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Dolutegravir versus raltegravir in antiretroviral-experienced discount ciprofloxacin 1000 mg with amex antibiotic resistance kit, integrase- inhibitor-naive adults with HIV: week 48 results from the randomised ciprofloxacin 500mg online infection 5 weeks after c-section, double-blind discount 500mg ciprofloxacin otc infection xpk, non-inferiority SAILING study. Raltegravir/etravirine dual therapy as a virologically safe treatment option in suppressed HIV-1-infected patients without previous NNRTI failure. Abstract WEPE516, IAS 2013, Kuala Lumpur Calza L, Manfredi R, Colangeli V, et al. Substitution of nevirapine or efavirenz for protease inhibitor versus lipid- lowering therapy for the management of dyslipidaemia. Significant sparing of peripheral lipoatrophy by HIV treatment with LPV/r + ZDV/3TC induction followed by LPV/r monotherapy compared with EFV + ZDV/3TC. SWIFT: Prospective 48-Week Study to Evaluate Efficacy and Safety of Switching to Emtricitibine/Tenofovir From Lamivudine/Abacavir in Virologically Suppressed HIV-1 Infected Patients on a Boosted Protease Inhibitor Containing Antiretroviral Regimen. Predictors of loss of virologic response in subjects who simplified to lopinavir/ritonavir monotherapy from lopinavir/ritonavir plus zidovudine/lamivudine. How to switch ART 219 Carr A, Workman C, Smith DE, Hoy J, Abacavir substitution for nucleoside analogs in patients with HIV lipoat- rophy: a randomized trial. Dolutegravir in Antiretroviral-Experienced Patients With Raltegravir- and/or Elvitegravir-Resistant HIV-1: 24-Week Results of the Phase III VIKING-3 Study. Simplification to atazanavir/ritonavir monotherapy for HIV-1 treated indi- viduals on virological suppression: the MODAt trial. Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based HAART in HIV-1-infected patients with undetectable plasma HIV-1 RNA. Safety and efficacy of maraviroc-raltegravir combination following 6 months induction with maraviroc-raltegravir-tenofovir-emtricitabine in naïve HIV-1-infected patients with CCR5 virus: interim analysis of the No Nuc No Boost study. The rate of accumulation of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in patients kept on a virologically failing regimen containing an NNRTI. From old to new nucleoside reverse transcriptase inhibitors: changes in body fat composi- tion, metabolic parameters and mitochondrial toxicity after the switch from thymidine analogs to tenofovir or abacavir. Simplified maintenance therapy with abacavir/lamivudine/zidovudine plus tenofovir after sustained HIV load suppression: four years of follow-up. Impact oft switching virologically suppressed, HIV-1-infected patients from twice-daily fixed-dose zidovudine/lamivudine to once-daily fixed-dose tenofovir disoproxil fumarate/emtric- itabine. HIV Clin Trials 2008, 9: 103-114 Di Giambenedetto S, Fabbiani M, Colafigli M, et al. Safety and feasibility of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients on stable treatment with two nucleos(t)ide reverse transcriptase inhibitors + atazanavir/ritonavir with virological suppression (AtLaS pilot study). A randomized phase 3 study comparing once-daily elvitegravir with twice-daily raltegravir in treatment-experienced subjects with HIV-1 infection: 96-week results. Treatment modification in human immunodeficiency virus-infected individ- uals starting combination antiretroviral therapy between 2005 and 2008. Switch to a raltegravir-based regimen versus continuation of a lopinavir-riton- avir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multi- centre, double-blind, randomised controlled trials. Randomized open-label trial of two simplified, class-sparing regimens following a first suppressive three or four-drug regimen. A randomized comparative trial of continued zidovudine/lamivudine or replacement with tenofovir disoproxil fumarate/emtricitabine in efavirenz-treated HIV-1-infected individuals. Final analysis of the Trilege induction-maintenance trial: results at 18 months. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. The effects of a nucleoside-sparing antiretroviral regimen on the pharma- cokinetics of ritonavir-boosted darunavir in HIV type-1-infected patients. Efficacy and safety of atazanavir-based HAART in pts with virologic suppression switched from a stable, boosted or unboosted PI treatment regimen: the SWAN Study. Non-inferiority of dual-therapy (DT) with lopinavir/ritonavir (LPV/r) plus lamivudine (3TC) vs triple-therapy (TT) with LPV/r plus two nucleos(t)ides (NRTIs) for maintenance of HIV-1 viral suppression: 48-week results of the OLE study. Unboosted atazanavir-based therapy maintains control of HIV type-1 repli- cation as effectively as a ritonavir-boosted regimen. TenofovirDF + efavirenz (TDF+EFV) vs tenofovirDF+ efavirenz + lamivu- dine (TDF+EFV+3TC) maintenance regimen in virologically controlled patients (pts): COOL Trial. Randomized controlled study demonstrating failure of LPV/r monother- apy in HIV: the role of compartment and CD4-nadir. Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine. Maintenance antiretroviral therapies in HIV infected patients with undetectable plasma HIV RNA after triple-drug therapy. Change to abacavir-lamivudine-tenofovir combination treatment in patients with HIV-1 who had complete virological suppression. A lamivudine (3TC)-based backbone in conjunction with a boosted protease inhibitor (PI) is sufficient to achieve virologic suppression in the presence of M184V mutations. Randomized, controlled, 48 week study of switching stavudine and/or pro- tease inhibitors to Combivir/abacavir to prevent or reverse lipoatrophy in HIV-infected patients. Ritonavir boosted indinavir treatment as a simplified maintenance “mono”- therapy for HIV infection. Maraviroc plus raltegravir failed to maintain virological suppression in HIV-infected patients with lipohypertrophy: results from the ROCnRAL ANRS 157 study. TRIZAL study: switching from successful HAART to Trizivir (abacavir lamivu- dine-zidovudine combination tablet): 48 weeks efficacy, safety and adherence results. Switch to efavirenz (EFV) after protease-inhibitor (PI)-failure: explorative analysis of outcome by baseline viral VS tolerability failure. Factors associated with virological failure in HIV-1-infected patients receiving darunavir/ritonavir monotherapy. Factors associated with virological failure in HIV-1-infected patients receiving darunavir/ritonavir monotherapy. Resistant minority species are rarely observed in patients on darunavir/ritonavir monotherapy. Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV-1-infected patients with multidrug-resistant virus: a multicentre pilot study. The safety and efficacy of switching stavudine to tenofovir df in com- bination with lamivudine and efavirenz in hiv-1-infected patients: three-year follow-up after switching therapy. Efficacy and safety of switching from boosted lopinavir to boosted atazanavir in patients with virological suppression receiving a LPV/r-containing HAART: the ATAZIP study. J AIDS 2009, 51:29-36 Marcelin AG, Lambert-Niclot S, Peytavin G, et al. Baseline HIV RNA ultrasensitive assay and viral DNA predict rise in plasma viral load in patients of MONOI-ANRS 136 Trial. Induction with abacavir/lamivudine/zidovudine plus efavirenz for 48 weeks followed by 48-week maintenance with abacavir/lamivudine/zidovudine alone in antiretroviral-naive HIV- 1-infected patients. Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir- lamivudine: a randomized, 96-week trial. Bone mineral density in HIV participants randomized to raltegravir and lopinavir/ritonavir compared with standard second line therapy. HIV lipodystrophy in participants randomised to lopinavir/ritonavir (LPV/r) +2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTI) or LPV/r + raltegravir as second-line anti- retroviral therapy.

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The most relapses in early and para-aortic lymph node sampling and biopsies cheap 750mg ciprofloxacin otc antibiotics for uti leukocytes. This is a favorable An omentectomy and cytoreduction are recom- location for salvage therapy with external and intra- mended in patients with advanced-stage endo- cavitary radiotherapy ciprofloxacin 1000 mg low cost 5th infection, surgery purchase ciprofloxacin 500 mg otc virus herpes, or both, but this can metrioid cancer, clear cell carcinoma or patients often only be done in special centers in resource- with uterine serous papillary carcinoma. A lymphadenectomy is factors may be followed up only, as in this group indicated in these patients In cases where bulky the prognosis is very good (Table 5). The PORTEC 2 study demonstrated that dicated in patients with co-morbid disease where a pelvic external beam radiotherapy (EBRT) did not laparotomy maybe hazardous. Several (retrospec- render a better survival or disease-free survival tive) studies have demonstrated that a vaginal compared to vaginal brachytherapy only5. Of hysterectomy does not have a negative effect on interest is that the patients in the PORTEC 2 study prognosis. Laparoscopic-assisted vaginal hysterec- did not undergo a lymphadenectomy, which tomy (LAVH) and BSO with or without pelvic suggests that rate of positive nodes in patients with lymphadenectomy has been shown to be an excel- high-intermediate-risk factors is relatively low. Several studies have demonstrated that a tion risk groups have been identified for stage I endo- laparoscopic approach does not compromise the metrial cancer prognosis of patients with endometrial cancer, with Low risk: stage IA, grade 1 and 2, endometrioid adeno- probably a more rapid recovery period and less carcinoma postoperative complications, which is, considering the profile of these patients, a distinct advantage. A Intermediate risk: number a limiting factors such as obesity and an en- 1. Stage I: • moderate to poorly differentiated tumor (grade 3) larged uterus may be contraindications for laparo- • presence of lympho-vascular invasion scopic surgery. A laparoscopic approach requires • outer third myometrial invasion (stage IB) special training and skills. Age ≥50 years with any two risk factors listed above; or is longer compared to an open approach and it is 3. Age ≥70 with any risk factor listed above still shown to be the more expensive procedure. Histological evaluation of specimens is manda- High risk: stage IB plus grade 3, non-endometrioid histology tory to determine possible adjuvant treatment. The histopathologist should report on grade or differen- tiation, size of the tumor, depth of myometrium invasion, lymph–vascular space invasion, cervical Table 5 Overview of treatment in stage I endometrial involvement and adnexal involvement. Although 7 cancer risk according to groups in Table 4 in the latest 2009 FIGO staging classification posi- tive washings do not change the stage, the presence Risk group Adjuvant treatment of malignant cells in the pouch of Douglas washing Low risk No adjuvant treatment should be reported (Table 4). Intermediate risk Brachytherapy • With 2 high-risk factors Adjuvant treatment (age >50 years) • With 1 risk factor (age Although in many low-resource countries, radio- >70 years) therapy is not easily available, it may be considered High risk External beam radio- for certain high-risk patients. The adjuvant treat- therapy and brachytherapy ment should be individually tailored. Low-risk 362 Cancer of the Uterine Corpus Risk factors for recurrent disease in stage I endo- including cancer, hypertension and diabetes. In metrial cancer include grade 3 tumors with infiltra- transitional but increasingly also in low-resource tion into the outer half of the myometrium. These settings a large proportion of society tend to be patients are certainly at risk for positive pelvic and obese. Communities need to be sensitized about or para-aortic lymph nodes. If the lymph node this link and the dangers associated with metabolic status is known and positive the patients should re- syndrome. Secondly, endometrial cancer has its ceive full pelvic radiation maybe including the peak incidence in postmenopausal women. As a consequence it tive pelvic and para-aortic lymph nodes can be is not sufficient to sensitize men and women about adequately treated with vaginal brachytherapy6. It is more frequently recognized that repro- EBRT is recommended. The role of systemic treat- ductive healthcare should be provided along a con- ment, i. In patients with a non-endometrioid cancer such as UTERINE SARCOMAS uterine serous papillary carcinoma and clear cell Uterine sarcomas represent only 3–8% of all uter- carcinomas it has become common practice to give ine malignancies. The low occurrence precludes intravenous chemotherapy including carbo- any prospective studies and most published data platinum and paclitaxel (see Chapter 28). A number concern retrospective studies and case histories. We nosarcoma (previously known as malignant mixed have to wait for further studies. Müllerian tumors or MMMT) are now seen as poorly differentiated epithelial carcinomas. In this Recurrence of endometrial cancer chapter, carcinosarcoma is discussed together with In a limited number of patients the disease will re- the uterine sarcomas. When the recurrence is local (vagina or vagina top) surgery by an experienced doctor or radio- Carcinosarcoma therapy can still cure the patient. In cases of distant These tumors represent <5% of all uterine cancers. A polypoid tumor on macroscopic positive progesterone receptors (medroxyproges- examination is shown in Figure 7. Palliative These are biphasic neoplasms involving malig- care is described in Chapter 32. The Community sensitization epithelial component is adenocarcinoma. The sar- There are two important points in health promo- comas may be heterologous with histological evi- tion activities around endometrial cancer. First, as dence of tissue not normally found in the uterus already mentioned, type I endometrial cancer is such as cartilage and bone (Figure 8). Only staging is according to that of epithelial (endo- recently, the WHO has acknowledged the im- metrioid) uterine malignancies as described above. A para-aortic lymphadenectomy may be considered although this would most likely represent a staging procedure without proven survival benefit8. Postoperatively, adjuvant treatment may be recommended if there is extrauterine disease, resi- dual disease or nodal disease, but the prognosis re- mains poor. Cytotoxic agents may play a role and active agents include carboplatinum, paclitaxel and Figure 7 Carcinosarcoma filling the uterine cavity. Due to infrequent occurrence of Courtesy of Dr Judy Whittaker carcinosarcomas it is difficult to assess the true efficacy of adjuvant chemotherapy. The same goes for postoperative radiotherapy where mainly retro- spective data are available. One prospective rando- mized trial found better local control in patients receiving adjuvant pelvic radiotherapy compared to patients who did not receive radiotherapy. Radiotherapy did however not result in a better progression-free survival or overall survival. Leiomyosarcoma For leiomyosarcoma, because of its classification as a true uterine sarcoma from a histological perspec- tive a different FIGO staging classification is used (Table 6). Although leiomyosarcoma is the most common Figure 8 Heterologous carcinosarcoma of the uterus. In most patients a preoperative diag- staging classification is appropriate for these highly nosis is uncommon as these patients undergo malignant tumors. The cornerstone of treatment is surgical and the metastatic pattern Table 6 FIGO staging of uterine sarcomas, 2009 has obvious consequences for the extent of a surgi- (leiomyosarcoma, endometrial stromal sarcoma and cal procedure.

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We compare the efficacy order 500mg ciprofloxacin antibiotic quizlet, effectiveness cheap 250 mg ciprofloxacin amex antibiotic resistance cost, and safety (adverse events) of donepezil order 250 mg ciprofloxacin otc antibiotic resistance scientific journal, galantamine, rivastigmine, tacrine, and memantine in patients with mild to severe AD. Although we will emphasize comparative head-to-head studies, the few published ones do not allow for a comprehensive evaluation. Accordingly, we will also include supplementary data from individual placebo-controlled trials and observational studies. The participating organizations of the Drug Effectiveness Review Project (DERP) are responsible for ensuring that the scope of the review reflects the populations, drugs, and outcome measures of interest to their constituencies. The Oregon Evidence-based Practice Center initially prepared preliminary key questions identifying the populations, interventions, and outcomes of interest, and we based the eligibility criteria for studies on these preliminary questions. Representatives of organizations participating in the DERP, in conjunction with experts in the fields of health policy, neurology, pharmacotherapy, and research methods reviewed, revised, and approved the questions and outcome measures. The participating organizations approved the following key questions: 1. How do donepezil, galantamine, rivastigmine, tacrine, and memantine or combinations of these drugs (i. How do donepezil, galantamine, rivastigmine, tacrine, and memantine (or combinations of these drugs) compare in their time to effect and in the time required to assess the clinical response? What are the comparative incidence and severity of complications of donepezil, galantamine, rivastigmine, tacrine, and memantine (or combinations of these drugs)? Does efficacy, effectiveness, or adverse events of donepezil, galantamine, rivastigmine, tacrine, or memantine (or combinations of these drugs) differ in subgroups of patients with (1) different demographic profiles (age, race, or gender), (2) Parkinsonian features or vascular dementia, or (3) use of other commonly prescribed drugs? We distinguish between efficacy (explanatory) studies and effectiveness (pragmatic) studies; studies conducted in primary care or office- based settings that use less stringent eligibility criteria (i. Studies conducted in more highly selected populations over shorter periods of time are characterized as efficacy studies. We summarize the results of efficacy and effectiveness studies separately as the results of effectiveness studies are more generalizable than results from highly selected populations (i. For assessing efficacy and effectiveness, our review includes methodologically valid comparative evidence from controlled clinical trials and fair- or good-quality systematic reviews. For evaluating safety we include controlled clinical trials, systematic reviews, and observational studies. A summary of outcome measures and study eligibility criteria can be found in Table 2; a more complete description of commonly used scales and outcome measures can be found in Appendix B. The second key question specifically addresses the time to achieve statistical and clinical differences between available drugs. Although we searched for direct and indirect evidence addressing time to statistical and clinical differences, several points should be considered. In general, determining time to effect and time required to assess clinical response are both difficult tasks given the progressive nature of AD, the design of most trials, and the nature of measurement scales. Because limited evidence compares one AD drug to another and because placebo-controlled trials are too heterogeneous with respect to study design, outcomes assessment, and populations to allow any inferences about the comparative time to effect, drawing conclusions about one drug compared to another is similarly difficult. Furthermore, given the fact that changes in cognition and global assessment can be reached only with sustained treatment with ChEIs and memantine, the clinical significance of time to effect is likely to be of minimal importance to physicians and patients. We review the available evidence below, but we caution readers about interpretation given the nature of the evidence and questionable significance of any differences reported across trials. Although a treatment may not demonstrate clinical improvement from baseline over time, it may be able to slow the rate of cognitive or behavioral deterioration. In this review we use the term “improvement” to reflect the degree to which patients improve with respect to their comparator. Because most of the evidence for these drugs stems from placebo-controlled trials, “improvement” commonly reflects differences between active- and placebo-treated patients. As equipotency among the reviewed antidementia drugs is not well established, we assume that dose comparisons made within the recommended daily dosing range are comparable (Table 1). Dose comparisons made outside the recommended daily dosing range are acknowledged in our report, but we do not use them to determine the quality of the evidence. Furthermore, we evaluate studies that assess only initial treatment with these drugs as independent agents; we do not consider the issue of switching from a ChEI to memantine or vice versa. Although some clinicians may use a combination of drugs in clinical practice, we do not specifically consider combination therapy in this report. However, because combination therapy has been addressed by at least one clinical trial, we contrast this trial with other available evidence. Considerations governing our work on key question 1 and 2 (i. Literature search We searched MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts to identify articles relevant to each key question. We used either Medical Subject Headings (MeSH or MH) as search terms when available or key words when appropriate. We combined terms for the selected indication (Alzheimer’s disease), drug interactions, and adverse events with a list of five specific Alzheimer’s drugs (donepezil, galantamine, rivastigmine, tacrine, and memantine); extended release dosage formulations were included in this search. We limited the electronic searches to “human” and “English language”, and searched sources from 1980 to 2005 (December) to identify literature relevant to the scope of our topic. We used the National Library of Medicine publication type tags to identify reviews, randomized controlled trials (RCTs), and meta-analyses. We manually searched reference lists of pertinent and relevant review articles and letters to the editor. All citations were imported into an electronic database (EndNote 8. Additionally, we hand-searched the Center for Drug Evaluation and Research (CDER) database to identify unpublished research submitted to the FDA. Finally, the Center for Evidence-based Policy at the Oregon Health and Science University (OHSU) contacted pharmaceutical manufacturers and invited them to submit dossiers, including citations, using a protocol available at www. We received dossiers from two pharmaceutical companies. Our searches found 1,109 citations, unduplicated across databases. We found an additional 58 articles from manually reviewing the reference lists of pertinent review articles. We included no studies originating from pharmaceutical dossiers; all studies submitted from pharmaceutical dossiers were present in our other searches. The total number of citations included in the database was 1,167. Study selection Two persons independently reviewed abstracts; if both reviewers agreed that the trial did not meet eligibility criteria we excluded it; we obtained the full text of all remaining articles. Records were considered for exclusion if they did not meet pre-established eligibility criteria with respect to study design or duration, patient population, interventions, outcomes, and comparisons to Alzheimer’s medications outside our scope of interest. We defined head-to-head trials as those comparing one Alzheimer’s drug with another. Included studies were RCTs lasting at least 12 weeks that had an outpatient study population with a total sample size greater than 100 participants. If we could not find sufficient evidence of efficacy or effectiveness from at least one randomized, double- blinded, head-to-head trial, we reviewed randomized, controlled, open-label trials.

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Only baclofen generic ciprofloxacin 750mg with visa infection 2010, dantrolene buy ciprofloxacin 250 mg with mastercard bacteria mod minecraft 152, and tizanidine are approved for the treatment of spasticity ciprofloxacin 1000 mg low cost 51 antimicrobial agents 1. These three antispasticity medications act by different 13, 14 mechanisms: baclofen blocks pre- and post-synaptic GABAB receptors, tizanidine is a 15, 16 centrally acting agonist of α2 receptors, and dantrolene directly inhibits muscle contraction 17 by decreasing the release of calcium from skeletal muscle sarcoplasmic reticulum. Medications from other classes have also been used to treat spasticity. Diazepam, a benzodiazepine, was the first medication thought to be effective for spasticity. It acts by 18, 19 central blockade of GABAA receptors. Other medications used to treat spasticity but not formally approved for this indication include other benzodiazepines, clonidine, gabapentin, and 17 botulinum toxin. The skeletal muscle relaxants carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine have been approved for treatment of Skeletal Muscle Relaxants Page 4 of 237 Final Report Update 2 Drug Effectiveness Review Project musculoskeletal disorders, but not for spasticity. They constitute a heterogeneous group of 20 medications. Cyclobenzaprine is closely related to the tricyclic antidepressants, carisoprodol 21 20 is metabolized to meprobamate, methocarbamol is structurally related to mephenesin, 22 chlorzoxazone is a benzoxazolone derivative, and orphenadrine is derived from 23 diphenhydramine. The mechanism of action for most of these agents is unclear, but may be related in part to sedative effects. These drugs are often used for treatment of musculoskeletal 12 conditions whether muscle spasm is present or not. Although there is some overlap between clinical usage (tizanidine in particular has been studied for use in patients with musculoskeletal 24 complaints), in clinical practice each skeletal muscle relaxant is used primarily for either spasticity or for musculoskeletal conditions. The purpose of this report is to determine whether there is evidence that one or more skeletal muscle relaxant is superior to others in terms of efficacy or safety. This report was originally submitted in February 2003 and updated annually. Update #1 was completed in January 2004 from searches performed in October 2003. Update #2 is based on searches performed in November 2004. New data for Update #2 are highlighted in the text and tables of this report. Since the last update, the Food and Drug Administration (FDA) has not approved any new skeletal muscle relaxants. Scope and Key Questions The scope of the review and key questions were originally developed and refined by the Oregon Evidence-based Practice Center with input from a statewide panel of experts (pharmacists, primary care clinicians, pain care specialists, and representatives of the public). Subsequently, the key questions were reviewed and revised by representatives of organizations participating in the Drug Effectiveness Review Project (DERP). The participating organizations of DERP are responsible for ensuring that the scope of the review reflects the populations, drugs, and outcome measures of interest to both clinicians and patients. The participating organizations approved the following key questions to guide this review: 1. What is the comparative efficacy of different muscle relaxants in reducing symptoms and improving functional outcomes in patients with a chronic neurologic condition associated with spasticity, or a chronic or acute musculoskeletal condition with or without muscle spasms? What are the comparative incidence and nature of adverse effects (including addiction and abuse) of different muscle relaxants in patients with a chronic neurologic condition associated with spasticity, or a chronic or acute musculoskeletal condition with or without muscle spasms? Are there subpopulations of patients for which one muscle relaxant is more effective or associated with fewer adverse effects? Skeletal Muscle Relaxants Page 5 of 237 Final Report Update 2 Drug Effectiveness Review Project Several aspects of the key questions deserve comment: Population. The population included in this review is adult or pediatric patients with spasticity or a musculoskeletal condition. We defined spasticity as muscle spasms associated with an upper motor neuron syndrome. Musculoskeletal conditions were defined as peripheral conditions resulting in muscle or soft tissue pain or spasms. We also excluded patients with restless legs syndrome or nocturnal myoclonus. We included the following oral drugs classified as skeletal muscle relaxants: baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, dantrolene, metaxalone, methocarbamol, orphenadrine, and tizanidine. Benzodiazepenes were not considered primary drugs in this report. However, diazepam, clonazepam, and clorazepate were reviewed when they were compared in head-to-head studies with any of the skeletal muscle relaxants listed above. Other medications used for spasticity but considered to be in another drug class, such as gabapentin (a neuroleptic) and clonidine (an antihypertensive), were also only reviewed when they were directly compared to an included skeletal muscle relaxant. Quinine was only included if it was compared to a skeletal muscle relaxant. The dose of skeletal muscle relaxants used in trials may affect either the efficacy or 25 adverse event profile. One clinical trial of cyclobenzaprine, for example, found equivalent efficacy at 10 and 20 mg tid, but increased adverse events with the higher dose. A study on dantrolene also found a ‘ceiling’ effect at doses of 200 mg daily, with no increased efficacy but 26 more side effects above that dose. Most trials titrated skeletal muscle relaxants to the maximum tolerated dose or a pre-specified ceiling dose, but there are no standardized methods of titration and determining target doses. The main efficacy measures were relief of muscle spasms or pain, functional status, quality of life, withdrawal rates, and adverse effects (including sedation, addiction, and abuse). We excluded non-clinical outcomes such as electromyogram measurements or spring tension measurements. There is no single accepted standard on how to measure the included outcomes. Clinical trials of skeletal muscle relaxants have often used different scales to measure important clinical outcomes such as spasticity, pain, or muscle 27 strength. Many trials have used unvalidated or poorly described methods of outcome assessment. Studies that use the same scale often report results differently (for example, mean raw scores after treatment, mean improvement from baseline, or number of patients “improved”). All of these factors make comparisons across trials difficult. Spasticity is an especially difficult outcome to measure objectively. The most widely used standardized scales to measure spasticity in patients with upper motor neuron syndromes 28 29 are the Ashworth and modified Ashworth scales. In these scales, the assessor tests the resistance to passive movement around a joint and grades it on a scale of 0 (no increase in tone) to 4 (limb rigid in flexion or extension). The modified Ashworth scale adds a “1+” rating between the 1 and 2 ratings of the Ashworth scale. For both of these scales, the scores are usually added for four lower and four upper limb joints, for a total possible score of 0-32, though scoring methods can vary.