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Clinically buy viagra vigour discount erectile dysfunction prostate, it has been associated with an increased risk of bleeding in a gene-dose-dependent fashion without significant impact on Several candidate gene studies and a genome-wide association stent thrombosis or the combined 30-day ischemic end point of study have identified loss-of-function CYP2C19 variants to be death cheap 800mg viagra vigour can erectile dysfunction cause prostate cancer, myocardial infarction generic viagra vigour 800 mg amex zolpidem impotence, or urgent target vessel revasculariza- independently associated with diminished inhibition of ADP- tion. The C3435T polymorphism has been variably associ- stent thrombosis compared with noncarriers. The 3435TT genotype has been confirmed in a meta-analysis of 9 studies of close to 10 000 patients associated with decreased peak plasma concentrations of clopi- 22-28 dogrel and its active metabolites. For clopidogrel, esterases shunt the should be noted that the PON1 Q192R was not associated with majority of ingested clopidogrel to a dead-end inactive pathway, clopidogrel pharmacologic effect in the previously published ge- with the remaining prodrug requiring a 2-step CYP-dependent nome-wide association study of clopidogrel pharmacogenomics,24 oxidation process to produce active clopidogrel metabolites; for and that the very study that identified this novel PON1 Q192R prasugrel, esterases are part of the activation pathway and activation polymorphism was unable to reproduce the well-replicated effect of of prasugrel requires only a single CYP-dependent oxidative step. Subse- quent pharmacology studies have now questioned the supposition The other third-generation P2Y12 inhibitor is ticagrelor, which is an that paraoxonase-1 plays a role in the bioactivation of clopi- active compound and not a prodrug, so it does not require hepatic dogrel. In the PLATO trial, ticagrelor com- a role for the Q192R polymorphism affecting cardiovascular pared with clopidogrel reduced the composite of vascular death, outcomes in patients treated with clopidogrel. As would be expected, In March 2010, the FDA approved a new label for Plavix, with the CYP2C19 polymorphisms do not affect either the pharmacologic or addition of a boxed warning on pharmacogenetics, noting dimin- 55 clinical response to ticagrelor. A genetic analysis within the ished effectiveness of therapy in poor metabolizers (defined as PLATO trial found ticagrelor to be superior to clopidogrel in the having 2 loss-of-function CYP2C19 alleles). The boxed warning treatment of ACS irrespective of CYP2C19 polymorphism, but also further states that “tests are available to identify a patient’s found that the magnitude of benefit tended to be greater in carriers of CYP2C19 genotype and can be used as an aid in determining 35 loss-of-function alleles. One issue is defining what treatment Escalating doses of clopidogrel would be given in the control arm (assuming that in the arm with Potential therapeutic modifications for individuals found to carry a genotyping, loss-of-function carriers all would receive a third- loss-of-function CYP2C19 allele include escalation of clopidogrel generation P2Y12 inhibitor). If the control arm receives clopidogrel, dosage or switching to an alternate agent. The ELEVATE-TIMI 56 one must bear in mind that the pivotal trials that demonstrated the trial demonstrated that tripling the maintenance dose of clopidogrel benefit of the third-generation P2Y12 inhibitors over clopidogrel to 225 mg daily in CYP2C19*2 heterozygotes would achieve required 15 000-20 000 patients each. If only 30% of the experi- on-treatment platelet reactivity comparable to that seen with the mental arm is getting a third-generation P2Y12 inhibitor, the sample standard 75 mg dose in wild-type individuals. Similar data exist from the CLOVIS-2 gave everyone in the control arm an (expensive) third-generation trial for increasing the loading dose. Therefore, the genetic substudies in the randomized controlled trials of prasugrel and ticagrelor are likely the best data Third-generation P2Y12 inhibitors we will have and, as noted above, both suggest greater benefit of Alternatively, one could use a third-generation P2Y12 inhibitor such using a third-generation P2Y12 inhibitor in patients who harbor a as prasugrel or ticagrelor. Prasugrel is also a thienopyridine that CYP2C19 loss-of-function allele. A genetic analysis within the TRITON-TIMI 38 trial ogy Foundation (ACCF)/American Heart Association (AHA) PCI found that loss-of-function polymorphisms in CYP2C19 did not guidelines do not mandate such testing, but rather simply note that Hematology 2014 345 “Genetic testing might be considered to identify whether a patient at nary Stenting and Antithrombotic Regimen: Choose Between 3 High high risk for poor clinical outcomes is predisposed to inadequate Oral Doses for Immediate Clopidogrel Effect) Trial. Impact of platelet reactivity on 12 favor their use. However, we recognize that clopidogrel continues to clinical outcomes after percutaneous coronary intervention: a collabora- tive meta-analysis of individual participant data. In patients with ACS undergoing PCI in which the 2011;58(19):1945-1954. Platelet reactivity and current literature supports the use of prasugrel or ticagrelor when clinical outcomes after coronary artery implantation of drug-eluting not contraindicated clinically in patients who carry a loss-of- stents (ADAPT-DES): a prospective multicentre registry study. Risk of adverse outcomes Disclosures associated with concomitant use of clopidogrel and proton pump Conflict-of-interest disclosures: M. Bristol Myers Squibb, Critical Diagnostics, Daiichi-Sankyo, Eisai, 15. Differential effects of omeprazole and pantoprazole on the pharmacodynamics and pharmaco- Genzyme, Intarcia, Merck, Roche Diagnsotics, Sanofi-Aventis, and kinetics of clopidogrel in healthy subjects: randomized, placebo- Takeda and has received honoraria from Amgen, AstraZeneca, controlled, crossover comparison studies. Pharmacodynamic Healthcare, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & effect and clinical efficacy of clopidogrel and prasugrel with or without Johnson, Sanofi-Aventis, Accumetrics, Nanosphere, and the Na- a proton-pump inhibitor: an analysis of two randomised trials. Clinical events as a function of proton drug use: Clopidogrel at doses beyond the approved dose. Sabatine, MD, MPH, TIMI Study Group, Division of 2011;123(5):474-482. Cardiovascular Medicine, Brigham and Women’s Hospital and Har- 18. Clopidogrel with or without omepra- vard Medical School, 75 Francis Street, Boston, MA 02115; Phone: zole in coronary heart disease. ACCF/ACG/AHA 2010 Expert Consensus Document on the concomitant use of proton pump inhibitors References and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 1. A randomized comparison expert consensus document on reducing the gastrointestinal risks of of antiplatelet and anticoagulant therapy after the placement of coronary- antiplatelet therapy and NSAID use. Cytochrome P450 2C19 loss-of- antithrombotic-drug regimens after coronary-artery stenting. N Engl function polymorphism is a major determinant of clopidogrel responsive- J Med. The Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic 21. Effects of clopidogrel in addition to aspirin in CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacody- patients with acute coronary syndromes without ST-segment elevation. Cytochrome P450 2C19 aspirin and fibrinolytic therapy for myocardial infarction with ST- 681G A polymorphism and high on-clopidogrel platelet reactivity segment elevation. Addition of clopidogrel to aspirin in ous coronary intervention with drug-eluting or bare-metal stents. JAm 45,852 patients with acute myocardial infarction: randomised placebo- Coll Cardiol. Impact of P-glycoprotein on phisms and Response to Clopidogrel. Association of cyto- major determinant of clopidogrel efficacy. Cuisset T, Morange PE, Quilici J, Bonnet JL, Gachet C, Alessi MC. Genetic determinants of Paraoxonase-1 and clopidogrel efficacy. Relation of cytochrome P450 CYP2C19 and PON1 in the mechanism of clopidogrel bioactivation and 2C19 loss-of-function polymorphism to occurrence of drug-eluting in vivo antiplatelet response. Cytochrome P450 2C19 loss-of- metabolization, and antiplatelet effects of 300-, 600-, and 900-mg function polymorphism and stent thrombosis following percutaneous loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoro- coronary intervention. Effects of CYP2C19 genotype on and the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Preven- outcomes of clopidogrel treatment. The relationship between polymorphisms on the effect of high- and standard-dose clopidogrel CYP2C19 polymorphisms and ischaemic and bleeding outcomes in after percutaneous coronary intervention: the GIFT (Genotype Informa- stable outpatients: the CHARISMA genetics study. Paraoxonase-1 is not a major genotype, clopidogrel metabolism, platelet function, and cardiovascular determinant of stent thrombosis in a Taiwanese population. CYP2C19 genotype and cardiovascu- variant and response to clopidogrel and prasugrel [abstract].

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Two trials of immediate-release 208 cheap 800 mg viagra vigour erectile dysfunction pumps review, 215 231 cheap 800mg viagra vigour with mastercard impotence medications, 233 generic viagra vigour 800mg on-line erectile dysfunction after age 40, 234 methylphenidate and 3 trials of methylphenidate SR focused only on patients with ADHD and comorbid substance abuse disorders. One trial of immediate-release methylphenidate 208 involved a broader population of patients with any alcohol or drug dependence, while the 215, 231 others focused on either patients with cocaine dependence, methadone-maintained 233 234 patients, or amphetamine abuse. The primary objectives of these trials were to investigate Attention deficit hyperactivity disorder 113 of 200 Final Update 4 Report Drug Effectiveness Review Project (1) whether use of immediate-release methylphenidate or methylphenidate SR in adult substance abusers with ADHD reduces ADHD symptoms to a similar extent as in non-substance abusers and with ADHD, and (2) what kind of impact immediate-release methylphenidate or methylphenidate SR use may have on the course of the substance abuse disorder. Overall, although use of immediate-release methylphenidate or methylphenidate SR in adult substance abusers with ADHD did not appear to negatively influence the course of the substance abuse disorder recovery process (cravings, abstinence duration, proportion of days of substance use, 215, amount of money spent on substances, or number of days until first negative urine sample), 231, 233 immediate-release methylphenidate or methylphenidate SR also did not appear to offer 208, 215, 231, 233, 234 much of a benefit in the reduction of these patients’ ADHD symptoms. Among the trials that reported response rates, in all but 1 of these trials, not only were there less robust treatment response rates in substance abusers with ADHD compared with non-substance abusers (34% to 47% compared with 38% to 78%), but the placebo response rates in the substance 208, abuser trials were also substantially greater (ranges 21% to 55% compared with 4% to 16%). What is the comparative or noncomparative evidence of misuse or illicit diversion of pharmacologic treatments for attention deficit disorders in patients with current or past substance use disorder comorbidities? Adolescents A retrospective chart review of 450 teens treated at a substance abuse center in Canada from 1993 to 1999 examined the prevalence of abuse of methylphenidate or immediate-release 399 dextroamphetamine. Twenty-three percent had ever used, and 6% were currently using methylphenidate or immediate-release dextroamphetamine, most often reported to be used as crushed tablets taken intranasally. Further assessment of covariates indicated that higher rates of abuse of methylphenidate or immediate-release dextroamphetamine were associated with the teen being out of school or having an eating disorder (P<0. An assessment of correlation of abuse of methylphenidate or immediate- release dextroamphetamine with abuse of other substances did not reveal any statistically significant results. The authors note that this population had a higher psychiatric comorbidity rate than the general adolescent population, which may have affected the results. Adults 208, 215 231, 233 Two trials each of immediate-release methylphenidate and methylphenidate SR focused only on patients with ADHD and comorbid substance abuse disorders. One trial of immediate-release methylphenidate involved a broader population of patients with any alcohol or 208 215, 231 drug dependence, while the others focused on either patients with cocaine dependence or 233 methadone-maintained patients. None reported results of direct assessment of misuse or illicit diversion outcomes. As a potential proxy measure of abuse/diversion, 3 trials reported Attention deficit hyperactivity disorder 114 of 200 Final Update 4 Report Drug Effectiveness Review Project 215, 231, 233 medication compliance. Patient self-reported compliance rates were similar in treatment and placebo groups across all 3 trials (88. Additionally, no differences were found between methylphenidate and placebo in the proportions of riboflavin positive fluorescence 231, 233 (range 0. SUMMARY Limitations of this Review The results of this review are summarized in Table 17, below. As with other types of research, it is important to recognize the limitations of this systematic review. These can be divided into those relating to generalizability of the results and those relating to methodology within the scope of this review. The generalizability of the results is limited by the scope of the key questions and inclusion criteria, and the generalizability of the studies included. The great majority of studies included narrowly or poorly defined patient populations who met strict criteria for case definition, had few comorbidities, and used few or no concomitant medications. One concern about this group of studies is the variation in diagnostic criteria, particularly comparing studies conducted recently to those conducted in previous decades. Another concern is the handling of subtypes of ADHD in these studies. While many studies identify the proportions of patients diagnosed with various subtypes, stratification or analysis of the results based on these is lacking. Similarly, common comorbid conditions are not well addressed by the studies. In large part, the failure to address either subtypes or comorbidities may be due to small sample sizes involved in most studies, but these are serious shortcomings that should not be ignored. The failure of these studies to assess the effect of prior medication exposure or concurrent treatment with other psychoactive medications on outcomes is another serious issue, particularly when comparing older studies where very few patients had prior exposure to newer studies where large proportions did have exposure. Minorities and the most seriously ill patients were underrepresented. Methodological limitations of the review within the defined scope include the exclusion of studies published in languages other than English, and the lack of a specific search for unpublished studies. Applicability The evidence in preschool-age children is most applicable to White boys, ages 4 to 5, with moderately severe symptoms. The evidence base is very small such that characterization of the studies beyond this is not possible, most do not report the proportions with specific subtypes of ADHD or comorbidities. Studies of elementary school age children with ADHD were characterized by under- reporting of baseline subtype classifications, race or ethnicity, co-occurring disorders, and illness severity, although ore recent studies report these data more consistently. Only one-quarter of all studies of school-aged children reported ADHD subtype prevalence rates. The mixed subtype was most common, occurring in 58% to 100% of participants across most study populations. The inattentive subtype was generally observed less frequently (prevalence rate range: 9% to 40%) and the hyperactive subtype was relatively rare (prevalence rate range: 1% to 8%). Only one-half Attention deficit hyperactivity disorder 115 of 200 Final Update 4 Report Drug Effectiveness Review Project of all studies of elementary school-aged children reported race or ethnicity among the baseline characteristics. The racial/ethnic make-up of the majority of these study populations was consistent with the current United States Census Bureau Estimates (White = 80. However, the prevalence of ADHD among ethnic groups may not correlate with these data. The evidence applies best to children 8 to 9 years old. Just over half of studies reported prevalence rates of co-occurring disorders, including oppositional defiant disorder (19% to 66. With the exception of depression, the ranges of comorbidities reported in these trials encompass the American Academy of Pediatrics estimates on prevalence of common comorbidities: Oppositional defiant disorder, 35%; conduct disorder, 359 26%; anxiety disorder, 26%; and depressive disorder, 18%. Illness severity was not presented as a baseline characteristic in most studies, and comparisons across studies based on scales used to assess symptoms are hampered by variation in scale choice and method of reporting. Seventy-two percent of studies used either the DSM III, DSM III-R, or DSM IV criteria to diagnose ADHD, however many used additional criteria and the clinical comparability of patients enrolled is not clear. The evidence in adolescents, although limited, is more diverse. While many studies reflect populations that are mainly white boys (mean age 14) with moderate to severe symptoms, a few studies included populations with close to 50% girls and 50% boys, and higher percentages of non-white teens. The combined type of ADHD was more prevalent; however few studies reported this characteristic. In adults, studies generally included populations in their mid-thirties that were fairly balanced in terms of sex. However, studies in adults were also characterized by under-reporting of baseline ADHD subtype classifications, race or ethnicity, and co-occurring disorders. In the small number of trials that reported these data, race was predominantly white, but prevalence varied widely for the inattentive and combined subtypes of ADHD and for co-occurring disorders. Studies Pending Review Two potentially relevant studies (one retrospective cohort study of cardiovascular harms in patients with ADHD and 1 systematic review of interventions for pre-school age children with 401, 402 ADHD) were published after our inclusion dates and have not been incorporated here. Summary of the evidence Comparison: Overall strength of the evidence Conclusion Key Question 1.

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Leisenring W best buy for viagra vigour impotence under 40, Friedman DL viagra vigour 800mg for sale erectile dysfunction pump as seen on tv, Flowers ME order viagra vigour on line amex impotence grounds for divorce, Schwartz JL, Deeg HJ. Nonmelanoma skin and mucosal cancers after hematopoietic cell Blood. Increased risk of breast (CHF) following hematopoietic cell transplantation. Risk for secondary thyroid and other late-onset non-infectious pulmonary complications following carcinoma after hematopoietic stem-cell transplantation: an EBMT Late allogeneic stem cell transplantation. Secondary Gastrointesti- tions after allogeneic hematopoietic stem cell transplantation: diag- nal cancer in childhood cancer survivors–a cohort study. Ann Intern nosis, monitoring, prevention, and treatment. High-resolution CT findings of in digestive organs after childhood cancer: a cohort-nested case-control bronchiolitis obliterans syndrome after hematopoietic stem cell transplan- study. Children’s Oncology Group: Long-term follow-up guidelines for survi- 17. National Institutes of vors of childhood, adolescent, and young adult cancers, version 4. Health consensus development project on criteria for clinical trials in Monrovia, CA: Children’s Oncology Group; 2013. Diagnosis and treatment of related quality of life, growth, and spiritual well-being after hematopoi- pulmonary chronic GVHD: report from the consensus conference on etic stem-cell transplantation. Schuttle CMS, Beelen DW: Bone loss following hematopoietic cell trial). Strategic approaches to osteoporosis in transplantation. Life expectancy in 502 American Society of Hematology patients surviving more than 5 years after hematopoietic cell transplan- Marrow Transplant Survivor Study. Recommended screening and screening practices in long-term survivors of hematopoietic cell trans- preventive practices for long-term survivors after hematopoietic cell plantation (HCT): A report from the BMT Survivor Study. The preventive health obesity, and mortality from cancer in a prospectively studied cohort of behaviors of long-term survivors of cancer and hematopoietic stem cell U. Burden of morbidity in 10 year survivors: a report from the Bone Marrow Transplant Survivor Study. Flowers1 1Winship Cancer Institute of Emory University, Atlanta, GA Given the paucity of randomized controlled trial data, defining the ideal strategy for surveillance imaging in patients with non-Hodgkin lymphoma (NHL) has become increasingly challenging. The routine use of frequent surveillance scans has been a common component of patient care. Emerging data from prospective and retrospective observational studies and modeling approaches have highlighted the performance characteristics of imaging modalities and the challenges with this form of secondary screening. The majority of patients with relapsed lymphoma have clinical signs or symptoms that prompt further evaluation, and only a small proportion of patients experience relapse detected on a routine scan while being otherwise asymptomatic. Surveillance imaging is costly, may expose patients to minimal risks of mortality due to radiation-related secondary malignancies, and can lead to false-positive findings, leading to unnecessary biopsies. In addition, no prospective study has demonstrated a significant improvement in overall survival for those patients whose disease is discovered on a routine scan versus those who present with clinical symptoms. In this chapter, we examine the baseline risks of relapse for various NHL subtypes that provide the context for surveillance, review the data on imaging modalities, and establish a framework for discussing optimal surveillance strategies with individual patients. Patients should be counseled on the risks and benefits of routine surveillance imaging and decisions regarding surveillance should be made on an individual basis using patient-specific risk factors, response to induction therapy, and patient preferences with a bias toward using surveillance imaging in the 2 years after treatment only in those NHL patients with the greatest likelihood of benefit. Despite an overall phoma, but the optimal follow-up for these patients remains a response rate of 88% for the most commonly used induction subject of intense debate, especially with regard to the appropriate regimens [R-CVP (rituximab, cyclophosphamide, vincristine, pred- use of routine surveillance imaging. Unfortunately, a significant nisolone), R-CHOP, and R-bendamustine], 25% of patients with portion of patients with non-Hodgkin lymphoma (NHL) who MCL and follicular lymphoma (FL) experience treatment failure within 3 years. In diffuse large B-cell lymphoma (DLBCL), for example, the CR rate MCL, although approaches combining high-dose cytarabine with for current standard therapy with R-CHOP (rituximab, cyclophos- autologous stem cell transplantation result in high response rates and increasing durations of response. Patients with a high-risk IPI who encouraging, with a median event-free survival of 83 months. Lymphoma-related survival curves by lymphoma subtype. HL indicates Hodgkin lymphoma; FL, follicular lymphoma; DLBCL, diffuse large B-cell lymphoma; BL, Burkitt lymphoma; and PTCL, peripheral T-cell lymphoma. The 3-year PFS for patients with therapy or novel agents that produce additional responses, although relapsed DLBCL who plan to undergo salvage therapy with R-ICE these are typically progressively shorter in duration. In many cases, Peripheral T-cell lymphoma (PTCL) is in general associated with a patients with relapsed indolent NHL can be observed without worse outcome than B-cell NHL and Hodgkin lymphoma (HL). Recently, agents targeting the meta-analysis reviewing outcomes for most T-cell lymphoma B-cell receptor signaling pathway have demonstrated tolerable, oral subtypes, the CR rate for anthracycline-containing induction regi- options for prolonged administration in relapsed/refractory MCL mens was 66% for anaplastic large cell lymphoma, 58% for NK/T and indolent NHL. However, when exclud- The timing and the risk of lymphoma-related death varies by ing anaplastic large cell lymphoma, the 5-year OS for patients with lymphoma subtype. Figure 1 displays data from the Surveillance PTCL was 37%24 because the majority of patients relapse and die Epidemiology and End Results (SEER) program on lymphoma- from disease. Consolidation with autologous stem cell transplanta- related survival for various lymphoma populations. SEER data also tion in first remission may improve PFS and OS for patients with indicate that, across all patients diagnosed with NHL, 1/3 will PTCL,25,26 but the benefit of this approach remains unproven. Because the majority of evaluation of multiple potential disease sites is important to identify evidence details outcomes for patients with DLBCL, this is the relapsed disease. Recently, the ASH Guidelines for surveillance in NHL Choosing Wisely campaign identified routine surveillance scans as For patients who are currently in remission after completion of an area for improvement in the clinical management of patients, induction therapy, surveillance scans can be considered a secondary suggesting that routine imaging surveillance for asymptomatic screening assessment for the early detection of relapsed disease. The application of these principles to postremission surveillance in NHL Among patients who experience a relapse, cure is possible in a can be challenging because aggressive subtypes are likely more significant portion of patients with aggressive NHL who are able to clinically significant but also less likely to be detected before 482 American Society of Hematology Table 1. Lifetime attributable cancer incidence (LCI) and lifetime attributable cancer mortality (LCM) for surveillance CT imaging and cumulative probability of lymphoma-related death by lymphoma subtype, age at diagnosis, and sex 5-y cumulative probability LCI from CT* LCM from CT* of lymphoma death32 Lymphoma subtype (age at diagnosis) Males Females Males Females Males Females NHL (any) 0. It remains a matter of debate whether earlier detection of Two patients had an asymptomatic relapse that was identified solely relapsed aggressive or indolent NHL results in improved OS, and due to a routine surveillance CT scan. Of the remaining patients who the data regarding this question are reviewed herein. Although surveillance imaging is not specifi- surveillance scan, although the frequency of chest CT was low in cally recommended for Burkitt lymphoma, the recommendations this older cohort from 1991. For patients with DLBCL, all of whom achieved a CR/unconfirmed CR advanced-stage DLBCL, the recommendations include CT scans no (CRu) to initial therapy, reported that only 22% of the relapses were more often than every 6 months for 2 years, followed by scans only identified on routine surveillance CT; the remaining patients were as clinically indicated. These recommendations are similar for identified based on symptoms, physical examination, or laboratory follicular lymphoma, but there are no specific recommendations for evaluations. There was no significant difference in OS from the time imaging for marginal zone lymphoma and MCL.

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A confidence interval is a measure of the uncertainty (due to the play of chance) associated with that estimate purchase 800mg viagra vigour with mastercard erectile dysfunction treatment otc. Pooling: The practice of combing data from several studies to draw conclusions about treatment effects order viagra vigour 800mg amex impotence at 50. Power: The probability that a trial will detect statistically significant differences among intervention effects viagra vigour 800 mg on-line erectile dysfunction treatment wikipedia. Studies with small sample sizes can frequently be underpowered to detect difference. Precision: The likelihood of random errors in the results of a study, meta-analysis, or measurement. The greater the precision, the less the random error. Confidence intervals around the estimate of effect are one way of expressing precision, with a narrower confidence interval meaning more precision. Prospective study: A study in which participants are identified according to current risk status or exposure and followed forward through time to observe outcome. Prevalence: How often or how frequently a disease or condition occurs in a group of people. Prevalence is calculated by dividing the number of people who have the disease or condition by the total number of people in the group. Disease-modifying drugs for multiple sclerosis Page 103 of 120 Final Report Update 1 Drug Effectiveness Review Project Probability: The likelihood (or chance) that an event will occur. In a clinical research study, it is the number of times a condition or event occurs in a study group divided by the number of people being studied. Publication bias: A bias caused by only a subset of the relevant data being available. The publication of research can depend on the nature and direction of the study results. Studies in which an intervention is not found to be effective are sometimes not published. Because of this, systematic reviews that fail to include unpublished studies may overestimate the true effect of an intervention. In addition, a published report might present a biased set of results (for example, only outcomes or subgroups for which a statistically significant difference was found). P value: The probability (ranging from zero to one) that the results observed in a study could have occurred by chance if the null hypothesis was true. Q-statistic: A measure of statistical heterogeneity of the estimates of effect from studies. It is calculated as the weighted sum of the squared difference of each estimate from the mean estimate. Random-effects model: A statistical model in which both within-study sampling error (variance) and between-studies variation are included in the assessment of the uncertainty (confidence interval) of the results of a meta-analysis. When there is heterogeneity among the results of the included studies beyond chance, random-effects models will give wider confidence intervals than fixed-effect models. Randomization: The process by which study participants are allocated to treatment groups in a trial. Adequate (that is, unbiased) methods of randomization include computer generated schedules and random-numbers tables. Randomized controlled trial: A trial in which two or more interventions are compared through random allocation of participants. Regression analysis: A statistical modeling technique used to estimate or predict the influence of one or more independent variables on a dependent variable, for example, the effect of age, sex, or confounding disease on the effectiveness of an intervention. Relative risk: The ratio of risks in two groups; same as a risk ratio. Retrospective study: A study in which the outcomes have occurred prior to study entry. Risk: A way of expressing the chance that something will happen. It is a measure of the association between exposure to something and what happens (the outcome). Risk is the same as probability, but it usually is used to describe the probability of an adverse event. It is the rate of events (such as breast cancer) in the total population of people who could have the event (such as women of a certain age). Risk difference: The difference in size of risk between two groups. In intervention studies, it is the ratio of the risk in the intervention group to the risk in the control group. A risk ratio of 1 indicates no difference between comparison groups. For undesirable outcomes, a risk ratio that is <1 indicates that the intervention was effective in reducing the risk of that outcome. Disease-modifying drugs for multiple sclerosis Page 104 of 120 Final Report Update 1 Drug Effectiveness Review Project Run-in period: Run in period: A period before randomization when participants are monitored but receive no treatment (or they sometimes all receive one of the study treatments, possibly in a blind fashion). The data from this stage of a trial are only occasionally of value but can serve a valuable role in screening out ineligible or non-compliant participants, in ensuring that participants are in a stable condition, and in providing baseline observations. A run-in period is sometimes called a washout period if treatments that participants were using before entering the trial are discontinued. This term (or the term ‘‘safe’’) should not be used when evidence on harms is simply absent or is insufficient. Sample size: The number of people included in a study. In research reports, sample size is usually expressed as "n. Larger sample sizes also increase the chance that rare events (such as adverse effects of drugs) will be detected. Sensitivity analysis: An analysis used to determine how sensitive the results of a study or systematic review are to changes in how it was done. Sensitivity analyses are used to assess how robust the results are to uncertain decisions or assumptions about the data and the methods that were used. Side effect: Any unintended effect of an intervention. Side effects are most commonly associated with pharmaceutical products, in which case they are related to the pharmacological properties of the drug at doses normally used for therapeutic purposes in humans. Standard deviation (SD): A measure of the spread or dispersion of a set of observations, calculated as the average difference from the mean value in the sample. Standard error (SE): A measure of the variation in the sample statistic over all possible samples of the same size. The standard error decreases as the sample size increases. Standard treatment: The treatment or procedure that is most commonly used to treat a disease or condition.