Loading

Forzest

By V. Julio. Milwaukee School of Engineering. 2019.

Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Results (mean changes in lipoprotein levels) Harms/Comments Schaefer et al order cheap forzest line. No safety data (adverse events and withdrawals) reported or discussed buy forzest us. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Funding Source Schaefer et al order forzest 20 mg free shipping. Supported by 2004 investigator-initiated R, OL, MC, ITT research contracts from crossover design Parke-Davis/Pfeixer, and Otsuka America 196 patients studied: 99 Pharmaceuticals, Inc. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Inclusion Criteria/ Patient Clinical Trial Population Exclusion criteria Intervention Wolffenbuttel et al. Men and women 18-70 years with Patients not eligible when they used lipid-lowering drugs after visit 1, 4-week dietary run-in then randomized to: 1998 LDL-c 160-240 mg/dl. Statins Page 75 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Results (mean changes in lipoprotein levels) Harms/Comments Wolffenbuttel et al. ADEs were similar between groups and no serious ADEs or withdrawal from 1998 LDL-c reduction from baseline: groups as a result of ADEs were reported. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Funding Source Wolffenbuttel et al. Supported by Parke- 1998 Davis; one author R, OL, MC. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Inclusion Criteria/ Patient Clinical Trial Population Exclusion criteria Intervention Fluvastatin vs. Mean baseline LDL-c 187 mg/dl Davidson et al, 2003 Men and women >20 years with TG Patients with myocardial infarction, coronary bypass surgery, or Fluva 20 or 40 mg qd or lova 10, 20, or 40 R, DB, MC, PC, level < 4. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Results (mean changes in lipoprotein levels) Harms/Comments Berger et al. Withdrawals due to AEs: R, OL, MC, ITT LDL-c reduction from baseline: 8 fulva vs. HDL-c increase from baseline at 6 weeks (NS): fulva 20 mg: 3. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Funding Source Berger et al. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Inclusion Criteria/ Patient Clinical Trial Population Exclusion criteria Intervention Nash 1996 Men or women previously 363 patients screened, 137 patients randomized. Mean baseline LDL-c Not reported Statins Page 81 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Results (mean changes in lipoprotein levels) Harms/Comments Nash 1996 Efficacy analysis for 137 patients. R, OL, MC, ITT LDL-c reduction from baseline at 8 weeks: fulva: men and women 26% Musculoskeletal abnormalities existed significantly more often as a 137 patients randomized lova: men 29%, women 26% (NS) background medical condition in the lova group. No lova: men 7%, women 4% details on what dose of fulva patients experienced these ADEs. Trigs reduction from baseline at 8 weeks: fulva: men 14%, women 10% lova: men 12%, women 20% Achieved LDL-c goal (<160 mg/dl) at 4 weeks: fulva: 85% lova: 91% (NS) Achieved LDL-c goal (<160 mg/dl) at 8 weeks: fulva: 89% lova: 91% (NS) Statins Page 82 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Funding Source Nash 1996 Funded by Sandoz R, OL, MC, ITT Pharmaceuticals. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Inclusion Criteria/ Patient Clinical Trial Population Exclusion criteria Intervention Fluvastatin vs. Analysis included both on treatment and intention to 6-week dietary/placebo run-in phase then, R, DB, MC, both ITT and LDL>160 mg/dl and trigs <400 treat population. Severe forms of hypercholesterolemia and those randomization to: on treatment analysis mg/dl with impaired renal function were excluded. No details provided on fulva 40 mg qd or numbers and reasons for excluding patients. Statins Page 84 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Results (mean changes in lipoprotein levels) Harms/Comments Jacotot et al. No patient R, DB, MC, both ITT and LDL-c reduction from baseline at 16 weeks: withdrew due to myopathic complaints or liver ADEs. More GI ADEs in fulva on treatment analysis fulva 40 mg bid: 29. No patient experienced clinically significant elevation in ALT, AST or parva 40 mg qd: 26. Trigs reduction from baseline at 16 weeks: Fluvastatin 40 mg bid ≈ pravastatin 40 mg qd. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Funding Source Jacotot et al. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Inclusion Criteria/ Patient Clinical Trial Population Exclusion criteria Intervention Fluvastatin vs. Simvastatin Bevilacqua M, et al Men and women with T2DM, Surgery, myocardial infarction, angioplasty in last 6 months, poorly 4 week dietary run-in; fluvastatin extended- 2005 triglycerides > 2. Analysis for LDL-c reduction did not include 4-week dietary/placebo run-in, then R, DB, MC, ITT less and a total cholesterol >250 17 patients due to missing or inappropriately done labs. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Results (mean changes in lipoprotein levels) Harms/Comments Bevilacqua M, et al LDL-c change from baseline at 8 weeks: No severe AEs reported, Data = NR 2005 fulva -51% vs. Number of patients reporting ADEs similar across all groups. GI ADEs were R, DB, MC, ITT LDL-c reduction from baseline at 6 weeks: more frequent in fulva vs. HDL-c increase from baseline at 6 weeks: Fluvastatin 40 mg qd = simvastatin 10 mg qd for NCEP goal reached. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Funding Source Bevilacqua M, et al NR 2005 RCT, OL, SC, ITT 94 patients randomized (n = fulva 48, simva 46) 8 weeks Ose et al. R, DB, MC, ITT 432 patients randomized 6 weeks Statins Page 89 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Inclusion Criteria/ Patient Clinical Trial Population Exclusion criteria Intervention Schulte et al. Active 4-week dietary run-in phase and R, DB LDL-c >185 mg/dl and trigs <300 liver or gallbladder disease, elevated aminotransferases or other randomized to: mg/dl. Patients with concomitant conditions such as myocardial infarction or 8-week dietary and 2 week-placebo run-in R, DB, MC, not ITT CVA within the past 6 months, planned angioplasty or coronary phase, then randomized to: Mean baseline LDL-c bypass surgery during the previous 6 months, unstable angina, fulva 20 mg qd or 113 patients randomized 185-187 mg/dl cardiac or renal failure, hepatic disease, uncontrolled hypertension, simva 20 mg qd 16 weeks partial ileal bypass, secondary hypercholesterolemia, or for 16 weeks. Statins Page 90 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Results (mean changes in lipoprotein levels) Harms/Comments Schulte et al. One patient in each group had R, DB LDL-c reduction from baseline at 4 and 10 weeks: elevations in AST or ALT >3x ULN. No clinically significant increase in CK was fulva 40 mg: 23. HDL-c increase from baseline at 4 and 10 weeks: Fluvastatin 80 mg qd = simvastatin 40 mg qd.

Placebo-controlled trials of patients with atherosclerosis Author Study Mean Percent LDL- Year Patient Duration Baseline LDL- c Reduction Study Name Study Characteristics Characteristics Intervention (mean) c from baseline Simoons 1994 Randomized order forzest cheap online, double- 404 men and women 30- Simvastatin 20 mg 4 years 169 mg/dl 31% Multicentre Anti- blind cheap forzest 20mg line, placebo- 67 years with 2 or > qpm or placebo (4 proven 20 mg forzest. BID=twice a day, CHD=coronary heart disease, IMT=intimal-medial thickness, MLD=minimum lumen diameter, MI=myocardial infarction, qpm=every evening Statins Page 245 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 3. Placebo-controlled trials of patients with atherosclerosis Author Primary Endpoint Year Results (clinical Clinical Outcomes Study Name Primary Endpoint health outcome only) Measured Clinical Outcome Results Simoons 1994 Per-patient average of mean N/A Clinical events were After 4 years, there was no difference in clinical Multicentre Anti- lumen diameters of all coronary reported spontaneously. There were a greater Atheroma Study segments(diffuse number of MI in the simvastatin vs placebo atherosclerosis) and the per- groups. There were more revascularizations in patient average of MLD of all the placebo vs. Neither of segments that were these were statistically different. Overall, there atheromatous at baseline, follow were 40 cardiac events in the simvastatin vs. Placebo-controlled trials of patients with atherosclerosis Author Year Study Name Comments/Conclusions Simoons 1994 There were no statistical differences in clinical events Multicentre Anti- in the simvastatin vs. Fair to poor in Atheroma Study quality to assess differences in clinical event due to duration of trial, however was a relatively small sample size. Simvastatin/Enala No differences were noted in any other clinical pril Coronary events. Fair in quality to assess differences in clinical Atherosclerosis events since clinical events were prespecified. However, there Coronary was a trend in favor of lovastatin. Mean lovastatin Atherosclerosis dose=36 mg/d and 69% met NCEP goal). Fair-poor in Intervention Trial quality to assess differences in clinical events. 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 Bertrand ME. Elisor after analysis for clinical Transluminal events. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 248 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 Bertrand ME. Transluminal Coronary Angioplasty (PREDICT) Flaker GC. There was a trend towards benefit with pravastatin in reducing repeat revascularization (RRR=18%, 95% CI 1-33%, p=0. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 249 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 4. Post-revascularization and miscellaneous trials Author Year Study Name Comments/Conclusions Bertrand ME. Prevention of placebo (80 events) groups (death, MI, CABG, re- Restenosis by PTCA of target lesion). Fair in quality to assess Elisor after differences in clinical events between groups Transluminal (Relatively short follow up period). There was a trend to reduced revascularizations in the pravastatin vs. Good in quality to assess differences in clinical events between groups. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 250 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 Kleeman A. Lovastatin was mmol/L) The Cholesterol treatment, blinded second vessel stenosis of titrated up to 80 mg qpm for Lowering angiographic >20% and LDL-c >135 LDL-c >120 mg/dl. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 251 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 Kleeman A. The only The Cholesterol mean segment diameter PTCA, PTCA of another significant difference was a reduction in the Lowering (diffuse coronary lesion, or death. Trial (CLAPT) nondilated and dilated segments and MLD (focal coronary atherosclerosis) of dilated lesions at 2 years as assessed by angiography. Serious cardiovascular adverse events occurred in 19 atorvastatin vs. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 252 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 4. Post-revascularization and miscellaneous trials Author Year Study Name Comments/Conclusions Kleeman A. Fair in quality to Lowering assess differences in clinical events between groups. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 253 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 Pitt B. Pravastatin Randomized, 1062 men or women 20- Pravastatin 20 mg qpm or 26 weeks 181 mg/dl (4. After 13 weeks, mmol/L) Group placebo-controlled, factors and a TC of 200- pravastatin could be 1993* intent to treat 300 mg/dl (5. CABG=coronary artery bypass graft; CVA=cerebrovascular accident; MI=myocardial infarction; MLD=minimal lumen diameter; PTCA=percutaneous transluminal coronary angioplasty Statins Page 254 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 Pitt B. Time to first ischemic Time to first ischemic event was longer in The Atorvastatin events: death from cardiac 37 (21%) of the angioplasty event. Events making up the majority of the trend in favor of atorvastatin: CABG and hospitalization for angina. 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.

purchase forzest discount

Different doses of omeprazole in the maintenance treatment of patients with peptic ulcers resistant to H2-blockers purchase forzest uk. Current Therapeutic Research buy discount forzest 20 mg line, Clinical & Experimental forzest 20 mg generic. Kovacs TO, Campbell D, Haber M, Rose P, Jennings DE, Richter J. Double blind comparison of lansoprazole 15 mg, lansoprazole 30 mg, and placebo in the maintenance of healed gastric ulcer. Agrawal NM, Campbell DR, Safdi MA, Lukasik Nl, Huang B, Haber MM. Superiority of lansoprazole vs ranitidine in healing nonsteroidal anti inflammatory drug associated gastric ulcers results of a double blind, randomized, multicenter study. Proton pump inhibitors Page 83 of 121 Final Report Update 5 Drug Effectiveness Review Project 154. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID induced Ulcer Management (OMNIUM) Study Group. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial Ranitidine versus Omeprazole for NSAID associated Ulcer Treatment (ASTRONAUT) Study Group. Gastroduodenal ulcers associated with the use of non-steroidal anti-inflammatory drugs: a systematic review of preventive pharmacological interventions. Quality of life in chronic NSAID users: a comparison of the effect of omeprazole and misoprostol. Prevention of NSAID-associated gastrointestinal lesions: a comparison study pantoprazole versus omeprazole. Rostom A, Wells G, Tugwell P, Welch V, Dube C, McGowan J. Cochrane Database of Systematic Reviews [computer file]. Ulcer prevention in long-term users of nonsteroidal anti-inflammatory drugs: results of a double-blind, randomized, multicenter, active- and placebo-controlled study of misoprostol vs lansoprazole. Bianchi Porro G, Lazzaroni M, Imbesi V, Montrone F, Santagada T. Efficacy of pantoprazole in the prevention of peptic ulcers, induced by non-steroidal anti- inflammatory drugs: A prospective, placebo-controlled, double-blind, parallel-group study. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. Primary prevention of diclofenac associated ulcers and dyspepsia by omeprazole or triple therapy in Helicobacter pylori positive patients: a randomised, double blind, placebo controlled, clinical trial. Efficacy and tolerability of pantoprazole compared with misoprostol for the prevention of NSAID-related gastrointestinal lesions and symptoms in rheumatic patients. Prevention of ulcers by esomeprazole in at- risk patients using non-selective NSAIDs and COX-2 inhibitors. Ulcer recurrence in high-risk patients receiving nonsteroidalanti-inflammatory drugs plus low-dose aspirin: results of a post HOC subanalysis. Proton pump inhibitors Page 84 of 121 Final Report Update 5 Drug Effectiveness Review Project 167. Efficacy of lansoprazole in eradicating Helicobacter pylori: a meta-analysis. Graham DY, Hammoud F, El-Zimaity HM, Kim JG, Osato MS, El-Serag HB. Meta- analysis: proton pump inhibitor or H2-receptor antagonist for Helicobacter pylori eradication. Laheij RJ, Rossum LG, Jansen JB, Straatman H, Verbeek AL. Evaluation of treatment regimens to cure Helicobacter pylori infection--a meta-analysis. Review article: treatment of Helicobacter pylori infection with ranitidine bismuth citrate- or proton pump inhibitor- based triple therapies. Meta-analysis: comparative efficacy of different proton-pump inhibitors in triple therapy for Helicobacter pylori eradication. Optimal PPI-based triple therapy for the cure of Helicobacter pylori infection: a single center comparison of four 14-day schedules. Comparative treatment of Helicobacter pylori-positive duodenal ulcer using pantoprazole at low and high doses versus omeprazole in triple therapy. Double-dose, new-generation proton pump inhibitors do not improve Helicobacter pylori eradication rate. A comparison of lansoprazole and omeprazole based triple combinations for the treatment of Helicobacter pylori associated gastritis and peptic ulcer. Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin. Polymorphism of interleukin-1beta affects the eradication rates of Helicobacter pylori by triple therapy. Incidence of duodenal ulcer healing after 1 week of proton pump inhibitor triple therapy for eradication of Helicobacter pylori. Randomized open trial for comparison of proton pump inhibitors in triple therapy for Helicobacter pylori infection in relation to CYP2C19 genotype. Effect of different proton pump inhibitors, differences in CYP2C19 genotype and antibiotic resistance on the eradication rate of Helicobacter pylori infection by a 1-week regimen of proton pump inhibitor, amoxicillin and clarithromycin. Proton pump inhibitors Page 85 of 121 Final Report Update 5 Drug Effectiveness Review Project 181. Efficacy of low-dose proton pump inhibitor (PPI) in the eradication of Helicobacter pylori following combination PPI/AC therapy in Japan. Eradication of Helicobacter pylori infection with proton pump based triple therapy in patients in whom bismuth based triple therapy failed. Esomeprazole-based one-week triple therapy with clarithromycin and metronidazole is effective in eradicating Helicobacter pylori in the absence of antimicrobial resistance. Efficacy of 1 week omeprazole or lansoprazole amoxycillin clarithromycin therapy for Helicobacter pylori infection in the Japanese population. Impact of rabeprazole, a new proton pump inhibitor, in triple therapy for Helicobacter pylori infection comparison with omeprazole and lansoprazole. Efficacy of reduced dosage of rabeprazole in PPI/AC therapy for Helicobacter pylori infection comparison of 20 and 40 mg rabeprazole with 60 mg lansoprazole.

buy cheap forzest 20 mg line

Asherman syn- endometrium has been stimulated by estrogens buy discount forzest 20 mg online. Obstet Gynecol 1995; This unopposed endometrial stimulation might be 85:8–9 a risk factor for endometrial cancer and in women 10 order forzest online from canada. J Obstet with no wish to conceive forzest 20 mg for sale, the oral contraceptive Gynecol 2007;27:55–9 pill should be advised. Sheehan’s syn- also has a positive effect on hirsutism when used for drome in a developing country, Nigeria: a rare disease 9 months or longer. Am J Med Sci 2010;340:402–6 used for women who wish to conceive: start with 13. Epidemiologic 50mg daily for 5 days to be increased to maximally aspects of postpartum pituitary hypofunction (Sheehan’s 150mg daily for 5 days (see Chapter 16 on syndrome). Delayed puberty: experience of a tertiary care centre in REFERENCES India. The Practice Committee of the American Society of Best Pract Res Clin Endocrinol Metab 2002;16:73–90 Reproductive Medicine. Fertil Steril 2008;90:S19–25 Consensus Workshop Group. Deligeoroglou E, Athanasopoulos N, Tsimaris P, et al. Fertil Steril 2004;81: Ann NY Acad Sci 2010;1205:23–32 19–25 3. International variability of ages at menarche and menopause: patterns Further reading (free e-books) and main determinants. HTM estimates of puberty timing in Senegalese adolescent girls. The prevalence of AUB is estimated at 12% in the general population Chronic abnormal uterine bleeding and increases with age, reaching 24% in those aged 36–40 years. When it is a single episode of irregular Chronic AUB is defined by the International Fed- blood loss in non-pregnant women, it is most of eration of Gynecology and Obstetrics (FIGO) as the time harmless, but it can also be a first sign of bleeding from the uterine corpus that is abnormal serious pathology such as cancer of the cervix. For in volume, regularity, and/or timing, and has been this reason it is important to do a full gynecological present for the majority of the past 6 months in history, a speculum examination and a vaginal non-pregnant women. For practical purposes it is important to rule out Acute abnormal uterine bleeding (unrecognized) pregnancy problems or infection in Acute AUB is defined as an episode of heavy bleed- AUB of short duration. A longer duration of AUB ing in non-pregnant women that, in the opinion of points to more structural abnormalities like fibroids, the clinician, is of sufficient quantity to require im- polyps or malignancies. This chapter will describe the problems and Acute AUB may present in the context of existing how to establish the diagnosis. A flow chart for chronic AUB or might occur without such a history. In Chapter 20 appropriate treatment of abnormal CAUSES OF UTERINE BLEEDING uterine bleeding will be explained. For bleeding after the menopause, please see Chapter 10. FIGO have developed a classification system for AUB (Table 1)2. Definition • Polyps and pendiculated fibroids: (generally) benign growths of uterine muscle (fibroids) or endo- Terms like menorrhagia, metrorrhagia, meno- metrium (polyps). Adenomyosis describes the pres- speak of ‘abnormal uterine bleeding’: ence of endometrial tissue in the myometrium. The main menstrual blood partly related to the absolute presence of endo- flow during a period is 35ml with 65% of metrial tissue in the myometrium and partly due women losing <60ml each period. PALM refers to structural abnormalities causing about 25–40%) and should be treated surgic- the abnormal bleeding, COEIN are non-structural causes ally. When no atypia is present conservative treatment with Mirena intrauterine device P Polyps C Coagulopathy (IUD) or cyclic progestogens (medroxy- A Adenomyosis O Ovulatory dysfunctions progesterone acetate (10mg/day for 12–14 L Leiomyoma E Endometrial days in the luteal phase of the cycle for 3 months), and repeated sampling is justified. M Malignancy or I Iatrogenic N Cervical ectopia or ectropion can cause spot- hyperplasia N Not yet classified ting and postcoital bleeding (often in young women or pill users). N Infections: Sexually transmitted infections (STIs) like chlamydia, urogenital schistoso- miasis or genital tuberculosis. Chapter 28) of the ovaries produce estrogen and N Tricyclic antidepressants like amitriptyline cause endometrial hyperplasia and AUB and may cause AUB. The term ovarian dysfunction HISTORY TAKING (OD) is used when hormonal imbalance is present. Common groups affected by OD are: • Duration of complaints (primary/secondary, N Young girls and perimenopausal women: how many months/years). Primary AUB starts both groups have anovulatory cycles (cycles from the first period, secondary AUB starts later without an ovulation). Cervical cancer is often accompa- menstrual cycle see Chapter 16 on subfertility. In obesity peripheral fat tissue produces estro- • Swelling in the abdomen is a symptom of gen and morbidly obese women have a high fibroids and ovarian masses but also of unrecog- level of estrogen that disturbs the menstrual nized pregnancy. Weight loss and emaceration can lead to • Easy bleeding tendency. Some women have in- anovulatory cycles and cause irregular periods herited bleeding disorders. They often have a • Endometrial causes of AUB are: history of prolonged bleeding during surgery, N A primary disorder of mechanisms regulating trauma or childbirth. It is difficult in low- local endometrial ‘hemostasis’ itself: endo- resource settings to establish the exact diagnosis metrial hemostasis is a very complex process but you can treat heavy periods in these women and local hormonal imbalance in the prosta- the same as in women without bleeding dis- glandin mechanism can cause AUB. Make women with N Endometrial hyperplasia is a precursor to inherited bleeding disorders aware that it is endometrial cancer and is classified as simplex important to deliver in a hospital with blood or complex and with or without atypia. Signs of hypothyroidism are irregular periods with weight gain, lethargy, obstipation, hair loss (especially at the eyebrows) and a dry skin. Signs of hyperthyroidism are sweating, menorrhagia, palpitations, weight loss, irritability and tremor. Signs of hyperprolactin- emia are bilateral galactorrhea (milk from the nipples), amenorrhea, anovulation and (when caused by macroadenoma) headache and disturb- ance of visual fields (see Chapter 16). Also many women with prolonged combined oral contra- ceptive use can face a period of spotting and postcoital bleeding. Are blood clots present during the hysterectomy period or flooding? If possible perform a test for pre-stadia of cervi- cal cancer like a human papillomavirus (HPV) test EXAMINATION or a visual inspection with acetic acid (VIA), see Chapter 26. Most of the time you can make the diagnosis and • Obesity or emaciation. Remember it is important to or vagina) and to look for signs and symptoms rule out curable life-threatening diseases like ecto- of: pic pregnancy, cervical cancer and STIs as soon as N Cervical carcinoma (see Chapter 26 on cervi- possible. If you do not have facilities for extra cal cancer)? An abnormal cervix can also be investigations and tests and your history taking and seen in genital schistosomiasis. If she is well and irregular blood N Cervical ectopia/ectropion?

The systematic review found no significant difference in symptom score (WMD = -0 purchase forzest 20 mg overnight delivery. Higher than licensed doses of LTRA did show a significant difference in improvement from baseline in asthma symptom scores (SMD= -0 order forzest uk. Those treated with both licensed and higher than licensed doses of LTRAs had a significant decrease in beta-agonists use compared to those treated with same dose ICSs (SMD -0 buy forzest 20 mg low price. There was no significant difference in quality of life (WMD 0. For ICS plus LTRA compared with increased doses of ICS, only 3 of the trials included in the systematic review compared licensed doses of LTRAs with increasing the dose of ICSs. The meta-analyses found no significant difference in any outcomes including the following: change from baseline in symptoms score with licensed (WMD 0. For ICS plus LTRA compared with the same ICS dose with tapering (seven studies), the systematic review found no significant difference in final symptom scores (WMD -0. There was a significant reduction in rate of withdrawals due to poor asthma control for those treated with ICS plus LTRA (RR 0. Budesonide (BUD)+ Montelukast (ML) compared with Budesonide (BUD) same dose 230 We found one fair RCT comparing the combination of BUD+ML with the same dose of BUD (Table 21). This fair-rated RCT (N = 639), the CASIOPEA study, compared low to high dose BUD (400 to 1600 mcg/day) plus placebo (N = 313) with low to high dose BUD (400 to 1600 Controller medications for asthma 128 of 369 Final Update 1 Report Drug Effectiveness Review Project 230 mcg/day) + ML 10 mg/day (N = 326) for 16 weeks. Subjects age 18 to 70 with poorly controlled mild to severe asthma currently being treated with a stable dose of ICS for at least 8 weeks were enrolled from hospital centers in Spain. At endpoint, there were no statistically significant differences in asthma symptom scores or quality of life. However, those treated with BUD+ML had fewer nocturnal awakenings, more asthma free days, fewer days with exacerbations, and greater decrease in rescue medicine use. The differences were reportedly independent of BUD dose. Beclomethasone (BDP) + Montelukast (ML) compared to Beclomethasone (BDP) same dose 118 We found one trial (N = 642) which compared four treatments for 16 weeks: low dose BDP (400 mcg/day) + ML (10 mg/day) (N = 193) compared with low dose BDP 400 mcg/day (N = 200) compared with ML 10mg/day (N = 201) compared with placebo (N = 48). Subjects with uncontrolled mild to moderate asthma treated with ICS who were age 15 or greater were enrolled from 18 countries and 70 different centers. At endpoint, those treated with BDP+ML had greater improvement in daytime asthma symptom scores (-0. BDP+ML showed no significant difference in % of patients with an asthma attack or difference in total puffs/day compared to BDP. Compliance was high with both inhaled and oral groups respectively. Budesonide (BUD)+ Montelukast (ML) compared with Budesonide (BUD) increased dose 228, 229, 231 We found two fair RCTs comparing the combination of BUD+ML with an increased dose of BUD (Table 21). One fair multinational trial (N = 889) compared medium dose BUD (800 mcg/day) plus ML (10 mg/day) (N = 448) compared with high dose BUD (1600 mcg/day) 228, 229 (N = 441) for 16 weeks. The trial enrolled subjects age 15 to 75 with uncontrolled asthma treated with medium dose ICS. At endpoint, there were no statistically significant differences between those treated with BUD+ML and those treated with BUD for percentage of asthma free days, daytime symptom score, percentage of nights with awakenings, percentage of days with an exacerbation, percentage of patients requiring oral steroids or hospitalization, rescue medicine use, or quality of life. Adherence was high for both the tablets and inhalers, with over 95% of days fully compliant. Subjects with moderate persistent asthma age 6 to 14 were enrolled from a Pediatric Asthma Clinic in India. At endpoint, those treated with increased dose of BUD had fewer exacerbations compared to BUD+ML (9. Adherence was high in both groups with only one patient declaring non-adherence. Fluticasone (FP)+Montelukast (ML) compared with Fluticasone (FP) increased dose 197 We found one fair RCT (N = 182) comparing the combination of FP+ML with an increased dose of FP in children and adolescents (6 to 17 years of age). Subjects with uncontrolled asthma while receiving FP (100 twice daily) were randomized to FP (250 twice daily), FP (100 twice daily) plus salmeterol, or FP (100 twice daily) plus montelukast. The primary outcome was a composite of exacerbations, number of asthma control days, and FEV1. One hospitalization for asthma-related symptoms occurred in each of Controller medications for asthma 129 of 369 Final Update 1 Report Drug Effectiveness Review Project the three treatment groups. A total of 120 prednisone bursts were prescribed for exacerbations (47 during treatment with FP compared with 43 during treatment with FP+ML, P = NR). Controller medications for asthma 130 of 369 Final Update 1 Report Drug Effectiveness Review Project Table 21. Characteristics of head-to-head studies comparing ICS + LTRA with ICS Study design Country N Study population Comparison Quality Study Duration Setting (total daily dose) rating ICS + LTRA compared with ICS same dose Ducharm et al. Systematic Review with meta-analysis 2 trials in children; 25 in adults LTRA plus ICS vs. ICS same dose, ICS same dose Good 226 2004 tapering, or ICS increased dose. RCT Spain BUD (400 – 1600) + placebo Fair 230 2003 vs. RCT Multinational BDP (400) + ML (10) Fair 118 1999 vs. Systematic Review with meta-analysis 2 trials in children; 25 in adults LTRA plus ICS vs. ICS same dose, ICS same dose Good 226 2004 tapering, or ICS increased dose. RCT Multinational ML (10) + BUD (800) Fair 228, 229 2003 vs. Characteristics of head-to-head studies comparing ICS + LTRA with ICS Study design Country N Study population Comparison Quality Study Duration Setting (total daily dose) rating Age 15 – 75 BUD (1600) COMPACT 16 weeks Multicenter Medium to High dose ICS Fluticasone (FP)+Montelukast (ML) compared with Fluticasone (FP) increased dose Lemanske et al. 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. Controller medications for asthma 132 of 369 Final Update 1 Report Drug Effectiveness Review Project 5. Combination products compared with Leukotriene Modifiers Summary of findings 127, 128, 232-234 We found 5 RCTs meeting our inclusion/exclusion criteria for this comparison (Table 22). All 5 compared low dose fluticasone plus salmeterol with montelukast. Two of the 127 RCTs were in adolescents and adults, one enrolled subjects over the age of six (~15% of 128, 234 subjects < 12 years of age), and 2 enrolled children ages 6-14. Overall, our meta-analysis and results from 5 RCTs found the combination of fluticasone plus salmeterol to be more efficacious than montelukast for the treatment of persistent asthma (Appendix I and Appendix H, Table H-14). Detailed Assessment Description of Studies 127, 128, 232-234 We found 5 RCTs meeting our inclusion/exclusion criteria (Table 22). Of the included studies, all compared montelukast with low dose fluticasone plus salmeterol.

Forzest
8 of 10 - Review by V. Julio
Votes: 274 votes
Total customer reviews: 274
Jaga