By W. Grobock. Patten College.
There was a reduction in Hormone therapy Page 38 of 110 Final Report Update 3 Drug Effectiveness Review Project investigator-assessed vaginal atrophy generic tadacip 20 mg overnight delivery, dryness purchase tadacip 20mg on line, and friability for estradiol acetate compared with 37 placebo (p<0 cheapest tadacip. A Cochrane systematic review compared efficacy and safety of intra-vaginal estrogen preparations (creams, pessaries, tablets, and estradiol-releasing ring) for the relief of symptoms 100 of vaginal atrophy (vaginal dryness, itching, discomfort, and painful sexual intercourse). Overall, the author concluded that the preparations appear to be equally effective for the symptoms of vaginal atrophy. CEE cream caused more side effects compared to estradiol tablets (uterine bleeding, breast pain, and perineal pain) or estradiol vaginal ring (endometrial overstimulation). For the comparison of the estradiol ring to CEE vaginal cream, there was no difference between groups in patient assessment of vaginal dryness or withdrawals due to adverse events, but there was more improvement in pruritis with the ring. For the comparison of estradiol ring versus estradiol tablet, vaginal dryness was improved more with tablets, but there was no difference between groups in genital pruritis or withdrawals due to adverse events. Symptom improvement was similar for tablet versus cream, but there were fewer withdrawals due to adverse effects with tablets compared with cream. There was no difference among all treatment comparisons for dysuria, nocturia, urgency, urge incontinence, participant symptom improvement in dryness, soreness, and irritation, loss of libido, and vaginitis. Quality-of-life A head-to-head comparison of CEE vs. A trial comparing oral E2 and intravaginal ring E2 found significant improvement on the Greene Climacteric Scale among 102 both treatment groups but no between-group differences. One trial of oral E2 conducted in HRT-naive women in Thailand observed no difference in mean Greene score 83 improvement compared with placebo after 12 months of treatment. A trial of low-dose oral E2 103 (1 mg per day) reported significant improvement from baseline at 6 and 12 weeks on six of nine domains of the Women’s Health Questionnaire (vasomotor symptoms, sexual behavior, depressed mood, somatic symptoms, anxiety/fear, and sleep problems). There was no difference between control and treatment groups on the memory concentration, menstrual symptoms, and attractiveness items of the scale. Seven trials of transdermal E2 and placebo indicated improved health related quality-of- life and well-being measured by various instruments: Nottingham Health Profile, Psychological General Well-Being Index, Women Health Questionnaire, Kupperman’s index, McCoy Sex 68, 70, 73, 74, 76, 96, 104 Scale, and psychological general well-being index. One trial indicated that women with high well-being and no vasomotor symptoms at baseline had no improvement with 105 treatment as measured by the Psychological General Well-Being Index. The HERS trial (CEE), using non-validated quality of life instruments (Duke Activity Status Index, RAND Mental Health Inventory, among others), found that quality of life scores were significantly lower among women who were older, had diabetes, hypertension, chest pain, 91 or heart failure, and that use of CEE had little effect. One trial found a significant decrease in 59 Kupperman’s index among women treated with E2V compared with placebo. A trial of Hormone therapy Page 39 of 110 Final Report Update 3 Drug Effectiveness Review Project esterified estrogens reported improvement in the Quality of Life Menopause Scale compared to 106 placebo. Health-related quality of life (HRQL) measures were collected on a subgroup of women 85 enrolled in the WHI randomized to CEE plus MPA or to placebo (n=16,608). Quality of life and functional status were assessed using the RAND 36-item Health Survey, which includes items about general health, physical functioning, limitations on usual role-related activities due to physical health problems, bodily pain, energy and fatigue, limitations on usual role-related activities due to emotional or mental problems, social function, and emotional or mental health. At 1-year follow-up, there were small but statistically significant positive effects of CEE/MPA on physical functioning (0. There were no differences from placebo in any other HRQL measure and by 3 years of follow-up (n=1511) there were no significant differences from placebo on any HRQL measure. Subgroup analyses detected no statistically significant interactions between baseline age, race, ethnicity, body mass index, or menopausal symptoms and HRQL. In a post hoc analysis of women 50 to 54 years of age who reported moderate-to-severe vasomotor symptoms at baseline, there was a positive effect on sleep disturbance, but no effect on other HRQL measures, despite significant improvement in vasomotor symptoms. At 1-year follow-up, there was a small positive effect of CEE on sleep disturbance (0. At 1- year follow-up of women who had moderate-to-severe vasomotor symptoms at baseline, 72. In a subsample (n=1,189) examined at 3-year follow-up there were no significant differences in any HRQL measure between treatment groups. For Update #3, none of the three new studies reporting HRQL or related outcomes showed significant effects between the treatment and placebo groups. The ULTRA study of 78 low-dose transdermal estrogen reported no significant improvements in the SF-36 subscales of 29 physical and mental function. The findings of Dayal and colleagues were similar in that conjugated equine estrogen did not improve vitality, general health status, or quality of life at 12- week follow-up. A third study of women over 70 years randomized to oral estradiol or placebo 26 also did not report significant changes in a “SF-36 score. What is the comparative effectiveness of different hormone therapy preparations when used by postmenopausal women or women in the menopausal transition stage for preventing low bone density and fractures? Outcomes include bone density measurements at lumbar spine, forearm, and hip sites and/or fracture data from one or more sites. Numbers of included studies are summarized in Table 7 below; trials are described in Evidence Tables 5 (head-to-head trials) and 6 (placebo- controlled trials), and quality ratings are presented in Appendix F. Quality ratings of studies added for Update #3 are shown in Appendix G. Hormone therapy Page 40 of 110 Final Report Update 3 Drug Effectiveness Review Project Table 7. Number of studies of estrogens with bone density or fracture outcomes Total Bone Density Fractures Head-to-head comparisons CEE and transdermal estradiol (E2) 3 3 0 Transdermal estradiol (E2) and estradiol 1 1 0 valerate (E2V) Placebo comparisons Estradiol (E2) Oral 16 16 1 Transdermal 15 15 2 Estradiol valerate (E2V) 5 5 1 Conjugated equine estrogen (CEE) 29 26 8 Conjugated synthetic estrogen 1 1 0 Esterified estrogen (EE) 1 1 0 Estropipate 0 0 0 Characteristics of the trials included: • Three trials with bone density outcomes compared estrogens head-to-head. Treatment refers to studies of women with pre-existing fractures or a diagnosis of osteoporosis at baseline. Bone density Head-to-head comparisons We identified no new head-to-head trials with bone density or fracture outcomes in this update. Four head-to-head trials compared different estrogen preparations, including three trials 108-110 of CEE compared to transdermal E2, and one trial of transdermal E2 compared to estradiol 111 valerate (Table 8 and Evidence Table 5). Hormone therapy Page 41 of 110 Final Report Update 3 Drug Effectiveness Review Project Table 8. Head-to-head trials with bone density outcomes Population Study/year Study design characteristics Interventions Main outcomes/results Oral CEE compared with transdermal E2 Castelo- Open label Postmenopausal CEE: 0. Oral CEE compared oral E2 Castelo- Blinding unclear Postmenopausal CEE: 0. N=73 Mean age 51 (45- days); E2V: 2 mg/day No significant differences between treatment 2 years 54 years) (11 days); groups at any site. In one trial, women using either CEE for 30 days or transdermal E2 for 25 days/month had an increase in lumbar spine 108 bone mineral content compared to placebo (CEE: +4. Use of CEE for 25 days/month did not show a significant change (+1. Similar results were 109 found when using these regimens in 118 women with prior hysterectomies. Increases in bone mineral density (BMD) occurred in all treatment groups after one year, and the increases did not differ significantly between the CEE and E2 groups. The addition of alendronate to either form of hormone therapy increased BMD significantly more than did 110 hormone therapy alone. One study of 73 healthy postmenopausal women age 45 to 54 years compared the effects 111 of oral E2 and E2V on forearm and spinal BMD. Both groups significantly gained bone density compared to placebo, and no significant differences between groups were found at any site. Placebo comparisons Sixty-four RCTs comparing an eligible estrogen preparation with placebo and reporting BMD outcome data met criteria for this review.
A ntich olinergicoveractive bladdersyndrom e drugs com pared with non-drug th erapy N um berwith drawn/ A uth or discount tadacip master card, lostto follow-up/ M eth od ofO utcom e A ssessm ent Y ear analyz ed and Tim ing ofA ssessm ent O utcom es G oode 92ex cludedfrom analy sis:28didnot Bladderdiary R eductioninVoiding frequency /24h:O x y -2 purchase generic tadacip line. R esultsin reasonsnotreported) 9subscalesandaG lobalSeverity 155analy z ed Index tadacip 20mg generic,50onany scaleisnorm al,63+ is"ex trem eenough tobeacase" Burgio 24withdrew/0losttof/u/190analy z ed Bladderdiaries,patientsatisfaction Changeinincontinenceepisodes: 1998 andoverallevaluationof perceived O x y 10. O x y ) Insubgroup of wom en(n= 131)with nocturia M eanreductioninnocturiafrom baseline: O x y :0. Behavioralto (ex tension analy z ed com binedtherapy 57. A ntich olinergicoveractive bladdersyndrom e drugs com pared with non-drug th erapy A uth or, A dverse effects assessed? W ith drawals due to Y ear H ow assessed adverse events C om m ents G oode N otreported N otreported N otenough datapresentedtofully evaluateresults. Burgio2001 Seeabove Seeabove Thisisasubgroup analy sisfrom theBurgiostudy ,of thosecom pleting psy chologicalanaly sis. N otreported 1998 D ry m outh O x y 97%,Beh 35%,Pl55% Inability tovoidO x y 22%,Beh 6%,Pl3% ConstipationO x y 39%,Beh 22%,Pl37% BlurredvisionO x y 15%,Beh 10%,Pl10% ConfusionO x y 8%,Beh 6%,Pl11% Burgio2000 N otreported N otreported Thisisasubgroup analy sisof patientsagreeableto (ex tension com binedtherapy postBurgio1998trial. A ntich olinergicoveractive bladdersyndrom e drugs com pared with non-drug th erapy N um ber A ge A uth or, Study Design screened/ G ender Y ear Setting eligible/enrolled Eth nicity Interventions (drug,regim en,duration) Soom ro R andom iz ed 43enrolled, M eanage O x y 2. Patientscontrolledam plitudeto Singlesite reported produceatickling sensation,at20Hz frequency andpulseof 0. Colom bo R CT 81screened, Age:O x y = 48, O x y 5m g threetim esdaily orbladdertraining x 6weeks 1995 Singlesite othersnot Beh= 49 U SA reported 100percentfem ale E thnicity not reported O xy= O xybutynin,B eh = B eh avior,Pl= Placebo,EN S = ElectricalN erveStimulation Overactive bladder 163 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 4. A ntich olinergicoveractive bladdersyndrom e drugs com pared with non-drug th erapy A uth or, O th erpopulationch aracteristics Y ear (diagnosis,etc) Eligibility criteria Exclusioncriteria Soom ro M eanfunctionalcapacity 154 Patientswith ahistory of frequency ,urgency and N otR eported 2001 urgeincontinencewhohadnotbeenpreviously treatedatthedepartm ent,including som ewhohad previously receivedtreatm entfrom ageneral practitioneratleast6m onthspriortostudy enrollm ent. Colom bo D etrusorinstability :O x y = 14,Beh= 13; Patientsshowing detrusorinstability ,low- Stablebladderatcy stom etry ;neurologic 1995 L ow-com pliancebladder:O x y = 9,Beh= 8; com pliancebladderandsensory bladder disease;detrusorhy perreflex ia;agegreater Sensory bladder:O x y = 15,Beh= 16 than65y ears;coex isting genuinestress urinary incontinence;genitalprolapse; postvoidresidualvolum egreaterthan50m l; previousgy necologicalorurogy necological operation;prioruseof any drug forthe treatm entof urinary urgeincontinence; urethraldiverticula;fistulas;urinary tract neoplasia;bacterialorinterstitialcy stitis; bladderstones;andpreviouspelvic radiotherapy O xy= O xybutynin,B eh = B eh avior,Pl= Placebo,EN S = ElectricalN erveStimulation Overactive bladder 164 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 4. A ntich olinergicoveractive bladdersyndrom e drugs com pared with non-drug th erapy N um berwith drawn/ A uth or, lostto follow-up/ M eth od ofO utcom e A ssessm ent Y ear analyz ed and Tim ing ofA ssessm ent O utcom es Soom ro N otR eported Voiding diary ,Bristolurinary R eductioninvoiding frequency /24h:O x y -2,E N S:-2 2001 sy m ptom questionnaireandQ uality Sy m ptom sby Bristolurinary sy m ptom questionnaire: of L ifequestionnaire significantchangesinscoreinboth groupsonfrequency ,and dissatisfactionwith spending restof lifewith currentsy m ptom s com paredtobaseline N odifferenceonleaking orhesitancy com paredtobaseline O x y only hadsignificantchangeinscoreforincom pleteem pty ing com paredtobaseline SF -36: N osignificantdifferencescom paredtobaseline Patientsfinding treatm enteffective: O x y 10,E N S 4 Colom bo 6withdrawn:O x y = 4dueto Clinicalcure:totaldisappearanceof Clinicalcure: 1995 anticholinergic adverseevents;Beh= 2 urgeincontinenceanddidnotrequire D etrusorinstability group:O x y = 93%,Beh= 62% consentwithdrawals protectivepadsorfurthertherapies L ow-com pliancebladdergroup O x y = 67%,Beh= 75% Sensory bladdergroup:O x y = 60%,Beh= 81% O xy= O xybutynin,B eh = B eh avior,Pl= Placebo,EN S = ElectricalN erveStimulation Overactive bladder 165 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 4. A ntich olinergicoveractive bladdersyndrom e drugs com pared with non-drug th erapy A uth or, A dverse effects assessed? W ith drawals due to Y ear H ow assessed adverse events C om m ents Soom ro Post-treatm entsideeffectsquestionnaire(at N otreported 2001 6wks) D ry m outh O x y 87%,E N S 6% BlurredvisionO x y 53%,E N S 6% D ry skinO x y 30%,E N S 28% SkinirritationO x y N A,E N S 11% D ifficulty using m achineE N S 13% Colom bo U nclear. O x y = 4(3duetodry 1995 O x y :D ry m outh= 15;constipation= 6; m outh;1dueto N ausea= 5;D iz z iness= 2;D ecreaseinvisual glaucom a) acuity = 1;Tachy cardia= 1; Beh = nonereported Beh = nonereported O xy= O xybutynin,B eh = B eh avior,Pl= Placebo,EN S = ElectricalN erveStimulation Overactive bladder 166 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 5. New overactive bladder syndrome drugs compared with placebo Mean Change in Number Author of Incontinence Year Dose Mean Change in Number of Micturitions/24h Episodes/24h OAB drug Placebo OAB drug Placebo (n) (n) (n) (n) Rentzhog TOL ↓20% (not given) Not reported ↓46% Not 1998 2mg BID (not given) reported Jacquetin TOL ↓1. Q uality assessm entofplacebo-controlled trials Internalvalidity A uth or, R andom iz ation A llocationconcealm ent G roups sim ilarat Eligibility criteria O utcom e assessors C are Y ear adequate? Zinner,2006 Yes N R Yes Yes "D ouble-blind"m ethods Yes N R Staskin,2007 Yes Yes Yes Yes Yes Yes Hill,2006 Yes Yes Yes Yes Yes Yes D m ochowski, Yes Yes Yes Yes "D ouble-blind"m ethods Yes 2008 N R Chapple,2007 Yes Yes Yes Yes Yes Yes Overactive bladder 171 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 6. Q uality assessm entofplacebo-controlled trials A uth or, Patientm asked? R eporting ofattrition, A ttrition: Intention-to-treat(ITT) Q uality F unding Y ear crossovers,adh erence,differential/h igh analysis R ating and contam ination Zinner,2006 Yes Attritiony es(15% N o Yes F air N ovartis overall) Pharm aAG CrossoverN R Protocolviolationswere reported Staskin,2007 Yes Attritiony es(11. Q uality assessm entofplacebo-controlled trials R udy ,2006 N otreported N otreported Yes Yes Yes Yes R ackley ,2006 N otreported N otreported Yes Yes Yes Yes Overactive bladder 173 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 6. Q uality assessm entofplacebo-controlled trials R udy ,2006 Yes Attrition-Yes,Crossover- Yes,L O CF F air Indevus N o,Adherence-N R , N o/N o Pharm aceut Contam ination-N R icalsInc N on com pleters: Trospium ‐7. A ssessm entofabstracts forpublicationbias M icturitions U rge incontinence A uth or Interventions m eanch ange episodes m eanch ange Y ear (Drug,dose,sam ple siz e) (tim e period) (tim e period) H ead-to-h ead VanK errebroeck A:Tolterodine2m g BID (n=120) A:-2. A ssessm entofabstracts forpublicationbias M icturitions U rge incontinence A uth or Interventions m eanch ange episodes m eanch ange Y ear (Drug,dose,sam ple siz e) (tim e period) (tim e period) M oore A:Tolterodine1m g BID A:-1. A ssessm entofabstracts forpublicationbias M icturitions U rge incontinence A uth or Interventions m eanch ange episodes m eanch ange Y ear (Drug,dose,sam ple siz e) (tim e period) (tim e period) J uz ba O x y buty nin 3m onths Cox regressiontheriskof 2001 Tolterodine discontinuationwasstatistically (form ulationsnotstated) significantly lowerinTolusers, whowere43% lesslikely to discontinue *Data notprovided Overactive bladder 177 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 8. O veractive bladdersyndrom e observationalstudies:A dverse events A uth or, Y ear Setting Study Design Eligibility criteria Exclusioncriteria Tolterodine (Tol) Siam i M ulticenter O penlabel, M enandwom enage18+with Pureorpredom inantlystressincontinence,indwelling 2002 U SA uncontrolled diagnosisof overactive orinterm ittentcatheter,sym ptom atic orrecurrentU TI, 12weeks bladderwith sym ptom sof hepatic orrenaldysfunction,program of urinaryfrequency(8+ electrostim ulation,bladdertraining orpelvic floor m icturitions/24h),urgency ex erciseswithin4weeks. Tol= Tolterodine,O xy= O xybutynin,IR = Immediaterelease,ER = Extendedrelease,R C T = R andom C ontrolledTrial,U TI= U rinarytractinfection Overactive bladder 178 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 8. O veractive bladdersyndrom e observationalstudies:A dverse events N um berscreened/ A ge A uth or, eligible/ G ender Y ear Interventions enrolled Eth nicity Tolterodine (Tol) Siam i Tol4m g E R oncedaily N um berscreenednot Agerange18-91 2002 reported. M eanagedrug naive60yr 1147enrolled M eanagepriortreatm ent62. M eandose2m g twice 2250enrolled M eanage61yrs 2002 daily 77% fem ale Appell Tol2m g twicedaily 939eligible/854enrolled AgeR ange19-89 2001 M ean60yrs 76% fem ale Tol= Tolterodine,O xy= O xybutynin,IR = Immediaterelease,ER = Extendedrelease,R C T = R andom C ontrolledTrial,U TI= U rinarytractinfection Overactive bladder 179 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 8. O veractive bladdersyndrom e observationalstudies:A dverse events W ith drawals due A uth or, to adverse Y ear H ow adverse effects assessed A dverse events reported events Tolterodine (Tol) Siam i Spontaneouslyreportedandelicitedduring visits(1,4and D rym outh wasthem ostcom m onadverseeventreported,at 90(8%) 2002 12wks). Adverseevents D ryM outh 28% (2% of allpatientshadseveredrym outh) 12duetodry classifiedasm ild,m oderate,severe. SevereAdverse U TI 12% m outh (1%) eventswereassessedforrelationship toTol. Abdom inalpain6% 13% reduceddosage 3seriousadverseeventswerejudgedpossiblyorprobably relatedtoTol(constipation,abdom inalpain,andtachycardia) 3casesof urinaryretention(0. O veractive bladdersyndrom e observationalstudies:A dverse events A uth or, Y ear C om m ents Tolterodine (Tol) Siam i Short-term 2002 M ichel R ealistic setting, 2002 butunclearif tolerability assessm entis m adebyphysician orpatient Appell 2001 Tol= Tolterodine,O xy= O xybutynin,IR = Immediaterelease,ER = Extendedrelease,R C T = R andom C ontrolledTrial,U TI= U rinarytractinfection Overactive bladder 181 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 8. O veractive bladdersyndrom e observationalstudies:A dverse events A uth or, Y ear Setting Study Design Eligibility criteria Exclusioncriteria Abram s M ulticenter O penlabel12m onths Patientscom pleting 4wkR CT N onespecified 2001 (m ultinational) study enrolledafter4-weekwashout period. K reder M ulticenter O penlabel12m onth Patientscom pleting 12wk N onespecified 2002 (m ultinational) study R CT enrolled Abram s,2001 M ulticenter,E urope O penlabel, m aleandfem alepatients,age clinicallysignificantstressincontinence,hepatic or uncontrolled,12 >18(≥65yinone4-week renaldisease,recurrentorsym ptom atic U TI, m onths study),urodynam icallyproven conditionscontraindicating antim uscarinic therapy, overactivebladderand clinicallysignificantvoiding difficultywith riskof sym ptom sof urinary urinaryretention,treatm entwith orinitiationduring the frequency(average(≥8 studyof,anyantim uscarinic drug oranydrug for m icturitions/24h),urgency, bladdercontrolproblem sorbladdertraining,within an/orurgeincontinence 14dpriortothebaselinevisit. M ichel, M ulticenter, O penlabel, none none 2005 G erm any uncontrolled,9 m onths Tol= Tolterodine,O xy= O xybutynin,IR = Immediaterelease,ER = Extendedrelease,R C T = R andom C ontrolledTrial,U TI= U rinarytractinfection Overactive bladder 182 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 8. O veractive bladdersyndrom e observationalstudies:A dverse events N um berscreened/ A ge A uth or, eligible/ G ender Y ear Interventions enrolled Eth nicity Abram s Tol2m g twicedaily 895eligible/714enrolled Agerange18-92 2001 M eanage60yrs 69% fem ale K reder TolE R 4m g oncedaily(nodoseadjustm ents 1337eligible/1077enrolled Agerange20-93 2002 allowed) M eanage60yrs 82% fem ale Abram s,2001 Tol2m g twicedailywith optionalreductionto screenedN R /895eligible m eanage59. O veractive bladdersyndrom e observationalstudies:A dverse events W ith drawals due A uth or, to adverse Y ear H ow adverse effects assessed A dverse events reported events Abram s Spontaneouslyreportedadverseevents,withdrawals,and 77% reportedanadverseevent. Adverseevents D rym outh 289(41%)(27% m ild,3% severe) classifiedasm ild,m oderate,severe. SevereAdverse U TI 10% eventswereassessedforrelationship toTol. K reder Spontaneouslyreportedadverseevents,withdrawals,and D rym outh 139(12. Severeadverse U R I 43(4%) reason: eventswereassessedforrelationship toTol. Blood 4seriousadverseeventsconsideredpossiblyrelatedtoTolE R : drym outh 19 chem istry/hem atology. Abram s,2001 spontaneouslyreportedAE ,withdrawalsanddosage 41% drym outh (27% m ild,10% m oderateand35severe)O ther105patients reductionsandat6m onth assessm entvisit. AE were AE :autonom ic nervoussystem disorders,generalbody (15%) classifiedasm ild(easilytolerated),m oderate(sufficient disorders,gastrointestinaldisordersandurinarydisorders. O veractive bladdersyndrom e observationalstudies:A dverse events A uth or, Y ear Setting Study Design Eligibility criteria Exclusioncriteria Takei, ex tensionof openlabel, 2005 Hom m a,2003,a uncontrolled,12 com parative m onths controlledR CT O xybutynin (O xy) G leason M ulticenter O penlabel12week M enandwom enwith U ncontrolledm edicalcondition,postvoidresidual 1999 U SA study idiopathic urgeincontinenceorvolum e>100m lorsignificantberuriaorpyuria.
Re-assessment has two pur- training from an experienced facilitator order discount tadacip on-line. A clear poses: to check progress following interventions link and support from the department management implemented and to identify new problem areas generic 20mg tadacip fast delivery. Documentation of each meet- The information collected during re-assessment ing must be done in order to be able to follow up will be compared with the results of the baseline and refer to the recommendations 20 mg tadacip with amex. Re-assessment should focus on quality improvement and beyond, but they do not the areas identified for improvement during the replace or work on behalf of the quality teams. Such circles should not be used as a forum for addressing staff demands, neither are they a solution Self-assessment to all challenges in the work place. This is a method of identifying one’s strengths and Assessment results and the gaps list can be chan- weaknesses. An individual or a team will conduct nelled to these quality circles for them to discuss assessment of their respective performance using and identify causes and solutions. They should be the same standards and tools which are used in ex- encouraged to make own action plans and follow ternal assessment. During the overall hospital (department) assess- ment, areas of strength and weakness are identified Step 8: Re-assessment by the assessors and communicated. Departmental It is the individual health worker at the facility who and functional unit action plans are developed with can make changes for the better. This is why self- the intention of addressing the performance gaps assessment becomes of crucial importance. Specific activities show the health worker who is doing the assess- are developed in line with responsible people and 451 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS time limits. After a period of implementation, the referred to as organization-wide involvement in individual or team would like to know what has quality improvement. This type allows the facility changed in the direction of filling the performance stakeholders (staff, management, users and the com- gaps. Using the same tools, a self-assessment is con- munity) to take part. Using the example above the performance users and the community to have a better health gap and planned action is reiterated as follows: facility are part of it. It will allow staff across the facility to discuss and give inputs that will make the Performance gap In the gynecology ward of Hospital management take into consideration disruptions of X only 50% of the patient vital information (regis- staff expectations, their fears and their life in the tration, medication and vital signs) is documented. This will positively support staff to Target Documentation of patient vital information manage changes more on an individual basis. Successful introduction and management of change will be reflected in the improvement Activity The Gynecology ward nurse in charge to of clinical outcomes, reduce errors in clinical care hold once-weekly assessment of documentation of and improved staff and patient safety. Clinical audit in gyneco- assessment to improve this indicator. At the end of logy mainly deals with postoperative complications. The nurse will also check all patient monitoring Clinical audit is a quality improvement process that sheets to ensure that patient vital signs are checked seeks to improve patient care and clinical outcomes and correctly filled in the sheets. Once every week, through systematic review of care against explicit the nurse in charge will do ward assessment to en- criteria and the implementation of change. The sure that patient information is correctly filled in aim is to find out what went wrong, why and how the appropriate registers. Once in a while, the ward this can be prevented in future. So audit is related staff may decide to assess all other performance to quality improvement and the use of clinical indicators related to their respective ward and iden- standards, e. The most tify their strengths in conformance to the standards. If there is anything all standards according to the defined indicators. Audit is well known and established in many CLINICAL AUDITS regions of the world for maternal mortality. Apart As it may seem clear from the descriptions above, from its role in quality improvement these audits quality improvement is an essential part of change have helped to produce global data on maternal management. In practical terms there are two types mortality as well. Figures on surgery-associated of change management: the classical type of change mortality and morbidity however are lacking. You can find out more about and later the decision is channelled to the rest of this initiative under http://www. The second type may be Saves Lives Measurement and Study Groups together 452 Quality Improvement and Clinical Audits with WHO have developed a checklist for surgical involve high costs where there is a possibility of interventions which can serve as a standard for improvement. This is called criterion-based audit as it auditing peri- and postoperative complications in deals with the assessment of one criterion only. It can be downloaded in sev- important criterion-based audit is the critical inci- eral different languages from http://www. This audit deals with inci- patientsafety/safesurgery/en/index. You are dents where something nearly happened and was encouraged to adapt the list to your circumstances. A near-miss Typically, the clinical audit process identifies audit is important because such an event can show performance gaps (areas of service which need im- weak spots in a process before someone gets hurt. The Figure 6 summarizes clinical audit process in identification of performance gaps through near- form of a cycle. A clinical audit team in gynecology miss or mortality audit will start with a case analysis. The audit cycle is similar to the analysis in step one of the quality circle. The same quality improvement cycle and will result in an accounts for example in the audit of a cluster intervention matrix as described above for per- of postoperative fever between January and formance assessments. December of year X, where you will go through several patient files. Identification of performance gaps A performance gap is the variation between the Define criteria and standards current performance and the performance accord- ing to standards. In step 4 of the quality circle, it is This step refers to the tasks to be accomplished by possible to identify clinical gaps which may be the audit. The audit should answer specific ques- found in the form of substandard care or clinical tions that will detail processes where standards were errors which will lead to clinical complications in- observed during the process of care, but also reveal cluding situations like postoperative hemorrhage, specific areas where standards were not adhered to. The most common audits will be mortality which are referred to as audit criteria.
Some of the Plasmodium species have diverged tens of millions of years ago purchase tadacip cheap, so it is not surprising that they have diﬀerent strategies for attach- ment effective tadacip 20mg, immune evasion purchase tadacip 20 mg mastercard, and antigenic variation. The parasite expresses only a small subset of these genes in an infected erythrocyte. Sera from twenty-ﬁve previously infected hosts provided a panel of antibodies to test for prior exposure to the vir gene products. One of the expressed proteins reacted with the serum from only one host, the other proteinreacted with sera from two hosts. Thus, vir gene products are immunogenic, but each variant appears to be expressed rarely—the hallmarks of antigenic variation from a large archival library. Sequences related to the vir family do not occur in P. Thediversityofgene families in Plasmodium that play a role in antigenic variation provides an excellent opportunity for comparative, evolutionary studies. Usually, each parasite expresses only one archival variant. New variants of archival copies may becreatedbyrecombination. They studiedtheDNAsequences of 11 vsp loci within a single clone. These vsp loci are silent, archival copies that can, by gene conversion, be copied into the single expression site. The genes diﬀer by 30–40% in amino acid sequence, providing suﬃcient diversity to reduce or elimi- nate antigenic cross-reactivity within the host. Those analysesfocuson attributes such as runs of similar nucleotides between loci that occur more often than would be likely if alleles di- verged only by accumulating mutations withineachlocus. Sharedruns can be introduced into diverged loci by recombination. The archival antigenic repertoire of Trypanosoma brucei evolves rap- idly (Pays and Nolan 1998). This species has a large archival library and multiple expression sites, but only one expression site is active at any time. New genes can be created within an active expression site when several donor sequences convert the site in a mosaic pattern (Pays 1989; Barbet and Kamper 1993). When an active expression site becomes inac- tivated, the gene within that site probably becomes protected from fur- ther gene conversion events (Pays et al. Thus, newly created genes by mosaic conversion become stored in the repertoire. Perhaps new genes in silent expression sites can move into more per- manent archival locations by recombination, but this has not yet been observed. Recombination between silent, archived copies may also oc- cur, which, although each event may be relatively rare, could strongly aﬀect the evolutionary rate of the archived repertoire. These examplesillustrate the scattered reports of recombination and the evolution of archived repertoires. These preliminary studiesshow the promise for understanding the interaction between mechanisms that create diversity and the strong forces of natural selectionimposed by immune recognition. Thecombination of generative mechanisms and selection shapes the archival antigenic repertoire. Segregation brings together chromosomes from diﬀerent lineages. Reassortment of inﬂuenza A’s neuraminidase and hemagglutinin sur- face antigens provides the most famous example (Lamb and Krug 2001). The genes for these antigens occur ontwoseparateRNAsegmentsofthe genome—the genome has a total of eight segments. When two or more viruses infect a single cell, the parental segments all replicate separately and then are packaged together into new viral particles. This process can package the segments from diﬀerent parents into a new virus. New neuraminidase-hemagglutinin combinations present novel anti- genic properties tothehost. Rare segregation events have introduced hemagglutinin from bird inﬂuenza into the genome of human inﬂuenza (Webster et al. The novel hemagglutinins cross-reacted very lit- tle with those circulating in humans, allowing the new combinations to sweep through human populations and cause pandemics. Intergenomic recombination occurs when chromosomes from diﬀer- ent lineages exchange pieces of their nucleotide sequence. In protozoan parasites such as Plasmodium and Trypanosoma,recombination hap- pens as part of a typical Mendelian cycle of outcrossing sex (Jenni et al. Recombination can occur in viruses when two or more particles infect a singlecell. DNA viruses may recombine relatively frequently because they can use the host’s recombination en- zymes (Strauss et al. RNA viruses may recombine less often be- cause the host lacks speciﬁc enzymes to mediate reciprocal exchange of RNA segments. However, many descriptions of RNA virus recombina- tion have been reported (Robertson et al. In all cases, even rare recombination can provide an important source for new antigenic variants. Horizontal transfer of DNA between bacteria introduces new nucle- otidesequences into a lineage (Ochman et al. Transformation occurs when a cell takes up naked DNA from the environment. Some species transform at a particularly high rate, suggesting that they have speciﬁc adaptations for uptake and incorporation of foreign DNA (Fus- senegger et al. For example, Neisseria species transform fre- quently enough to have many apparently mosaic genes from interspecies 68 CHAPTER 5 transfers (Spratt et al. Horizontal transfer also occurs when bacteriophage viruses carry DNA fromonehost cell to another or when two cells conjugate to transfer DNA from a donor to a recipient (Ochman et al. Intense immune pressure favors the generation of antigenic variants. However, variants, like any mutations, may have associated costs. To what extent have molecular attributes of antigenic genes been shaped by the costs and beneﬁts of generat- ing variants? Do microbes under intense immune pressure have higher genome-wide mutation rates compared with similar organisms that do not face immune attack? To what extent have nucleotide sequences of antigens been shaped by the tendency of particular motifs to generate replication errors—a form of local hypermutation? Selection of mechanisms that control switching between archival variants. Idescribed various mechanisms bywhichgene expression shifts between archived variants.