By T. Jerek. Thomas Jefferson University. 2018.
Sitagliptin or placebo added to two oral hypoglycemic agents buy apcalis sx 20mg low cost erectile dysfunction treatment in thailand. generic apcalis sx 20mg on line impotence and prostate cancer............................................... Initial combination of sitagliptin plus metformin compared with placebo and individual agents................................................................................................................................................................. Adverse events of sitagliptin compared with oral hypoglycemic agents................................. Quality assessment methods for drug class reviews for the Drug Effectiveness Review Project...................................................................................................................................................... Drug class review on newer drugs for the treatment of diabetes mellitus. These organizations selected the topic and had input into the Key Questions for this review. The content and conclusions of the review are entirely determined by the Evidence-based Practice Center researchers. The authors of this report have no financial interest in any company that makes or distributes the products reviewed in this report. Acknowledgments: We extend our appreciation to the clinical advisors listed below for their thoughtful advice and input during our research process. Marshall Dahl, MD University of British Columbia Diane Elson, MD University of Wisconsin, Madison Irl Hirsch, MD University of Washington John Newcomber, MD Washington University The investigators greatly appreciate the technical assistance provided by Judith Logan, MD, MS, our database manager, and Arkady Mak, MD, PhD, and Leah Williams-Morris, our manuscript editors. Diabetes Page 5 of 99 Final Report Drug Effectiveness Review Project INTRODUCTION Diabetes mellitus (diabetes) is a chronic and insidious disease affecting more than 20 million 1 Americans, approximately 7% of the population. Of those diagnosed, 90-95% have type 2 diabetes, while 5-10% have type 1 diabetes. Type 1 diabetes is characterized by autoimmune destruction of beta cells of the pancreas resulting in absolute insulin deficiency. Type 2 diabetes encompasses a heterogeneous group of disorders characterized by slow progressive loss of beta cell function and mass leading to variable degrees of insulin resistance, impaired insulin secretion, and increased hepatic glucose production. Among the counterregulatory hormones, higher glucagon levels relative to insulin also plays a significant role in the pathogenesis and management of type 2 diabetes, making optimal control difficult to maintain. The 2008 American Diabetes Association treatment guidelines recommend achieving and maintaining an A1c goal of <7% in nonpregnant patients with the caveat that less stringent goals may be appropriate for certain populations, all the while maintaining minimal hypoglycemia in 2 order to prevent micro- and perhaps macrovascular outcomes. Pharmacologic options for type 2 diabetes have primarily included sulfonylureas, biguanides, thiazolidinediones, meglitinides, alpha-glucosidase inhibitors, and insulin. Because of the progressive nature of diabetes, practitioners and patients experience challenges in reaching and sustaining American Diabetes Association goals. In fact, it is estimated that more than 50% of persons with type 2 diabetes will require more than one oral hypoglycemic agent after 3 years of diagnosis and approximately 70% will require combination oral therapy with or without 3 insulin 6 to 9 years from diagnosis. Within the last 1 to 2 years, three new antihyperglycemic agents have been approved: pramlintide, exenatide, and sitagliptin (Table 1). These agents offer mechanisms of glycemic control beyond that of “traditional” oral agents and insulin by targeting alternate gluco- regulatory receptors and hormones such as amylin, glucagon-like peptide-1 (GLP-1), glucose- dependent insulinotropic peptide (GIP), and dipeptidyl peptidase-4 (DPP-4). Amylin is a neuroendocrine hormone co-secreted with insulin from beta cells in response to elevated blood glucose concentrations and complements the actions of insulin. GLP-1 and GIP are secreted by L-and K-type cells in the intestinal tract in response to a combination of endocrine and neural signals initiated by the entry of food into the gut. Both endogenous GLP-1 and GIP are rapidly degraded by the proteolytic enzyme DPP-4. Diabetes Page 6 of 99 Final Report Drug Effectiveness Review Project Table1. Characteristics of pram lintide,exenatide,andsitagliptin Drug Drugclass Brandnam e (M anufacturer) F DA indications Contraindications Dose Approvaldate Dosage M ono-orcom bined Precautions adjustm ents Country How supplied therapy Pregnancycategory M onitoring Adjunctivetherapyin DM 1,DM 2,adults Decreaserapid- DM 1:Initiateat15m cg only,whouse orshort-acting subQ beforem ajor prandialinsulinand insulins, m eals(≥30g of faileddesired including fix ed- carbohydrate)and glucosecontrol m ix insulins titrateby15m cg every Contraindications: despiteoptim al (such as70/30) 3daysto30or60 Hypersensitivityto therapy(+/-SU by50% to m cg/m ealastolerated. Patientswho of the45or60m cg dose, confirm eddiagnosis m eetanyof the hypoglycem ia. Pram lintide considered:Poor glucoseand subQ beforem ajor Precautions: Am ylinom im etic/am ylin com pliancewith A1c frequently. M arch 2005 self-bloodglucose m onitoring If nauseapersistsat Pregnancycategory: U S m onitoring,A1c data,historyof the120m cg dose,m ay C > 9%,recurrent hypoglycem ia, decreaseto60m cg.
On some order apcalis sx 20mg free shipping erectile dysfunction drugs australia, but not all trusted 20mg apcalis sx erectile dysfunction doctor tampa, measures of sexual function and sexual quality of life, there was more improvement in women who used transdermal E2 compared with oral E2. This study is not published in full-text form and the brief reports do not provide sufficient detail to assess quality. A trial of CEE reported significantly improved vaginal dryness and urinary frequency, but no significant improvement on six other items related to sexual function on a General Health 61 Questionnaire compared to placebo. The HERS trial found that women with at least one episode of incontinence per week at baseline who received CEE/MPA had worsening 99 incontinence after approximately 4 years of follow up compared to women taking placebo. The WHI reported on genital symptoms, as noted above under the section ‘Hot 81 flashes/flushes’. In Update #3, the ULTRA study found no differences between treatment with low-dose 30 39 transdermal estradiol on vaginal dryness or on urinary incontinence. There was a reduction in Hormone therapy Page 38 of 110 Final Report Update 3 Drug Effectiveness Review Project investigator-assessed vaginal atrophy, dryness, and friability for estradiol acetate compared with 37 placebo (p<0. A Cochrane systematic review compared efficacy and safety of intra-vaginal estrogen preparations (creams, pessaries, tablets, and estradiol-releasing ring) for the relief of symptoms 100 of vaginal atrophy (vaginal dryness, itching, discomfort, and painful sexual intercourse). Overall, the author concluded that the preparations appear to be equally effective for the symptoms of vaginal atrophy. CEE cream caused more side effects compared to estradiol tablets (uterine bleeding, breast pain, and perineal pain) or estradiol vaginal ring (endometrial overstimulation). For the comparison of the estradiol ring to CEE vaginal cream, there was no difference between groups in patient assessment of vaginal dryness or withdrawals due to adverse events, but there was more improvement in pruritis with the ring. For the comparison of estradiol ring versus estradiol tablet, vaginal dryness was improved more with tablets, but there was no difference between groups in genital pruritis or withdrawals due to adverse events. Symptom improvement was similar for tablet versus cream, but there were fewer withdrawals due to adverse effects with tablets compared with cream. There was no difference among all treatment comparisons for dysuria, nocturia, urgency, urge incontinence, participant symptom improvement in dryness, soreness, and irritation, loss of libido, and vaginitis. Quality-of-life A head-to-head comparison of CEE vs. A trial comparing oral E2 and intravaginal ring E2 found significant improvement on the Greene Climacteric Scale among 102 both treatment groups but no between-group differences. One trial of oral E2 conducted in HRT-naive women in Thailand observed no difference in mean Greene score 83 improvement compared with placebo after 12 months of treatment. A trial of low-dose oral E2 103 (1 mg per day) reported significant improvement from baseline at 6 and 12 weeks on six of nine domains of the Women’s Health Questionnaire (vasomotor symptoms, sexual behavior, depressed mood, somatic symptoms, anxiety/fear, and sleep problems). There was no difference between control and treatment groups on the memory concentration, menstrual symptoms, and attractiveness items of the scale. Seven trials of transdermal E2 and placebo indicated improved health related quality-of- life and well-being measured by various instruments: Nottingham Health Profile, Psychological General Well-Being Index, Women Health Questionnaire, Kupperman’s index, McCoy Sex 68, 70, 73, 74, 76, 96, 104 Scale, and psychological general well-being index. One trial indicated that women with high well-being and no vasomotor symptoms at baseline had no improvement with 105 treatment as measured by the Psychological General Well-Being Index. The HERS trial (CEE), using non-validated quality of life instruments (Duke Activity Status Index, RAND Mental Health Inventory, among others), found that quality of life scores were significantly lower among women who were older, had diabetes, hypertension, chest pain, 91 or heart failure, and that use of CEE had little effect. One trial found a significant decrease in 59 Kupperman’s index among women treated with E2V compared with placebo. A trial of Hormone therapy Page 39 of 110 Final Report Update 3 Drug Effectiveness Review Project esterified estrogens reported improvement in the Quality of Life Menopause Scale compared to 106 placebo. Health-related quality of life (HRQL) measures were collected on a subgroup of women 85 enrolled in the WHI randomized to CEE plus MPA or to placebo (n=16,608). Quality of life and functional status were assessed using the RAND 36-item Health Survey, which includes items about general health, physical functioning, limitations on usual role-related activities due to physical health problems, bodily pain, energy and fatigue, limitations on usual role-related activities due to emotional or mental problems, social function, and emotional or mental health. At 1-year follow-up, there were small but statistically significant positive effects of CEE/MPA on physical functioning (0. There were no differences from placebo in any other HRQL measure and by 3 years of follow-up (n=1511) there were no significant differences from placebo on any HRQL measure. Subgroup analyses detected no statistically significant interactions between baseline age, race, ethnicity, body mass index, or menopausal symptoms and HRQL. In a post hoc analysis of women 50 to 54 years of age who reported moderate-to-severe vasomotor symptoms at baseline, there was a positive effect on sleep disturbance, but no effect on other HRQL measures, despite significant improvement in vasomotor symptoms. At 1-year follow-up, there was a small positive effect of CEE on sleep disturbance (0. At 1- year follow-up of women who had moderate-to-severe vasomotor symptoms at baseline, 72.
In other primary outcome measures the efficacy of sertraline and venlafaxine ER was similar (CAPS 20mg apcalis sx sale erectile dysfunction 3 seconds, CGI-S buy apcalis sx 20 mg visa smoking weed causes erectile dysfunction, Assessment of Functioning [GAF], Vulnerability to the Effects of Stress Scale [SVS]). Both treatment groups had statistically significant improvements on all outcome measures compared with placebo. SSRIs compared to placebo in adult outpatients with PTSD Fluoxetine compared with placebo Three placebo-controlled RCTs provide conflicting results on the general efficacy of fluoxetine 204, 205 for the treatment of PTSD. A small fair-rated study enrolled 54 patients to 12 weeks of Second-generation antidepressants 63 of 190 Final Update 5 Report Drug Effectiveness Review Project 204 fluoxetine (10-60 mg) or placebo. Using the Duke Global Rating for PTSD cut-off score of 1 (no symptoms) to define responders, the fluoxetine group had significantly more responders than the placebo group (59% compared with 19%; P<0. According to Duke Global Rating for PTSD cut-off scores of 1 (no symptoms) or 2 (minimal symptoms) to define responders, a nonstatistically significant trend toward fluoxetine was observed (P=0. Health-related secondary outcome measures (SIP, disability and stress subscales) showed significantly greater improvements for fluoxetine (P<0. A Kaplan-Meier analysis reported a significantly faster onset of efficacy for fluoxetine (P<0. Two additional, fair studies did not detect any statistically significant differences between fluoxetine and placebo for the treatment of PTSD. One study was a 12-week, fixed-dose 205 (fluoxetine 20 or 40 mg/d) trial (N=411) that enrolled primarily women (71%) with PTSD. At study endpoint both primary outcome measures (TOP-8, CAPS) showed similar efficacy outcomes between fluoxetine and placebo. The other trial (N=88) was an 8-week flexible-dose RCT that compared fluoxetine (20-60 mg/d) to placebo, psychotherapy, or eye movement 206 desensitization and reprocessing. No significant differences in CAPS scores were detected at endpoint between fluoxetine- and placebo-treated patients. Venlafaxine compared with placebo A fair, 6-month, placebo-controlled RCT assessed the efficacy of venlafaxine ER (37. Overall improvements were significantly greater for patients on venlafaxine ER than on placebo (CAPS, CGI-S, HAM-D). After 6 months, 51 percent of patients on venlafaxine ER achieved remission compared with 38 percent on placebo (P=0. Patients on venlafaxine ER had also greater improvements than the placebo group with respect to quality of life and functional capacity. Summary of the evidence We identified one head-to-head trial comparing citalopram to sertraline, one study comparing sertraline to nefazodone and one study comparing sertraline to venlafaxine. Effectiveness We did not identify any study with a high degree of generalizability. Efficacy Three head-to-head trials did not detect any differences in efficacy between citalopram and 200 201 203 sertraline, sertraline and nefazodone, and sertraline and venlafaxine ER. FDA-approved evidence exists for the general efficacy of paroxetine and sertraline for treating PTSD. Placebo- controlled trials report general efficacy of venlafaxine but not of fluoxetine in the treatment of PTSD. Significant differences in population characteristics make this evidence insufficient to identify differences between treatments based on placebo-controlled evidence. Second-generation antidepressants 64 of 190 Final Update 5 Report Drug Effectiveness Review Project Table 17. Interventions, numbers of patients, and quality ratings of controlled trials in adults with post-traumatic stress disorder Quality Author, Year Interventions N Results rating SSRIs compared with SNRIs 203 Sertraline compared with Davidson et al. Social Anxiety Disorder Currently, three SSRIs – fluvoxamine CR, paroxetine and sertraline – are approved by the FDA for the treatment of social anxiety disorder. In addition, the extended release formulation of one SNRI – venlafaxine – is approved for the treatment of social anxiety disorder. Three head-to-head trials (with placebo arms) compared one second-generation 208-210 antidepressant to another for the treatment of social anxiety disorder. Two 12-week trials 208, 210 compared paroxetine to venlafaxine ER; a 24-week trial compared escitalopram to 209 paroxetine. All three trials included measures of functional capacity in addition to efficacy and tolerability. We reviewed additional evidence from placebo-controlled trials if they assessed a second-generation antidepressant not currently FDA-approved for social anxiety disorder.
Time to first ischemic Time to first ischemic event was longer in The Atorvastatin events: death from cardiac 37 (21%) of the angioplasty event apcalis sx 20mg overnight delivery erectile dysfunction protocol ebook free download. Events making up the majority of the trend in favor of atorvastatin: CABG and hospitalization for angina buy generic apcalis sx 20 mg erectile dysfunction treatment with exercise. Pravastatin Change in serum lipids (TC, N/A Reported clinical events Significantly more serious cardiovascular Multinational Study LDL-c, HDL-c, triglycerides) as part of safety events were reported in the placebo (13) vs. Group analysis, although pravastatin (1) groups 1993* cardiovascular events (p<0. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 255 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 4. Post-revascularization and miscellaneous trials Author Year Study Name Comments/Conclusions Pitt B. Approximately 70% of patients in the Revascularization angioplasty group received a statin. Mean LDL-c 119 Treatment mg/dl in angioplasty group vs. There was a trend in reduction in clinical events with atorvastatin vs. Poor in quality for assessment of differences in clinical events between groups. Pravastatin There was a significant reduction in serious Multinational Study cardiovascular events in the pravastatin vs. Fair in quality to assess differences in clinical 1993* events between groups (relatively short follow up period). 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. 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.
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