Why a Safe but Challenging Environment Is Important

Medical Decision Making http://mdm. sagepub. com/ Do Patient Decision Aids Meet Effectiveness Criteria of the International Patient Decision Aid Standards Collaboration? A Systematic Review and Meta-analysis Annette M. O'Connor, Carol Bennett, Dawn Stacey, Michael J. Barry, Nananda F. Col, Karen B. Eden, Vikki Entwistle, Valerie Fiset, Margaret Holmes-Rovner, Sara Khangura, Hilary Llewellyn-Thomas and David Rovner Med Decis Making published online 14 September 2007 DOI: 10. 1177/0272989X07307319.   A more recent version of this article was published on – Oct 5, 2007 Published by: http://www. sagepublications. com On behalf of: Society for Medical Decision Making Additional services and information for Medical Decision Making can be found at: Email Alerts: http://mdm. sagepub. com/cgi/alerts Subscriptions: http://mdm. sagepub. com/subscriptions Reprints: http://www. sagepub. com/journalsReprints. nav Permissions: http://www. sagepub. com/journalsPermissions. nav Version of Re cord – Oct 5, 2007 ;; OnlineFirst Version of Record – Sep 14, 2007 What is This? Downloaded from mdm. sagepub. com by guest on July 22, 2012 Med Decis Making OnlineFirst, published on September 14, 2007 as doi:10. 1177/0272989X07307319 Do Patient Decision Aids Meet Effectiveness Criteria of the International Patient Decision Aid Standards Collaboration? A Systematic Review and Meta-analysis Annette M. O’Connor, RN, PhD, Carol Bennett, MSc, Dawn Stacey, RN, PhD, Michael J. Barry, MD, Nananda F. Col, MD, MPH, MPP, Karen B. Eden, PhD, Vikki Entwistle, PhD, Valerie Fiset, MScN, Margaret Holmes-Rovner, PhD, Sara Khangura, Hilary Llewellyn-Thomas, PhD, David Rovner, MD Objective. Related article: Explain the Post 16 Options 2017 To describe the extent to which patient decision aids (PtDAs) meet effectiveness standards of the International Patient Decision Aids Collaboration (IPDAS). Data sources. Five electronic databases (to July 2006) and personal contacts (to December 2006). Results. Among 55 randomized controlled trials, 38 (69%) used at least 1 measure that mapped onto an IPDAS effectiveness criterion. Measures of decision quality were knowledge scores (27 trials), accurate risk perceptions (12 trials), and value congruence with the chosen option (3 trials). PtDAs improved knowledge scores relative to usual care (weighted mean difference [WMD] = 15. %, 95% confidence interval [CI] = 11. 7 to 18. 7); detailed PtDAs were somewhat more effective than simpler PtDAs (WMD = 4. 6%, 95% CI = 3. 0 to 6. 2). PtDAs with probabilities improved accurate risk perceptions relative to those without probabilities (relative risk = 1. 6, 95% CI = 1. 4 to 1. 9). Relative to simpler PtDAs, detailed PtDAs improved value cong ruence with the chosen option. Only 2 of 6 IPDAS decision process criteria were measured: feeling informed (15 trials) and feeling clear about values (13 trials). PtDAs improved these process measures relative to usual care (feeling uninformed WMD = –8. , 95% CI = –11. 9 to –4. 8; unclear values WMD = –6. 3, 95% CI = –10. 0 to –2. 7). There was no difference in process measures when detailed and simple PtDAs were compared. Conclusions. PtDAs improve decision quality and the decision process’s measures of feeling informed and clear about values; however, the size of the effect varies across studies. Several IPDAS decision process measures have not been used. Future trials need to use a minimum data set of IPDAS evaluation measures. The degree of detail PtDAs require for positive effects on IPDAS criteria should be explored. Key words: decision support techniques; patient education; patient participation; randomized controlled trials. (Med Decis Making 2007;XX:xx–xx) Received 23 July 2007 from the Ottawa Health Research Institute, Canada (AMO, SK, CB); University of Ottawa, Canada (AMO, DS); Massachusetts General Hospital, Boston (MJB); Maine Medical Center, Portland, Maine (NFC); Oregon Health and Science University, Portland (KBE); Social Dimensions of Health Institute, Dundee, UK (VE); Algonquin College, Ottawa, Canada (VF); Michigan State University, East Lansing (MH-R, DR); and Dartmouth Medical School, Hanover, New Hampshire (HL-T). Financial support for this study was provided by a group grant of the Canadian Institutes of Health Research. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, and writing and publishing the report. Address correspondence to Annette M. O’Connor, RN, PhD, University of Ottawa, Ottawa Health Research Institute, 1053 Carling Avenue, ASB, Ottawa, Ontario, Canada K1Y 4E9; e-mail: [email  protected] ca. DOI: 10. 1177/0272989X07307319 P atient decision aids (PtDAs) are adjuncts to counseling that explain options, clarify personal values for the benefits versus harms, and guide patients in deliberation and communication. With the rapid proliferation of these tools, the International Patient Decision Aids Collaboration (IPDAS) has reached agreement on criteria for judging the quality of PtDAs. 1 IPDAS is a network of more than 100 researchers, practitioners, patients, and policy makers from 14 countries. These collaborators developed a checklist of criteria that payers, patients, practitioners, developers, and researchers can use to assess PtDAs they encounter. The criteria address 3 domains of quality: clinical content, the development process, and effectiveness. 554 †¢ MEDICAL DECISION MAKING/MON–MON 2007 Downloaded from mdm. sagepub. com by guest on July 22, 2012 Copyright 2007 by Society for Medical Decision Making.DECISION AIDS â€Å"EFFECTIVENESS CRITERIA OF DECISION AIDS†This article addresses the 3rd domain, the evaluation of PtDAs’ effectiveness in fostering a high-quality decision process and a high-quality choice. Over the past decade, there has been considerable debate about the definition of a good decision when there is no single best therapeutic action and choices depend on how patients value benefits versus harms. 2–6 To select criteria for decision quality, IPDAS participants were asked to identify â€Å"the things that you would nee d to observe in order to say that after using a patient decision aid, the way the decision was made was good and the choice that was made was good. IPDAS endorsed the following criteria for establishing that a decision aid is effective: †¢ Decision quality: The PtDA improves the match between the chosen option and the features that matter most to the informed patient. †¢ Decision processes leading to decision quality: The PtDA helps patients to recognize that a decision needs to be made, know options and their features, understand that values affect the decision, be clear about the option features that matter most, discuss values with their practitioner, and become involved in preferred ways. Our study objectives were 1) to describe the number and types of measures used in randomized controlled trials (RCTs) that correspond to IPDAS criteria for effectiveness and 2) to determine the extent to which RCTs of PtDAs meet these new IPDAS criteria for effectiveness. METHODS We have been updating the Cochrane Review of decision aids since the late 1990s. 7–9 This review differed from previous reviews by focusing on the new IPDAS criteria. Moreover, we used a new systematic review software, TrialStat SRS, to manage the search and data extraction; therefore, our search, screen, and data extraction were redone completely. Data sources included 1) electronic databases to July 2006 (MEDLINE, PsycINFO, CINAHL, and EMBASE), 2) Cochrane Controlled Trials Register (2006, issue 2), and 3) contact with known developers and evaluators to December 2006. The search strategy is described in the appendix. The search was not restricted on the basis of language. PtDAs were defined as interventions designed to help people make specific, deliberated choices among options (including the status quo) by providing information about the options and outcomes (e. . , benefits, DECISION AIDS: PAST, PRESENT, AND FUTURE harms) in sufficient detail that an individual could judge their value implicitly. Patient decision aids may also include information about the clinical condition, outcome probabilities tailored to personal risk factors, an explicit values clarification exercise (e. g. , a relevance chart, utility assessments of probable outcome states, a weigh scale), descriptions of others’ experiences, and guidance in the steps of decision making and communicating with others. This definition excludes interventions focused solely on lifestyle changes, hypothetical situations, clinical trial entry, or general advanced directives; education programs not geared to a specific decision; and interventions designed to promote adherence to a recommended option or to elicit passive informed consent. In the current review, we also excluded studies whose PtDAs were not available for inspection to catalogue their elements according to the new IPDAS domains. As a consequence, a few studies reported in the previous reviews were not included. We included published RCTs comparing 1) PtDAs to usual-care controls or 2) detailed PtDAs to simpler ones (which may not have the level of detail or may not contain all of the IPDAS elements). Participants were deciding about screening or treatment options for themselves, for a child, or for an incapacitated significant other. Two reviewers independently screened each study (CB, SK, DS, AMO, VF), extracted data (CB, SK), and assessed study quality (C. B. , S. K. ) using standardized forms, including the Jadad scale. 0 Inconsistencies were resolved by consensus. Trial results were described individually. Metaanalysis was used for decision quality and for decision process measures because these effects were expected to be independent of the type of decision. Meta-analysis was performed only on those outcomes with similar types of measures. Review Manager 4. 211 was used to estimate a weighted treatment effect (with 95% confidence intervals [CIs]), defined as weighted mean differences ( WMDs) for continuous measures and pooled relative risks (RRs) for dichotomous outcomes. The data used in each meta-analysis can be viewed in the online supplement available at http://mdm. sagepub. com/cgi/ content/full/Volume/Issue/Page#/DC1. All data were analyzed with a DerSimonian and Laird12 random effects model because of the diverse nature of the trials. Forest plots were used to assess and display potential heterogeneity, and funnel plots were used to explore publication bias. Because of statistically significant heterogeneity for most of the outcomes, we performed post hoc subanalyses to explore the potential causes of heterogeneity. Heterogeneity was explored according 555 Downloaded from mdm. sagepub. com by guest on July 22, 2012 O’CONNOR AND OTHERS to the following factors: type of decision (treatment versus screening), type of media of decision aid (video/ computer versus audio booklet/pamphlet), and a possible ceiling effect based on good usual-care scores (removal of studies with lower knowledge and realistic risk perception scores; removal of studies with higher decisional conflict scores for subscales feeling uninformed and unclear values). We analyzed the effects of removing the biggest outlier(s) defined by visual inspection of the forest plots. In addition, a post hoc analysis was performed to examine the effect of 1) excluding trials of low methodological quality and 2) excluding trials that were outliers and contributed to heterogeneity.RESULTSOf the 22,778 unique citations obtained in the review, we identified 1293 as relevant by title and then screened those abstracts (see Figure 1). Of these, 130 citations were retrieved for full-text review. Sixty-four studies were excluded for the following reasons: the study was not focused on making a choice (n = 33), the study was not an RCT (n = 14), the decision support intervention did not meet the definition of a PtDA (n = 8), the study involved a hypothetical situation (n = 6), and no outcome data were provided (n = 3). In all, 55 eligible trials (66 references) were found for duplicate data extraction and analysis. The 55 published RCTs evaluating individual PtDAs13–78 used 51 different PtDAs that focused on 23 different screening or treatment topics (see Table 1). Among the 51 different PtDAs, the elements most frequently included were information about the options and outcomes in sufficient detail to judge their value implicitly (100% by definition), information about the clinical condition (98%), outcome probabilities (84%), examples of others’ experiences (59%), explicit values clarification exercises (55%), and guidance in the steps of decision making (47%). Quality ratings in the trials ranged from 0/5 to 3/5. All studies lost 2 points because patients or practitioners could not be blinded to the intervention. As shown in Table 2, 38 of the 55 trials (69%) reported at least 1 outcome that could be mapped onto an IPDAS criterion for effectiveness; 33 (60%) measured some aspect of decision quality, and 15 (27%) measured a decision process leading to decision quality. Decision Quality As noted above, the definition of decision quality has 2 elements: the extent to which decisions are 556 †¢ MEDICAL DECISION MAKING/MON–MON 2007 informed and based on personal values. Trials used 3 measures corresponding to this definition: knowledge test results, accuracy of risk perceptions, and value congruence with chosen option. Knowledge. Twenty-seven of the 55 studies examined the effects of PtDAs on knowledge; 18 of these compared PtDAs to usual care, and 9 compared PtDAs with more or less detail. The studies’ knowledge tests were based on information contained in the PtDA, thereby establishing content validity. The proportion of accurate responses was transformed to a percentage scale ranging from 0% (no correct responses) to 100% (perfectly accurate responses). In the comparison of PtDAs to usual care15,16,18,26,28,29, 31,36,39,41,43,48,50,64,65,69,73,78 (Figure 2), PtDAs had higher average knowledge scores (WMD = 15. 2%, 95% CI = 11. 7, 18. 7). The 9 studies comparing detailed with simpler PtDAs22,24,30,35,54,60,61,63,66 (Figure 3) showed a smaller effect (WMD = 4. 6%, 95% CI = 3. 0, 6. 2). Accurate risk perceptions. Eleven of 55 studies examined the effects of including probabilities of PtDAs on the accuracy of patients’ perceived probabilities of outcomes. 4,28,41,43–45,54,63,73,74,77 Eight studies measured perceived probabilities as percentages,24,28,43–45,54,73,74 and 3 gauged probabilities in words. 41,63. 77 Perceived outcome probabilities were classified as accurate according to the percentage of individuals whose judgments corresponded to the scientific evidence about the chances of an outcome for similar people. In 4 of 5 studies that elicited perceived probabilities for multiple outcomes,24,44,54,60 the propo rtion of realistic expectations was averaged; in the remaining study,43 the most conservative result was chosen for meta-analysis. People who received a detailed PtDA with descriptions of outcomes and probabilities were more likely to have accurate risk perceptions than those who did not receive this information; the pooled RR of having accurate risk perceptions was 1. 6 (95% CI = 1. 4, 1. 9; Figure 4). The pooled relative risk for probabilities described in words was 1. 3 (95% CI = 1. 1, 1. 5). The pooled relative risk for probabilities described as numbers was 1. 8 (95% CI = 1. 4, 2. 3). Value congruence with chosen option. Four of 55 studies measured value congruence with the chosen option; however, Lerman and others41 did not calculate differences between interventions. The 3 trials comparing interventions were similar in that they 1) focused on the decision to take menopausal hormone replacement therapy (HRT) and 2) compared 2 active interventions. However, these trials used different measures of value (text continued on p 565) Downloaded from mdm. sagepub. com by guest on July 22, 2012 DECISION AIDS â€Å"EFFECTIVENESS CRITERIA OF DECISION AIDS† 2,778 unique citations identified for initial screening (screening based on review of the title) 1,293 potentially relevant citations identified and screened (based on review of the abastract) for retrieval 130 citations retrieved for full-text review 64 excluded: study not focused on making a choice (n = 33); study was not RCT (n = 14); decision support intervention did not meet the definition of a PtDA (n = 8); study involved a hypothetical situatio n (n = 6); no outcome data provided (n = 2); protocol only (n = 1) 5 eligible trials (66 references) for duplicate data extraction Data entry & RCT meta- analysis Figure 1 Flowchart of the procedural steps in the systematic review. RCT = randomized controlled trial; PtDA = patient decision aid. DECISION AIDS: PAST, PRESENT, AND FUTURE Downloaded from mdm. sagepub. com by guest on July 22, 2012 557 Table 1 Elements in DAs Characteristics of 55 Trials Included in the Systematic Review of Patient Decision Aids 558 Number of Enrollees in Intervention + Comparison: Options Considered Quality Rating (Jadad) Others’ Experiences Comparison of Most and Least Intensive Intervention Options and Clinical Outcomes Problem Explicit Outcome Values Probability Clarification Guidance in Steps of DM Source, Year, Location Auvinen and others13,14 2004, Finland 3/5 1/5 2/5 3/5 2/5 2/5 — X — X X X — — X X X — — X — X X — — X X — — X — X — — — X — — X X X — X — — — X — — — — — X — — — X — — — X — — — — — — — — X — — Barry and others15 1997, United States Bekker and others,16,17 2004, United Kingdom Bernstein and others18 1998, United States Pamphlet PtDA Standard care by clinical guideline Interactive videodisc PtDA Usual care Decision analysis plus consultation Usual care Video PtDA Usual care Clancy and others19 1988, United States 30 + 30 men: prostate cancer treatment 67 + 61 women: HRT 1/5 — X X X X X X X X X — X X X X X 103 + 100 men: prostate cancer treatment 104 + 123 men: benign prostate hypertrophy treatment 59 + 58 women: prenatal diagnostic screening for Down syndrome 65 + 53 patients: ischemic heart disease treatment 753 + 263 physicians: hepatitis B vaccine Davison and Degner20 1997, Canada Deschamps and others21 2004, Canada 3/5 — X X X — X — X — X — — — X — X — X — X — X — — — X — — — X — X Downloaded from mdm. sagepub. com by guest on July 22, 2012 Deyo and others22 2000; Phelan and others23 2001, United States 2/5 Dodin and others24 2001, Canada 50 + 47 adults: colon cancer screening 3/5 2/5 3/5 143 + 144 parents: infant polio vaccine schedules 112 + 114 men: PSA testing 190 + 203 patients: herniated disc or spinal stenosis treatment 52 + 49 women: HRT Pamphlet + decision analysis PtDA Usual care Written materials, PtDA, and audiotape of consultation Usual care Audiotape and booklet Pharmacist consultation Interactive videodisc PtDA Simple PtDA pamphlet Audiotape booklet PtDA Simple PtDA pamphlet Dolan and Frisina25 2002, United States Dunn and others26 1998, United States Frosch and others27 2003, United States — X — X X X X X X X — X — X X — — — — — — X — X X — — — — — Computer: analytic hierarchy process and pamphlet PtDA Usual care Video and pamphlet PtDA Usual care Video PtDA Internet presentation mirroring content of video continued) Gattellari and Ward28 2003, Australia 3/5 3/5 3/5 X X — X — X — X X — X X — X — X X — — X — — — — — X X — — — X — — X — — — X — X â⠂¬â€ X — X — X X X X X X — X — X — X — — — — — X — — — — — X — X — X — X — X — X — — — — — 140 + 140 men: PSA testing 86 + 50 women: breast cancer surgery 1/5 126 + 122 men: PSA testing Gattellari and Ward29 2005, Australia Goel and others30 2001, Canada Green and others31 2001, United States 3/5 CD-ROM PtDA plus counseling Genetic counseling Pamphlet PtDA Usual care Pamphlet PtDA General information leaflet Pamphlet PtDA General information leaflet Audiotape and booklet PtDA Simple PtDA pamphlet CD-ROM PtDA plus counseling Usual care Green and others32,33 2004, United States 0/5 2/5 Herrera and others34 1983, United States Hunter and others35 2005, Canada 3/5 3/5 2/5 3/5 Audiotape and booklet PtDA Usual care Audiotape and booklet Individual genetic counseling Decision board PtDA Usual care Video plus booklet PtDA Usual care Booklet PtDA Personal risk profile X — X — X — X — X X X — 2/5 X X X — X — X X X — X X X — X X 9 + 14 higher risk women: breast cancer genetic testing 106 + 105 higher risk women: breast cancer genetic testing 56 + 47 parent(s): circumcision of male newborns 116 + 126 women: prenatal diagnostic testing X — X — X X X — X X X — X X — — X — X — X — X — X — — — Downloaded from m dm. sagepub. com by guest on July 22, 2012 Johnson and others36 2006, United States Kennedy and others37 2002, United Kingdom Lalonde and others38 2006, Canada — — X — X — X — X — X — — — — — X — X — X — X — X — X — (continued) Laupacis and others39 2006, Canada 2/5 Legare and others40 2003, Canada 122 + 164 women: breast cancer genetic testing 100 + 101 women: prenatal diagnostic testing 1/5 32 + 35 patients: dental surgery 300 + 298 women: menorrhagia treatment 13 + 13 patients: cardiovascular health treatment 60 + 60 patients: preoperative autologous blood donation 97 + 87 women: HRT erman and others41 1997, United States Leung and others42 2004, China Audiotape booklet PtDA Simple pamphlet PtDA Discussion PtDA and counseling Usual care wait list control Interactive multimedia PtDA Video and pamphlet 559 Table 1 Elements in DAs continued) 560 Number of Enrollees in Intervention + Comparison: Options Considered Quality Rating (Jadad) Others’ Experiences Comparison of Most and Least Intensive Intervention Options and Clinical Outcomes Problem Explicit Outcome Values Probability Clarification Guidance in Steps of DM Source, Year, Location Man-Son-Hing and others43 1999, Canada — X X X X — — — 3/5 1/5 2/5 X X X X X X — X — X — X — X — X — X — X — X — X — X — — — X — X 3/5 Audiotape and booklet PtDA Usual care X X X X X — X — X — — — — — — X — X — X — — — — — — McAlister and others44 2005, Canada McBride and others45,46 2002, United States Miller and others47 2005, United States 139 + 148 aspirin users in atrial fibrillation trial: move to warfarin 219 + 215 patients: antithrombotic therapy 289 + 292 women: HRT 279 women: BRCA1 BRCA2 gene testing Montgomery and others48,49 2003, United Kingdom 52 + 55 + 51 + 59 adults: hypertension treatment 3/5 Downloaded from mdm. sagepub. com by guest on July 22, 2012 Morgan and others50 2000, Canada 3/5 3/5 — X — X — X — X X — X — X — X — X X — X — X — X — — — — — — — — — — X — — X — X — X — — — — — — — — — — X — Murray and others51 2001, United Kingdom 3/5 2/5 Murray and others52 2001, United Kingdom Myers and others53 2005, United States 121 + 121 men: PSA testing 120 + 120 patients: ischemic heart disease treatment 57 + 55 men: benign prostate hypertrophy treatment 102 + 102 women: HRT Audiotape and booklet PtDA Usual care Pamphlet PtDA Usual care Discussion PtDA and general information pamphlets General information pamphlets Decision analysis PtDA Video and booklet PtDA Decision analysis, video and booklet PtDA Standard care Interactive videodisc PtDA Usual care Interactive videodisc PtDA Usual care O’Connor and others54 1998, Canada 81 + 84 women: HRT 1/5 X X X X X — X — X — X — Interactive videodisc PtDA Usual care Discussion PtDA and general information pamphlet General information pamphlet Audiotape and booklet PtDA Simple PtDA pamphlet O’Connor and others55 1999, Canada 3/5 X X X X X X 1/5 3/5 0/5 — X — X — X — X — X — — — — — — — X — — X X X X X X — X X X X X — — — X 16 + 17 women: osteoporosis treatment 384 + 384 men: PSA testing 37 + 37 patients: dental orthognathic surgery 3/5 3/5 X X X — X — X — X — — — — — — — — X — X 101 +100 women: HRT Oakley and Walley56 2006, United Kingdom Partin and others57 2004, Canada Phillips and others58 1995, United States Pignone and others59 2000, United States Audiotape and booklet PtDA DA without explicit values clarification Audiotape and booklet PtDA Usual care Video PtDA Usual care Video imaging of facial reconstruction PtDA Usual care Video PtDA Usual care — — — X Rostom and others60 2002, Canada X X X X X X — X X X X X X X X X — X — — — 125 + 124 adults: colon cancer screening 25 + 26 women: HRT X X X X — — — — — — — — — — X X — — — — — 83 + 89 women: HRT 1/5 Computer PtDA with testing + feedback regarding knowledge Audiotape with booklet Lecture with personal decision exercise PtDA Simple PtDA pamphlet Booklet PtDA Simple PtDA pamphlet Booklet PtDA Usual care Rothert and others61 1997; Holmes-Rovner and others62 1999, United States Schapira63 2000, United States 1/5 2/5 Downloaded from mdm. sagepub. com by guest on July 22, 2012 Schwartz and others64 2001, United States 2/5 Booklet PtDA Usual care Shorten and others65 2005, Australia X — X — X — X — — — X — Street and others66 1995, United States 1/5 22 + 135 men: prostate cancer screening 191 + 190 Ashkenazi Jewish women: breast cancer genetic testing 85 + 84 pregnant women: birthing options after previous cesarean delivery 30 + 30 women: breast cancer surgery Interactive multimedia PtDA Simple PtDA X X X X — — — — X — X — (continued) 561 562 Table 1 Elements in DAs (continued) Source, Year, Locat ion Number of Enrollees in Intervention + Comparison: Options Considered Quality Rating (Jadad) Comparison of Most and Least Intensive Intervention Options and Clinical Outcomes Problem Explicit Outcome Values Probability Clarification Others’ Experiences Guidance in Steps of DM VanRoosmalen and others67,68 2004, the Netherlands X X — X — X — X — X — X — X — X X — — X — X — X — — X — — X — X — X — X — X — X — X X X X — — — — — — — — — — — — — X — 44 + 44 women with BRCA1/2 mutation: prophylactic surgery 3/5 X X X X — — X — — — — — — — X — — — — — X X — — — — — — — — — — — — — — Volk and others69,70 1999, United States 3/5 3/5 3/5 80 + 80 men: prostate cancer screening Vuorma and others71,72 2003, Finland Video and brochure PtDA with decision analysis Same video and brochure PtDA pamphlet Video with pam phlet PtDA Usual care Booklet PtDA Usual care Whelan and others73 2003, Canada 3/5 2/5 184 + 179 women: menorrhagia treatment 82 + 93 women: breast cancer chemotherapy Downloaded from mdm. sagepub. com by guest on July 22, 2012 Whelan and others74 2004, Canada Wolf and others75,76 1996, United States 1/5 2/5 Script PtDA Usual care Pamphlet PtDA Usual care 94 + 107 women: breast cancer surgery 103 + 102 men: prostate cancer screening Decision board PtDA and booklet Usual care with booklet Decision board PtDA Usual care Script PtDA Usual care Wolf and Schorling77 2000, United States Wong and others78 2006, United States 266 + 133 seniors: colon cancer screening 162 + 164 women: pregnancy termination Note: DM = decision making; PtDA = patient decision aid; HRT = hormone replacement therapy; PSA = prostate-specific antigen. Table 2 Cumulative Studies Still in 2007 Review Reporting Outcome in Each Cochrane Review Update Year % n/N Lead Author 15 50 18 Trials Measuring Outcomes That Map onto the International Patient Decision Aid Standards (IPDAS) Criteria Outcome Decision quality 2007 1999 2003 15 27 2/13 8/30 49 27/55 Knowledge scores 999 2003 54 57 7/13 17/30 Realistic expectations, accurate risk perceptions Barry, Morgan, Bernstein, Lerman,41 Rothert,61 O’Connor,54 Street66 As above plus Schwartz,64 Man-Son-Hing,43 Volk,69 Dunn,26 Green,31 Goel,30 Shapira,63 Rostom,60 Phelan,23 Dodin24 As above plus Bekker,16 Gattellari,28 Johnson,36 Whelan,73 Shorten,65 Montgomery,48 Gattellari,29 Laupacis,39 Wong,78 Hunter35 OConnor,54 Lerman41 As above plus Wolf,77 McB ride,45 Man-Son-Hing,43 Rostom,60 Shapira,63 Dodin24 As above plus Whelan,74 Whelan,73 McAlister,44 Gattellari28 Value congruence with chosen option Decisional Conflict Scale (DCS) 2007 1999 2003 2007 1999 2003 2007 80 2007 1999 2003 2007 1999 2003 57 15 30 27 15 33 24 15/55 2/13 10/30 13/55 2/13 9/30 17/30 Downloaded from mdm. sagepub. com by guest on July 22, 2012 22 0 10 5 15 30 12/55 0/13 3/30 3/55 2/13 9/30 Decision process leading to decision quality Feeling informed, subscale of the DCS Feeling clear about values, subscale of DCS O’Connor,55 Holmes-Rovner,62 Dodin24 As above OConnor,54 Morgan50 As above plus Murray,51 Murray,52 Dolan,25 Man-Son-Hing,43 Dodin,24 Goel,30 OConnor55 As above plus Montgomery,48 Shorten,65 Laupacis,39 Whelan,74 McAlister,44 Lalonde,38 Legare,40 Hunter35 O’Connor,54 Morgan50 As above plus Murray,51 Murray,52 Dolan,25 Man-Son-Hing,43 Dodin,24 Goel,30 OConnor55 As above plus Montgomery,48 Laupacis,39 McAlister,44 Wong,78 Bekker,16 Lalonde38 O’Connor,54 Morgan50 As above plus Murray,51 Murray,52 Dolan,25 Man-Son-Hing,43 Dodin,24 Goel,30 OConnor55 As above plus Montgomery,48 Laupacis,39 McAlister,44 Lalonde38 Note: Trials included in 1999 and 2003 but not in 2007 are Davison and others (measuring feeling informed, clear values); Maisels and others,81 Michie and others82 (measuring knowledge scores), and Thornton and others. 83 These authors were eliminated because we were unable to verify what was in their decision aid to meet the IPDAS definition of a decision aid. 563 O’CONNOR AND OTHERS Study or subcategory y Bekker 2004 Gattellari 2003 Johnson 2006 Whelan 2003 Schwartz 2001 Man-Son-Hing 1999 Morgan 2000 Shorten 2005 Montgomery 2003 Gattellari 2005 Laupacis 2006 Volk 1999 Lerman 1997 Barry 1997 Wong 2006 Bernstein 1998 Dunn 1998 Green 2001 N Decision Aid Mean (SD) 74. 00(14. 50) 50. 00(18. 40) 92. 60(11. 00) 80. 20(14. 40) 65. 71(14. 29) 75. 91(15. 72) 76. 00(32. 04) 75. 33(15. 00) 75. 00(17. 00) 57. 20(21. 30) 83. 00(19. 50) 48. 00(22. 40) 68. 90(19. 00) 75. 00(45. 00) 85. 00(26. 70) 83. 00(16. 00) 83. 67(23. 13) 95. 00(7. 00) N Usual Care Mean (SD) 71. 50(16. 00) 45. 00(15. 90) 85. 20(15. 60) 71. 70(13. 30) 57. 14(15. 71) 66. 46(16. 07) 62. 00(32. 04) 60. 53(17. 07) 60. 00(18. 00) 42. 20(16. 70) 67. 40(17. 00) 31. 00(18. 30) 49. 00(21. 70) 54. 00(45. 00) 60. 00(21. 70) 58. 00(16. 00) 55. 53(22. 80) 65. 00(21. 00) W MD (random) 95% CI W eight % 5. 68 6. 3 5. 49 6. 16 6. 41 6. 24 4. 61 6. 04 5. 43 6. 03 5. 32 5. 50 6. 00 3. 84 5. 81 5. 61 5. 83 3. 97 100. 00 W MD (random) 95% CI 2. 50 [-3. 31, 8. 31] 5. 00 [0. 39, 9. 61] 7. 40 [0. 98, 13. 82] 8. 50 [4. 37, 12. 63] 8. 57 [5. 55, 11. 59] 9. 45 [5. 68, 13. 22] 14. 00 [4. 81, 23. 19] 14. 80 [10. 23, 19. 37] 15. 00 [8. 39, 21. 61] 15. 00 [10. 40, 19. 60] 15. 60 [8. 64, 22. 56 ] 17. 00 [10. 61, 23. 39] 19. 90 [15. 17, 24. 63] 21. 00 [9. 25, 32. 75] 25. 00 [19. 60, 30. 40] 25. 00 [18. 95, 31. 05] 28. 14 [22. 83, 33. 45] 30. 00 [18. 71, 41. 29] 15. 22 [11. 71, 18. 73] 50 106 32 82 191 137 90 99 50 131 53 78 122 104 154 61 143 29 6 108 35 93 190 136 97 92 58 136 53 80 164 123 159 48 144 14 Total (95% CI) 1712 1786 Test for heterogeneity: ? 2 = 130. 32, df = 17 (P ; 0 . 00001), I? = 87. 0% Test for overall effect: Z = 8. 50 (P ; 0. 00001) -50 Favors Usual Care 0 50 Favors Decision Aid Figure 2 Effect of patient decision aids on patients’ mean scores on knowledge tests: decision aid versus usual care. WMD = weighted mean difference; CI = confidence interval. Study N Goel 2001 Rothert / H-Rovner O'Connor 1998-RCT Hunter 2005 Schapira 2000 Street 1995 Rostom 2002 Deyo / Phelan Dodin 2001 Total 77 83 81 116 122 30 25 41 52 627 Detailed DA Mean (SD) 81. 67(11. 1) 86. 79(11. 34) 75. 00(20. 00) 64. 53(19. 61) 83. 33(12. 78) 82. 60(11. 60) 93. 80(9. 00) 71. 76 (17. 06) 71. 04(15. 45) N Simple DA Mean (SD) 80. 00(12. 22) 83. 75(11. 54) 71. 00(21. 00) 60. 13(19. 00) 78. 33(15. 00) 76. 40(13. 80) 87. 10(11. 80) 62. 35(23. 53) 61. 20(17. 90) WMD (random) 95% CI Weight % 14. 31 21. 90 6. 62 10. 92 22. 45 6. 23 7. 85 3. 67 6. 06 100. 00 WMD (random) 95% CI 1. 67 [-2. 59, 5. 93] 3. 04 [-0. 40, 6. 48] 4. 00 [-2. 26, 10. 26] 4. 40 [-0. 47, 9. 27] 5. 00 [1. 60, 8. 40] 6. 20 [-0. 25, 12. 65] 6. 70 [0. 95, 12. 45] 9. 41 [1. 00, 17. 82] 9. 84 [3. 30, 16. 38] 4. 63 [3. 02, 6. 24] 48 87 84 126 135 30 26 49 49 634 Test for heterogeneity: ? 2 = 7. 18, df = 8 (P = 0. 52 ), I? = 0% Test for overall effect: Z = 5. 63 (P < 0. 00001) -50 Favours Simple 0 50 Favours Detailed Figure 3 Effect of patient decision aids (DAs) on patients’ mean scores on knowledge tests: detailed versus simple decision aids. WMD = weighted mean difference; CI = confidence interval. 564 †¢ MEDICAL DECISION MAKING/SEP–OCT 2007 Downloaded from mdm. sagepub. com by guest on July 22, 2012 DECISION AIDS â€Å"EFFECTIVENESS CRITERIA OF DECISION AIDS† Study or subcategory y Decision Aid n/N 90/122 189/266 73/94 109/265 82/122 33/52 58/81 47/82 70/187 88/139 57/106 1516 Usual Care n/N 108/164 72/133 62/107 82/274 62/135 21/49 39/84 34/92 27/165 40/148 11/108 1459 RR (random) 95% CI W eight % 11. 11 10. 83 10. 55 10. 01 10. 16 7. 66 9. 45 8. 54 7. 54 9. 04 5. 12 100. 00 RR (random) 95% CI 1. 12 [0. 96, 1. 31] 1. 31 [1. 10, 1. 56] 1. 34 [1. 10, 1. 63] 1. 37 [1. 09, 1. 73] 1. 46 [1. 17, 1. 83] 1. 48 [1. 01, 2. 17] 1. 54 [1. 18, 2. 02] 1. 55 [1. 12, 2. 15] 2. 29 [1. 55, 3. 38] 2. 34 [1. 75, 3. 14] 5. 28 [2. 93, 9. 50] 1. 61 [1. 35, 1. 92] Lerman 1997 Wolf 2000 Whelan 2004 McBride 2002 Schapira 2000 Dodin 2001 O'Connor 1998-RCT Whelan 2003 McAlister 2005 Man-Son-Hing 1999 Gattellari 2003 Total (95% CI) Total events: 896 (Decision Aid), 558 (Usual Care) Test for heterogeneity: ? 2 = 52. 06, df = 10 (P ; 0. 00001), I? = 80. 8% Test for overall effect: Z = 5. 34 (P ; 0. 00001) 0. 1 0. 2 0. 5 1 Favours Usual Care 2 5 10 Favours Decision Aid Figure 4 Effect of patient decision aids on the proportion of patients classified as having accurate risk perceptions. RR = relative risk; CI = confidence interval. congruence. Holmes-Rovner and others62 measured the correlation between the subjective expected value of hormones and women’s likelihood of taking HRT, converted here to the percentage of variance in likelihood explained by alues. Dodin and others24 measured the percentage of variance in decisions explained by values. O’Connor and others55 used logistic regression to estimate the percentage agreement between values and choice. PtDAs improved value congruence with the chosen option in 2 of 3 studies. In the trial by Dodin and others,24 24% of the variance in HRT decisions wa s explained by personal values when a detailed PtDA with explicit values clarification was used; in contrast, 14% of the variance in decisions was explained when a simpler PtDA was used (P = 0. 003). In the study by Holmes-Rovner and others,62 the percentage of variance in the likelihood of choosing HRT that was explained by women’s expected values was greater when a more detailed PtDA was used (13%–14%) than when a simpler PtDA was used (0. 09%–2%). O’Connor and others55 found that the addition of an explicit values clarification exercise in a PtDA did not improve agreement between values and the chosen option. However, in the subgroup of women who chose HRT, women who used the PtDA with explicit values clarification DECISION AIDS: PAST, PRESENT, AND FUTURE ad a trend toward better agreement (40%) than did those who used an identical PtDA without explicit values clarification (0%, P = 0. 06). Decision Processes Leading to Decision Quality There were no trials evaluating the extent to which PtDAs helped patients to recognize that a decision needs to be made, understand that values affect the decision, and discuss values with their practitioner. Althoug h 8 trials evaluated effects on patient participation, none focused on helping patients become involved in preferred ways. Some studies measured patients’ self-reports about feeling informed and clear about personal values. The measures used to evaluate these 2 criteria were 2 subscales of the Decisional Conflict Scale (DCS). The DCS is reliable, discriminates between those who make or delay decisions, is sensitive to change, and discriminates between different decision support interventions. 54,79 The scores are standardized to range from 0 (no decisional conflict) to 100 points (extreme decisional conflict). Scores of 25 or lower are associated with follow through with decisions, whereas scores that exceed 38 are associated with delay in decision making. 54 When PtDAs are compared with usual care, 565 Downloaded from mdm. agepub. com by guest on July 22, 2012 O’CONNOR AND OTHERS Study or subcategory y Decision Aid N Mean (SD) 22. 17(9. 47) 27. 56(10. 51) 16. 25(13. 75) 29. 93(17. 26) 15. 75(13. 00) 20. 00(21. 50) 15. 75(13. 25) 15. 00(12. 50) 21. 67(15. 83) 32. 50(15. 00) Usual Care N Mean (SD) 58 45 54 93 37 94 148 215 159 56 959 49. 14(25. 40) 38. 88(20. 02) 27. 25(15. 00) 38. 89(22. 53) 24. 50(21. 25) 27. 50(21. 50) 21. 00(14. 75) 20. 00(15. 00) 25. 83(19. 17) 31. 67(14. 17) WMD (random) 95% CI Weight % 8. 64 9. 09 10. 03 9. 73 7. 93 9. 28 11. 82 12. 25 11. 33 9. 90 100. 00 WMD (random) 95% CI -26. 97 [-34. 1, -19. 93] -11. 32 [-17. 83, -4. 81] -11. 00 [-16. 43, -5. 57] -8. 96 [-14. 73, -3. 19] -8. 75 [-16. 67, -0. 83] -7. 50 [-13. 79, -1. 21] -5. 25 [-8. 49, -2. 01] -5. 00 [-7. 60, -2. 40] -4. 16 [-8. 05, -0. 27] 0. 83 [-4. 74, 6. 40] -8. 35 [-11. 89, -4. 80] 02 Uninformed Subscale Montgomery 2003 50 Murray BPH 2001 52 Laupacis 2006 54 Murray HRT 2001 93 Dolan 2002 41 Morgan 2000 86 Man-Son-Hing 1999 139 McAlister 2005 219 Wong 2006 154 Bekker 2004 50 Subtotal (95% CI) 938 Test for heterogeneity: 48. 12, df = 9 (P ; 0. 00001), I? = 81. 3% Test for overall effect: Z = 4. 61 (P ; 0. 0001) -50 0 Favours Decision Aid 50 Favours Usual Care ?2 = Figure 5 Effect of patient decision aids on patients’ scores on the Uninformed subscale of the Decisional Conflict Scale: d ecision aid versus usual care. WMD = weighted mean difference; CI = confidence interval. Study or subcategory y Detailed DA N Mean (SD) 22. 50(17. 50) 17. 50(12. 50) 20. 75(10. 75) 22. 50(17. 50) 38. 25(12. 00) Simple DA N Mean (SD) 84 49 45 100 12 27. 50(20. 00) 22. 25(14. 75) 24. 00(16. 00) 20. 00(17. 50) 31. 25(10. 75) W MD (random) 95% CI W eight % 20. 52 21. 72 22. 00 23. 42 12. 34 100. 00 W MD (random) 95% CI -5. 0 [-10. 73, 0. 73] -4. 75 [-10. 10, 0. 60] -3. 25 [-8. 51, 2. 01] 2. 50 [-2. 34, 7. 34] 7. 00 [-2. 12, 16. 12] -1. 32 [-5. 27, 2. 62] 02 Uninformed Subscale O'Connor 1998-RCT 81 Dodin 2001 52 Goel 2001 76 O'Connor Wells 1999 101 Lalonde 2006 12 Subtotal (95% CI) 322 290 Test for heterogeneity: ? 2 = 9. 24, df = 4 (P = 0. 06), I? = 56. 7% Test for overall effect: Z = 0. 66 (P = 0. 51) -50 0 Favours Detailed DA 50 Favours Simple DA Figure 6 Effect of patient decision aids on patients’ scores on the Uninformed subscale of the Decisional Conflict Scale: detailed ve rsus simple decision aid (DA). WMD = weighted mean difference; CI = confidence interval. a negative score indicates a reduction in decisional conflict, which is in favor of the PtDA. In our review, 15 trials used the DCS subscale for feeling informed and 13 trials used the DCS subscale for feeling clear about values. Because this DCS subscale measures self-reported comfort with knowledge and not actual knowledge, we elected to consider it a process measure and to reserve the gold standard of objective knowledge tests in assessing decision quality. The WMD in feeling uninformed about options, benefits, and harms was –8. (95% CI = –11. 9 to –4. 8) in the 10 trials16,25,39,43,44,48,50–52,78 that compared the PtDAs to usual care (Figure 5). The 5 trials that compared detailed with simpler PtDAs24,30,38,54,55 had a WMD in feeling uninformed of –1. 3 (95% CI = –5. 3 to 2. 6; Figure 6). Eight trials comparing PtDA to usual care25,39,43,44,48,50–52 had a WMD of –6. 3 (95% CI = –10. 0, –2. 7) for feeling clear about values (Figure 7). Five trials compared detailed to simpler PtDAs. 24,30,38,54,55 For these trials, the WMD in feeling clear about values was –1. 1 (95% CI = –4. 8 to 2. ; Figure 8). 566 †¢ MEDICAL DECISION MAKING/MON–MON 2007 Downloaded from mdm. sagepub. com by guest on July 22, 2012 DECISION AIDS â€Å"EFFECTIVENESS CRITERIA OF DECISION AIDS† Study or sub-category Decision Aid N Mean (SD) 50 54 41 82 53 139 219 86 724 28. 50(12. 50) 18. 75(16. 50) 19. 75(15. 75) 37. 50(15. 00) 35. 38(12. 33) 16. 25(12. 50) 15. 00(12. 50) 30. 00(3. 25) Usual Care N Mean (SD) 58 55 37 84 45 148 215 94 736 51. 29(25. 73) 30. 00(17. 00) 29. 25(24. 00) 42. 85(16. 57) 40. 56(16. 44) 19. 00(14. 75) 17. 50(15. 00) 30. 00(3. 25) WMD (random) 95% CI Weight % 9. 8 11. 11 8. 15 12. 88 11. 64 14. 75 15. 30 16. 40 100. 00 WMD (random) 95% CI -22. 79 [-30. 26, -15. 32] -11. 25 [-17. 54, -4. 96] -9. 50 [-18. 61, -0. 39] -5. 35 [-10. 16, -0. 54] -5. 18 [-11. 02, 0. 66] -2. 75 [-5. 91, 0. 41] -2. 50 [-5. 10, 0. 10] 0. 00 [-0. 95, 0. 95] -6. 33 [-9. 98, -2. 69] 03 Unclear Values Subscale Montgomery 2003 Laupacis 2006 Dolan 2002 Murray HRT 2001 Murray BPH 2001 Man-Son-Hing 1999 McAlister 2005 Morgan 2000 Subtotal (95% CI) Test for heterogeneity: 57. 71, df = 7 (P ; 0. 0 0001), I? = 87. 9% Test for overall effect: Z = 3. 40 (P = 0. 007) -50 Favours Decision Aid 0 50 Favours Usual Care ?2 = Figure 7 Effect of patient decision aids on patients’ scores on the Unclear Values subscale of the Decisional Conflict Scale: decision aid versus usual care. WMD = weighted mean difference; CI = confidence interval. Study or sub-category y Detailed DA N Mean (SD) 81 77 52 12 97 25. 00(17. 50) 24. 00(12. 50) 25. 00(13. 75) 39. 50(10. 75) 22. 50(15. 00) N 84 45 49 12 100 Simple DA Mean (SD) 32. 50(17. 50) 25. 75(15. 75) 24. 75(13. 50) 37. 50(13. 00) 20. 00(15. 00) W MD (random) 95% CI W eight % 21. 23 21. 09 21. 32 10. 94 25. 42 100. 0 W MD (random) 95% CI -7. 50 [-12. 84, -2. 16] -1. 75 [-7. 13, 3. 63] 0. 25 [-5. 07, 5. 57] 2. 00 [-7. 54, 11. 54] 2. 50 [-1. 69, 6. 69] -1. 05 [-4. 81, 2. 70] O'Connor 1998-RCT Goel 2001 Dodin 2001 Lalonde 2006 O'Connor Wells 1999 Subtotal (95% CI) 319 290 Test for heterogeneity: ? 2 = 9. 02, df = 4 (P = 0. 06 ), I? = 55. 7% Test for overall effect: Z = 0. 55 (P = 0. 58) -50 0 Favours Detailed DA 50 Favours Simple DA Figure 8 Effect of patient decision aids on patients’ scores on the Unclear Values subscale of the Decisional Conflict Scale: detailed versus simple decision aid (DA). WMD = weighted mean difference; CI = confidence interval. Post hoc Analysis Effects of study quality. To examine the effect of possible bias from including trials of low methodological quality, the 13 trials15,21,31,34. 41,45,54,56,58,61,63,66,77 with Jadad scores of 0 or 1 were excluded from the analysis. Overall, the results remained the same. There was a significant improvement in knowledge scores for the comparison of PtDAs to usual-care controls (WMD = 14. 0%, 95% CI = 2. 4, 8. 6) and for the comparison of detailed to simpler PtDAs (WMD = 5. 5%, 95% CI = 2. 4, 8. 6). The proportion of patients having accurate risk perceptions was greater for patients receiving PtDAs with information on outcome probabilities (RR = 2. 0, 95% CI = 1. 4, 2. 8). Publication bias. There were too few studies to explore potential publication bias for all of the outcomes, with the exception of knowledge for the comparison of PtDAs to usual care. The funnel plot for this outcome (Figure 9) points to the absence of smaller negative studies. DECISION AIDS: PAST, PRESENT, AND FUTURE Downloaded from mdm. sagepub. com by guest on July 22, 2012 567 O’CONNOR AND OTHERS Comparison: 01 Decision Aids versus Usual Care Outcome: 0 07 Knowledge: Decision Aids vs Usual Care SE(WMD) 2 4 6 8 -100 -50 0 50 100 WMD (fixed) Figure 9 Funnel plot of all 18 randomized controlled trials comparing patient decision aids to usual care (knowledge). WMD = weighted mean difference. Heterogeneity. There was statistically significant heterogeneity when PtDAs were compared with usual care for 4 outcomes: knowledge test scores, realistic risk perceptions, feeling uninformed, and feeling unclear regarding personal values (Table 3). It should be noted that the heterogeneity of the effect was not in the direction but in the size. When we explored the potential factors contributing to heterogeneity (Table 3), we found that none of the factors eliminated heterogeneity for the outcomes of knowledge scores. When grouped into treatment and screening decisions, the WMD for knowledge scores was slightly higher for the treatment group (16. 6% v. 13. 1%), but there was still statistically significant heterogeneity. For the outcomes of accurate risk perceptions, heterogeneity was not significant when we removed 3 studies with lower accurate risk perception scores in the usual-care control group (P = 0. ). 28,43,44 For the outcome of feeling uninformed, heterogeneity was no longer significant with 1) removal of 3 studies with higher uninformed scores in the usual-care control group (P = 0. 11), 2) inclusion of only audio booklet/ pamphlet decision aids (P = 0. 06), and 3) removal of an outlier48 (P = 0. 06). None of the factors eliminated heterogeneity for the outcomes of unclear values scores. DISCUSSION The majority o f trials report on at least 1 IPDAS effectiveness measure, predominately knowledge test scores. Of those reporting IPDAS measures, we found that PtDAs were superior to usual practices in 568 †¢ MEDICAL DECISION MAKING/SEP–OCT 2007 meeting the new IPDAS standards 1) for decision quality and 2) for 2 process measures (feeling informed and feeling clear about personal values). Detailed PtDAs had superior effects over simpler PtDAs on value congruence with the chosen option and on accurate risk perceptions but not on knowledge test scores or on self-reports about feeling informed and feeling clear about values. We also identified the gaps in the use of measures of effectiveness endorsed by IPDAS, notably, value congruence with the chosen option and most of the decision process measures. There are some study limitations. Study quality ratings of all trials included in the review were low because they all lost 2 points for lack of blinding. Although not an a priori exclusion criterion for this review, in the future, we may consider using study quality ratings for the selection of included trials. The conclusions of this review are limited by 1) inadequate power to detect important differences in effectiveness in subgroups and 2) the wide variability in the decision contexts, the elements within the PtDAs, the type of comparison interventions, the targeted outcomes, and the evaluation procedures. This article focuses solely on measures of effectiveness, not harms. The small number of studies for most outcomes did not allow for analysis of publication bias because of the failure to publish negative studies. Moreover, there may have been publication bias because of failure to report all negative findings in a published study. Lastly, several of the outcomes demonstrated statistically significant heterogeneity. It reflects differences across clinically diverse studies; therefore, the pooled effect size and CI should be interpreted as a range across conditions, which may not be applicable to a specific condition. There are several implications for future research. Studies are needed to evaluate the effects of PtDAs on congruence between values and chosen options. Moreover, the methods for quantifying value congruence should be explored. The IPDAS decision processes criteria leading to decision quality should also be measured. It would be helpful to develop a standardized approach to measurement. With the addition of more trials to the database, it may be possible to tease out the reason for heterogeneity of results, including variability in 1) study quality, 2) comparison intervention, 3) elements within PtDAs, 4) decision type, and 5) format of decision aid (e. g. , video, Internet, booklet). The degree of detail in PtDAs that is required for positive effects on IPDAS criteria should also be explored. Downloaded from mdm. sagepub. com by guest on July 22, 2012 Table 3 Exploration of Potential Factors Affecting Heterogeneity Outcome Overall Effect Treatment Decision Screening Decision Video/Computer Decision Aid Audio/Pamphlet Decision Aid Baseline Risk in Usual-Care Groupa Removal of Outliers Knowledge 1. 6 (1. 4, 1. 9) –3. 5 (–12. 9, 5. 8) 1. 6 (1. 1, 2. 3) No data 15. 2 (11. 7, 18. 7) 16. 6 (12. 0, 21. 2) 13. 1 ( 7. 7, 18. 5) 21. 4 (16. 5, 26. 2) 11. 9 (8. 3, 15. 6) 1. 6 (1. 4, 1. 9) 15. 6 (11. 3, 19. 9) 1. 3 (1. 2,1. 5)* 1. 6 (1. 4, 1. 9) 17. 316,28,36 (13. 7, 20. 9) 1. 528 (1. 3, 1. 7) –8. 4 (–11. 9, –4. 8) –9. 4 (–13. 3 –5. 5) 12. 6 (–19. 5, –5. 8) –4. 9 (–7. 6, –2. 3)*** –5. 4 (–7. 7, –3. 2)** –6. 248 (–8. 4, –4. 1)*** –8. 0 (–15. 1, –1. 0) –4. 5 (–8. 4, –0. 6) –3. 6 (–6. 8, –0. 5) –4. 0 r48 (–6. 7, –1. 3) Downloaded from mdm. s agepub. com by guest on July 22, 2012 Accurate risk perceptions Uninformed Subscale of the Decisional Conflict Scale Unclear values subscale of the Decisional Conflict Scale –6. 0 (–9. 8, –2. 3) Insufficient data –6. 3 (–10. 0, –2. 7) Note: Values are presented as the weighted mean treatment effect (95% confidence interval). Chi-square heterogeneity test P value

Autobiography in psychology

Ms. Darlene Gigabits August 12, 2014 Chocolate Hills The Chocolate Hills are probably Boll's most famous tourist attraction. They look like giant mole hills, or as some say, women's breasts, and remind us of the hills in a small child's drawing. Most people who first see pictures of this landscape can hardly believe that these hills are not a man-made artifact. To get back to Dignitary, you will have to walk back to the main road, and wait for a bus to pass by.The last bus room Carmen to Dignitary leaves at four P. M. Alternatively, you can use the services of the motorcyclists who often wait here for tourist, and ride ‘habit-habit,' or motorbike taxi. Boll was gifted with very amazing land formations such as these hills. It may not give you a majestic aura but it can make you appreciate how mysterious these natural wonders are. The viewing deck area may need to undergo a few more improvements El Indo Palatal Rocks and corals would hurt your feet so for those who have not been here yet, don't forget to bring and wear your best aqua shoes to avoid going home with cuts.Also, a dry bag to keep your things will make you happy especially if your camera is not water proof. As a divers, you should do at least one or two days of diving in El Indo. There are many nice dive sites in El Indo. I especially loved the rock formations and caves and of course the turtles Island hopping tours are a must in El Indo! Do them all for there is several and they are all different from each other and really fantastic. The lunches are usually cooked over a charcoal fire on a deserted beach.Kayak Tours to the lagoons and beaches around Million are many travelers favorite. For he fittest, I highly recommend you climb the cliff, towering El Indo town for a challenging hike and a breathtaking view Mayo Volcano Despite its tragic past, Caws Ruins continues to invite tourists to visit the place because of its spectacular view of the Mayo Volcano where everyone can see it with their nak ed eyes. The rich diversity of history, place and the people could be seen through the number of tourists that came over to from different part of the world.There, tourists can buy handicrafts, souvenir shirts and meet hospitable photographers who can direct you for picture-perfect shots. Drank Falls Drank Falls is one of the very accessible natural destinations in the province of Racial. The natural beauty of Drank Falls enchants visitors and guests. Its natural beauty, serenity, swimming with clean waterfalls, friendly staff, environment friendly ambiance, and other activities like rock balancing, river trekking, etc. Makes the visit to Drank Falls complete.Lunette Park Lunette park is one of the tourist spots in Manila. One thing that I like in this park is the man-made lake that has a relief map of the Philippines in the middle. Lots of people visit this place every Sunday for picnics. You will also see that some groups of martial artists are using this park every morning for pr actice like Seekers,Filipino Martial Arts, and ATA Chi practitioners. Met. Punctuation A desolate place transformed into a refuge for adventure seekers, Met. Punctuation now boasts breathtaking sceneries comparable to other tourist attractions across the country. He true Journey begins as you embark on a long and exciting trek to the volcano-mountain's center. You don't need to worry about the whole trekking thing because the reward is very promising: a paradise hidden at the heart of the mountain. Polaroid Junkies must take advantage of the place's astonishing backdrop, which is perfect for photo shoots. Portray Borealis a beautiful small island surrounded bifocal reefs and located one km north-west of Panky island in Visas of the Philippines.It is the most popular beach in the country's the most visited tourist spot in the Philippines. A peaceful atmosphere – though' fairly busy- and friendly locals. The sand is remarkably white, soft Banana Rice Terraces The Philippines ha s been visited by countless tourists from different countries due to the various tourist spots that are absolutely stunning. One of those places which have captured the eyes of many foreigners is the Banana Rice Terraces. In fact, this spot has been considered as the eighth wonder of the world.Campaign island One is simply at a loss for words to describe this lovely island which the tourists end caringly call â€Å"The Island of your Imagination†. Campaign is said to be the country's most peaceful island-paradise Campaign island is a one of an island that popular to visit the tourist and vacationers because of the unique wonderful nature and beauty, and so many beautiful places or hot spots that you enjoy or explore and Filipino students are so polite and hospitality to the tourist, many exotic food and delicious food you can avail, so we start to introduce to you a beautiful places resides in campaign.Sabbath Island The province of Batons is at the top most of the Philippine archipelago and it is the entrance of most storms in our country. No traffic, fresh air, full of culture and friendly people. You would be greeted by the locals with a refreshing good morning when you meet them on the street. The place is a bit backward which makes it more inviting especially for people from the urban Manila. It seems that everyone knows everybody. The expensive airfare makes it difficult for a local tourist to visit the place often.Corridor Island If you're a fan of war movies or military equipment, you will enjoy Corridor. Though heavily bombed during WI, the island still has some of its artillery standing The whole island is too big to be explored on foot – a new tour, though, aims to explore the sites around the parade grounds and part of Middlesex. But there's more to Corridor than Just the past. The island also has forest trails, a Jungle survival camp, bird watching opportunities, scenic boat rides, and even a beach. End your Corridor trip in a relaxi ng way.

How phylosophers contribute to build western civilisation Essay

How phylosophers contribute to build western civilisation - Essay Example These great philosophers are up to today greatly remembered for their work including others like St. Augustine, J. J Rosseau, and Karl Marx among many others. In this essay, only the mentioned philosophers will be reviewed; their work and the way it influenced the growth of Western Civilization. Body Plato, Socrates, and Aristotle During ancient Greek civilization, there existed an individual who was extremely well understood like an influential philosopher; he was called Socrates. In his era, he was termed a very elegant; however, extremely eccentric individual. He coined several unique philosophies all the while appearing and behaving very distinct from the normal philosophers of his era. He often dressed in cheap garments, was typically barefoot, and not at all bothered much concerning his look. This was not an ordinary feature of thinkers of his era. He not at all taught for cash; however, he made his philosophy understood simply through introducing his view in simple dialogue. P eople found that extremely fascinating that an individual may become one of the major well-recognized philosophers about teaching and he did not yet levy for his philosophies. Socrates was hugely recognized for his teachings on morals. He thought that if every person concentrated on being ethically correct, people could be pleased. People have regularly discovered a few of the pleased individuals have very minor; and a few of the unhappiest individuals have extra than they understand what to do with. In fact, this is not correct in each case; however, it is a common conclusion from people. For Socrates, everything concentrated on ethical and moral philosophies. A few honored his teachings whereas others were hugely upset by his philosophies. Sadly, during 399 Socrates was imprisoned for not having faith in the gods he was assumed to, which led to his capital punishment (Plato & Rowe, 2010, 54). Plato Plato was among the Socrates immense students and when Socrates was sentenced to de mise, it proved difficult for Plato. He had a hard moment bearing it; he fled from his household and transformed his job. Plato turned to be a philosopher and is currently recognized as the major popular teacher of the Western Civilization. Plato established a school bestowed to tutoring philosophy, mathematics, and hypothetical astronomy. The school stayed for 900 decades. Plato permitted males and females to learn in his school in an era where females were not considered equal to males. This demonstrates how correctly over his era this philosopher was. He scripted a manuscript with his notion for â€Å"utopia† including forming some philosophical hypotheses. His hypothesis of dualism remained very influential. Dualism is a thought â€Å"that people possess an immortal soul different from their entities. Plato had faith in the hypothesis, although he existed in the eras of Greek gods where Christianity was not a regular religion. This hypothesis is not founded on Christiani ty; however, the hypothesis is very alike to the general declaration of many Christians. As Socrates, Plato coached an extremely clever student who turned out very popular and well recognize in the Western Civilization; Aristotle (Plato & Rowe, 2010, 67). Aristotle Aristotle was recognized for not just turning to a well-recognized philosopher and teacher; however, he as well was a scientist. Aristotle pursued Plato’

Social Media and the Affects on Personal Relationships Research Paper

Social Media and the Affects on Personal Relationships - Research Paper Example Such a framework of ethics is especially important in a scenario where there is a world where multiculturalism is an important part. In such an environment, it is important that there are many ways in which people from all over the world are able to understand the methods that are used by one another at least at the virtual plane that social media exists at. This is then an important part of the entire enterprise of social media and its use by people of a particular organization. The paper shall look at the ethics of politicization of media and the role of social media within this. It shall also look at how personal relationships are affected by all of this. Relationships between customers and sellers have been fast changing as a result of social media. In traditional approaches to the ways in which customers and the people who used to sell commodities and services interacted, there would often be a system that would enable consumers to talk to the managers of their companies and the managers would then be able to talk to the consumers. This would be different in a modern setup as the consumers are able to talk to each other through social networking sites (Mangold and Faulds, 2009). They are able to communicate with each other the problems that they may face in dealing with the managers of a company. This would alter the paradigms of the relationships between the consumers and the managers of the company. Apart from this, it would also alter the paradigms of the relationships between the different consumers of the same product. This would then need to adhere to certain norms of ethics to lead to a constructive process. Rules of professionalism need to be adhered to even in such circumstances. If not, there would... This report approves that relationships between customers and sellers have been fast changing as a result of social media. In traditional approaches to the ways in which customers and the people who used to sell commodities and services interacted, there would often be a system that would enable consumers to talk to the managers of their companies and the managers would then be able to talk to the consumers. This would be different in a modern setup as the consumers are able to talk to each other through social networking sites. There are plenty of such websites that are willing to provide information free of cost to people who wish to access it. This then becomes a point where several people from different parts of the globe can converge and possibly even, through an exchange of information regarding places, build persona relationships. This can then point towards a situation where people from different parts of the world can form bonds merely on the basis of knowledge. One then see s the importance of knowledge and an ethical and honest use of it within the space of social media for it to be constructive for it users across the world. This essay makes a conclusion that political relations between people too form a part of the matrix of personal relations that people form amongst themselves in the society. This then points to the role that social media plays in the creation of political relationships between people. Clay Shirky talks of the different roles that are played by forms of social media in creating new forms of political relationships in the world. Shirky attributes the development of political awareness to a certain extent to social media and the different forms of it

In the instructions Essay Example | Topics and Well Written Essays - 500 words

In the instructions - Essay Example This practice was sustained and the Babylonians in 1750 BC invented a method where the trader would borrow assets to financially support his cargo of merchandises (Tramposh 1991). He gave the lender an extra amount of cash and in trade for this extra amount, the lender authorized the invalidation of the loan should the cargo be damaged, embezzled, or lost. According to Tramposh (1991), this practice was documented roughly 1750 BC in the Code of Hammurabi. Prior to the early 20th century, worker’s compensation remained absent in the United States. At the moment, most individuals provided labor or services. However, for people who did not, in the initial period of the industrial revolution, when a laborer was harmed in the workplace, the issue had to be pursued through the web of legal courts. Injured laborers usually fail in these cases (Lencsis 1998). Most businesses or organizations were much better prepared or knowledgeable than their injured workers in manipulating the courts. Because of this it became apparent that workers should have some level of security from the trouble of injuries or damages on the job. In Indiana, the current worker’s compensation system is obligatory, implying that companies are obliged to give worker’s compensation insurance for their workers. Complete healthcare benefits are given to workers eligible for worker’s compensation benefits (Schoening 2003). Compensations are given for temporary total disability (TTD) and permanent total disability (PTD) in a sum decided by a fraction of the employee’s earnings. Compensation may be accessible for permanent disfigurement which incapacitates the potential worth of prospects of the worker. Occupational and physical treatment compensations are accessible. Death benefits are allocated to a worker’s living spouse or children, founded on a fraction of the worker’s salaries

Philosophy of Education Essay Example | Topics and Well Written Essays - 1000 words - 1

Philosophy of Education - Essay Example Understanding students allow the teacher to know their capability and inability that will enable him address their needs effective. The definition that best fits education is Plato’s perspective. Plato views education as process of getting the prisoner out of the cave and empowering his with the skill that will enable him go for fellow prisoner left in the cave. This view illustrates the concept in all aspect prove what it should refill in an individual and the importance of the transformed individual to the society and the country at large. Eric’s comparison off education with value also draws my attention (John, 1693). According to him, education like value and irreproachable character cannot be realized by punishing or reward because when the reward will not be promised the student will not perform. This paper covers my theory of education, pedagogy, social and political component of education. After going through such elaborate and detailed experience in Plato’s parable and other issues, Aristotle’s Virtue Ethics and philosopher’s release, I now believe education is beyond the dictionary definition I knew. I view a student as volcano with the capability of erupt but lacking a trigger to induce the eruption. In my understanding, I consider education to as a trigger that can induce this objective. Every individual has the dream to attain; however, their potential may not be realized if the individual lacks the right information and if the imparting techniques employed in delivering this information right. I fully agree with Plato’s view of education. His description of education in his article Line and cave captures all the whole process of education in accurate and visual way than could be met by any definition. His view of education as getting a prisoner out of the cave prison, and empowering him with the right information, which will enable hi m go back and lift other prisoner effectively cover

Education for the Unemployed Coursework Example | Topics and Well Written Essays - 250 words

Education for the Unemployed - Coursework Example Education for the unemployed is a move that will cater for the education of parents so they too may be helpful in the education of their children. The budget to carry out this project is one that proves there is a lot of emphasis on the education materials that are to be used and thus push for there being an element of seriousness in the project (Jeffrey & Jeffery et al., 2008). The move is one that will encourage parents to push their children to try and give their all in the classroom and be able to get a future that is stable. Education the unemployed without asking them for anything in return but to give their children an education, the parents will be more than helpful if they aim to ensure that their children are as well educated. The budgetary allocation of $100,000 was to make sure that the education program was to go on without a hitch. $30,000 is to be used for the salaries top the teachers and the staff that are involved in the teaching process. $10,500 is to be allocated to the curriculum materials that the parents would use to learn, $2000 for the training of the staff and the teachers that would be teaching the parents as well. Furthermore, the money would be used to train the parents as well in the methods and means that are used in teaching. $9,500 would be used for administrative purposes, $1,500 for the development of the project and as a result $8,000 would be used in the benefits of program. With education there is always the requirement for there to be some out-of-class experience, thus there are bound to be trips, thus the allocation of $30,000 for travel, with $3,500 used for the operations of the school and $2,000 for the receipt of licenses so as to ensure that the school is as well legitim ate in the eyes of the government and the education governing boards. There will be a need for some miscellaneous funds and it is with this that $3,000 is allocated for ‘other’ services

Disgusting Things Essay Example | Topics and Well Written Essays - 250 words

Disgusting Things - Essay Example The unconditional response is the nausea that I feel after tasting it. The conditioned stimulus is eating the soup and the conditioned response is vomiting as a result of eating it. Viewing rats disgusts me because I am allergic to them: The Unconditioned Stimulus is the factor that results in allergies like the hair, hygiene or other factors of the rat. The unconditioned response is the resulting sickness, itching or flu that I catch. The conditioned stimulus is the rat itself and conditioned response is the feeling of disgust and loath from the rat. Once I had a large portion of pasta at dinner and felt nausea. I decline eating Pasta from that day. The unconditioned stimulus is sickness caused by overeating. The unconditioned response is nausea. The conditioned stimulus is Pasta which resulted in the conditioned response that pasta caused nausea. I opened a can of pineapples and found a snail in it. I never use canned pineapples now. The conditioned stimulus canned pineapples resulted in an conditioned response of abstaining from the tin-packed pineapples. The unconditioned stimulus is the snail found inside the tin that resulted in an unconditioned response of disgust from tin-packed

Case study report Essay Example | Topics and Well Written Essays - 1250 words

Case study report - Essay Example Marie Forsythe is the Operations Director of FCCC. Her function in the company is to ensure smooth running of tasks to achieve set objectives. Forsythe refurbished the call center by purchasing new office facilities and building extra offices. These changes were implemented to increase employees’ performance in work, but the progress has remained stagnated. Forsythe decided to carry out a survey on how to improve the performance of each employees thus contributing to overall output and improving the living standards of all parties. The key issues in the company include organizational change, workforce diversity, motivation, leadership, communications systems and social structures. Organizational change is an important issue in FCCC because of the rearrangement of workforce from the previous setting. The construction of new offices in different floors and new office facilities change employees work stationsby creating an open work station with desks that have wide computer screens. Teamwork is another key issue in FCCC because different teams work in different floors. This arrangement exists because of the new offices that divide different departments into different offices. Communication with other teams in different departments occurs through the telephones thus limiting personal contact or direct communication. Motivation in the call center is through recreational facilities, rewards, bonuses, healthcare benefits and a shopping center. Employees have a recreational facility where they relax during office breaks by listening to music and chatting. The company has a local gym that is designed to meet the needs of employees through exercise. Exercise is essential for the mental health of call center workers that perform under pressure. Workforce diversity is an importance issue in Finance Co Call Center because it improves socialization between male and female employees. The

Prejudice And Discrimination Article Essay Example for Free

Prejudice And Discrimination Article Essay One of the most interesting places to visit in this world is India. Located in South Asia it is officially called the Republic of India. India is well-known for being the second most populous nation in the world next to China.   There are many diverse ethnic groups among the people of India. The six (6) main ethnic groups are Negrito, Proto (Australoids or Austrics), Mongoloids, Mediterranean or Dravidian, Western Brachycephals and the Nordic Aryans (â€Å"People of India,† n.d.). India is also known to be the country from which one of the world’s largest religious congregations has originated, Hinduism. Thus, â€Å"about 80% of the population is Hindu, and 14% is Muslim. Other significant religions include Christians, Sikhs, and Buddhists. There is no state religion (â€Å"India,† n.d.).† India and the large number of its population is home to a vast array of culture and people, and a distinct classification of its Hindu believing population of the structural and hierarchical classification of its own members known as the caste system.   Ã¢â‚¬Å"The caste is a closed group whose members are severely restricted in their choice of occupation and degree of social participation. Marriage outside the caste is prohibited. Social status is determined by the caste of ones birth and may only rarely be transcended† (â€Å"Caste,† n.d.). The caste system is an intricate classification of its population and many people can directly associate the said term with the â€Å"untouchables† or the Panchamas or Dalits who are the lowest ranked within the system and are tasked to perform the most menial tasks of the community (â€Å"Caste,† n.d; â€Å"Dalit,† n.d.). Even though the Constitution of the Republic of India disallows â€Å"untouchability† the caste remains to be very influential in Indian Society (â€Å"India,† n.d.). Likened to other countries or states, India is also home to its own indigenous people, one of which is the so called Adivasis or literally the original inhabitants† who comprise a substantial indigenous minority of the population of India.   These Indian tribes are also called Atavika (forest dwellers, in Sanskrit texts), Vanvasis or Girijans (hill people, e.g. by Mahatma Gandhi) (â€Å"Adivasi,† n.d.).† Together with the Dalits, the Adivasis form the most discriminated group of people in the Indian community. These groups of people are said to be constantly subjected to ridicule and shame all over India in a constant basis. A study conducted by Mayell, H. (2003) has chronicled some atrocities committed particularly against the Dalits who are historically the only   ones referred to as â€Å"untouchables† by citing that â€Å"Statistics compiled by Indias National Crime Records Bureau indicate that in the year 2000, the last year for which figures are available, 25,455 crimes were committed against Dalits. Every hour two Dalits are assaulted; every day three Dalit women are raped, two Dalits are murdered, and two Dalit homes are torched.† Furthermore, she stated that â€Å"No one believes these numbers are anywhere close to the reality of crimes committed against Dalits. Because the police, village councils, and government officials often support the caste system, which is based on the religious teachings of Hinduism, many crimes go unreported due to fear of reprisal, intimidation by police, inability to pay bribes demanded by police, or simply the knowledge that the police will do nothing (Mayell, 2003.)† The Dalits can trace its being oppressed from the fact that India being largely a country of people adhering to Hindu beliefs from which the caste system is derived, are the people who are supposed to be the untouchables or, as discussed, ranked at the lowest. As a result of this, naturally the Dalits are can be rightfully perceived and treated the way religion, tradition and history has treated them, which is sadly bordering on slavery.   However, without passing judgment, albeit being quite possibly insensitive, the plight of the Dalits can easily be viewed as part of the natural made up of the Hinduism belief from which any non-Hindu society member can not and should not question. Religiously speaking, based on the Hindu belief a Dalit is a person who has does not have any varnas. Varna refers to the Hindu belief that most humans were supposedly created from different parts of the body of the divinity Purusha. The part from which a Varna was supposedly created defines a persons social status with regards to issues such as who they can marry and which professions they could hold (â€Å"Dalit,† n.d.). For their parts, the Adivasis being the original dwellers of India had their own unique way of societal structure, culture and tradition which has like most indigenous tribes all over the world become outmoded as the modern world around them evolved. The discrimination and pitiful situation of the Adivasis are not directly rooted to Hinduism but possibly to a mix of modernization and the former. This possible mix can not be easily discounted knowing the fact that most people in India are Hindu or believers of Hinduism. It is important to stress that the Adivasis as a classification within the Indian population is not brought about or classified as such by Hinduism per se or as part of its caste system. As discussed, the Adivasis is an ethnic group who are original inhabitants of India possibly even prior to the birth of Hinduism whose culture has failed to completely cope up with the modern world. Thus, Bijoy, C. (2003) said â€Å"relegating the Adivasis to the lowest rung in the social ladder was but natural and formed the basis of social and political decision making by the largely upper caste controlled mainstream. The ancient Indian scriptures, scripted by the upper castes, also further provided legitimacy to this.† Hence, even though that the Adivasis can mostly trace their own problems from the failure of their culture and practices to conform to the modern world, as contrast to that of the Dalits, which can easily trace their own problems from its religion, the Adivasis by simply being not well-equipped enough to cope with the modern world are easily lumped together with the Dalits. As a result, together the Dalits and Adivasis form the most oppressed people in India who are more known as the untouchables. According to Tarique (2008) it is not only a struggle for dignity and self-respect that these poor groups of Indian people are fighting for. They are also engaged in the â€Å"struggle for their rights and entitlements for land, access to natural resources, livelihood, employment and to market in general. (Tarique, 2008.)† It is sad to note that these said factual happenings in a modern world such as ours are still happening.   It is but a semblance of irony knowing that the problems that these people are facing and fighting everyday are rooted to one of man’s most sacred possessions, his religious beliefs, which in itself has taught us notions of goodness and the proper way to which we should live our lives; religion, from which ideas of turning away from sin and helping one’s own fellowman being the exact cause of a structuralized system of discrimination and oppression.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Strictly speaking it is difficult to question the plight of these untouchables more so with the Dalits than the Adivasis because the former’s pitiful situation can be justified by the fact that society has adapted it as part of its religious beliefs. An outsider or any non-Hindu looking into the said situation may not have the proper perspective to look into the plight of these untouchables.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   However, it is without a doubt that when one adapts the globally accepted notion of humane treatment, the sorry plight of these untouchables more so that of the Adivasis who are clearly not directly   Hindu in origin, but more of an â€Å"accidental untouchables†, are well   below the world standards of humane treatment.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Today as the world has chosen to progress and adapt globally its own evolving norms of legal and illegal, acceptable and taboo, good or bad, the world has given more emphasis to equality among ALL MEN without qualifications based on race, gender, birth, color of skin and etc. It is without a doubt that the untouchables of India both the Dalits and Adivasis are victims of a society who have failed to progress with the times.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   Adapting the global perspective and the trend to which modern world is predominantly practicing, today’s world would put any country into shame when one does not act upon or even question the sad and pitiful plight of the Dalits and the Adivasis, the so called untouchables, the accidental slaves of society, people who are as early as birth are discriminated.   Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   In fact as already pointed out, it shall be everyone’s dream to realize and fulfill the perceived mandate of the Indian Constitution itself that outlaws this form of treatment of the so called untouchables. Perhaps only then one can give more emphasis and be prouder to claim India as a country truly rich in culture and proud history. References: Adivasi. (n.d.). Wikipedia, the free encyclopedia. Retrieved January 8, 2008, from Reference.com website: http://www.reference.com/browse/wiki/Adivasi Bijoy, C. (2003). The Adivasis of India. A History of Discrimination, Conflict and Resistance. PUCL Bulletin. Retrieved January 8, 2008, from http://www.pucl.org/Topics/Dalit-tribal/2003/adivasi.htm Caste. (n.d.). Columbia Electronic Encyclopedia. Retrieved January 8, 2008, from Reference.com website: http://www.reference.com/browse/columbia/caste Dalit. (n.d.). Wikipedia, the free encyclopedia. Retrieved January 8, 2008, from Reference.com website: http://www.reference.com/browse/wiki/Dalit India. (n.d.). Columbia Electronic Encyclopedia. Retrieved January 10, 2008, from Reference.com website: http://www.reference.com/browse/columbia/India Mayell, H. (2003). India’s â€Å"Untouchables† Face Violence, Discrimination. National Geographic News. Retrieved January 9, 2008, from http://news.nationalgeographic.com/news/2003/06/0602_030602_untouchables.html People of India. (n.d.). People of India. Retrieved January 9, 2008, from http://www.webindia123.com/india/people/people.htm Tarique (2008). Fact Finding Mission on the Violence against Dalit and Adivasis Kundahamal District. India News. Retrieved January 10, 2008, from http://www.indianmuslims.info/news/2008/jan/09/fact_finding_mission_violence_against_dalit_and_adivais_kundahamal_district.html

N Acetylcysteine Quality Control

N Acetylcysteine Quality Control N-acetylcysteine (C5H9NO3S Mr 163.2) is the N-acetyl derivative of the naturally occurring amino acid, l-cysteine. The drug occurs as a white, crystalline powder with a slight acetic odor. N-acetylcysteine is freely soluble in water and in alcohol. N-acetylcysteine is commercially available as aqueous solutions of the sodium salt of the drug. It is used as a mucolytic or as an antidote for paracetamol. The British Pharmacopoeia contains a number of tests for this compound designed to ensure the quality. N-acetylcysteine acts to reduce mucus viscosity by splitting disulfide bonds linking proteins present in the mucus (mucoproteins). Inhaled N-acetylcysteine is indicated for mucolytic (mucus-dissolving) therapy as an adjuvant in respiratory conditions with excessive and/or thick mucus production. Such conditions include emphysema, bronchitis, tuberculosis, bronchiectasis, amyloidosis, pneumonia. It is also used post-operatively, as a diagnostic aid, and in tracheostomy care. It may be considered ineffective in cystic fibrosis (Rossi, 2006). However, a recent paper in the Proceedings of the National Academy of Sciences reports that high-dose oral N-acetylcysteine modulates inflammation in cystic fibrosis and has the potential to counter the intertwined redox and inflammatory imbalances in CF (Tirouvanziam et al., 2006). Oral N-acetylcysteine may also be used as a mucolytic in less serious cases. N-acetylcysteine also acts to augment glutathione reserves (depleted by toxic paracetamol metabolites) in the body and, together with glutathione to directly bind to toxic metabolites. These actions serve to protect hepatocytes in the liver from toxicity due to paracetamol overdose. Intravenous N-acetylcysteine is indicated for the treatment of paracetamol (acetaminophen) overdose. Oral N-acetylcysteine for this indication is uncommon as it is poorly tolerated owing to the high doses required (due to poor oral bioavailability), unpleasant taste or odour and adverse drug reactions (particularly nausea and vomiting). However, some people have shown an adverse allergy to intravenous N-acetylcysteine which includes extreme breathing difficulty, light-headedness, rashes, severe coughing and sometimes also vomiting. Repeated overdoses will cause the allergic reaction to get worse and worse. N-acetylcysteine is prone to both hydrolysis and oxidation and some of the impurities from these reactions are shown below. Scheme 2 2. Experimental: 2.1. Materials: The materials used in this experiment were N-acetylcysteine powder, disodium edentate solution, 1M sodium hydroxide and mixed phosphate buffer pH 7.0, water, dilute hydrochloric acid, potassium iodine solution, 0.05M iodine, 0.1M sodium hydroxide, starch, phenol red and phenolphthalein as indicators. The apparatus used were optical rotation analyser, conical flasks, 10mL and 50mL pipettes, burette, electronic weigh balance and beakers. 2.2. Methods: a) Specific optical rotation: +21ÃÅ'Ã…   to +27ÃÅ'Ã…   1.25g N-acetylcysteine powder was weighed and allowed dissolve in a mixture of 1ml of 10g/L solution of disodium edentate, 7.5ml of 1M sodium hydroxide and sufficient amount of mixed phosphate buffer pH 7.0 to 25ml total volume. Optical rotations of the freshly prepared solution and the old solutions of N-acetylcysteine provided were measured and recorded. b) ASSAY: 98.0%-101.0% C5H9NO3S (as dried material) 0.14g N-acetylcysteine powder was weighed by difference and poured into a conical flask. 60 ml of water and 10ml dilute hydrochloride acid were measured and added into the conical flask. The conical flask was shaking to ensure the N-acetylcysteine powder was fully dissolved. The solution was left to cool. Another 10ml of potassium iodide solution was added into the cooled solution in the conical flask. The solution was then titrated with 0.05M iodine by using starch as indicator. Second titration was carried out to ensure accurate and precise result. c) Assay by titration with 0.1M sodium hydroxide 0.3g N-acetylcysteine powder was weighed by difference and poured into a clean conical flask. Approximately 50 ml of distilled water was measured and added into the conical flask. The conical flask was shaking to ensure the N-acetylcysteine powder was fully dissolved. The solution was titrated with 0.1M sodium hydroxide using phenol red as indicator. Second titration was carried out to ensure accurate and precise result. 0.3g N-acetylcysteine powder was weighed by difference and poured into a clean conical flask. Approximately 50 ml of distilled water was measured and added into the conical flask. The conical flask was shaking to ensure the N-acetylcysteine powder was fully dissolved. The solution was titrated with 0.1M sodium hydroxide using phenolphthalein as indicator. Second titration was carried out to ensure accurate and precise result. d) Zinc: Not more than 10ppm Zinc 1.00g of N-acetylcysteine powder was weighed and dissolved in 0.001M hydrochloric acid. The solution was diluted to 50ml with 0.001M hydrochloric acid and solution 1 was obtained. Three solutions were prepared for analysis. The first solution consists of 10ml solution 1 diluted to 20ml with 0.001M hydrochloric acid, second solution consists of 10ml solution 1 and 1ml of 5ppm zinc standard diluted to 20ml with 0.001M hydrochloric acid and the third solution consists of 10ml solution 1 and 2ml of 5ppm zinc standard diluted to 20ml with 0.001M hydrochloric acid. The absorbance of each solution was measured at 213.8nm using an atomic absorption spectrophotometer. The absorbance for each solution was tabulated. The zinc content in each sample was calculated using the method of standard addition. e) Loss on drying: Not more than 1.0%w/w A sample of N-acetylcysteine was dried at 70ÃÅ'Ã…   C in vacuo for 3 hours and the data was recorded and the percentage loss on drying of this sample was calculated. f) Related substances The chromatograms obtained from the HPLC analysis of both fresh solution and old solution of N-acetylcysteine was examined. 3. Results: a) Specific optical rotation: Mass of weighing boat(g) 26.6089 Mass of weighing boat + sample (g) 27.8609 Mass of weighing boat + residue (g) 26.6079 Mass of sample transferred (g) 1.253 Table 1: The mass of N-acetylcysteine used to make a solution for measurement of specific optical rotation. Calculations: According to British Pharmacopoeia (BP 1999; page 40-41), it states that the specific optical rotation is +  21.0 to +  27.0. To obtain the angle of rotation, the equation below is used, Where, [ÃŽÂ ±] = specific optical rotation ÃŽÂ ± = observed angle of rotation C = concentration of active substance in g/100mL of the solution l = length of column in 2dcms For freshly prepared solution: Angle obtained (ÃŽÂ ±): 2.45à ¢Ã‚ Ã‚ ° Concentration of N-acetylcysteine (c): 5.012 %w/v Path length = 2 dm Specific optical rotation: = 100 x 2.45à ¢Ã‚ Ã‚ ° 2 x 5.012g/ml = +24.5à ¢Ã‚ Ã‚ ° For old solution: Angle obtained (ÃŽÂ ±): -3.29à ¢Ã‚ Ã‚ ° Concentration of N-acetylcysteine (c): 5.012 %w/v Path length = 2 dm Specific optical rotation: = 100 x 3.29à ¢Ã‚ Ã‚ ° 2 x 5.012g/ml = -32.9à ¢Ã‚ Ã‚ ° b) ASSAY: 98.0%-101.0% C5H9NO3S (as dried material) Sample 1 Sample 2 Mass of boat + sample (g) 3.8797 3.8777 Mass of boat + residue (g) 3.7393 3.7398 Mass of Acetylcysteine transferred (g) 0.1404 0.1379 Table 2: The mass of N-acetylcysteine powder in sample 1 and sample 2 for titrations with iodine. First reading Second reading Initial volume (mL) 17.40 26.70 Final volume (mL) 26.40 35.50 Volume of 0.05M iodine used (mL) 9.00 8.80 Table 3: The volume of iodine used for both titration using sample 1 and sample 2 of N-acetylcysteine solution and starch as indicator. Calculations: Actual concentration of iodine used: 0.0476M Molecular weight of N-acetylcysteine (C5H9NO3S): 163.2 The balanced equation for the reaction between N-acetylcysteine and iodine: 2 C5H9NO3S + I2 à   C5H8NO3SSC5H8NO3 + 2HI 2KI à   I2 + 2K+ According to British Pharmacopoeia, 1mL of 0.05M iodine is equivalent to 16.32mg of C5H9NO3S. This means, 2 mole of C5H9NO3S equal to one mole of iodine. Therefore when 1mL of 0.05M iodine = 16.32mg of C5H9NO3S, 1mL of 0.0476M iodine = 0.0476M x 16.32mg/ 0.05M = 15.54mg of C5H9NO3S First titration: 1mL of 0.0476M iodine = 15.54mg of C5H9NO3S So, 9.00mL of 0.0476M iodine = 9.00mL x 15.54mg/ 1mL = 139.86mg = 0.13986g of C5H9NO3S Second titration: 1mL of 0.0476M iodine = 15.54mg of C5H9NO3S So, 8.80mL of 0.0476M iodine = 8.80mL x 15.54mg/ 1mL = 135.52mg = 0.13552g of C5H9NO3S Calculation of Percentage of Purity: Sample 1 of N-acetylcysteine Sample 2 of N-acetylcysteine Mass transferred Actual mass calculated Mass transferred Actual mass calculated 0.1404 0.1399 0.1379 0.1355 According to British Pharmacopoeia (BP), the percentage of purity should be within 98.0 101.0% of dried substance. Equation of the Percentage of Purity: Sample 1: Sample 2: c) Assay by titration with 0.1M of sodium hydroxide i) Titration by using phenol red indicator Sample 1 Sample 2 Mass of boat + sample (g) 3.8916 3.9199 Mass of boat + residue (g) 3.5913 3.6198 Mass of N-acetylcysteine transferred (g) 0.3003 0.3001 Table 4: The mass of N-acetylcysteine powder in sample 1 and sample 2 for titrations with 0.1M of sodium hydroxide. First reading Second reading Initial volume (mL) 1.00 1.00 Final volume (mL) 18.15 18.10 Volume of 0.05M iodine used (mL) 17.15 17.10 Table 5: The volume of 0.1M sodium hydroxide used for both titration using sample 1 and sample 2 of N-acetylcysteine solution and phenol red as indicator. Calculations: Actual concentration of sodium hydroxide (NaOH) used: 0.1062M Molecular weight of N-acetylcysteine (C5H9NO3S): 163.2 The balanced equation for the reaction between N-acetylcysteine and sodium hydroxide (NaOH): C5H9NO3S + NaOH à   C5H8NO3SNa + H2O From the equation, one mole of N-acetylcysteine reacts with one mole of NaOH. So the reaction is a 1:1 ratio. To find out the number of mole of NaOH, the equation below is used: First titration: Moles of NaOH = (0.1062M x 17.15mL)/1000 = 1.821 x10-3 moles As the reaction is 1:1 ratio so the number of moles of N-acetylcysteine is equal to the number of moles of NaOH used which is 1.821 x10-3 mole. Mass of N-acetylcysteine = 1.821 x10-3 moles x 163.2 = 0.2972g Second titration: Moles of NaOH = (0.1062M x 17.10mL)/1000 = 1.816 x10-3 moles As the reaction is 1:1 ratio so the number of moles of N-acetylcysteine is equal to the number of moles of NaOH used which is 1.821 x10-3 mole. Mass of Acetylcysteine = 1.816 x10-3 mole x 163.2 = 0.2964g Calculation of Percentage of Purity: Sample 1 of N-acetylcysteine Sample 2 of N-acetylcysteine Mass transferred Actual mass calculated Mass transferred Actual mass calculated 0.3003 0.2972 0.3001 0.2964 According to British Pharmacopoeia (BP), the percentage of purity should be within 98.0 101.0% of dried substance. Equation of the Percentage of Purity: Sample 1: Sample 2: ii) Titration by using Phenolphthalein as the indicator Sample 1 Sample 2 Mass of boat + sample (g) 3.8916 3.9195 Mass of boat + residue (g) 3.5915 3.6195 Mass of N-acetylcysteine transferred (g) 0.3001 0.3000 Table 6: The mass of N-acetylcysteine powder in sample 1 and sample 2 for titrations with 0.1M of sodium hydroxide. First reading Second reading Initial volume (mL) 18.20 17.10 Final volume (mL) 36.80 36.95 Volume of 0.05M iodine used (mL) 18.60 19.85 Table 7: The volume of 0.1M sodium hydroxide used for both titration using sample 1 and sample 2 of N-acetylcysteine solution and phenolphthalein as indicator. Calculations: Actual concentration of sodium hydroxide (NaOH) used: 0.1062M Molecular weight of N-acetylcysteine (C5H9NO3S): 163.2 The balanced equation for the reaction between N-acetylcysteine and sodium hydroxide (NaOH): C5H9NO3S + NaOH à   C5H8NO3SNa + H2O From the equation, one mole of a N-acetylcysteine reacts with one mole of NaOH. So the reaction is a 1:1 ratio. To find out the number of mole of NaOH, the equation below is used: First titration: Moles of NaOH = (0.1062M x 18.60mL)/1000 = 1.975 x10-3 mole As the reaction is 1:1 ratio so the number of moles of N-acetylcysteine is equal to the number of moles of NaOH used which is 1.821 x10-3 mole. Mass of N-acetylcysteine = 1.975 x10-3 mole x 163.2 = 0.3224g Second titration: Moles of NaOH = (0.1062M x 19.85mL)/1000 = 2.108 x10-3 mole As the reaction is 1:1 ratio so the number of moles of N-acetylcysteine is equal to the number of moles of NaOH used which is 1.821 x10-3 mole. Mass of N-acetylcysteine = 1.816 x10-3 mole x 163.2 = 0.3440g Calculation of Percentage of Purity: Sample 1 of N-acetylcysteine Sample 2 of N-acetylcysteine Mass transferred Actual mass calculated Mass transferred Actual mass calculated 0.3001 0.3224 0.3000 0.3440 Calculation of Percentage of Purity: According to British Pharmacopoeia (BP), the percentage of purity should be within 98.0 101.0% of dried substance. Equation of the Percentage of Purity: Sample 1: Sample 2: d) Zinc: Not more than 10ppm Zinc (Zn): To determine the concentration of Zinc metal present in a standardised sample, atomic absorption spectrophotometer was applied. This was done so as to comply with the British Pharmacopoeia (BP) standards, where the detected concentration of Zinc should not be more than 10ppm. Mass of Acetylcysteine sample used: 1.00g This sample was diluted accordingly and then analysed or measured by an atomic absorption spectrophotometer at a set wavelength of 213.8nm. According to the laboratory transcript, the absorbances were given, so the calculation was carried out to determine the concentrations for each solution. Solution Concentration (mg/L) Absorbance (at 213.8nm) (a) 0.00 0.056 (b) 0.25 0.115 (c) 0.50 0.173 Table 8: The absorbance of solution a, b and c using atomic absorbance spectrophotometer. From the table 8 above, a standard additions calibration graph of concentration of zinc in mg/L against absorbance at 213.8nm is plotted. A rather small absorbance indicates that there is a trace or small amount of Zinc (Zn) present in Solution A, which practically contained only the N-acetylcysteine sample. Hence, we can plot a line of best fit and extrapolate to find the concentration of Zn present within our sample. Note that the amount of Zn present is proportional to the absorbance detected at 213.8nm wavelength. Graph 1: The graph of absorbance against concentration of Zinc. Extrapolated value= -0.24 Solution A = 0.24ppm Solution 1 = 0.24 ÃÆ'- 2 = 0.48 ppm Solution 1 0.48g in 100 000 mL = 2.4 ÃÆ'- 10-4g in 50 mL If 1g of N-acetylcysteine contains 2.4 ÃÆ'- 10-4g of zinc ions, 104g of acetylcysteine will contain 2.4g of zinc ions. So concentration of zinc ions in N-acetylcysteine = 2.4ppm Using the calibration graph, we obtained an equation for the line of best fit as shown below: Using the line of best fit we can calculate the concentration of Zinc (Zn) present within Solution 1. This is determined by the difference between the origin (x = 0) and where the line of best fit intercepts the x-axis. To be more accurate, the equation of the line of best fit can be used by assuming the absorbance of N-acetylcysteine at 213.8nm (y-axis) is 0 (y = 0). We can then calculate and find the exact concentration of Zn added (x-axis in mg/L) which gives an absorbance reading of 0.0562 at the wavelength of 213.8 nm. This calculation is shown below where absorbance y = 0. Concentration of Zinc in solution (a) where no Zinc is added:- (Concentration comes in positive value) Therefore, the diluted Solution 1 contains an exact concentration of 0.2402mgL-1 or 0.2402ppm. We can now use this concentration and work backwards from the dilution to obtain the mass of Zn within the 20mL Solution 1, as shown in the calculation below, Mass of Zinc in Solution 1:- From the mass of Zinc present in Solution 1 as calculated, we can say that this equals to the 10mL of N-acetylcysteine sample in Solution (a). This is because Solution 1 was diluted to 20mL using 0.001M hydrochloric acid and contained no other sources of Zinc. Hence, 4.8034ÃŽÂ ¼g of Zinc in 20mL of Solution 1 is equal to 4.8034ÃŽÂ ¼g of Zinc in 10mL of Solution (a). Now using this mass of 4.8034ÃŽÂ ¼g in 10mL of Solution (a) we can find out the total mass of Zinc within 50mL. However, the total mass of Zinc within 50mL of Solution (a) is equivalent to 1.00g of N-acetylcysteine sample which is the original sample mix. Using these data, the mass of Zinc can be calculated as shown in the calculation below, Mass of Zinc in 1.00g of N-acetylcysteine: Hence, 2.4017ÃŽÂ ¼gmL-1 of Zinc is present in 1.00g. We can now calculate an exact concentration of Zinc in parts per million (ppm) as shown in the calculation below, Concentration of Zinc within sample in ppm:- e) Loss on drying: Not more than 1.0% w/w:- Initial mass of N-acetylcysteine sample (g) 1.0965 Mass after drying under specified conditions (g) 1.0893 f) Related substances 1) Acetylcysteine: fresh sample 8.57mg/mL From British Pharmacopoeia, the retention time for the N-acetylcysteine substances as below. Substance Retention time (min) L- cystine About 2.2 L- cysteine About 2.4 2-methyl-2 thiazoline-4 carboxylic acid About 3.3 N,N-diacetyl-L- cystine About 12 N,N-diacetyl-L- cysteine About 14 acetylcysteine About 6.4 1) Acetylcysteine: fresh sample 8.57mg/mL Substance Retention time (min) Peak retention time obtained Concentration L- cystine About 2.2 1.93 0.5948 L- cysteine About 2.4 2-methyl-2 thiazoline-4 carboxylic acid About 3.3 3.25 0.0794 N,N-diacetyl-L- cystine About 12 N,N-diacetyl-L- cysteine About 14 13.623 0.3944 Acetylcysteine About 6.4 6.972 94.7507 Calculation of impurities: Peak area/ Total area x 100 Substance Area Concentration Impurity L- cystine 238606 0.5948 0.5948 L- cysteine 2-methyl-2 thiazoline-4 carboxylic acid 31861 0.0794 0.0794 N,N-diacetyl-L- cystine N,N-diacetyl-L- cysteine 158211 0.3944 0.3944 Acetylcysteine 38007440 94.7507 94.7507 Total area= 40113072 2) Acetylcysteine: old sample 2.5mg/mL Substance Retention time (min) Peak retention time obtained Concentration L- cystine About 2.2 2.11 0.7214 L- cysteine About 2.4 2-methyl-2 thiazoline-4 carboxylic acid About 3.3 3.256 0.8946 N,N-diacetyl-L- cystine About 12 N,N-diacetyl-L- cysteine About 14 13.415 15.3284 Acetylcysteine About 6.4 6.34 33.7241 Calculation of impurities: Peak area/ Total area x 100 Substance Area Concentration Impurity L- cystine 62935 0.7214 0.7214 L- cysteine 2-methyl-2 thiazoline-4 carboxylic acid 78046 0.8946 0.8946 N,N-diacetyl-L- cystine N,N-diacetyl-L- cysteine 1337263 15.3284 15.3284 Acetylcysteine 2942118 33.7241 33.7241 Total area= 8724087 3) Cysteine/ cystine: 0.5mg/mL Substance Retention time (min) Peak retention time obtained Concentration L- cystine About 2.2 2.018 5.2956 L- cysteine About 2.4 2.323; 2.65 2.3189; 2.384 2-methyl-2 thiazoline-4 carboxylic acid About 3.3 3.008; 3.207 24.9029; 65.0987 N,N-diacetyl-L- cystine About 12 N,N-diacetyl-L- cysteine About 14 Acetylcysteine About 6.4 Calculation of impurities: Peak area/ Total area x 100 Substance Area Concentration Impurity L- cystine 87001 5.2956 5.2956 L- cysteine 38097; 39167 2.3189; 2.384 2.3189; 2.384 2-methyl-2 thiazoline-4 carboxylic acid 409128; 1069503 24.9029; 65.0987 24.9029; 65.0987 N,N-diacetyl-L- cystine N,N-diacetyl-L- cysteine Acetylcysteine Total area= 1642895 4. Discussion: a) Specific optical rotation: The specific rotation of a chemical compound [ÃŽÂ ±] is defined as the observed angle of optical rotation ÃŽÂ ± in stereochemistry, when plane-polarized light is passed through a sample with a path length of 1 decimetre (dm) and a sample concentration of 1 gram (g) per 1 millilitre (mL). The specific rotation of a pure material is an intrinsic property of that material at a given wavelength and temperature. The reading should be accompanied by the temperature at which the measurement was performed and the solvent in which the material was dissolved, and this often assumed to be room temperature. The exact unit for specific rotation values is deg dmà ¢Ã‹â€ Ã¢â‚¬â„¢1cm3 gà ¢Ã‹â€ Ã¢â‚¬â„¢1 or can use degrees (ÃÅ'Ã…  ). Levorotatory rotation (l) means a negative reading obtained and the rotation being to be left. While dextrorotatory rotation (d) means a positive reading and the rotation is being to be right. The specific optical rotation for the freshly prepared solution of N-a cetylcysteine is +24.5à ¢Ã‚ Ã‚ ° which it is dextrorotatory rotation and the old solution of N-acetylcysteine is -32.9à ¢Ã‚ Ã‚ ° which means levorotatory rotation. Measurement of optical rotation is a way to assess optical purity of a sample containing a mixture of enantiomers. An enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable or not identical much as ones left and right hands are the same but opposite. The specific optical rotation of N-acetylcysteine solution is within the range +21ÃÅ'Ã…   to approximately +27ÃÅ'Ã…  . The freshly prepared of N-acetylcysteine solution is found to be in the range however the old N-acetylcysteine solution is not in the range. This reveals stability alteration occurred in the old N-acetylcysteine solution. The impurities have found in the old N-acetylcysteine solution because the presence of small amount of impurities can affect the rotation of the sample. The actual optical rotation value for freshly prepared N-acetylcysteine solution is measured by single polarimeter because if the sample is very concentrated or it has very large specific rotation or the sample larger than 180 °, single polarimeter cannot be used. The variation of specific rotation with wavelength is the basis of optical rotary dispersion (ORD) which used to elucidate the absolute configuration of certain samples. High performance liquid chromatography (HPLC) is used to determined the enantiomeric ratio with a chiral column because the aggregation in the N-acetylcysteine solution cause optical rotation of a sample maybe not linear dependent due to enantiomeric excess. b) ASSAY: 98.0%-101.0% C5H9NO3S (as dried material) From the result obtained above, the mass obtained from the titration of N-acetylcysteine solution with iodine with starch as indicator for first titration is 0.13986g and second titration is 0.13552g. The percentage of purity obtained from the experiment for first sample is 99.64%. The percentage of purity from second sample is 98.26%. According to British Pharmacopoeia (BP), the percentage of should be within 98.0 101.0% of dried substance. The percentage of purity for both samples is within the range stated in the BP. BP prefer the iodine titration to a titration using sodium hydroxide because iodine is a very useful oxidising titrant which react with reducing agent ,N-acetylcysteine solution using starch as indicator. Iodine forms an intensely dark blue complex with starch. Starch is an oxidation reduction indicator that shows a reversible colour change between the oxidised and reduced forms. It is not affected by the presence of iodide (I-). Both starch and iodide must be prese nt for the starch to change colour during the titration. Iodine is consumed by thiosulfate in the titration step. The amount of thiosulfate used is proportional to the amount of iodine liberated from the salt. Sodium hydroxide is a strong base. It is more useful in acid- base titration using weak acid or base indicator. c) Assay by titration with 0.1M of sodium hydroxide From the result obtained in this experiment, the mass obtained from the titration of N-acetylcysteine solution with0.1M sodium hydroxide with phenol red as indicator for first titration is 0.2972g and second titration is 0.2964g. The percentage of purity obtained from the experiment for first sample is 98.97%. The percentage of purity from second sample is 98.77%. According to British Pharmacopoeia (BP), the percentage of should be within 98.0 101.0% of dried substance. The percentage of purity for both samples is within the range stated in the BP. The mass obtained from the titration of N-acetylcysteine solution with 0.1M sodium hydroxide with phenolphthalein as indicator for first titration is 0.3224g and second titration is 0.3440g. The percentage of purity obtained from the experiment for first sample is 107.43%. The percentage of purity from second sample is 114.67%. According to British Pharmacopoeia (BP), the percentage of should be within 98.0 101.0% of dried substance. The percentage of purity for both samples is out of the range stated in the BP. Phenol red and phenolphthalein are acid-base indicators. The un-dissociated form of the indicator is a different colour than the iogenic form of the indicator. An Indicator does not change colour from pure acid to pure alkaline at specific hydrogen ion concentration, but rather, colour change occurs over a range of hydrogen ion concentrations. This range is termed the colour change interval. It is expressed as a pH range. The pH range for phenol red is 6.8- 8.4 and phenolphthalein is 8.0- 10.0. The selection of indicator will depend on the actual expected pH at the equivalence point which selects an indicator with a pKa right in the middle of the pH change at the equivalence point. N-acetylcysteine solution has pKa 4.0 and 9.5, and a weak acid indicator has to be used to determine the end point of the titration. Phenol red produce a good result compared to the phenolphthalein as indicator when titrate N-acetylcysteine solution with 0.1M sodium hydroxide. d) Zinc: Not more than 10ppm Zinc (Zn): By performing the atomic absorbance technique, we have determined that the N-acetylcysteine sample contained a Zinc concentration of 2.4017ppm. This sample complied with the requirement from the British Pharmacopoeia (BP) monograph standards by not having a Zinc concentration of greater than 10ppm. Atomic absorbance technique can only detect specifically one heavy metal at a time. So, it is very time consuming to detect a wide spectrum of heavy metal impurities within our sample. Plus, the N-acetylcysteine monograph only indicates the need to monitor the level of Zinc present within the sample by atomic absorbance spectrometry. Therefore, to detect other heavy metals we would prefer to use the more generic Limit Test C for Heavy Metals as specified in the British Pharmacopoeia (2008), Volume IV, and Appendix VII. e) Loss on drying: Not more than 1.0% w/w:- According to British Pharmacopoeia (BP), it states that there should be no more than 1.0% in mass. This sample is complied with the BP monograph standards with a loss of only 0.66% in mass. f) Related substances:- HPLC is used in pharmaceutical analysis to quantitative determinations of drugs in formulations. These analyses do not require long time to optimising mobile phase and selecting columns and detectors. Some formulations contain more than one active ingredient and may present more of an analytical challenge since the different ingredients may have quite different chemical properties and elute at very different times from HPLC column. 5. Conclusions: Quality control is an essential operation of the pharmaceutical industry. Drugs must be marketed as safe and therapeutically active formulations whose performance is consistent and predictable. A bundle of sophisticated analytical methods are being developed for the drugs evaluation in pharmaceutical industry. Requirements governing the quality control of pharmaceuticals in accordance with the British Pharmacopoeia (BP) or European Pharmacopoeia. Titration is a procedure used in chemistry in order to determine the molarity of an acid or a base. A chemical reaction is set up between a known volume of