Loading

Aktualności

2019, Gwynedd-Mercy College, Jaroll's review: "Order online Amoxil cheap no RX - Effective Amoxil online no RX".

The eight RCTs meeting the inclusion/exclusion criteria for our review are summarized 235 in Table 23 250 mg amoxil with visa antibiotic resistance pictures. Six of the eight trials were included in the systematic review with meta-analysis 240 described above cheap amoxil 500 mg fast delivery how do antibiotics for acne work. One of those not included was a fair-rated RCT, the SOLTA study. It compared low dose FP (200 mcg/day) plus SM (100 mcg/day) (N = 33) with low dose FP (200 mcg/day) plus ML 10 mg/day (N = 33) for 12 weeks in 66 adults (age 18 to 50) with uncontrolled mild to moderate asthma. The ICS/LABA combination was delivered via a single inhaler. Patients being treated with medium dose ICSs were enrolled from multiple centers in the United Kingdom. At endpoint, there were no statistically significant differences in asthma symptoms, but the trends in direction of the effect sizes favored the ICS/LABA combination (symptoms-free days: mean difference in change from baseline: 13. There was no significant difference in daytime rescue use (median % rescue free days at endpoint 73% compared with 70%; P = NS), but there was a difference in rescue use at night favoring FP/SM (median rescue free nights at endpoint: 93% compared with 82%; P = 0. The other trial (BADGER) not included in the systematic review described above 197 enrolled 182 children and adolescents (6 to 17 years of age). The trial used a triple cross-over Controller medications for asthma 139 of 369 Final Update 1 Report Drug Effectiveness Review Project design. 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 for 16 weeks of each treatment (total of 48 week treatment phase). The primary outcome was a composite of exacerbations, number of asthma control days, and FEV1. The response to LABA step-up therapy was most likely to be the best response compared with LTRA step-up (relative probability, 1. One hospitalization for asthma- related symptoms occurred in each of the three treatment groups. A total of 120 prednisone bursts were prescribed for exacerbations (30 during treatment with FP+SM compared with 43 during treatment with FP+ML, P = NR). We do not describe all of the other included RCTs in detail because they generally found results consistent with the overall conclusions of the meta-analysis. For all of our outcomes of interest, most trials reported favorable results for subjects treated with ICS+LABA; the others reported no statistically significant differences (Evidence Tables A and B). Controller medications for asthma 140 of 369 Final Update 1 Report Drug Effectiveness Review Project Table 23. Characteristics of head-to-head studies comparing ICS+LABA with ICS+leukotriene modifiers Study design N Comparison Quality Study Duration Study population (total daily dose) rating LTRA plus ICS compared with LABA plus ICS Ducharme et al. Systematic Review 1 trial in children; 10 in adults LABA (salmeterol 100 mcg or formoterol 24 mcg) plus Good 235 2006 with meta-analysis ICS vs. Multinational (37 countries - eastern Europe) ML (10mg) plus FP (200 mcg) Good RCT vs. Age 15 – 72, mild to severe persistent asthma IMPACT 1490 SM (100 mcg) plus FP (200 mcg) currently uncontrolled on low dose ICS, smoking 48 weeks status NR Same Low dose ICS Multicenter (148) 237 Fish et al. Age 15 and older, moderate to severe persistent 948 ML plus baseline ICS (10mg) asthma despite low to high dose ICS, smoking 12 weeks status NR Same Low to High dose ICS Multicenter (71) 238 Ilowite et al. Age 14 – 73, mild to severe persistent asthma 1473 ML (10 mg) plus FP (220 mcg) uncontrolled on ICS, smoking status NR 48 weeks Unspecified whether ICS dose changed from baseline Multicenter (132) to study low dose ICS Lemanske et al. Age 6-17 182 FP/SM (200 mcg/100 mcg) BADGER Multicenter vs. Characteristics of head-to-head studies comparing ICS+LABA with ICS+leukotriene modifiers Study design N Comparison Quality Study Duration Study population (total daily dose) rating 239 Nelson et al. Age 15 and older, moderate to severe persistent 447 FP (200 mcg) plus ML (10 mg) asthma uncontrolled don low dose ICS, smoking 12 weeks status NR Same Low dose ICS Multicenter 240 Pavord et al. Age 18 – 50, mild to moderate persistent 66 FP (200 mcg) plus ML (10 mg) asthma uncontrolled on medium dose ICS, 12 weeks excluded smokers Decrease to Low dose ICS Multicenter 241 Ringdal et al. Age 15 and older, mild to severe persistent 805 FP (200 mcg) plus ML (10 mg) asthma on low to high dose ICS at baseline, 12 weeks excluded patients with a 10 pack-year history of Decreased to Low dose ICS and had to remain smoking uncontrolled. Multicenter (114) Montelukast plus budesonide compared with formoterol plus budesonide 242 Ceylan et al. Age 15 – 60, moderate persistent asthma 48 BUD (400 mcg) plus ML (10 mg) uncontrolled on unspecified ICS dose, excluded 8 weeks smokers Unspecified change from baseline to Low dose ICS University based clinics Abbreviations: BUD = Budesonide; CI = confidence interval; DPI= Dry Powder Inhaler; FM = Formoterol; FP = Fluticasone Propionate; ICS = Inhaled Corticosteroids; LABAs = Long- Acting Beta-2 Agonists; LTRAs = Leukotriene receptor antagonists; MA=meta-analysis; ML = Montelukast; NR = not reported; NS = not statistically significant; OR= odds ratio; QOL = quality of life; RCT= randomized controlled trial; SM = Salmeterol;; SR=systematic review. 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 142 of 369 Final Update 1 Report Drug Effectiveness Review Project 7. LTRA+LABA compared with ICS+LABA Summary of findings We found one fair quality RCT comparing LTRA plus LABA with ICS plus LABA (Appendix 243 H, Table H-16 and Table 24). The fair-rated, placebo-controlled, multi-center RCT (N = 192) compared ML (10mg/day) plus SM (100 mcg/day) plus placebo ICS (N = 98) compared with low dose BDP (160 mcg/day) plus SM (100 mcg/day) plus placebo LTRA (N = 92) for 14 243 weeks, washout for 4 weeks, then crossover for another 14 weeks. Subjects age 12 to 65 with moderate asthma were enrolled from multiple sites in the United States. There was a 4-week run- in period that involved a single-blind treatment with both BDP (160 mcg/day) and ML (10 mg/day). The primary objective of the study was to assess time until treatment failure. The trial was terminated early because the Data and Safety Monitoring Board determined that the primary research question had been answered. Those treated with LTRA+LABA had significantly shorter time to treatment failure than those treated with ICS+LABA (P = 0. Controller medications for asthma 143 of 369 Final Update 1 Report Drug Effectiveness Review Project Table 24. Characteristics of head-to-head studies comparing ICS+LABA with LTRA+LABA Study design Country N Study population Comparison Study Duration Setting (total daily dose) Quality rating Montelukast plus salmeterol compared with beclomethasone plus salmeterol Deykin et al. United States ML (10mg) + SM (100 mcg) plus placebo ICS vs. Fair 243 RCT 2007 BDP (160 mcg) + SM (100 mcg) plus placebo LTRA 192 Age 12 to 65 Low dose ICS 14 weeks, washout for 4 weeks, then Multicenter crossover for 14 weeks Abbreviations: BDP = Beclomethasone dipropionate; ICS = Inhaled Corticosteroids; LABAs = Long-Acting Beta-2 Agonists; LTRAs = Leukotriene receptor antagonists; ML = Montelukast; RCT= randomized controlled trial; SM = Salmeterol. 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 144 of 369 Final Update 1 Report Drug Effectiveness Review Project Key Question 2. Adverse Events What is the comparative tolerability and frequency of adverse events for controller medications used to treat outpatients with persistent asthma? Inhaled Corticosteroids Summary of Findings 22, 23, 244-248 27-33, 35-50, 52-55, 58-70, 249-258 We found seven systematic reviews, 50 RCTs and 12 259-269 observational studies reporting the tolerability or frequency of adverse events for inhaled corticosteroids meeting our inclusion/exclusion criteria (Table 7 and Evidence Tables A and B). Few RCTs were designed to assess adverse events as primary outcomes; most published studies designed to assess adverse events were observational studies. The overall incidence of adverse events and withdrawals due to adverse events are similar for equipotent doses of ICSs; results from head-to-head RCTs suggest no significant differences between ICSs (moderate strength of evidence). Overall summaries for specific adverse events are described below in the specific adverse events section.

amoxil 250mg visa

generic amoxil 250mg online

A to Z Yes Yes Yes Attrition yes purchase amoxil 250 mg with mastercard antibiotic quiz pharmacology, No de Lemos cheap amoxil 500mg mastercard antibiotics for uti cefuroxime, 2004 AFCAPS Yes Yes Yes Attrition-yes, crossovers-no actual numbers No 1998 provided, adherence-yes and contamination- no actual numbers provided. ALLHAT-LLC No Yes NR Attrition unclear; Crossover(years 2/4/6): No (open trial) 8. Internal validity of controlled clinical trials Study or Author Score Year (good/ fair/ poor) Studies from Evidence Table 2 (CHD) 4S Good 1994 A to Z Fair de Lemos, 2004 AFCAPS Good 1998 ALLHAT-LLC Fair-Good (open trial) Patti et al, 2007 Fair (ARMYDA-ACS) Statins Page 316 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Study or Author Randomization Allocation Eligibility criteria Outcome assessors Care provider Year adequate? Arntz et al, 2000 Method not reported Not reported Yes Yes Yes Yes (L-CAD) ASCOT NR NR Yes Yes Yes Yes Cannon et al, 2004 Method not reported Not reported History of peripheral arterial Yes Yes Not reported (PROVE-IT) disease more common in prava group, uneven treatment group sizes. Colhoun, 2004 Yes Yes Yes Yes Yes Yes (CARDS) CARE Yes Yes Yes Yes Yes Yes 1996 Den Hartog Yes Not reported Some differences Yes Yes Not reported (Pilot Study) Statins Page 317 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Patient Different or overall high Study or Author unaware of Intention-to-treat Maintained Reported attrition, crossovers, loss to follow- Year treatment? Arntz et al, 2000 Yes Yes- able to calculate Yes Attrition yes, others no Yes: 9 patients in control (L-CAD) group withdrew consent after learning treatment assignment. ASCOT Yes Yes NR Attrition unclear; others NR No Cannon et al, 2004 Yes Not clear Yes Attrition yes, others no No. No (CARDS) able to calculate CARE Yes Yes Yes Attrition: yes, crossovers-no, adherence-no, No 1996 and contamination-yes Den Hartog Yes Yes No Attrition yes, others no No, 2 placebo vs 0 prava (Pilot Study) lost to followup. High discontinuation rate (22%) and more placebo patients discontinued overall (26. Internal validity of controlled clinical trials Study or Author Score Year (good/ fair/ poor) Arntz et al, 2000 Fair (L-CAD) ASCOT Fair-Good Cannon et al, 2004 Fair (PROVE-IT) Colhoun, 2004 Good (CARDS) CARE Good 1996 Den Hartog Poor (Pilot Study) Statins Page 319 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Study or Author Randomization Allocation Eligibility criteria Outcome assessors Care provider Year adequate? Heljic B, 2009 Method not reported Not reported Yes Yes NR NR Hogue J, 2008 Method not reported Not reported Yes Yes NR NR Holdaas NR Adequate; serially- Yes Yes Yes Yes numbered identical medication packs HPS NR Adequate; Unclear; "good balance" Yes Yes Yes centralized indicated; data NR Pederson, 2005 NR NR Yes Yes Yes No- open label, (IDEAL) blinded endpoint classification Statins Page 320 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Patient Different or overall high Study or Author unaware of Intention-to-treat Maintained Reported attrition, crossovers, loss to follow- Year treatment? Heljic B, 2009 NR Unclear--not reported Unclear NR NR NR NR NR Hogue J, 2008 NR Unclear--not reported (5% Unclear Yes No in atorva arm vs 1. No (IDEAL) endpoint classification Statins Page 321 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Study or Author Score Year (good/ fair/ poor) Heljic B, 2009 Poor Hogue J, 2008 Fair-Poor Holdaas Good HPS Good Pederson, 2005 Fair (IDEAL) Statins Page 322 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Study or Author Randomization Allocation Eligibility criteria Outcome assessors Care provider Year adequate? Ridker P, 2008 Yes Yes Yes Yes Stated "double-blind" Stated "double-blind" JUPITER but no details but no details Liem et al, 2002 Method not reported Not reported Yes Yes States "double blind," Not reported (FLORIDA) but no details. LIPID Yes Not reported Yes Yes Yes Yes 1998 Nakamura et al, 2006 Yes, computer- Not reported Yes Yes Yes, endpoint Open-label MEGA generated list assessors were blinded and were reviewed by the endpoint committee. Schwartz et al, Method not reported Not reported Yes Yes Yes Yes 2001 (MIRACL) Thompson, 2004 Method not reported Not reported Higher total cholesterol in Yes Yes Yes (PACT) placebo group, more placebo patients on HRT, and more prava patients on anticoagulants. Asselbergs, 2004 Yes Not reported Appear similar Yes Yes No details given (PREVEND IT) Statins Page 323 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Patient Different or overall high Study or Author unaware of Intention-to-treat Maintained Reported attrition, crossovers, loss to follow- Year treatment? Ridker P, 2008 Yes Yes Yes Attrition-yes, others-no No JUPITER Liem et al, 2002 States "double blind," Yes Yes Attrition and adherence yes, crossover and No (FLORIDA) but no details. Asselbergs, 2004 Yes Yes Yes Yes No (PREVEND IT) Statins Page 324 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Study or Author Score Year (good/ fair/ poor) Ridker P, 2008 Good JUPITER Liem et al, 2002 Fair (FLORIDA) LIPID Good 1998 Nakamura et al, 2006 Fair MEGA Schwartz et al, Fair 2001 (MIRACL) Thompson, 2004 Fair-Poor (PACT) Asselbergs, 2004 Fair (PREVEND IT) Statins Page 325 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Study or Author Randomization Allocation Eligibility criteria Outcome assessors Care provider Year adequate? Stone et al, 2005 NR NR atorva group higher weight Yes Yes Not specified (198 lbs vs 188 lbs control), otherwise similar. Wanner et al, 2005 Yes NR Yes Yes Yes Not specified (but described as double- blind) Statins Page 326 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Patient Different or overall high Study or Author unaware of Intention-to-treat Maintained Reported attrition, crossovers, loss to follow- Year treatment? No numbers and reasons for numbers withdrawing withdrawal are given. Wanner et al, 2005 Not specified (but Yes Yes Attrition and adherence reported. No described as double- blind) Statins Page 327 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Study or Author Score Year (good/ fair/ poor) PROSPER Good Sakamoto T, 2006 Fair-Poor Stone et al, 2005 Fair Wanner et al, 2005 Fair Statins Page 328 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Study or Author Randomization Allocation Eligibility criteria Outcome assessors Care provider Year adequate? WOSCOPS, 1995 Yes Yes Yes Yes Yes Yes Xu K, 2007 NR NR Yes Yes NR NR Studies from Evidence Table 4: Post-revascularization LIPS NR Adequate; serially- No, more fluva patients with Yes Yes Yes numbered identical diabetes mellitus (14. Internal validity of controlled clinical trials Patient Different or overall high Study or Author unaware of Intention-to-treat Maintained Reported attrition, crossovers, loss to follow- Year treatment? WOSCOPS, 1995 Yes Both intention to treat and Yes Attrition-yes, crossovers-no, adherence-no No on treatment analysis. Internal validity of controlled clinical trials Study or Author Score Year (good/ fair/ poor) WOSCOPS, 1995 Good Xu K, 2007 Fair-Poor Studies from Evidence Table 4: Post-revascularization LIPS Fair Studies from Evidence Table 5: Fixed-dose combination products Ballantyne et al, Fair 2005 (Vyva study) Ballantyne et al, Poor 2008 (SEACOAST I) Statins Page 331 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Study or Author Randomization Allocation Eligibility criteria Outcome assessors Care provider Year adequate? Barrios et al, Yes NR Yes Yes NR NR 2005 Bays et al, Method NR NR Yes Yes NR NR 2003 Bays et al, Method NR NR Yes Yes NR NR 2004 Catapano et al, Yes Yes Yes Yes NR NR 2006 Constance et al, Yes NR Yes Yes NR NR 2007 Farnier et al, Yes NR Yes Yes NR NR 2007 Goldberg et al, Yes NR Yes Yes NR NR 2006 (Vytal study) Guyton et al, Method NR Yes Yes Yes NR Yes both methods NR 2008 Lin et al, 2006 Method NR NR Yes Yes NR NR Ose et al, 2007 Yes Yes Yes Yes Yes Yes Reckless et al, Yes NA Yes Yes NR NR 2008 Roeters van Lennep Yes NA Yes Yes NR NR et al, 2008 Shankar et al, NR NR Yes Yes NR NR 2007 Other controlled clinical trials Bays H, 2003 Statins Page 332 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Patient Different or overall high Study or Author unaware of Intention-to-treat Maintained Reported attrition, crossovers, loss to follow- Year treatment? Barrios et al, Yes but method not Yes Yes Attrition-16 (4%), crossovers-no, adherence- No 2005 reported no details and contamination-no Bays et al, No open label Yes Yes NR NR 2003 Bays et al, Yes Modified ITT Yes Attrition-33 (8. Internal validity of controlled clinical trials Study or Author Score Year (good/ fair/ poor) Barrios et al, Fair 2005 Bays et al, Poor 2003 Bays et al, Fair 2004 Catapano et al, Fair 2006 Constance et al, Fair 2007 Farnier et al, Fair 2007 Goldberg et al, Fair 2006 (Vytal study) Guyton et al, Fair 2008 Lin et al, 2006 Fair Ose et al, 2007 Fair Reckless et al, Fair 2008 Roeters van Lennep Fair et al, 2008 Shankar et al, Fair 2007 Other controlled clinical trials Bays H, 2003 Statins Page 334 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Study or Author Randomization Allocation Eligibility criteria Outcome assessors Care provider Year adequate? Bonnet F, 2007 Yes, centrally following Not reported No, there were differences in Yes Study states "double- Study states "double- a computer-generated number of males in each blinded" but no details blinded" but no details random number list group, and protease inhibitor given given exposure was >2x longer for those in the placebo group (52 mos) than pravastatin group (21 mos). Brown B, 2001 Method not reported Not reported Yes Yes Yes Study states "double- blinded" but no details given Fellstrom B, 2006 Yes Not reported (see Yes Yes Not reported (see Not reported (see (companion to ALERT) original trial) original trial) original trial) Franceschini G, 2007 Randomization stated, NR Yes Minimal Unclear, "double- Unclear, "double- but methods NR blind", but methods NR blind", but methods NR Hanefeld M, 2007 (PIOSTAT) Hogue J, 2008 Randomization stated, Yes Yes Yes Yes Yes but methods NR Insull W, 2004 Method not reported Not reported Yes Yes Study states "double- Study states "double- blinded" but no details blinded" but no details given. Iwata A, 2006 Kayikcioglu M, 2002 Method not reported Not reported Yes Yes Not reported (possibly Not reported (possibly (PTT) open-label) open-label) Statins Page 335 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6. Internal validity of controlled clinical trials Patient Different or overall high Study or Author unaware of Intention-to-treat Maintained Reported attrition, crossovers, loss to follow- Year treatment? Bonnet F, 2007 Study states "double- Yes Yes Yes No blinded" but no details NR No given NR NR Brown B, 2001 Yes Yes Yes Yes Unable to determine- NR differential Yes No-overall NR Fellstrom B, 2006 Not reported (see Not reported (see original Yes Yes Not reported (see original (companion to ALERT) original trial) trial) NR trial) NR NR Franceschini G, 2007 Yes Unclear NR NR Unable to assess Hanefeld M, 2007 (PIOSTAT) Hogue J, 2008 Yes NR NR NR Unable to assess Insull W, 2004 Study states "double- Not reported Yes Yes Yes-differential blinded" but no details NR No-overall given. Yes NR Iwata A, 2006 Kayikcioglu M, 2002 Not reported (possibly Yes Yes Yes No (PTT) open-label) NR No NR NR Statins Page 336 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 6.

A 3-week study using over-encapsulation for blinding enrolled 327 children order amoxil 250mg on-line antibiotic honey, ® comparing immediate-release methylphenidate to Equasym (sold in the United States as ® Metadate CD ) buy amoxil with paypal antimicrobial resistance fda. The study analyzed only 87% of patients in the main per-protocol analysis with 47 unclear description of those excluded. The study included a non-inferiority analysis, assuming a difference of ≤ 1. At weeks 1, 2, and 3 immediate-release methylphenidate ® was found equivalent to Equasym. Intent-to-treat analysis as well as subgroup analyses (country, dose, ADHD subtype) was reported in the discussion as supporting these results. Additional analysis examined the effects of the drugs in the morning and afternoon, but a direct comparison was made only to the placebo group as both methylphenidate groups were found similarly superior to placebo at both time points throughout the study. Immediate-release methylphenidate compared with methylphenidate multilayer-release ® (Biphentin ). Two small, fair-quality, crossover studies compared immediate-release ® methylphenidate to methylphenidate multilayer-release (Biphentin , available in Canada, not 53, 54 available in the United States as of September 2011). In the first study, 90 children were randomized to either immediate-release methylphenidate or methylphenidate multilayer-release and had dose titration over 2-3 weeks, with observation by parent, teacher, and investigator over 54 2 weeks. Discontinuations were similar between groups (86% methylphenidate multilayer- release, 89% immediate-release methylphenidate), and mean daily doses were similar between treatments (0. Using the Conners’ scales, “normal” was defined as a final T-score of <65 on each of the 4 subscales. After 5 weeks of treatment, more children taking immediate- release methylphenidate had achieved a normal score on the ADHD Index compared with those taking methylphenidate multilayer-release (90% compared with 79% on the teacher scale and Attention deficit hyperactivity disorder 43 of 200 Final Update 4 Report Drug Effectiveness Review Project 81% compared with 77% on the parent scale). The authors reported that the mean ADHD Index T-scale score was statistically significantly better (lower) with immediate-release methylphenidate based on the teacher scale (mean differences, 3. No other differences were found between treatment groups. The second, smaller study (N=18) reported only single-day measurements after 1 week of 53 immediate-release methylphenidate, methylphenidate multilayer-release, or placebo. This study found no statistically significant differences between drug treatments on the Conners’ IOWA scale, although baseline scores differed across treatment groups such that these findings should be interpreted with caution; the analyses attempted to control for differences in baseline scores, including assessing for carryover effects. Analyses of time-course responses were not able to identify consistent differences among the drugs compared with placebo. Other measures of comparative effectiveness of immediate-release compared with sustained-release formulations Clinical trials of extended-release compared with immediate-release formulations were too short to demonstrate differences in long-term health outcomes. However, the intermediate outcome measure of persistence (the proportion of patients continuing to take or refill prescriptions for a medication after some longer period of time) is thought to be a good proxy for extension of benefits seen in the short-term, or if none were found, evidence of a difference in longer-term, real-life settings. Persistence is an intermediate outcome with unknown validity because direct evidence of a relationship between persistence rates and long-term health outcomes with ADHD drugs is lacking. In 5 observational studies (6 publications), persistence with treatment with long-acting stimulant formulations (methylphenidate OROS or methylphenidate ER) was significantly longer compared with shorter-acting formulations (immediate-release methylphenidate or immediate- 55-58 release mixed amphetamine salts) over periods of 6 months and 12 months following index prescription. One of these studies examined only adults treated with methylphenidate OROS (median duration of treatment 68 days; 95% CI, 65 to 71) compared with immediate-release 59 methylphenidate (39 days; 95% CI, 33 to 52). The findings of these studies should be interpreted with caution, however, until confirmed by a randomized controlled trial that would serve to rule out potential sources of bias, including between-group baseline differences in unmeasured clinical characteristics, physicians’ prescribing preferences, and differences in reasons for discontinuation (e. Data were derived from the Integrated Health Care Information Services National Managed Care Benchmark Database in 2 studies from the same group of researchers, with overlapping data. Using a definition of persistence as less than a 15-day gap in prescription refills, the studies found methylphenidate OROS to be associated with greater persistence rates 56 than immediate-release methylphenidate (12% compared with 1%, P<0. The second study also reported persistence using less than a 30-day gap in refills as the definition and found 33% persistent with methylphenidate OROS and 57, 58 5% with immediate-release methylphenidate. There was uncertainty about how well this study population represented patients in actual practice as ethnicity and comorbidity characteristics were not reported and there were age and diagnosis differences between those receiving methylphenidate OROS compared with immediate-release methylphenidate. Attention deficit hyperactivity disorder 44 of 200 Final Update 4 Report Drug Effectiveness Review Project California Medicaid claims files from a 3-year period were examined to identify youth 55 prescribed methylphenidate (N=11 537). This study population involved a lower than average proportion of White patients (45. Total mean duration (days) of treatment without any 30-day gaps was greater for patients taking extended-release formulations (combined group of methylphenidate OROS = 83%, methylphenidate ER = 8. Subgroup analysis results suggested that persistence duration was greatest for methylphenidate OROS (147. Together, extended-release formulations extended persistence duration regardless of ethnicity. The Texas Medicaid Vendor Drug Program database was used to identify claims for 60 newly started stimulants (2001-2002 school year). Proportion of days of treatment without any 15-day gaps was greater for patients taking methylphenidate OROS than for immediate-release methylphenidate or immediate-release mixed amphetamine salts (0. Within those days of treatment, compliance rates, as measured using the Medication Possession Ratio, were higher in patients taking methylphenidate OROS compared with immediate-release methylphenidate or immediate-release mixed amphetamine salts (0. Comparisons of sustained-release formulations ® ® Methylphenidate OROS (Concerta ) compared with methylphenidate CD (Metadate CD ). Results from the fair-quality COMACS crossover study of 184 children suggested that relative improvements in SKAMP deportment and attention scale scores differed for the comparison of methylphenidate OROS 18-54 mg and methylphenidate CD 20-60 mg (both given once daily) 61, 62 depending on time of assessment. Methylphenidate CD was associated with significantly larger effect sizes than methylphenidate OROS in the morning, while treatment effects were similar in the afternoon, and methylphenidate OROS was superior in the evening. This study presented several problems, however, in that the SKAMP scale has been criticized for lack of sensitivity to change in symptoms, and that ANOVA analysis found the interaction of site x treatment x sequence (the order to randomization within patients) was found to be statistically significant. This finding resulted in the authors conducting additional analyses; however the effect of sequence was not included in these subsequent analyses. Therefore, these findings should be interpreted with caution. Two small crossover studies have found methylphenidate SODAS superior to methylphenidate OROS. A small 1-week crossover study of methylphenidate SODAS 20 mg compared with 63 methylphenidate OROS 18 mg and 36 mg found methylphenidate SODAS superior on the attention or deportment subscores of the SKAMP scale depending on the time-point and dose Attention deficit hyperactivity disorder 45 of 200 Final Update 4 Report Drug Effectiveness Review Project comparison. Secondary outcome assessment also found methylphenidate SODAS superior on 1 measure (proportion correct on math test). These limited differences were mitigated by concerns over the assessment tool (SKAMP) sensitivity, use of a simulated classroom, involvement of study sponsor in authorship, and differences in groups at baseline. A similar second crossover study of methylphenidate OROS (18 and 36 mg) and methylphenidate SODAS (20 and 40 mg) also assessed children in a simulated classroom setting after a single dose of the study 64 medication using the SKAMP scale. Here methylphenidate SODAS 40 mg was found superior to methylphenidate OROS 36 mg at all time points (0-4, 0-8, and 0-12 hours) based on the SKAMP attention subscale score area under the curve analyses, while methylphenidate SODAS 20 mg was not significantly different to either dose of methylphenidate OROS. Here, concerns over the clinical importance of the difference in area under the curve, involvement of study sponsor in authorship, and the impact of sequence of randomized treatment (analysis of treatment sequence was stated to be planned but results not reported) were present. Dexmethylphenidate ER compared with methylphenidate OROS. A single, small (N=84) fair- quality crossover study compared 2 doses of dexmethylphenidate ER with 2 doses of 65 methylphenidate OROS or placebo using a simulated classroom assessment. The primary outcome was the mean change in the SKAMP combined score from zero to 2 hours post dose in the dexmethylphenidate ER 20 mg daily group compared with the methylphenidate OROS 36 mg daily group. Children were given the intervention for 7 days prior to the assessment.