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By C. Harek. Baylor College of Medicine. 2018.

RCT cheap fincar 5 mg on line man health 4 me app, DB generic fincar 5mg free shipping man health problems in urdu, DD Multinational (6 countries worldwide) FP DPI (400) Yes (medium) Fair 44 1999 vs. RCT, open-label France BDP MDI (800) Yes (all high) Fair 27 2005 vs. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating 47 Ringdal et al. RCT, single-blind Multinational (17) Mometasone DPI (200) No (only for M Fair 48 2000 vs. BUD, 730 Age ≥ 12, moderate, on ICS, smokers Mometasone DPI (400) both medium) excluded vs. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating Ciclesonide compared with flunisolide No systematic reviews or head-to-head trials found Ciclesonide compared with fluticasone 63 Bateman 2008 RCT Multinational - Europe, North America, CIC HFA-MDI (640) Yes (high) Fair South Africa vs. Fair Controller medications for asthma 45 of 369 Final Update 1 Report Drug Effectiveness Review Project Table 7. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating vs. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating publication 19% smokers 321 and 332 Multicenter 8 weeks and 6 weeks Flunisolide compared with mometasone No systematic reviews or head-to-head trials found Flunisolide compared with triamcinolone No systematic reviews or head-to-head trials found Fluticasone compared with mometasone 57 Harnest et al. RCT, DB Multinational (20) MF DPI (200) No (only for Fair 52 2001 vs. RCT, DB, triple- dummy US FP MDI (196) + Salmeterol (84) Yes (medium Fair 53 1999 vs. Controller medications for asthma 47 of 369 Final Update 1 Report Drug Effectiveness Review Project Table 7. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating 12 weeks TAA MDI (1200) Multicenter, Pulmonary/allergy medicine clinics (50) Condemi et al. Note: “No difference” in the above results section indicates that there was no statistically significant difference between active treatments with ICSs; results are written in the same order as the drugs are entered in the comparison column for each study. Symbol use: Drug X > Drug Y = statistically significant difference in outcomes favoring Drug X; Drug X > Drug Y trend = point estimate favors Drug X, but the difference is not statistically significant or tests of statistical significance were NR; No difference = no statistically significant difference or tests of statistical significance were not reported and outcomes are similar. Note: “No difference” in the above results section indicates that there was no statistically significant difference between active treatments with ICSs; results are written in the same order as the drugs are entered in the comparison column for each study. Controller medications for asthma 48 of 369 Final Update 1 Report Drug Effectiveness Review Project Table 8. Characteristics of head-to-head studies comparing inhaled corticosteroids that included children Study Design N Comparison Equivalent Quality Study Duration Study Population (total daily dose) dosing Rating Beclomethasone compared with budesonide Adams, N et al. Systematic review with meta- Majority in Europe BDP Yes Good 22 2002 analysis vs. Systematic review with meta- Multinational (most in Europe) FP vs. BDP (33 trials) For some of Good 23 2007 analysis the included Severity ranged from mild to severe FP vs. BUD (37) studies 71 trials (14,602 participants), 59 persistent parallel, 14 cross-over (four had FP vs. BDP/BUD (2) a washout) 38 studies had FP: BDP/BUD Majority of studies (47) were dose ratio of between 6 weeks and 5 months; 1:2; 22 had dose ratio 1:1; 14 were ≤ 4 weeks remainder had multiple dose ratio comparisons or ratio was unclear Lasserson et al. Systematic review with meta- Multinational (most in Europe) FP compared with extrafine HFA Yes Good 24 2010 analysis BDP Severity ranged from mild to severe 9 trials (1265 participants) persistent 3 to 12 weeks 2/9 trials in children De Benedicts et RCT, DB Multinational (7 countries: Holland, FP DPI (400) Yes (medium) Fair 31 al. RCT, DB Multinational (11 worldwide) FP MDI (200) Yes (medium) Fair 34 1993 vs. Characteristics of head-to-head studies comparing inhaled corticosteroids that included children Study Design N Comparison Equivalent Quality Study Duration Study Population (total daily dose) dosing Rating controlled on current meds, smoking 6 weeks status NR Multicenter (32) Budesonide compared with Ciclesonide von Berg et al. RCT, DB, DD Multinational - Australia, Germany, CIC HFA-MDI (160) Yes (low) Fair 62 2007 Hungary, Poland, Portugal, Serbia vs. Systematic review with meta- Multinational (most in Europe) FP vs. BDP (33 trials) For some of Good 23 2007 analysis the included Severity ranged from mild to severe FP vs. BUD (37) studies 71 trials (14,602 participants), 59 persistent parallel, 14 cross-over (four had FP vs.

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For controlled-release 97 cheap 5mg fincar otc mens health 3 bean chili, 100 metoprolol cheap fincar 5 mg visa androgen hormone yang, results of quality-of-life assessments were mixed across 2 trials. In the ENECA study, reductions in Minnesota Living with Heart Failure Questionnaire scores were similar for 98 nebivolol compared with placebo. Outcomes in placebo-controlled trials of beta blockers for heart failure All-cause Sudden Death due New York mortality death to heart Heart rates rates failure Association Study Beta P value P value P value class Exercise Quality Year blocker NNT NNT NNT improvement capacity of life 10% vs. Sturm Atenolol 16% NR 39% NR NR NR 2002 NS NS Improvement Anonymous 16. Class III/IV 6-minute improvement US Carvedilol Carvedilol 5. Head-to-head trials There are no direct comparator trials comparing 2 or more of the drugs proven to reduce mortality (bisoprolol, carvedilol, and sustained release metoprolol succinate). We are aware of 1 trial in process that compares the tolerance of bisoprolol and carvedilol in elderly patients (>65 101 years) with systolic or diastolic chronic heart failure. Otherwise, we found 6 fair-quality, head-to-head trials comparing immediate-release metoprolol tartrate to carvedilol in patients with heart failure and 1 trial that compared nebivolol to carvedilol (see Evidence Tables 11 and 12 for characteristics and quality assessments and 102-107 Evidence Table 13 for outcomes). These trials recruited stable patients with Class II-IV (mainly II and III) heart failure, most of whom took ACE inhibitors and diuretics. Only 1 trial (COMET) was adequately powered to evaluate mortality and cardiovascular events (N=3029). The target dose of carvedilol was 25 mg twice a day and the target for metoprolol tartrate was 50 mg twice a day. Beta blockers Page 41 of 122 Final Report Update 4 Drug Effectiveness Review Project When COMET was designed, extended-release metoprolol was not yet available, and immediate-release metoprolol was a logical comparator because in the MDC trial metoprolol tartrate was clearly effective, even though it did not change mortality. Specifically, metoprolol tartrate improved ejection fraction, left ventricular end diastolic pressure, and exercise time and prevented clinical deterioration, reducing the need for transplantation by almost 90% during the 94 followup period. Mortality In COMET, after a mean followup of 58 months (nearly 5 years), the intention-to-treat analysis showed an all-cause mortality reduction in favor of carvedilol (34% compared with 40%; number needed to treat, 18; P<0. The annual mortality rate was 10% for metoprolol tartrate and 8. For comparison, the rates were for metoprolol succinate in MERIT-HF (7. There was no difference between carvedilol and metoprolol in the combined endpoint of deaths plus all-cause admissions (74% compared with 76%). COMET demonstrates unequivocally that carvedilol 25 mg twice a day was better than immediate-release metoprolol (metoprolol tartrate) twice a day. There is disagreement, however, about the relevance of the result, because immediate-release metoprolol had not been shown to reduce mortality in previous trials. Several years ago, after metoprolol tartrate failed to reduce mortality in the Metoprolol in Dilated Cardiomyopathy (MDC) trial, it was hypothesized that the patients who received it were subjected to daily variations in the degree of beta blockade. In COMET, the mean dose of metoprolol tartrate was less than that used in the MDC trial (85 mg daily compared with 108 mg daily), and the mean decrease in heart rate was also less (11. Subsequently, extended-release metoprolol (metoprolol succinate) was proven to reduce mortality in heart failure patients in the MERIT-HF trial. In MERIT-HF, the mean dose of metoprolol succinate was 159 mg daily and the mean reduction in heart rate was 14 beats per minute. Evidence on numerous secondary outcomes from the 108, 109, 110 COMET trial have been published. Carvedilol was superior to immediate-release metoprolol in reducing rates of cardiovascular death, sudden death, stroke, cardiovascular events, and unstable angina, and similar to immediate-release metoprolol in reducing death due to circulatory failure and other cardiovascular deaths, as well as in reducing days lost due to 108, 109 impaired well being. Greater reductions in rates of first hospitalization due to potential complication of heart failure treatment were more associated with immediate-release metoprolol than with carvedilol. Both interventions had similar effects on rates of overall hospitalization and cause-specific 108, 109 hospitalizations, with 1 exception. Rates of non-cardiovascular death, worsening heart failure, change in New York Heart Association classification, and medication withdrawal were 108 similar for carvedilol and immediate release metoprolol. With regard to combined endpoints, carvedilol was superior in reducing rates of fatal or nonfatal myocardial infarction and the combination of cardiovascular death, heart transplantation, hospitalization for nonfatal acute myocardial infarction, or worsening heart failure and was similar to immediate-release metoprolol in reducing the combined rate of all- 108 cause mortality and cardiovascular hospitalizations. Another combined endpoint of days of life Beta blockers Page 42 of 122 Final Report Update 4 Drug Effectiveness Review Project lost due to death, hospitalization, impaired well-being, or need to increase diuretic use (deemed the ‘patient journey’) found carvedilol to be superior to metoprolol over 4 years when compared 109 to baseline composite scores (P=0. It is important to note however, that this combined endpoint considered all factors to be equal; days lost due to death were considered equivalent to days lost due to hospitalization.

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Bcl-2 is a druggable target that is expressed in both GCB and ABC DLBCL buy fincar 5 mg amex man health news za, albeit through different mechanisms fincar 5 mg without a prescription prostate cancer 30 years old. Although some older Summary studies found an association between bcl-2 expression and poor Although DLBCL remains curable in advanced stages, up to outcome in DLBCL, later studies have shown a more complex one-third of patients will ultimately fail initial therapy and the association. Gascoyne et al Anthracycline-based chemotherapy and rituximab have been his- showed that bcl-2 overexpression was only associated with a poor toric breakthroughs in the management of DLBCL, with notable outcome in the absence of a t(14:18), which indicates that the effects on survival. DLBCL is a heterogeneous disease composed of mechanism of expression and not the protein itself is more relevant molecular subtypes that are as different from one another as they are to prognosis. This is reflected in their different ing the relationship of bcl-2 expression to the molecular subtype of mechanisms of pathogenesis and druggable targets. We have 588 American Society of Hematology entered the “molecular era” of defining DLBCL, when we must 12. R-CHOP14 versus identify and target oncogene and non-oncogene addictions within R-CHOP21: Result of a randomized phase III trial for the distinct molecular subsets of DLBCL. Numerous small molecules treatment of patients with newly diagnosed diffuse large B-cell are at various stages of development and demonstrate promise. ASCO 2011 Annual Meeting Ab- realize the goal of personalized precision therapy for DLBCL, it is stracts. Conflict-of-interest disclosure: The author declares no competing 2011;378:1858-1867. Off-label drug use: ibrutinib and bortizomib for 14. Wilson, MD, PhD, Metabolism Branch, National Lymphoma Group study. Cancer Institute, National Institutes of Health, Building 10, Room 15. A Cancer and Leukemia 4N/115, 9000 Rockville Pike, Bethesda, MD 20892; Phone: 301-435- Group B multi-center study of DA-EPOCH-rituximab in un- 2415; Fax: 301-480-4087; e-mail: wilsonw@mail. The use of molecular histogenesis, FDG-PET, and short-course EPOCH with dose- profiling to predict survival after chemotherapy for diffuse dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large-B-cell lymphoma. Garcia-Suarez J, Banas H, Arribas I, De Miguel D, Pascual T, diffuse large B-cell lymphoma arise by distinct genetic path- Burgaleta C. Inhibition of fas death signals diffuse large B-cell lymphoma: results from a prospective by FLIPs. Molecular diagnosis of dexamethasone plus rituximab (DA-EDOCH14-R) in poor- primary mediastinal B cell lymphoma identifies a clinically prognostic untreated diffuse large B-cell lymphoma. Br J favorable subgroup of diffuse large B cell lymphoma related to Haematol. Primary efficacy of bortezomib plus chemotherapy within molecular mediastinal large B-cell lymphoma: a clinicopathologic study subtypes of diffuse large B-cell lymphoma. Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL, et al. Comparison of a response to lenalidomide in relapsed/refractory diffuse large standard regimen (CHOP) with three intensive chemotherapy B-cell lymphoma in nongerminal center B-cell-like than in regimens for advanced non-Hodgkin’s lymphoma. Exploiting synthetic 3-weekly CHOP chemotherapy with or without etoposide for lethality for the therapy of ABC diffuse large B cell lymphoma. The Bruton’s tyrosine the treatment of young patients with good-prognosis (normal kinase (BTK) inhibitor, Ibrutinib (PCI-32765), has preferential LDH) aggressive lymphomas: results of the NHL-B1 trial of the activity in the ABC subtype of relapsed/refractory de novo DSHNHL. CHOP-like multicenter, open-label, phase 2 study [abstract]. Blood (ASH chemotherapy plus rituximab versus CHOP-like chemotherapy Annual Meeting Abstracts). Random- cell lymphoma: a randomised controlled trial by the MabThera ized phase II study of R-CHOP plus enzastaurin versus International Trial (MInT) Group. Temsirolimus has elderly patients with aggressive CD20 B-cell lymphomas: a activity in non-mantle cell non-Hodgkin’s lymphoma subtypes: randomised controlled trial (RICOVER-60). Phase II trial of lymphomas treated within randomized trials of the German single-agent temsirolimus (CCI-779) for relapsed mantle cell High-Grade Non-Hodgkin’s Lymphoma Study Group lymphoma. Relationship of p110 selective phosphatidylinositol-3-kinase inhibitor for the p53, bcl-2, and tumor proliferation to clinical drug resistance in treatment of B-cell malignancies, inhibits PI3K signaling and non-Hodgkin’s lymphomas. A small-molecule significance of Bcl-2 protein expression and Bcl-2 gene rear- inhibitor of BCL6 kills DLBCL cells in vitro and in vivo.

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Randomized buy fincar 5 mg on line prostate urinary problems, placebo-controlled comparison of early use of frovatriptan in a migraine attack versus dosing after the headache has become moderate or severe cheap 5mg fincar with amex prostate enlargement photo. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. Two double-blind, multicenter, randomized, placebo-controlled, single-dose studies of sumatriptan/naproxen sodium in the acute treatment of migraine: function, productivity, and satisfaction outcomes. Medgenmed [Computer File]: Medscape General Medicine. Multimechanistic (sumatriptan-naproxen) early intervention for the acute treatment of migraine. Triptans Page 53 of 80 Final Report Update 4 Drug Effectiveness Review Project 117. Consistency of response to sumatriptan/naproxen sodium in a placebo controlled, crossover study. Sumatriptan/Naproxen sodium for migraine: efficacy, health related quality of life, and satisfaction outcomes. Welch KMA, Mathew NT, Stone P, Rosamond W, Saiers J, Gutterman D. Tolerability of sumatriptan: Clinical trials and post-marketing experience. Schoenen J, Pascual J, Rasmussen S, Sun W, Sikes C, Hettiarachchi J. Patient preference for eletriptan 80 mg versus subcutaneous sumatriptan 6 mg: results of a crossover study in patients who have recently used subcutaneous sumatriptan. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Efficacy, safety and tolerability of oral eletriptan in the acute treatment of migraine: results of a phase III, multicentre, placebo-controlled study across three attacks. Zolmitriptan is effective and well tolerated in Japanese patients with migraine: a dose-response study. The efficacy of zolmitriptan is unaffected by the relationship to menses. Paper presented at: 10th Congress of the International Headache Society2001; New York. Silberstein SD, Massiou H, Le Jeunne C, Johnson-Pratt L, KA MC, Lines CR. Treatment of menstruation-associated migraine headache with subcutaneous sumatriptan. Naratriptan as short-term prophylaxis of menstrually associated migraine: a randomized, double-blind, placebo-controlled study. A pilot study of oral sumatriptan as intermittent prophylaxis of menstruation-related migraine. Triptans Page 54 of 80 Final Report Update 4 Drug Effectiveness Review Project Appendix A. Glossary This glossary defines terms as they are used in reports produced by the Drug Effectiveness Review Project. Some definitions may vary slightly from other published definitions. Absolute risk: The probability or chance that a person will have a medical event. It is the ratio of the number of people who have a medical event divided by all of the people who could have the event because of their medical condition. Add-on therapy: An additional treatment used in conjunction with the primary or initial treatment.

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Hyper- speculum examination and bimanual vaginal exam- plasia with atypical cytological features is more ination purchase fincar 5mg mens health nutrition. Many women need additional tests like likely to progress into uterine cancer (25–40%) visual inspection with acetic acid (VIA) and ultra- than hyperplasia without atypical cytological sound to rule out cervical (pre)malignancy and features that becomes malignant in only a few endometrial cancer or bleeding from other sources patients fincar 5 mg on-line mens health vegan. Definition Sometimes the polyp is ‘born’ and visible on A woman is postmenopausal if her periods have speculum examination. CAUSES OF POSTMENOPAUSAL VAGINAL • Endometrial cancer: blood loss is often the first BLEEDING sign. It is very uncommon in women below • Atrophy: the cells of the urogenital system have the age of 40 years, but in all postmenopausal estrogen receptors. After the menopause the women with bleeding problems it should be urogenital system becomes atrophic and the considered. Other symptoms uterus is more common in black women. Blood are dyspareunia (pain during intercourse), urine loss, pain and abdominal mass are the most fre- incontinence or urinary frequency (frequent quent symptoms. Sarcoma can present pre- or need to urinate) or vaginal discharge. This can cause vaginal bleed- • Urogenital schistosomiasis: this can cause abnormal ing due to infection. Treatment is simple: re- bleeding in postmenopausal women and can move the IUD. A cervical biopsy can be • Contraception before menopause (IUD)? For EXAMINATION endometrial sampling (do this in postmeno- pausal women with thickened endometrium • Obesity: women with morbid obesity [body >3–4mm on ultrasound) you could use the mass index (BMI) >30; see Chapter 8 on how to smallest cannula of a manual vacuum aspiration calculate BMI] have a high level of estrogen. The big advantage of N Signs of atrophy: pale, dry vagina sometimes a MVA is that you can perform this without with petechia (small red spots caused by sub- anesthesia in most women. D&C is that if postmenopausal blood loss is N Prolapse with pressure sores? Make sure you can send the sample N Vaginal discharge? N If possible perform a test for pre-stadia of • Hysteroscopy is an advanced diagnostic test: cervical cancer like a human papillomavirus with a scope you can inspect the inside of the (HPV) test or a VIA; see Chapter 26. In many low-resource settings this is not N Presence of grainy sandy patches – alterations available yet (see Chapter 1). If you suspect TREATMENT advanced cervical carcinoma do a rectal exami- Endometrial malignancies need a hysterectomy nation as described in Chapter 1. Second-best therapy is oral progestogens like medroxyprogesterone acetate (10mg/day for 3 months). In both cases repeat the sampling of the ADDITIONAL TESTS endometrium after 3 months. When performing an • HPV or VIA tests to screen for pre-stadia of cer- MVA after 3 months you can leave the IUD in situ! If you work in a Polyps protruding through the cervix can be facility in which a PAP smear can be made this grasped with a sponge-holding forceps and you can is a useful test in postmenopausal bleeding: you twist them off. Report of an informal working and for prolapse Chapter 23. Geneva: WHO, 2009 FLOWCHART: POSTMENOPAUSAL Kaur J, Dey P, Saha SC, et al. Cervical cytology in patients with postmenopausal bleeding. Diagn Cytopathol 2009; BLEEDING 38:496–8 All women with postmenopausal bleeding should Timmermans A, Opmeer BC, Khan KS, et al. Endometrial have detailed history taking and full gynecological thickness measurement for detecting endometrial cancer in examination (as in Chapter 1): do speculum, vagi- women with postmenopausal bleeding: a systematic review nal examination and screen for pre-stadia of cervi- and meta-analysis. Obstet Gynecol 2010;116:160–7 cal cancer (Figure 1). Oral pro- gestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and meta- FURTHER READING analysis. Am J Obstet Gynecol 2010;203:547e1–10 Marret H, Fauconnier A, Chabbert-Buffet N, et al.

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