies to improve 36 who did not experience comprehensive care purchase caverta 50 mg without a prescription. Current literature documents deﬁciencies in pain man- agement and patient centeredness purchase caverta 100mg amex. Such a system may equate follow-up as major concerns discount caverta 100 mg. The PCMH resource Variable access to providers and shortages in hematologists in adult organization purchase caverta 50mg amex, TransforMED,37 has developed a detailed model of practice indicate that new models of care are needed to address the PCMH implementation. Currently, adults framework to model SCD pain management. Because multiple 434 American Society of Hematology Table 1. Application of the PCMH model to pain management PCMH element SCD pain management strategy Access to care and information Same-day appointments Same day appointments for early pain symptoms After-hours access coverage Extended ofﬁce hours to prevent delays in care or avoidable emergency care use Phone triage to facilitate home pain management Accessible patient and laboratory information; online Online resources provided for nonpharmacologic pain management patient services Electronic visits Telehealth visits for pain management Group visits Interactive visits for coping with pain Practice-based services Comprehensive care for acute/chronic conditions Multidisciplinary approach to pain management Prevention screening and services Routine screening for precipitators of pain Ancillary therapeutic and support services Increased use of physicians assistants, nurse practitioners, and registered nurses for care Care management Population management Creation of SCD registry for practice site Wellness promotion Creation of clinical dashboards for SCD Patient engagement/education Distribution of hardcopy and online resources Leverage of automated technologies Routine reporting on pain-related outpatient visits, ER use, and hospitalizations Care coordination Community-based resources Connection with community pain support groups, therapy, patient forums Collaborative relationships with ER, hospitals, specialists, Individualized pain management plan has input from multiple providers pharmacies, physical therapy, case management Individualized pain management plan maintained across different sites of care Care transition Active involvement of outpatient team in discharge planning from ER, hospitalization Practice-based care team Clinician-led multidisciplinary team Inclusion of physicians assistants, nurse practitioners, registered nurses, social workers, child life specialists, psychologists on care team Shared mission and vision Active patient engagement on pain management Effective communication Multiple means for patient to communicate with team (in-person, telephone, texting, email) Task designation by skill set Tasks are delegated to team members with appropriate expertise Families made aware of which team members are responsible for speciﬁc tasks related to pain management AdaptedwithpermissionfromtheTransforMedPatientCenteredModel,availablefrom:http://www. Nonphysician providers may serve as the ﬁrst line of proactive pain management through outpatient visits and telephone communica- Access to care and information tion. They may encourage and teach self-management skills, To prevent unnecessary delays in care and avoidable high-acuity including nonpharmacologic methods of pain reduction, stress health care utilization, patients must have appropriate access to management, and coping. They may also aid patients in identifying outpatient care. Patient-centered strategies to improve access to care precipitators of pain. In the PCMH model, nonphysicians in must include same-day appointments and extended ofﬁce hours. New models of telecommunication are increasingly being Care management incorporated into clinical care to increase access and convenience. Population management may require more formalization of how These enhanced modes of communication may facilitate real-time patients with SCD are identiﬁed and tracked within a practice. Modes of assess pain management practices, track patients’ self-management communication may include 2-way video, e-mail, and text messag- goals, determine the most effective therapies for treatment, and ing. Preliminary studies show that such modes of communication identify areas for practice improvement. Clinical dashboards are computerized visual tools that also offer news ways to share information among patients with allow practitioners to monitor real-time, clinically relevant informa- chronic pain, but little is known about how such models would work tion at the group or individual provider level. Population Hematology 2013 435 management may also involve more active distribution of educa- technologies are currently being tested in pediatric SCD care to tional materials on pain management to assist patients and family assess medication adherence, clinic attendance, and clinical out- members. Connection with community-based resources represents a key Strategies will need to be developed to ensure that care providers aspect of care coordination. With case managers, patient navigators, and others involved with the patient’s care have the information or social workers, patients can be connected with resources in the they need at the time they need it. A priority for PCMH will be community, such as pain support groups, online patient forums, and integrating electronic medical records across clinical settings so that alternative therapies for pain management. More collaborative pain management can be more consistent. Such collaborative efforts may prevent and coordinated care for pain. This may require practice transforma- rehospitalization. Prior work has demon- such a multidisciplinary approach, coding and billing should be strated that low-income African-American adults with SCD may be prioritized to ensure that the practice is adequately reimbursed for at increased risk for dental caries, which may be a precursor to oral services rendered. Practices must explore PCMH payment struc- pain episodes. Such payment structures may Practice-based care team justify practice investment in PCMH care for SCD pain. Practices As already described, a clinician-led multidisciplinary team will be may also experiment with incentives for performance to improve essential to practice management. Team members may include the quality of pain management.
Pooled analysis Patients with 362 NR 12 weeks Alefacept between patients older and younger than 65 Fair 2005 of efficacy trials plaque psoriasis years Significantly higher risk factor for bacterial Takeuchi et Postmarketing 350 5000 6 months Infliximab Patients with RA pneumonia in patients older than 70 vs discount caverta 100mg mastercard. Prospective 3694 Etanercept Patients younger than 65 years had better 42 52 weeks Patients with RA Fair 2006 cohort study Infliximab response Race Significantly higher response rates in Japanese Asahina 2010 Patients with 238 RCT 169 24 weeks Adalimumab patients treated with drug compared with Fair plaque psoriasis placebo No significant difference in ACR 20 response Chen order caverta 50 mg with mastercard, 2009 RCT 47 12 Adalimumab Patients with RA rates in Taiwanese patients treated with drug Fair 74 compared with placebo Significantly higher response rates with drug Tsai 2011 Patients with 366 RCT 121 36 weeks Ustekinumab compared with placebo in Taiwanese Fair plaque psoriasis and Korean patients 7345 person- Prospective years Adalimumab Dixon 2010 cohort study DMARD discount caverta 50 mg visa, Incidence rate of tuberculosis statistically 271 13739 Etanercept Patients with RA Fair BSRBR 34025 significantly higher in non white patients Infliximab Registry person- years anti- TNF Comorbidities Infliximab-treated (10 mg) patients were more Chung et al purchase caverta 100 mg free shipping. Pooled analysis Patients with 362 NR 12 weeks Alefacept diabetic and obese patients compared with the Fair 2005 of efficacy trials plaque psoriasis general study population 16126 Adalimumab Significantly reduced risk of myocardial infarction Dixon et al caverta 50 mg amex. Retrospective 334 10840 person etanercept, Patients with RA in responders to anti-TNF treatment compared Good 2007 cohort study years infliximab with non responders Schiff et al. More SAEs in abatacept-treated patients with 353 NR 52 weeks Patients with RA Fair al. Patients with RA 364 RCT 535 16 weeks incidence of SAEs in patients with diabetes and Fair al. Retrospective Patients on anti-TNF treatment had a lower rate 328 13171 2 years Anti-TNF Patients with RA Fair 2004 cohort study of CHF than patients on traditional RA therapy Concomitant medications Patients treated with both anakinra and Genovese et Anakinra + etanercept had a 7% rate of serious infection, 50 RCT 242 24 weeks Patients with RA Fair al. The adverse event profiles were similar for Tesser et al. Gender Prospective Kristensen 367 observational 1565 3 months Anti-TNF Patients with RA Gender did not influence treatment response Fair 2008 study Takeuchi et Postmarketing Significantly higher risk factor for bacterial 350 5000 6 months Infliximab Patients with RA NA al. Targeted immune modulators 106 of 195 Final Update 3 Report Drug Effectiveness Review Project SUMMARY Our conclusions are based on the review of 5210 abstracts and the inclusion of 163 studies. The large majority of these studies were funded by the pharmaceutical industry and could be classified as efficacy trials with highly selected patients. Few studies existed that enrolled less selected, primary care based populations. Overall, however, results between efficacy trials and more generalizable effectiveness studies appear to be consistent with only small variations in the magnitude of effects (see Table 21). In summary, insufficient evidence exists for most comparisons about the efficacy, effectiveness, and safety of abatacept, adalimumab, alefacept, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, natalizumab, rituximab, tocilizumab, and ustekinumab for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The most obvious differences that might be clinically decisive for choosing a targeted immune modulator involve dosage and administration. Infliximab, natalizumab, rituximab, and tocilizumab require intravenous administration. Abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, and ustekinumab can be administered subcutaneously. Furthermore, administration intervals differ substantially: adalimumab requires an injection once every other week, anakinra has to be administered daily, etanercept once a week, certolizumab pegol every other week, tocilizumab every 4 weeks, golimumab monthly, and ustekinumab every 4 to 12 weeks. Comparative Effectiveness Rheumatoid Arthritis One fair-quality, double-blinded head-to head trial provided evidence of moderate strength that abatacept and infliximab do not differ in efficacy for the treatment of rheumatoid arthritis up to 6 months. The safety profile, however, appeared to be better for abatacept than for infliximab with fewer serious adverse events (9. Other direct comparisons of targeted immune modulators for the treatment of rheumatoid arthritis are limited to one small randomized controlled trial and multiple observational studies rendering evidence of low strength. These studies indicated no differences in efficacy and safety between adalimumab and etanercept but greater response rates for adalimumab and etanercept compared with infliximab. No differences in safety were obvious in these studies. All of the observational studies were population-based and had high applicability. None of these studies provided any evidence on radiographic outcomes. Adjusted indirect comparisons suggested greater efficacy for etanercept than abatacept, adalimumab, anakinra, and infliximab for the treatment of rheumatoid arthritis. One landmark 53,54 trial was excluded from our analyses because of heterogeneity of population. If this trial is included in the indirect comparisons no statistical advantage for etanercept remains. The general efficacy of abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, infliximab, and rituximab for the treatment of rheumatoid arthritis was well established by multiple good to fair randomized controlled trials and meta-analyses.
There was a trend in reduction in clinical events with atorvastatin vs discount caverta 50mg free shipping. Poor in quality for assessment of differences in clinical events between groups cheap 50mg caverta otc. Pravastatin There was a significant reduction in serious Multinational Study cardiovascular events in the pravastatin vs discount caverta 50mg amex. Fair in quality to assess differences in clinical 1993* events between groups (relatively short follow up period) generic 50 mg caverta fast delivery. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 256 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 4 purchase caverta 100mg. Post-revascularization and miscellaneous trials Author Study Year Study Duration Mean Baseline Percent LDL-c Study Name Characteristics Patient Characteristics Intervention (mean) LDL-c Reduction Serruys PW. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 257 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 4. Post-revascularization and miscellaneous trials Author Primary Endpoint Results Year (provided only if it is a clinical Other Clinical Study Name Primary Endpoint health outcome) Outcomes Measured Other Clinical Outcome Results Serruys PW. When death and MI were Angiographic the loss of MLD during intervention. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 258 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 4. Post-revascularization and miscellaneous trials Author Year Study Name Comments/Conclusions Serruys PW. Angiographic placebo groups s/p successful balloon angioplasty. The Restenosis Trial composite of major clinical events which included (FLARE) death/MI/CABG/re-intervention was not different between groups (p=0. Fair-poor in quality for assessment of differences in clinical events between groups (relatively short follow up period, insufficiently powered). Adverse Lescol Intervention effects were not statistically different between groups. Prevention Study Fair-good in quality for assessment of differences in (LIPS) clinical events between groups (Number of diabetics was not equal between groups). CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 259 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 4. Post-revascularization and miscellaneous trials Author Study Year Study Duration Mean Baseline Percent LDL-c Study Name Characteristics Patient Characteristics Intervention (mean) LDL-c Reduction The Post Coronary Randomized, intent 1351 men or women 21- Aggressive LDL-c lowering 4. CABG 1-11 years prior titrated to 80 mg qpm (goal group. Warfarin 1 mg qd or placebo qd (titrated to 4 mg qd or INR of 2 or >) (2X2 design). CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 260 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 4. Post-revascularization and miscellaneous trials Author Primary Endpoint Results Year (provided only if it is a clinical Other Clinical Study Name Primary Endpoint health outcome) Outcomes Measured Other Clinical Outcome Results The Post Coronary Mean percentage per N/A Prespecified clinical There were no differences in the composite Artery Bypass Graft patient of grafts with a endpoints as a or individual clinical outcomes between Trial decrease of 0. There was a 29% reduction of 1997 lumen diameter of initially individually: Death from revascularization in the aggressive lovastatin Post Coronary patent grafts as assessed cardiovascular or group vs. There was a Restenosis Trial trend towards more MI in the lovastatin vs. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 261 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 4. Post-revascularization and miscellaneous trials Author Year Study Name Comments/Conclusions The Post Coronary There was a significant difference in the rate of Artery Bypass Graft atherosclerotic progression favoring aggressive LDL-c Trial lowering with lovastatin. There were no differences in 1997 composite or individual clinical outcomes between Post Coronary groups. There was a trend toward the aggressive Artery Bypass Graft lovastatin group in reducing revascularization. Fair in Trial (PCABG) quality to assess differences in degree of LDL-c lowering and its effect on clinical outcomes, although no difference was noted.
Beriplex P/N compared with plasma for rapid reversal of 5 cheap caverta 100 mg mastercard. Off-label use of recombinant coagulopathy induced by vitamin K antagonists in subjects factor VIIa in U purchase caverta 100mg on line. Ogawa S caverta 100mg amex, Szlam F order caverta 100 mg with amex, Ohnishi T buy caverta 50 mg otc, Molinaro RJ, Hosokawa K, coagulopathy: a porcine model. Taketomi T, Szlam F, Bader SO, Sheppard CA, Levy JH, SD) in correcting supratherapeutic international normalized Tanaka KA. Effects of recombinant activated factor VII on ratio due to warfarin overdose. Riess HB, Meier-Hellmann A, Motsch J, Elias M, Kursten FW, 10. Prothrombin complex concentrate (Octaplex) in management of anticoagulant therapy: antithrombotic therapy patients requiring immediate reversal of oral anticoagulation. Beriplex P/N anticoagu- prothrombin complex concentrates in reversing warfarin antico- lation reversal study group. Prothrombin complex concentrate agulation: a review of the literature. Three-factor prothrombin complex concentrate and hemostasis 2011;9(2):148-155. Sniecinski RM, Chen EP, Levy JH, Szlam F, Tanaka KA. Coagulopathy after cardiopulmonary bypass in Jehovah’s Wit- 28. What is the evidence for the ness patients: management of two cases using fractionated off-label use of recombinant factor VIIa (rFVIIa) in the acute components and factor VIIa. Sniecinski RM, Chen EP, Makadia SS, Kikura M, Bolliger D, bin complex concentrate in surgical patients: retrospective Tanaka KA. Changing from aprotinin to tranexamic acid results evaluation of Vitamin K antagonist reversal and treatment of in increased use of blood products and recombinant factor VIIa severe bleeding. Marlu R, Hodaj E, Paris A, Albaladejo P, Crackowski JL, controlled trial in the setting of bleeding after cardiac surgery. Effect of nonspeciﬁc reversal agents on anticoagu- Circulation. Factor IX complex for the crossover ex vivo study in healthy volunteers. Lambourne MD, Eltringham-Smith LJ, Gataince S, et al. The effect of Prothrombin complex concentrates reduce blood loss in murine recombinant activated factor VII on mortality in combat-related coagulopathy induced by warfarin, but not in that induced by casualties with severe trauma and massive transfusion. Reversal of dabigatran concentrate: an effective therapy in reversing the coagulopathy anticoagulation by prothrombin complex concentrate (Beriplex of traumatic brain injury. Hemostatic therapy in reversal: a 3-factor prothrombin complex concentrate and experimental intracerebral hemorrhage associated with the recombinant factor VIIa cocktail for intracerebral hemorrhage. Reversal of rivaroxaban 50 American Society of Hematology anticoagulation by haemostatic agents in rats and primates. Eerenberg E, Kamphuisen P, Sijpkens M, Meijers JC, Buller for the reversal of oral anticoagulants in patients undergoing HR, Levi M. Reversal of rivaroxaban and dabigatran by cardiopulmonary bypass surgery: A randomized study. Vox prothrombin complex concentrate: a randomized, placebo- Sang. Warkentin TE, Margetts P, Connolly SJ, Lamy A, Ricci C, (FEIBA) for the reversal of warfarin-induced coagulopathy. Recombinant VIIa (rFVIIa) and hemodialysis J Emerg Med. Perioperative hemostatic factor IX: a ﬁrst human dose trial in patients with hemophilia B.