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Viral escape at the molecular level explained by quantitative T-cell recep- tor/peptide/MHC interactions and the crystal structure of a peptide/MHC complex finasteride 5mg amex hair loss in men 39 s wearhouse coupons. The rate of antigenic variation in fly-transmitted and syringe-passaged infections of Trypanosoma brucei generic 1mg finasteride free shipping hair loss on cats. Antigenic variation in Trypanosoma brucei infections: an holistic view purchase 5mg finasteride free shipping hair loss vitamin deficiency. Inhibition of growth of Trypanosoma brucei parasites in chronic infections. High frequency of antigenic variation in Trypanosoma brucei rhodesiense infections. Mapping of antigenic changes in the haemagglutinin of Hong Kong influenza (H3N2) strains using a large panel of monoclonal antibodies. An antigenic map of the haemagglutinin of the influenza Hong Kong subtype (H3N2), constructed using mouse monoclonal antibod- ies. A Mu gin complementing 308 REFERENCES function and an invertible DNA region in Escherichia coli K-12 are situated on the genetic element e14. HLA antigens in pa- tients with various courses after hepatitis B virus infection. From absolute to exquisite specificity: reflec- tions on the fuzzy nature of species, specificity and antigenic sites. Measurement of antigen-antibody interactions with biosensors. Unprecedented degree of human immunodeficiency virus type 1 (HIV-1) group M genetic diversity in the Democratic Republic of Congo suggests that the HIV-1 pan- demic originated in central Africa. Antigen-specific early primary humoral responses modulate immunodomi- nance of B cell epitopes. Proteases involved in MHC class II antigen presentation. Qual- itative and quantitative analysis of HLA-DRB gene expression. Critical determinants of host receptor targeting by Neisseria meningitidis and Neisseria gonorrhoeae: identification of Opa adhesiotopes on the N-domain of CD66 molecules. The majority of neutralizing Abs in HIV-1 infected patients recognize linear V3 loop sequences. Recent origin of Plasmodium falciparum from a single progenitor. Substitution rate variation among sites in hypervariable region Iofhuman mitochondrial DNA. Mutagenesis and inducible responses to deoxyribonucleic acid damage in Escherichia coli. Comparative analyses of the specificities of anti-influenza hemagglutinin antibodies in human sera. Genetic and fit- ness changes accompanying adaptation of an arbovirus to vertebrate and invertebrate cells. Neutral- ization serotypes of HIV-1 field isolates are not predicted by genetic subtype. Antigenic structure and variation in an influenza virus N9 neuraminidase. Evolution and ecology of influenza viruses: interspecies transmission. Antigenic and biological characterization of influenza virus neuraminidase (N2) with monoclonal an- tibodies. Influenza: interspecies transmission and emergence of new pandemics. FEMS Immunology and Med- ical Microbiology 18:275–279. Structural insights into the evolution of an antibody combining site. Emergence of virus escape mutants after immunization with epitope vaccine. Relationship among immunodominance of single CD8+ Tcellepi- topes, virus load, and kinetics of primary antiviral CTL response. Immunodominance in the T-cell response to multiple non-H-2 histocompatibility antigens. Neutral- ization of poliovirus by polyclonal antibodies requires binding of a single molecule per virion. Antiviral 310 REFERENCES CD4 and CD8 T-cell memory: differences in the size of the response and activation requirements. Philosophical Transactions of the Royal Society of London B 355:373–379. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Fimbrial phase variation in Bordetella pertussis: anovelmechanism for transcriptional regulation. Structural basis of immune recognition of influenza virus hemagglutinin. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution. Neutralization of adenoviruses: kinetics, stoichiometry and mechanisms. Extensive homologous recombination among widely diver- gent TT viruses. Evolutionary aspects of recombination in RNA viruses. Widespread intra-serotype recombination in natural populations of dengue virus. Proceedings of the National Academy of Sciences USA 96:7352–7357. A family of clostridial and streptococcal ligand-binding pro- teins with conserved C-terminal repeat sequences. Interval mapping of quantitative trait loci controlling humoral immunity to exogenous antigens. PCR-restriction fragment length poly- REFERENCES 311 morphism (RFLP) analyses reveal both extensive clonality and local genetic differences in Candida albicans. Reevaluation of amino acid vari- ability of the human immunodeficiency virus type 1 gp120 envelope glyco- protein and prediction of newdiscontinuous epitopes.

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C h em oth erapy:H ead-to-h ead trials A uth or Y ear A ge Setting A llow oth er G ender H esketh rating Design Subpopulation Intervention m edication R un-in/W ash -out Eth nicity Tan Allreceived20m g of iv 57 discount finasteride 5 mg without prescription hair loss in young males. N R 4 purchase finasteride 1 mg with mastercard hair loss on legs in men,5 Antiemetics Page 115 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1 generic 5mg finasteride with mastercard hair loss vitamin d. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Screened/ W ith drawn/ Setting Eligible/ L ostto fu/ H esketh rating Enrolled A nalyz ed O th erpopulationch aracteristics L ym phom a(prim arycancersite):46% Tan L ungs(prim arycancersite):15% 2002 L arynx (prim arycancersite):15% N R /N R /26 0/0/26 SingleCenter U terus(prim arycancersite):12% 4,5 O thersites:12% Patientsreceiving highlyem etogenic chem o:92% Antiemetics Page 116 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating R esults D olasetronvsG ranisetron Totalcontrol:nonausea,noem esis,noneedforrescueantiem etic W ithin24h following chem o:69. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating A dverse events C om m ents Allchem o-naïvepatientswere5-HT3antagonistnaïve,butthiswasnot statedif itwasaneligibilitycriterion. N ospecific dataonadverseevents Tan givenforthetotalpopulationnorforeitherstudygroup;ageneralstatem ent 2002 thatpatientsinboth groupscom plainedof occasionalheadachesbutno SingleCenter statisticallysignificantdifferenceswerefoundbetweengroupswasallthat 4,5 wasstatedpertaining torAE s. C h em oth erapy:H ead-to-h ead trials A uth or Y ear A ge Setting A llow oth er G ender H esketh rating Design Subpopulation Intervention m edication R un-in/W ash -out Eth nicity Palonsetron L ow tom oderately em etogenic chem otherapyagents 51. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating R esults Palonsetron Palon0. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating A dverse events C om m ents Palonsetron Palon0. Com plete control:D atagivenfordelayedandoverallintervals,with both Palonosetron O ndansetronvsPalon0. C h em oth erapy:H ead-to-h ead trials A uth or Y ear A ge Setting A llow oth er G ender H esketh rating Design Subpopulation Intervention m edication R un-in/W ash -out Eth nicity 54. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Screened/ W ith drawn/ Setting Eligible/ L ostto fu/ H esketh rating Enrolled A nalyz ed O th erpopulationch aracteristics Chem otherapynaïve:67% Chem otherapynonnaive:33% Corticosteroiduse:yes;5% Corticosteroiduse:no:95% Eisenberg Alcoholuse:none:67% 2003 N R /N R /592 23/0/569 Alcoholuse:rare:14% M ulticenter Alcoholuse:occasional:13% 3 Alcoholuse:regular:5% Breastcarcinom a:61% L ung carcinom a:8% N onHodgkinslym phom a:4% Antiemetics Page 124 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating R esults Pal0. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating A dverse events C om m ents Palonosetron0. O f theoriginal592whowererandom iz ed,9didnotreceive Eisenberg F atigue(total:treatm entandnon-treatm entrelated):21% vs26% vs24%, treatm ent,which leavesagroup of 583,andonepersoninthisgroup was 2003 N S ex cludedfrom ITT analysisbecausetheyhadchem owith unacceptablylow M ulticenter D eath:0. O f therem aining 582patients,13wereex cluded 3 SeriousAE s(notspecifiedastowhattheseare):2. C h em oth erapy:H ead-to-h ead trials A uth or Y ear A ge Setting A llow oth er G ender H esketh rating Design Subpopulation Intervention m edication R un-in/W ash -out Eth nicity G ranisetronivvs G ranisetronpo 49. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating R esults G ranisetronivvs G ranisetronpo G ranpovsG raniv Com pleteresponse(CR ):noem esis Allpatients:9. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating A dverse events C om m ents G ranisetronivvs G ranisetronpo G ranpo1vsG raniv2 Headache:8% vs8%,N S Sedation:4% vs%,N S Ptsundergoing peripheralbloodprogenitorycellandbonem arrow D iarrhea:4% vs9%,N S transplantation;chem owasadm inisteredfor10days. Ptswerestratified Hypertension:2% vs2%,N S basedontransplanttypeand conditioning regim en. Balancebetweenthe Hypotension:3% vs0%,N S twogroupswasobtainedthrough random blocksof two. PtsreceivedG ran Insom nia:3% vs3%,N S (+placebo)every12h untileitherthedayof m arrow orstem cellinfusion J ittery/E PS:3% vs6%,N S (day0),oruntiltheptex perienced3 ≥ em etic episodeswithinany24h 1 Hiccups:1% vs6%,N S period. Adm inistrationof prochloroperaz ine,loraz epam ,andprom ethaz ine Anx iety:2% vs4%,N S perm ittedduring study. W ithdrawals:8pts(G ranpo= 5ptsandG raniv= 3 Sinuscongestion:2% vs1%,N S ptshadem esispriortostudym edicationandwereex cludedfrom analysis. Indigestion:1% vs3%,N S O nept,initiallyrandom iz ed,receivedtherapyfor9daysandthenvoluntarily M ucositis:1% vs2%,N S withdrew [studydidnotsaywhy]andwascensoredfrom theefficacy D eath:0% vs6. Confusion:0% vs2%,N S Constipation:0% vs2%,N S Totalwithdrawals:18. C h em oth erapy:H ead-to-h ead trials A uth or Y ear A ge Setting A llow oth er G ender H esketh rating Design Subpopulation Intervention m edication R un-in/W ash -out Eth nicity L -758,298 vs O ndansetron R escuetherapy, N R /N ouseof C ocquyt 56 D BR CT L -758,298iv60or100m g determ inedby antiem etic agent 2001 N one 53% m ale Parallel O ndansetron32m g investigator,was within1weekof M ulticenter E thnicityN R allowed studyday1 L -758,298iv100m g day1andM K - Allreceived 869days2-5(L 100) dex am ethasone N R /N ouseof VanB elle 58 D BR CT L -758,298iv100m g day1and 20m g ivpriorto antiem etic agent 2002 N one 63% m ale Parallel placebodays2-5(L Plac) cisplatin. R escue within72hoursof M ulticenter E thnicityN R O ndansetroniv32m g day1and m edicationwas studyday1 placebodays2-5(O nd) perm itted Antiemetics Page 131 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Screened/ W ith drawn/ Setting Eligible/ L ostto fu/ H esketh rating Enrolled A nalyz ed O th erpopulationch aracteristics L -758,298 vs O ndansetron Typeof cancer L ung:17% C ocquyt G astrointestinal:24. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating R esults L -758,298 vs O ndansetron L -758,298vsO ndansetron Proportionof patientswithoutem esis:acutephase(day1) 37% vs52% Proportionof patientswithoutem esis:delayedphase(day2-7) 72% vs30% (p= 0. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating A dverse events C om m ents L -758,298 vs O ndansetron L -758,298vsO ndansetron Constipation:40% vs39% D iarrhea:60% vs9% Anorex ia:40% vs35% Headache:47% vs39% C ocquyt Abdom inalpain:17% vs9% 2001 Asthenia:40% vs30% M ulticenter Haem atologicaldecrease Totalwhitebloodcells:3% vs0% N eutrophils:3% vs0% Transam inaseelevations AST:0% vs0% AL T:3% vs0% L 100vsL Plac vsO nd Anorex ia:10% vs12% vs9% Constipation:8% vs7% vs14% D iarrhea:23% vs23% vs5% VanB elle N ausea:11% vs19% vs5% 2002 D iz z iness:8% vs11% vs5% M ulticenter Headache:13% vs19% vs12% Hiccups:8% vs11% vs4% Asthenia:16%$vs19% vs12% Abdom inalpain:8% vs7% vs11% Antiemetics Page 134 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear A ge Setting A llow oth er G ender H esketh rating Design Subpopulation Intervention m edication R un-in/W ash -out Eth nicity O ndansetronvs O ndansetron N R /N o m edicationswith antiem etic activity O ndansetronconventionaltablet8m g orm edications Pectasides 53 R CT (O T) R escuem edication which could 2007 N one G enderN R Parallel O ndansetrondisintegrating table8m g wasallowed confoundthe SingleCenter E thnicityN R (O D T) efficacy evaluationinthe 24hourspriorto inclusion Antiemetics Page 135 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Screened/ W ith drawn/ Setting Eligible/ L ostto fu/ H esketh rating Enrolled A nalyz ed O th erpopulationch aracteristics O ndansetronvs O ndansetron Pectasides D iseasestage 2007 N R /N R /134 N R /N R /N R /134 E arly:O D T= 97% vsO T= 96% SingleCenter Advanced:O D T= 3% vsO T= 4% Antiemetics Page 136 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 1. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating R esults O ndansetronvs O ndansetron O D T vsO T Proportionwith noem esis:55% vs65% (p= 0. C h em oth erapy:H ead-to-h ead trials A uth or Y ear Setting H esketh rating A dverse events C om m ents O ndansetronvs O ndansetron Pectasides O D T vsO T 2007 AE sattributedtodrug:9% vs10% (p>0. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or Subpopulation R un-in/W ash out Screened/ W ith drawn/ R andom iz ation A llocation G roups sim ilaratEligibility Y ear Eligible/ L ostto fu/ baseline criteria Setting Enrolled A nalyz ed specified Type ofC h em o C h ildren F orni ch ildren N R /N R N R /N R /90 N R /0/90 N R N R Inadequate data Y es 2000 N otspecified 5 Jaing ch ildren,females 4 wk run-inwith 35/33/33 0/0/33 N R N R N R Y es 2004 antiemetics acc. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or C are Patients A ttrition L oss to follow up Intention-to-treat Postrandom iz ation Q uality rating Y ear provider m asked C rossover analysis exclusions Setting m asked A dh erence Type ofC h em o C ontam ination C h ildren F orni Y es,but Y es,but N R U nable to determine Y es N o F air 2000 not not N o N otspecified described described N o 5 N o Jaing N o N o Y es U nable to determine N o Y es Poor 2004 N o M ulticenter N o 3 N o O rch ard Y es,but Y es,but Y es U nable to determine N o Y es F air 1999 not not N o Single C enter described described N o 5 N o C orapcioglu Y es Y es Y es N o U nclear N o Poor 2005 N o 5 N o N o Sepulveda-Vildosola Y es Y es N o N o N R N o F air 2008 N o Single C enter N o 2-5 N o W h ite Y es Y es Y es U nable to determine Y es N o F air 2000 N o M ulticenter N o 4,5 N o Antiemetics Page 140 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 2. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or C ontrolled F unding Y ear groupstandard Setting ofcare Type ofC h em o C h ildren F orni Y es N R 2000 N otspecified 5 Jaing Y es Supported inpartby a 2004 grantfrom th e M ulticenter C h ildh ood C ancer 3 F oundationofTaiwan. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or Subpopulation R un-in/W ash out Screened/ W ith drawn/ R andom iz ation A llocation G roups sim ilaratEligibility Y ear Eligible/ L ostto fu/ baseline criteria Setting Enrolled A nalyz ed specified Type ofC h em o A dults A prepitantvs ondansetron Sch m oll N one N R /N o 5-H T3 R A s 516/N R /489 29/3/484 Y es U nclear Y es Y es 2006 with in48 h ours of N R day 1 >3 G ranisetronvs O ndansetron A bali none N R /N R N R /N R 158 N R /N R /158 N o N o Y es N o 2007 4,5 Barrajon women,alcoh olics, N R /N R N R /N R /136 16/0/120 Y es Y es Y es Y es 2000 priorch emo Single C enter 5 C h iou none N o/N R N R /N R /51 0/0/51 N R N R Y es Y es 2000 Single C enter 4,5 Antiemetics Page 142 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 2. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or C are Patients A ttrition L oss to follow up Intention-to-treat Postrandom iz ation Q uality rating Y ear provider m asked C rossover analysis exclusions Setting m asked A dh erence Type ofC h em o C ontam ination A dults A prepitantvs ondansetron Sch m oll Y es Y es Y es Y es,2 inaprepitant Y es -modified ITT N o G ood 2006 N o group,1 incontrol = 5 patients N R Y es group excluded from >3 N o analysis. G ranisetronvs O ndansetron A bali N o N o N R N o N o N o Poor 2007 N R 4,5 N R N R Barrajon Y es Y es Y es N o N o Y es F air 2000 N o Single C enter N o 5 N o C h iou N o N o Y es N o Y es N o F air 2000 N o Single C enter N o 4,5 N o Antiemetics Page 143 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 2. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or C ontrolled F unding Y ear groupstandard Setting ofcare Type ofC h em o A dults A prepitantvs ondansetron Sch m oll Y es M erck & C o,Inc 2006 N R >3 G ranisetronvs O ndansetron A bali N o N R 2007 4,5 Barrajon Y es N R 2000 Single C enter 5 C h iou Y es Smith K line Beech am 2000 Taiwansupplied Single C enter granisetronforth e 4,5 study. Antiemetics Page 144 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 2. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or Subpopulation R un-in/W ash out Screened/ W ith drawn/ R andom iz ation A llocation G roups sim ilaratEligibility Y ear Eligible/ L ostto fu/ baseline criteria Setting Enrolled A nalyz ed specified Type ofC h em o C h ua none N R /N R 94/89/89 0/0/89 Y es N R N R Y es 2000 Single C enter 5 DelF avero kinetosis N R /N R N R /N R /973 6/1/966 Y es N R Y es Y es 1995 M ulticenter 5 deW it none N o/N R N R /45/40 0/0/40 N R N R Y es Y es 2001 N R 5 F ox-G eiman BM T;TBI N R /N R N R /N R /102 6/0/102 Y es Y es Y es Y es 2001 Single C enter 5 G ebbia none N R /N R N R /N R /182 16/0/166 N R N R Y es Y es 1994a Single C enter 5 Antiemetics Page 145 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 2. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or C are Patients A ttrition L oss to follow up Intention-to-treat Postrandom iz ation Q uality rating Y ear provider m asked C rossover analysis exclusions Setting m asked A dh erence Type ofC h em o C ontam ination C h ua N o N o Y es U nable to determine N o Y es Poor 2000 N o Single C enter N o 5 N o DelF avero Y es Y es Y es N o N o Y es (7/973) F air 1995 N o M ulticenter N o 5 N o deW it Y es Y es Y es N o N o Y es F air 2001 N o N R N o 5 Y es F ox-G eiman Y es Y es Y es N o U nable to determine N o F air 2001 N o Single C enter N o 5 N o G ebbia N R N R Y es N o N o Y es F air 1994a N o Single C enter N o 5 N o Antiemetics Page 146 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 2. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or C ontrolled F unding Y ear groupstandard Setting ofcare Type ofC h em o C h ua Y es N R 2000 Single C enter 5 DelF avero Y es Supported inpartby a 1995 grantfrom th e U mbrian M ulticenter C ancerA ssociation 5 (A. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or Subpopulation R un-in/W ash out Screened/ W ith drawn/ R andom iz ation A llocation G roups sim ilaratEligibility Y ear Eligible/ L ostto fu/ baseline criteria Setting Enrolled A nalyz ed specified Type ofC h em o G ebbia none N R /N R N R /N R /164 8/0/158 N R N R Y es Y es 1994b Single C enter 3 G ralla corticosteroids N R /N R N R /N R /1054 13/0/1054 N R N R Y es Y es 1998 M ulticenter 5 Antiemetics Page 148 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 2. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or C are Patients A ttrition L oss to follow up Intention-to-treat Postrandom iz ation Q uality rating Y ear provider m asked C rossover analysis exclusions Setting m asked A dh erence Type ofC h em o C ontam ination G ebbia N R N R Y es N o N o Y es F air 1994b N o Single C enter N o 3 N o G ralla Y es,but Y es,but Y es N o Y es N o F air 1998 not not N o M ulticenter described described N o 5 N o Antiemetics Page 149 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 2. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or C ontrolled F unding Y ear groupstandard Setting ofcare Type ofC h em o G ebbia N o U niversity ofPalermo; 1994b Palermo,Italy Single C enter 3 G ralla Y es Smith K line Beech am 1998 Ph armaceuticals M ulticenter 5 Antiemetics Page 150 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 2. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or Subpopulation R un-in/W ash out Screened/ W ith drawn/ R andom iz ation A llocation G roups sim ilaratEligibility Y ear Eligible/ L ostto fu/ baseline criteria Setting Enrolled A nalyz ed specified Type ofC h em o H errington women N o/N R 65/61/61 0/0/61 N R N R unable to Y es 2000 determine M ulticenter (reported for 4 evaluated pts) K alaycio A SC T,women N R /N R 48/48/48 3/45/45 N R N R Y es Y es 1998 N R 5 Jantunen none N o/N o N R /N R /166 34/2/130 Y es Y es N R Y es 1993 M ulticenter 3,4 L eonardi none N R /N R N R /N R /118 3/0/118 N R N R N R Y es 1996 M ulticenter 3,4,5 M antovani none N R /N R N R /N R /117 0/0/117 N R N R Y es Y es 1995 Single C enter 5 Antiemetics Page 151 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 2. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or C are Patients A ttrition L oss to follow up Intention-to-treat Postrandom iz ation Q uality rating Y ear provider m asked C rossover analysis exclusions Setting m asked A dh erence Type ofC h em o C ontam ination H errington N o N o N o N o N o Y es Poor 2000 N o M ulticenter N o 4 N o K alaycio Y es Y es Y es U nable to determine N o Y es Poor 1998 N o N R N o 5 N o Jantunen N o N o Y es Y es N o Y es Poor 1993 N o 36/166 notevaluated M ulticenter N o 3,4 N o L eonardi N R N R Y es U nable to determine Y es N o Poor 1996 N o M ulticenter Y es 3,4,5 N o M antovani N R Y es,but N o N o Y es N o F air 1995 not Y es Single C enter described N o 5 N o Antiemetics Page 152 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 2. Q uality assessm ents ofch em oth erapy h ead-to-h ead trials A uth or C ontrolled F unding Y ear groupstandard Setting ofcare Type ofC h em o H errington Y es F unded inpartby 2000 Smith K line Beech am M ulticenter Ph armaceuticals 4 K alaycio Y es N R 1998 N R 5 Jantunen Y es N R 1993 M ulticenter 3,4 L eonardi Y es N R 1996 M ulticenter 3,4,5 M antovani Y es Th e auth ors state th at 1995 no supportforth is Single C enter study came directly 5 from a ph armaceutical company.

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Did it start Do ask for other accompanying symptoms: acutely or gradually? Was it already present be- • Abdominal cramping pain: acute cheap 1 mg finasteride visa hair loss in men 2 syndrome, continuous buy finasteride 5 mg cheap hair loss in men lh, fore pregnancy? Also try to estimate the amount localized or general cheap finasteride online mastercard hair loss while breastfeeding. Be aware though, as an ectopic preg- • Did she lose any tissue vaginally? This might nancy can present with little loss of blood. This could present with lacerations and It could also be a symptom of an infection which STI. Sometimes a urinary tract infection cal bleeding, ectopic pregnancy and miscarriage. Painless macro- hematuria is a sign for urinary schistosomiasis. This could point towards You should be aware that the patient might be sexually transmitted infection (STI) such as concerned about losing her pregnancy and there- gonorrhea. Chlamydia classically presents with fore she could be emotional. Pay special attention painless bleeding or bleeding after intercourse. She might have had an earlier treat- sure, temperature and pulse rate. An • Risk of criminal abortion Did the woman try to ectopic pregnancy can reoccur. Sometimes women do not dare to N Fundal height to assess the gestational age. More likely in (and most of the times septic) abortion. Then consider STI, pelvic abscesses or non- Assess her past medical history: gynecological causes of peritonitis (see • Obstetric history Is this her first pregnancy? Some drugs are known gynecological tumors (see Chapter 12 on to increase the risk of miscarriage, e. You might want to originates from the cervix, vagina or the uterine check your pharmaceutical reference guides for cavity. Sometimes the cervix is very friable in possible association between drugs and mis- pregnancy. Toxins such as lead, mercury, formal- speculum, it starts to bleed. Be sure to perform the vaginal • Did she have any operations in the past? An examination carefully in cases where you suspect ectopic pregnancy due to pelvic inflammatory an ectopic pregnancy. HIV infection is also a risk factor for that cervical evaluation is not reliable in dis- developing cervical carcinoma and these patients tinguishing between complete and incom- may have had other STIs. Sometimes products of 23 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS conception are still present in the ostium of leukocyte count are both slightly elevated in the cervix and can be removed during digital pregnancy. If the ostium is closed, Urine: this could indicate a threatening miscarriage, • UPT: urine pregnancy test to confirm preg- missed abortion or ectopic pregnancy. This could indicate an infection or ectopic pregnancy. Make sure you explain to the N Assess for foreign bodies. If no blood is found on digital and visual vaginal examination, perform an inspection Direct light microscopy: of the entire genital area. Sometimes patients have diffi- is not responding to standard treatment. Schisto- culties assessing the origin of the blood loss soma in the urine may indicate (concomitant) themselves, especially in rural areas where no genital tract schistosomiasis but can be false proper sanitary facilities are present. If your facility has an ultrasound machine, every patient with first-trimester bleeding Other investigations should receive an ultrasound investigation to estab- lish a viable intrauterine pregnancy. Rule of thumb Ultrasound for referral is: if a patient (who has not been labelled Chapter 1 on gynecological examination presents as having a serious, possibly life-threatening, condi- detailed information on how to perform an tion which calls for imminent referral) presents ultrasound. However, the diagnosis Laboratory investigations depends on the quality of the ultrasound equip- ment, the experience of the sonographer, the speci- It should be noted that most of the causes of vaginal fic signs and symptoms of the patient and presence bleeding in the first trimester can be identified after of physical factors such as fibroids. The first two thorough history taking and physical examination. Additional laboratory investigations hardly contri- So, beware, a pregnant patient with peritoneal pain bute to the diagnosis. Blood: If no intrauterine pregnancy is visible on ultra- • Hemoglobin and cross-matching in case of sound, check for adnexal masses or clear ectopic severe bleeding or suspected ectopic pregnancy. An empty It helps you to estimate the amount of blood uterus on ultrasound in a patient with a positive lost and helps to anticipate a possible blood UPT should raise the suspicion of ectopic preg- transfusion. In case of a ruptured ectopic • Erythrocyte sedimentation rate (ESR) or leuko- pregnancy, free fluid (blood) will be seen in cytes supposing an infection might be present. Douglas’ pouch in ultrasound (see Chapter 12 on (Fever measured by rectal thermometer is more ectopic pregnancy for more information on diag- accurate/reliable. If pain with a closed cervix on digital vaginal you are seriously considering ectopic pregnancy examination might be labelled as threatened and an ultrasound is not feasible in your setting and miscarriage, but could in fact be an ectopic culdocentesis does not produce clear results or has pregnancy. Pain in miscarriage is usually failed, you might want to consider a diagnostic cramping. Pain in ectopic pregnancy is usu- (mini) laparotomy as the negative predictive value 4 ally continuous and/or accompanied with of culdocentesis is poor. If in doubt perform a Diagnostic problems could evolve if a preg- culdocentesis. If an ultrasound machine is nant woman (confirmed by a positive UPT) present, assess for the presence of intrauterine shows no intrauterine pregnancy on vaginal ultra- pregnancy products and or blood in the sonography, has no fluid in Douglas’ pouch and pouch of Douglas. If still in doubt perform an has no signs of ectopic masses or gestational sacs. In this case she could have the following • Little tissue is obtained on performing an conditions: manual vacuum aspiration (MVA). In this • she could have had a complete miscarriage, case you might have mistaken an ectopic • she could have a pregnancy too early to be seen pregnancy for an incomplete abortion or you on ultrasound, might have left the gestational sac and its • she could have a spontaneously resolving intra- contents behind. One should always obtain uterine or tubal pregnancy, tissue when performing an MVA. This means In this case it may be appropriate to admit the that the patient has signs of hypovolemic patient and reassess her regularly in order not to shock which cannot be explained by the miss the ectopic pregnancy about to rupture. The monitor the patient’s vital signs on a daily basis. Only after 2 liters of take some time, depending on the gestational age) blood, or more, have been lost, a pregnant is it safe to discharge her.