Cellulaire kinetiek van de populatie van Lisocabtagene Maraleucel

Cellulaire kinetiek van de populatie van Lisocabtagene Maraleucel, een autoloog CD19-gericht chimeer antigeenreceptor  T- celproduct,  bij patiënten met recidiverend/refractair grootcellig B-cellymfoom

samenstelling, 4-1BB chimeer antigeenreceptor (CAR) T-celproduct toegediend in gelijke doeldoses van CD8 +  en CD4 +  CAR +  T-cellen. Bij CAR T-celtherapieën is een grote variabiliteit tussen proefpersonen vastgesteld; patiëntkenmerken kunnen bijdragen aan de variabiliteit van CAR T-celexpansie. We ontwikkelden een populatie-cellulair kinetisch mannequin om de kinetiek van het liso-cel transgen te karakteriseren, through kwantitatieve polymerase kettingreactie beoordeling na intraveneuze infusie van liso-cel, en om covariaten te begrijpen die de liso-cel kinetiek bij individuele patiënten zouden kunnen beïnvloeden .

Methoden:  We hebben niet-lineaire mixed-effects-modellering gebruikt om een ​​populatie-cellulair kinetisch mannequin voor liso-cel te ontwikkelen. De cellulaire kinetische populatieanalyse werd uitgevoerd met 2524 transgene observaties na infusie van 261 patiënten met recidiverend/refractair grootcellig B-cellymfoom die werden behandeld met een enkele dosis liso-cel in TRANSCEND NHL 001. Covariaten voor de analyse omvatten intrinsieke factoren bij aanvang zoals leeftijd, ziektekenmerken bij baseline en factoren van liso-cel en gelijktijdige toediening.

Resultaten:  Liso-cel cellulaire kinetiek werd goed beschreven door een stuksgewijs mannequin van cellulaire groeikinetiek met lag, exponentiële groei en bi-exponentiële vervalfasen. Populatiegemiddelden (95% betrouwbaarheidsinterval) van de duur van de lag-fase, verdubbelingstijd, tijd tot maximale niveaus, initiële afnamehalfwaardetijd en terminale halfwaardetijd waren 3,27 (2,71-3,97), 0,755 (0,667-0,821) , 9,29 (8,81). -9,70), 5,00 (4,15-5,90) en 352 (241-647) dagen, respectievelijk. De omvang van het impact op de liso-cel-expansiemetrieken toonde aan dat de covariabele associaties kleiner waren dan de resterende variabiliteit tussen proefpersonen in de populatie.

Conclusies:  De geteste covariaten werden niet geacht een betekenisvolle invloed te hebben op de kinetiek van liso-cel.

robegids
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Borrelia Afzelii Antigen

NAT41583-500 0.5
EUR 1176.24
Description: Harvested bacteria are washed and detergent solubilized to produce a cytoplasmic extract enriched with lipoproteins and outer surface proteins (OSPs). The antigen is presented in phosphate buffered saline containing 1 % n-octyl-β-D-glucopyranoside.

Borrelia Garinii Antigen

NAT41584-100 0.1
EUR 391.66
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NAT41602-100 0.1
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Canine Adenovirus 2 Antigen

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Ross River Virus Recombinant Antigen

REC31969-500 0.5
EUR 2844.92
Description: Recombinant Ross River virus antigen expressed in HEK293 cells as virus-like particles and purified by sucrose density gradients and precipitation. Virus-like particles were then solubilized in PBS containing 0.2% SDS to prevent aggregation of particles. The preparation is not particulate. Antigens in the preparation include Envelope proteins 1 and 2 and Nucleoprotein.

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Hepatitis B Virus Core Antigen (HBcAg)

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Hepatitis C Virus Core Antigen (HCcAg)

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EUR 1455.64
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EUR 270.46
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Legionella pneumophila antigen (native extract)

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EUR 391.66
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EUR 391.66
Description: Inactivated Streptococcus pneumoniae antigen from culture.

Leptospira Biflexa Antigen (Strain Patoc 1)

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EUR 391.66
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EUR 1176.24
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EUR 275.56
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EUR 275.56
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EUR 275.56
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EUR 275.56
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EUR 275.56
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EUR 276.84
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MAB12298-500 0.5
EUR 695.29
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Mouse Anti-Hepatitis B Virus E Antigen Antibody (M133)

MAB12299-100 0.1
EUR 276.84
Description: Mouse monoclonal antibody specific for Hepatitis B virus e antigen (M133)

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EUR 695.29
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EUR 111

Zika Virus Envelope Protein, Suriname Strain (SCL)

REC31998-100 0.1
EUR 723.36
Description: Recombinant Zika virus envelope protein expressed in HEK293 mammalian cells, with C terminal 6-His tag.

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REC31998-250 0.25
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Scl-70 ELISA

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EUR 495

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REC32027-100 0.1
EUR 491.53
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EUR 2418

human anti-human Scl-70 IgG

E4A11C26 50ug
EUR 275
Description: Biotin-Conjugated, FITC-Conjugated , AF350 Conjugated , AF405M-Conjugated ,AF488-Conjugated, AF514-Conjugated ,AF532-Conjugated, AF555-Conjugated ,AF568-Conjugated , HRP-Conjugated, AF405S-Conjugated, AF405L-Conjugated , AF546-Conjugated, AF594-Conjugated , AF610-Conjugated, AF635-Conjugated , AF647-Conjugated , AF680-Conjugated , AF700-Conjugated , AF750-Conjugated , AF790-Conjugated , APC-Conjugated , PE-Conjugated , Cy3-Conjugated , Cy5-Conjugated , Cy5.5-Conjugated , Cy7-Conjugated Antibody

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EUR 826.8

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E02S0243-192T 192 tests
EUR 1524
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Rat Anti SCL 70 antibody ELISA kit

E02S0243-48 1 plate of 48 wells
EUR 624
Description: A competitive ELISA for quantitative measurement of Rat Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Rat Anti SCL 70 antibody ELISA kit

E02S0243-96 1 plate of 96 wells
EUR 822
Description: A competitive ELISA for quantitative measurement of Rat Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Dog Anti SCL 70 antibody ELISA kit

E08S0243-192T 192 tests
EUR 1524
Description: A competitive ELISA for quantitative measurement of Canine Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Dog Anti SCL 70 antibody ELISA kit

E08S0243-48 1 plate of 48 wells
EUR 624
Description: A competitive ELISA for quantitative measurement of Canine Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Dog Anti SCL 70 antibody ELISA kit

E08S0243-96 1 plate of 96 wells
EUR 822
Description: A competitive ELISA for quantitative measurement of Canine Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Pig Anti SCL 70 antibody ELISA kit

E07S0243-192T 192 tests
EUR 1524
Description: A competitive ELISA for quantitative measurement of Porcine Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Pig Anti SCL 70 antibody ELISA kit

E07S0243-48 1 plate of 48 wells
EUR 624
Description: A competitive ELISA for quantitative measurement of Porcine Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Pig Anti SCL 70 antibody ELISA kit

E07S0243-96 1 plate of 96 wells
EUR 822
Description: A competitive ELISA for quantitative measurement of Porcine Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Rat Anti SCL 70 antibody ELISA kit

E01A16556 96T
EUR 700
Description: ELISA

Goat Anti SCL 70 antibody ELISA kit

E01A51459 96T
EUR 700
Description: ELISA

Goat Anti SCL 70 antibody ELISA kit

E06S0243-192T 192 tests
EUR 1524
Description: A competitive ELISA for quantitative measurement of Goat Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Goat Anti SCL 70 antibody ELISA kit

E06S0243-48 1 plate of 48 wells
EUR 624
Description: A competitive ELISA for quantitative measurement of Goat Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Goat Anti SCL 70 antibody ELISA kit

E06S0243-96 1 plate of 96 wells
EUR 822
Description: A competitive ELISA for quantitative measurement of Goat Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Sheep Anti SCL 70 antibody ELISA kit

E01A103753 96T
EUR 700
Description: ELISA

Mouse Anti SCL 70 antibody ELISA kit

E01A25303 96T
EUR 700
Description: ELISA

Mouse Anti SCL 70 antibody ELISA kit

E03S0243-192T 192 tests
EUR 1524
Description: A competitive ELISA for quantitative measurement of Mouse Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Mouse Anti SCL 70 antibody ELISA kit

E03S0243-48 1 plate of 48 wells
EUR 624
Description: A competitive ELISA for quantitative measurement of Mouse Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Mouse Anti SCL 70 antibody ELISA kit

E03S0243-96 1 plate of 96 wells
EUR 822
Description: A competitive ELISA for quantitative measurement of Mouse Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Human Anti SCL 70 antibody ELISA kit

E01S0243-192T 192 tests
EUR 1524
Description: A competitive ELISA for quantitative measurement of Human Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Human Anti SCL 70 antibody ELISA kit

E01S0243-48 1 plate of 48 wells
EUR 624
Description: A competitive ELISA for quantitative measurement of Human Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Human Anti SCL 70 antibody ELISA kit

E01S0243-96 1 plate of 96 wells
EUR 822
Description: A competitive ELISA for quantitative measurement of Human Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Human Anti SCL 70 antibody ELISA kit

E01A7811 96T
EUR 700
Description: ELISA

Rabbit Anti SCL 70 antibody ELISA kit

E01A34025 96T
EUR 700
Description: ELISA

Canine Anti SCL 70 antibody ELISA kit

E01A68887 96T
EUR 700
Description: ELISA

Bovine Anti SCL 70 antibody ELISA kit

E01A86326 96T
EUR 700
Description: ELISA

Monkey Anti SCL 70 antibody ELISA kit

E01A77606 96T
EUR 700
Description: ELISA

Monkey Anti SCL 70 antibody ELISA kit

E09S0243-192T 192 tests
EUR 1524
Description: A competitive ELISA for quantitative measurement of Monkey Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Monkey Anti SCL 70 antibody ELISA kit

E09S0243-48 1 plate of 48 wells
EUR 624
Description: A competitive ELISA for quantitative measurement of Monkey Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Monkey Anti SCL 70 antibody ELISA kit

E09S0243-96 1 plate of 96 wells
EUR 822
Description: A competitive ELISA for quantitative measurement of Monkey Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Rabbit Anti SCL 70 antibody ELISA kit

E04S0243-192T 192 tests
EUR 1524
Description: A competitive ELISA for quantitative measurement of Rabbit Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Rabbit Anti SCL 70 antibody ELISA kit

E04S0243-48 1 plate of 48 wells
EUR 624
Description: A competitive ELISA for quantitative measurement of Rabbit Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Rabbit Anti SCL 70 antibody ELISA kit

E04S0243-96 1 plate of 96 wells
EUR 822
Description: A competitive ELISA for quantitative measurement of Rabbit Anti SCL 70 antibody in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.

Porcine Anti SCL 70 antibody ELISA kit

E01A60177 96T
EUR 700
Description: ELISA

Chicken Anti SCL 70 antibody ELISA kit

E01A95038 96T
EUR 700
Description: ELISA

DNA Topoisomerase I (TOP1, Scl-70) Antibody

30267-05111 150 ug
EUR 215

Rat Scl-70 Ab ELISA Kit

ERS0249 96Tests
EUR 625.2

Immunodominantie van epitopen en beschermende werkzaamheid van HI-  antigeen  worden differentieel gewijzigd met behulp van verschillende adjuvantia in een muismodel van  Staphylococcus aureus  bacteriëmie

HI, een fusie-eiwit dat bestaat uit het alfa-toxine (Hla) en het N2-domein van ijzeroppervlakdeterminant B (IsdB), is een van de antigenen in het eerder gerapporteerde  S. aureus-  vaccin rFSAV en is al in fase II klinische onderzoeken ingegaan . Eerdere research hebben aangetoond dat HI in hoge mate immunogeen is bij zowel muizen als gezonde vrijwilligers, en de humorale immuunrespons speelt een sleutelrol bij HI-gemedieerde bescherming. In deze studie hebben we de beschermende werkzaamheid van immunisatie met HI plus vier verschillende adjuvantia verder onderzocht in een bacteriëmiemodel bij muizen De resultaten toonden aan dat HI-gemedieerde bescherming was veranderd in reactie op verschillende adjuvantia.

Met behulp van antisera van geïmmuniseerde muizen identificeerden we zeven B-cel immunodominante epitopen op Hla en IsdB, waaronder 6 nieuwe epitopen (Hla 1-18 , Hla 84-101 , Hla 186-203 , IsdB 342-359 , IsdB 366-383 en isdB 384-401 ). De immunodominantie van B-celepitopen, totale IgG-titers en de niveaus van IFN-γ en IL-17A van muizen die waren geïmmuniseerd met HI plus verschillende adjuvantia waren verschillend van elkaar, wat het verschil in beschermende immuniteit dat in elke geïmmuniseerde groep werd waargenomen, kan verklaren. Onze resultaten geven dus aan dat adjuvantia grotendeels de immunodominantie van epitopen en de beschermende werkzaamheid van HI beïnvloedden, wat verdere adjuvans kan leidenscreening voor vaccinontwikkeling en -optimalisatie.

Nanodeeltjes ontworpen als kunstmatige  antigeen- presenterende cellen induceren menselijke CD4  +  en CD8  +  Tregs die functioneel zijn in gehumaniseerde muizen

Kunstmatige antigeenpresenterende cellen (aAPC’s) zijn synthetische versies van natuurlijk voorkomende antigeenpresenterende cellen (APC’s) die, vergelijkbaar met natuurlijke APC’s , efficiënte T-effectorcelreacties  in vitro bevorderen . Dit rapport beschrijft een methode voor het produceren van acellulaire tolerogene aAPC’s gemaakt van biologisch afbreekbare polymelk-co-glycolzuur (PLGA) nanodeeltjes (NP’s) en het inkapselen van IL-2 en TGF-β voor een paracriene afgifte aan T-cellen. We documenteren dat deze aAPC ‘s zowel menselijke CD4 +-  als CD8 +  -T-cellen kunnen induceren om FoxP3 +  T-regulerende cellen (Tregs) te worden.

De aAPC NP-geëxpandeerde menselijke Tregs zijn functioneel  in vitro  en kunnen systemische auto-immuniteit in vivo moduleren   in gehumaniseerde NSG-muizen. Deze bevindingen vormen een proof-of-concept voor het gebruik van PLGA NP’s als aAPC’s voor de inductie van humane Tregs  in vitro  en  in vivo , en benadrukken het immunotherapeutische potentieel van deze gerichte benadering om IL-2- en/of TGF-β-defecten te herstellen die zijn gedocumenteerd in bepaalde auto- immuunziekten zoals systemische lupus erythematosus.

Een niet-menselijk primaatmodel met lymfodepletie voor de beoordeling van acute on-target en off-tumortoxiciteit van humane chimere  antigeenreceptor  -T-cellen

Doelstellingen:  Chimere antigeenreceptor (CAR)-T-celtherapie kan onverwachte toxiciteiten op het doel veroorzaken die levensbedreigend kunnen zijn. Niet-menselijke primaten (NHP’s) delen aanzienlijke structurele homologie- en expressieprofielen van de meeste eiwitten met mensen en worden daarom gebruikt als diermodel voor niet-klinische veiligheidsstudies. We hebben een NHP-model ontwikkeld met lymfdepletie door de dieren te conditioneren met immunosuppressieve chemotherapie die is ontworpen om klinische praktijkomstandigheden te simuleren, om voorbijgaand gemengd chimerisme te induceren vóór de toediening van menselijke CAR-T-cellen die zijn omgeleid naar doel-Ephrin type-B-receptor 4 (EPHB4-CAR-T cellen) om de toxiciteit van deze cellen te evalueren.

Methoden:  We hebben 60 mg m -2  dag -1  fludarabine gedurende Four dagen en 30 mg kg -1  dag -1  cyclofosfamide gedurende 2 dagen intraveneus toegediend aan cynomolgus makaken voor lymfodepletie; Vervolgens, 3,Three x 10 6  kg -1  van niet-getransduceerde of EphB4-CAR-T-cellen werd geïnfuseerd in de makaken, respectievelijk. Alle makaken werden gedurende 7 dagen nauwlettend gevolgd en beoordeeld op mogelijke toxiciteit.

Resultaten:  Lymfodepletie werd met succes bereikt op dag -1 vóór infusie van T-cellen en hield aan gedurende 7 dagen zonder ernstige orgaantoxiciteiten. Een enkele toediening van menselijke EPHB4-CAR-T-cellen induceerde geen openlijke orgaantoxiciteiten, hoewel EPHB4-CAR-T-cellen in vivo werden geactiveerd  ,  zoals blijkt uit de verhoging van het aantal kopieën van het CAR-transgen 24 uur na infusie.

Conclusie:  Hoewel dit NHP-model beperkt is voor de volledige evaluatie van de toxiciteit van menselijke CAR-T-cellen en het conditioneringsprotocol verder moet worden geoptimaliseerd, zou dit NHP-model met lymfdepletie kunnen worden gebruikt om acute on-target/off-tumor toxiciteiten van CAR-T-cellen te beoordelen. T-cellen.

De verschillen in incidentie van prostaatkanker en Sterfte in Neder-Saksen (Duitsland) en de provincie Groningen (Nederland): potentiële influence van Prostaat Specifiek  Antigeen  Testing

Achtergrond:  Prostaatkanker (PCa) is de meest voorkomende kanker bij mannen in Europa. Verschillen in PCa-incidentie over de hele wereld kunnen gedeeltelijk worden verklaard door variaties in aanbevelingen voor prostaatspecifiek antigeen (PSA), met identify voor vroege detectie. Zo is het PSA-testbeleid in Nederland conservatiever dan in Duitsland. Om de relatie tussen PSA-testaanbevelingen en PCa-incidentie, stadiumverdeling en mortaliteit beter te begrijpen, vergeleken we deze variabelen in de tijd tussen Nedersaksen in het noordwesten van Duitsland en de naburige provincie Groningen in Nederland.

Methoden:  Bevolkingsgegevens, tumorstadium- en leeftijdsgroepspecifieke PCa-incidentie (ICD-10 C61) en sterftecijfers voor Nedersaksen en Groningen werden verkregen uit de Nedersaksische Epidemiologische Kankerregistratie, de Nederlandse Integrale Kankerorganisatie en het CBS voor 2003 -2012. Incidentie- en sterftecijfers per 100.000 persoonsjaren werden gestandaardiseerd naar leeftijd (ASR, oude Europese norm). Tendencies in voor leeftijd gestandaardiseerde incidentiecijfers (ASIR) en sterftecijfers (ASMR) voor specifieke leeftijdsgroepen werden beoordeeld met behulp van joinpoint-regressie.

Resultaten:  De gemiddelde jaarlijkse PCa ASIR tussen 2003 en 2012 was gemiddeld 19,9% hoger in Nedersaksen dan in Groningen (120,5 vs. 100,5 per 100.000), terwijl de gemiddelde jaarlijkse ASMR in Nedersaksen gemiddeld 24,3% lager was dan in Groningen ( 21,5 versus 28,Four per 100.000). Tussen 2003 en 2012 veranderde de gemiddelde jaarlijkse procentuele verandering (AAPC) in PCa-incidentie niet important in Nedersaksen (-1,8%, 95% BI -3,5, 0,0) of Groningen (0,2%, 95% BI -5,0, 5.7). Daarentegen daalde de AAPC in sterftecijfer important in dezelfde periode in Nedersaksen (-2,5%, 95% BI -3,0, -2,0) maar niet in Groningen (0,1%, 95% BI -2,4, 2,6).

Conclusies:  In Nedersaksen werd een hogere PCa-incidentie en lagere PCa-gerelateerde mortaliteit gevonden dan in Groningen. Hoewel aanbevelingen over PSA-testen een rol kunnen spelen, konden de beoordeelde gegevens geen duidelijke verklaring bieden voor de waargenomen verschillen. Daarom is verder onderzoek nodig, inclusief gegevens over het daadwerkelijke gebruik van PSA-testen, andere invloeden (bijvoorbeeld voedings- en etnische factoren) en een betere gegevenskwaliteit om verschillen tussen de regio’s te verklaren.

 

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