Z. Mannig. State University of New York Institute of Technology at Canton.
Do cyclooxygenase-2 inhibitors provide benefits similar to those of traditional nonsteroidal anti-inflammatory drugs cheap suhagra 100 mg mastercard, with less gastrointestinal toxicity? Memorandum: Analysis and recommendations for Agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk buy suhagra 100mg on line. Current methods of the US Preventive Services Task Force: a review of the process. York, UK: NHS Centre for Reviews and Dissemination; 2001. Grading the strength of a body of evidence when comparing medical interventions. Methods Guide for Comparative Effectiveness Reviews. Grading the strength of a body of evidence when comparing medical interventions-Agency for Healthcare Research and Quality and the Effective Health Care Program. Methods for Meta-Analysis in Medical Research: John Wiley & Sons, Inc. Nonsteroidal antiinflammatory drugs (NSAIDs) 41 of 72 Final Report Update 4 Drug Effectiveness Review Project 17. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. Explaining heterogeneity in meta-analysis: a comparison of methods. Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial. Analgesic effectiveness of celecoxib and diclofenac in patients with osteoarthritis of the hip requiring joint replacement surgery: a 12-week, multicenter, randomized, double-blind, parallel-group, double-dummy, noninferiority study. Reduced incidence of gastroduodenal ulcers with celecoxib, a novel cyclooxygenase-2 inhibitor, compared to naproxen in patients with arthritis. Comparative efficacy and safety of celecoxib and naproxen in the treatment of osteoarthritis of the hip. McKenna F, Borenstein D, Wendt H, Wallemark C, Lefkowith JB, Geis GS. Celecoxib versus diclofenac in the management of osteoarthritis of the knee. 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Comparison of two different dosages of celecoxib with diclofenac for the treatment of active ankylosing spondylitis: results of a 12-week randomised, double-blind, controlled study. Emery P, Kong S X, Ehrich E W, Watson D J, Towheed T E. Dose-effect relationships of nonsteroidal anti-inflammatory drugs: a literature review (Structured abstract). Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. JAMA : the journal of the American Medical Association. Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the Safety and Efficacy Large-scale Evaluation of COX-inhibiting Therapies (SELECT) trial in osteoarthritis. Efficacy, safety and dose response of meloxicam up to 22. A double-blind, randomized trial to compare meloxicam 15 mg with diclofenac 100 mg in the treatment of osteoarthritis of the knee. 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A comparative clinical trial evaluating efficacy and safety of fixed dose combination of nimesulide (100 mg) and racemethionine (50 mg) (namsafe) versus reference drug (nimesulide) and other NSAIDs in the treatment of osteoarthritis. A short-term comparative trial of salsalate and indomethacin in rheumatoid arthritis. Nonsteroidal antiinflammatory drugs (NSAIDs) 44 of 72 Final Report Update 4 Drug Effectiveness Review Project 60. Salsalate, a nonacetylated salicylate, is as efficacious as diclofenac in patients with rheumatoid arthritis. Riedemann PJ, Bersinic S, Cuddy LJ, Torrance GW, Tugwell PX.
New estimates and trends regarding unsafe abortion mortality buy suhagra 100mg with mastercard. Unsafe abortion: global and regional estimates of the incidence of unsafe abortion and associated mortality in 2000 discount 100mg suhagra with mastercard, 4th edn. Incidence and outcome of bleeding before the 20th week of pregnancy: prospective study from general practice. A longitudi- nal study of pregnancy outcome following idiopathic recurrent miscarriage. Gemzell-Danielsson K, Ho PC, Gómez Ponce de León R, et al. Misoprostol to treat missed abortion in the first trimester. Medical treat- ments for incomplete miscarriage less than 24 weeks. Role of clinical and ultrasound findings in the diagnosis of re- tained products of conception. Medical abortion: issues of choice and accept- ability. World Health Organ Tech Rep Ser 1997;871:i-vii, 1–110 14. Complications from legally- Figure 2 Manual vacuum aspiration procedure. Obstet Gynecol Surv 1979;34: other steps are: Step 1, Diagnosis, counseling; Step 3, Pain 177–91 management plan; Step 5, Hold the anterior cervix with a 15. Cochrane Database Syst Rev2005;1:CD003037 132 Abortion 16. Unsafe abortion: the methods for first trimester abortion. Lancet Sexual and Reproductive Syst Rev 2004;1:CD002855 Health Series. Expectant care ment of incomplete abortion and miscarriage with versus surgical treatment for miscarriage. Misoprostol in obstetrics and gyne- pharmacokinetic profiles, effects on the uterus and side- cology. Misoprostol for the termination of pregnancy with a live APPENDIX fetus at 13 to 26 weeks. Essential Elements of Postabortion Care: An Expanded • USAID: http://www. Contraception 2012;85:413–18 • WHO 1992: Clinical guidelines for emergency 23. Geneva: control in first trimester surgical abortion. Cochrane WHO, 1992 Database Syst Rev 2009;2:CD006712 24. Music for surgical Manual vacuum aspirator and procedure abortion care study: a randomized controlled pilot study. Contraception 2012;85:496–502 • Sustainable supplies: http://www. In brief: fact sheet; facts on in- Topics/Abortion_Technologies. Geneva: WHO, 1994 • IPAS International instruction booklet: http:// 27. And indeed, approxi- mately 50% of all conceptions are lost and the The loss of a wanted pregnancy at any stage is a majority occur before even being noticed. Careful history taking risk increases with the number of pregnancies a from both partners regarding the general medical woman has. The chance of having a single miscar- health and past obstetric history remains a key to riage in one pregnancy is around one in six (16. Numerous causes and increases to 31% with two pregnancies, 42. However, the chance of having gations and management options. However, some consecutive sporadic miscarriages is much less com- of the suggested causes have not been consistently mon with 1 in 36 and 1 in 216 women, respec- shown as the culprit and many of the investigations tively, having two or three sporadic miscarriages and treatment options have not been properly consecutively. The aim The majority of sporadic pregnancy loss is due of this chapter is to provide an overview on the 2,3 to a random fetal chromosomal abnormality , causes, investigations and management of couples 4 which increases with increasing maternal age. The with recurrent miscarriage and highlight the up- vast majority of miscarriages occur early, before 12 dated evidence, which is particularly important in completed weeks of gestation (first trimester). The streamlining management in areas where resources incidence of late miscarriage (second-trimester are limited. MISCARRIAGE RECURRENT MISCARRIAGE Miscarriage is the spontaneous loss of a pregnancy before the fetus has reached viability, most com- The most widely accepted definition of recurrent monly defined as before 24 weeks or with a birth miscarriage is three or more consecutive pregnancy weight of less than 500g (Table 1). This is about clinically recognized pregnancies, ~15% (almost 1 twice the incidence (1% vs 1 in 216) that would be Table 1 Definition and prevalence of miscarriages Definition Prevalence Early miscarriage/first-trimester miscarriage Before 12 weeks ~15% (single sporadic event) Late miscarriage Between 13 weeks and 23 completed weeks ~2% (single sporadic event) Recurrent miscarriage Three or more consecutive pregnancy losses ~1% 134 Recurrent Miscarriage including Cervical Incompetence expected by chance alone. A woman’s risk of mis- Maternal cigarette smoking has an adverse effect carriage has been shown to correlate with the out- on trophoblast invasion and proliferation and has come of her previous pregnancies7–10. Women with been suggested to have dose-dependent increased a history of recurrent miscarriage are more likely to risk of miscarriage, although current evidence is in- have reproductive characteristics (demographics, sufficient to confirm the association18,19. Heavy physical attributes) associated with a poor prognosis alcohol assumption is toxic to the embryo and the for future pregnancy outcome than women suffer- fetus and even moderate consumption of ≥5 units ing sporadic miscarriage11–13. In contrast to women per week may increase the risk of sporadic mis- with sporadic miscarriage, those with recurrent carriage20. Caffeine consumption has also been miscarriage are more likely to lose pregnancies with implicated with an increased risk of spontaneous a normal chromosome complement2,14. These all miscarriage in a dose-dependent manner with risk indicate the likelihood of additional pathology in becoming significant with more than three cups a women with recurrent miscarriage other than ran- day (~300mg caffeine)19,21. Obesity is becoming an dom chromosomal abnormality of embryos. Accumulating evidence has shown obesity is a risk factor for infertility, sporadic and recurrent RISK FACTORS FOR RECURRENT miscarriage, as well as obstetrics complications and MISCARRIAGE 22–25 perinatal morbidities. Epidemiological factors Maternal age Antiphospholipid syndrome Risk of miscarriage increases with advancing Antiphospholipid syndrome (APS) is the most im- maternal age, secondary to the increase in chromo- portant treatable cause of recurrent miscarriage. It somally abnormal conceptions15 and decline in refers to the association between antiphospholipid ovarian function. The risk increases steeply after 35 antibodies, most commonly lupus anticoagulant years of age from 11% at 20–24 years to 25% at and anticardiolipin antibodies26,27. Advanced nancy outcomes in APS include: paternal age has also been identified as a risk factor • Three or more consecutive miscarriages before with the highest risk in couples with maternal age 16 10 weeks of gestation. Previous reproductive history • One or more preterm births before the 34 weeks of gestation due to placental disease. Reproductive history is an independent predictor of future pregnancy outcome and history of pre- ‘Primary APS’ affects patients with no identifiable vious miscarriage is the single most important underlying systemic connective tissue disease, factor7. Risk of a further miscarriage increases after whereas APS in patients with chronic inflamma- each successive pregnancy loss, reaching 45% after tory diseases, such as systemic lupus erythematosus, three and 54% after four consecutive pregnancy is referred to as ‘secondary APS’. However, a previous live birth does not Worldwide, antiphospholipid antibodies are preclude women from experiencing recurrent mis- present in ~15% of women with recurrent mis- carriage in the future17. Adverse pregnancy out- comes may be due to the inhibition of tropho- Environmental factors 28–32 blastic function and differentiation , activation Most data on environmental risk factors are based of complement pathways at maternal fetal interface on studies with women having sporadic rather than resulting in a local inflammatory response33, and, in recurrent miscarriage. The results are conflicting later pregnancy, thrombosis of the uteroplacental and understandably biased with difficulties in con- vasculature34–36. Live birth rate in pregnancies with trolling for confounding factors and inaccuracy in no pharmacological intervention has been reported quantifying the dose of exposure. The a balanced reciprocal or Robertsonian transloca- malformation ranges from the mildest form with tion13,38,39 (Figure 1). Carriers of balanced transloca- slight indentation at the fundus (arcuate uterus) to tion are usually phenotypically normal and unaware the most extreme form with complete duplication of the condition. However, up to 70% of their (uterus didelphys) (Figure 2). This leads to alies in both the general population and women with a much higher risk of miscarriage, or rarely result- recurrent miscarriages is not clear.
The remaining trial compared non-equivalent doses (relative potency of fluticasone was greater at the doses given) and found FP to be superior to BUD for symptoms purchase suhagra 100mg online, rescue medicine use generic 100mg suhagra visa, and missed days of work, but found no difference in exacerbations. Budesonide compared with mometasone 48 49 One fair-rated 12-week RCT and one fair-rated 8-week trial compared BUD and mometasone. Overall, the trials reported no significant differences for equipotent doses for most outcomes of interest, but there were some dose-related differences favoring mometasone over BUD when comparing non-equipotent doses. The 12-week trial randomized 730 persons 12 years and older with moderate persistent asthma to medium dose (800 mcg/day) BUD or low-, 48 medium-, or high-dose (200, 400, 800 mcg/day, respectively) mometasone. They found no statistically significant differences between medium-dose BUD and medium-dose mometasone for symptoms or nocturnal awakenings, but patients treated with medium-dose mometasone had a greater decrease in rescue medicine use than those treated with medium-dose BUD (-90. The 8-week trial compared once daily low-dose (400 mcg/day) BUD with once daily medium-dose (440 mcg/day) mometasone in 262 persons 49 12 years and older with moderate persistent asthma. The trial reported statistically significant differences in evening asthma symptoms (P < 0. Budesonide compared with triamcinolone 50 One fair-rated 52-week RCT met our inclusion/exclusion criteria for this comparison. The trial randomized 945 adults ≥18 with mild, moderate, or severe persistent asthma to BUD DPI (mean dose at start and end: 941. On average, patients were treated with medium doses, but starting doses and dose adjustments were left to the discretion of the clinical investigator. Patients treated with BUD had Controller medications for asthma 33 of 369 Final Update 1 Report Drug Effectiveness Review Project greater improvements in symptom- and episode-free days (P < 0. Ciclesonide compared with flunisolide We did not identify any good or fair quality systematic reviews or head-to-head trials that compared ciclesonide to flunisolide. Ciclesonide compared with fluticasone 63-70 Eight fair-quality RCTs meeting our inclusion criteria compared ciclesonide with fluticasone. Three were conducted in subjects with mild to severe persistent asthma; two in 64, 65 70 subjects with moderate persistent asthma; and one each in mild to moderate and moderate 63 to severe persistent asthma. One trial did not report sufficient information to determine the 66 66 severity of persistent asthma. All but one trial compared equipotent doses of ICSs. Five of the trials comparing equipotent doses compared low dose ciclesonide with low dose fluticasone; 64 63 one compared medium doses and one compared high doses. All but one trial used HFA-MDI 64 for delivery of both medications. All eight RCTs were funded by pharmaceutical companies producing ciclesonide. Overall, the evidence from these studies supports the conclusion that there is no difference in the outcomes of interest between equipotent doses of ciclesonide and FP. All seven trials comparing equipotent doses reported non-inferiority of ciclesonide compared to FP or no statistically significant difference for the outcomes of interest with one exception. All of the trials used some measure to assess symptoms and rescue medication use; all but one assessed exacerbations; and four assessed quality of life. The one exception was reported in a 12 week trial of 474 subjects, finding greater improvement in quality of life with ciclesonide than with FP 64 (mean change from baseline in AQLQ: 0. The same trial reported non-inferiority or no statistically significant difference between medications for symptoms. We conducted meta-analyses of these studies for exacerbations, symptoms, and rescue medication use and found no statistically significant differences between ciclesonide and FP (Appendix I). There was no statistically significant difference between ciclesonide and FP for exacerbations requiring treatment with oral steroids (OR 0. There was no significant statistical 2 heterogeneity for any of these analyses (I = 0 for all). Ciclesonide compared with mometasone We did not identify any good or fair quality systematic reviews or head-to-head trials that compared ciclesonide with mometasone. Ciclesonide compared with triamcinolone We did not identify any good or fair quality systematic reviews or head-to-head trials that compared ciclesonide with triamcinolone. Controller medications for asthma 34 of 369 Final Update 1 Report Drug Effectiveness Review Project 16. Flunisolide compared with fluticasone 51 We found two RCTs reported in one publication that compared flunisolide and fluticasone meeting our inclusion/exclusion criteria. Both were fair-quality trials comparing non-equipotent doses that randomized patients to high-dose FP MDI (500 mcg/d) or medium-dose flunisolide MDI (1000 mcg/d). One was an 8-week double-blind RCT (N = 321) and the other was a 6-week open-label RCT (N = 332). There was a trend toward greater improvement in symptom-free days for patients treated with high-dose FP (P NR for either). Flunisolide compared with mometasone We did not identify any good or fair quality systematic reviews or head-to-head trials that compared beclomethasone to flunisolide. Flunisolide compared with triamcinolone We did not identify any good or fair quality systematic reviews or head-to-head trials that compared beclomethasone to flunisolide. Fluticasone compared with mometasone 52, 57, Three fair-rated trials comparing FP with mometasone met our inclusion/exclusion criteria. The investigators found no statistically significant differences at endpoint between patients treated with medium-dose fluticasone and those treated with medium- and high-dose mometasone with respect to wheeze and cough scores, nighttime awakenings, or rescue medication use (P > 0. However, patients treated with medium-dose fluticasone had significantly greater improvement in the number of nighttime awakenings (P < 0. In addition, patients on medium-dose fluticasone had significantly better morning difficulty breathing scores than did patients on either low- or medium-dose mometasone (P < 0. Another study was a multinational trial (N=203) that compared high dose mometasone 57 (800 mcg/day) with high dose fluticasone (1000 mcg/day) for 12 weeks. The investigators found no statistically significant differences at endpoint with respect to rescue medication use, symptoms, and exacerbations. The third study did not compare equipotent doses; it compared 71 medium dose mometasone with high dose fluticasone. Fluticasone compared with triamcinolone 53-55 Three fair-rated trials comparing FP to TAA met our inclusion/exclusion criteria. The only 53 one of the three trials comparing equipotent doses found greater improvements in subjects 54, 55 treated with FP. The other two trials comparing non-equipotent doses reported greater improvements for FP-treated subjects for some outcomes and no difference for the others. Subjects were at least 12 years of age and were poorly controlled on ICS therapy. FP-treated subjects had better improvements in symptoms, nighttime awakenings, and rescue medicine use. Controller medications for asthma 35 of 369 Final Update 1 Report Drug Effectiveness Review Project 54, 55 The two comparing non-equipotent doses were similarly designed fair-rated RCTs conducted in 24 outpatient centers. Subjects in both were randomized to medium-dose FP (500 mcg/day by DPI), low-dose TAA (800 mcg/day by MDI with spacer), or placebo for 24 weeks. Both were conducted in subjects 12 years or older previously being treated with ICS. No differences were found in symptom scores or in the percentage of symptom-free days. Subjects treated with FP had greater improvements in rescue medicine requirements in both studies than those treated with TAA. One of the trials reported greater improvement in nighttime 55 54 awakenings for those treated with FP, but the other reported no difference. One reported significantly better improvements in quality of life for FP-treated patients compared to TAA- 55 treated patients. Controller medications for asthma 36 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 Beclomethasone compared with budesonide 22 Adams et al. RCT, open-label France BDP MDI (800) Yes (all high) Fair 27 2005 compared with 460 Age 18-60, moderate to severe persistent, BUD DPI (1600) not controlled on ICS, smoking status NR compared with 12 weeks FP DPI (1000) Multicenter, subspecialty clinics (69 pulmonologists) 28 Worth et al. 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 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 29 Barnes et al. RCT, DB Multinational (7 countries: Holland, FP DPI (400) Yes (medium) Fair 31 2001 Hungary, Italy, Poland, compared with 434 Argentina, Chile, South Africa) BDP DPI (400) 52 weeks Age 4-11, prepubertal, severity and smoking status NR Multicenter (32) 32 Fabbri et al.