Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease

OBJECTIVE: In statin-treated patients with stable coronary artery disease (CAD), residual risk of cardiovascular events is partly explained by plasma levels of low-density lipoprotein cholesterol (LDL-C). This study aimed to estimate individual benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in CAD patients already treated with high-dose statin. METHODS: Individual lifetime benefit was estimated in months gain free of stroke or myocardial infarction (MI) until age 80 years. Predictions were based on two competing risk models developed in data from 4853 patients with CAD originating from the atorvastatin 80 mg arm of the Treating to New Targets (TNT) trial. The relative effect of PCSK9 inhibition was added to the models and was assumed based on average estimates from large clinical trials. We accounted for individual LDL-C levels, assuming 50% LDL-C reduction by PCSK9 inhibition and 21% cardiovascular risk reduction per mmol/L (39 mg/dL) LDL-C lowering. RESULTS: Estimated individual gain was 1.8 mmol/L (>70 mg/dL). Estimated benefit was lowest (≤5 months) in older patients (≥70 years), in particular if LDL-C and other risk factors levels were low. CONCLUSION: The individual estimated lifetime benefit from PCSK9 inhibition in patients with stable CAD on high-dose statin varied from <6 to ≥12 months free of stroke or MI. Highest benefit is expected in younger patients (age 40-60 years) with high risk factor burden and relatively high LDL-C levels. TRIAL REGISTRATION NUMBER: NCT00327691; Post-results

Individualized Vascular Disease Prevention in High-Risk Patients

In the pharmacologic prevention of vascular events, clinicians need to translate average effects from a clinical trial to the individual patient. Prediction models can contribute to individualized vascular disease prevention by selecting patients for treatment based on estimated risk or expected benefit from treatment. For patients with diabetes or vascular disease, currently no individualized approach for vascular disease prevention is applied, as these patients are generally all considered high-risk. An individualized approach may however provide several opportunities for these patients: the intensity of secondary prevention of major vascular events can be determined based on estimated prognosis and predictions can be used to inform the patient. In thesis, it was shown that there is wide variation in 10-year absolute treatment effects of moderate-intensity statin therapy in patients with type 2 diabetes, ranging from very low (50) to very high (>5% 10-year absolute risk reduction, or iNNT 30% 10-year risk. Even if all risk factors would be at guideline-recommended target, the 10-year residual risk would be estimated to be 40%). Next, we developed and externally validated the internationally applicable REACH-SMART model that can be used to make lifetime predictions for individual patients with vascular disease. Subsequently, the estimation of individualized treatment effect was taken a step further by showing how preventive treatment effect in terms of disease-free life-years gained in individual patients can be predicted based on randomized clinical trial data. It was shown that highest treatment effect is generally achieved in the younger patients with otherwise high cardiovascular risk factors, but not necessarily high estimated 10-year risk. Such an approach was applied to estimate the expected lifetime benefit from PCSK9-inhibition in high-dose statin-treated patients with coronary artery disease, which was shown to vary from <6 months to ≥18 months free of stroke or MI. Highest benefit was expected if treatment is initiated in younger patients (age 40-60) with relatively high levels of LDL-c and other risk factors. The findings presented in this thesis support an individualized approach for vascular disease prevention in patients with diabetes or clinical vascular disease, that are currently considered high-risk. Also, this thesis provides a basis for future research on the translation of group-level evidence to the individual patient in the consulting room

Individualized Vascular Disease Prevention in High-Risk Patients

In the pharmacologic prevention of vascular events, clinicians need to translate average effects from a clinical trial to the individual patient. Prediction models can contribute to individualized vascular disease prevention by selecting patients for treatment based on estimated risk or expected benefit from treatment. For patients with diabetes or vascular disease, currently no individualized approach for vascular disease prevention is applied, as these patients are generally all considered high-risk. An individualized approach may however provide several opportunities for these patients: the intensity of secondary prevention of major vascular events can be determined based on estimated prognosis and predictions can be used to inform the patient. In thesis, it was shown that there is wide variation in 10-year absolute treatment effects of moderate-intensity statin therapy in patients with type 2 diabetes, ranging from very low (50) to very high (>5% 10-year absolute risk reduction, or iNNT 30% 10-year risk. Even if all risk factors would be at guideline-recommended target, the 10-year residual risk would be estimated to be 40%). Next, we developed and externally validated the internationally applicable REACH-SMART model that can be used to make lifetime predictions for individual patients with vascular disease. Subsequently, the estimation of individualized treatment effect was taken a step further by showing how preventive treatment effect in terms of disease-free life-years gained in individual patients can be predicted based on randomized clinical trial data. It was shown that highest treatment effect is generally achieved in the younger patients with otherwise high cardiovascular risk factors, but not necessarily high estimated 10-year risk. Such an approach was applied to estimate the expected lifetime benefit from PCSK9-inhibition in high-dose statin-treated patients with coronary artery disease, which was shown to vary from <6 months to ≥18 months free of stroke or MI. Highest benefit was expected if treatment is initiated in younger patients (age 40-60) with relatively high levels of LDL-c and other risk factors. The findings presented in this thesis support an individualized approach for vascular disease prevention in patients with diabetes or clinical vascular disease, that are currently considered high-risk. Also, this thesis provides a basis for future research on the translation of group-level evidence to the individual patient in the consulting room

Different answers to different questions. Exploring clinical decision making by general practitioners and psychiatrists about depressed patients

Contains fulltext : 129670.pdf (publisher's version ) (Open Access)Purpose: Exploring three perspectives on differences between general practitioners (GP) and psychiatrists in clinical decision making about depressed patients. The gold standard perspective focuses on differences in decisions (output) as a result of lack of expertise, the input perspective relates differences to different information use and to other roles, and the throughput perspective attributes differences to other information processing. Methods: Twenty-six psychiatrists and 25 GPs gave their clinical judgment on four on-line vignettes of increasingly severely depressed patients. Supplementary information on 15 themes could be asked for by clicking on underlined phrases. Dependent variables were the amount and type of extra information used, time needed and judgments of the severity of symptoms, appropriate treatment and health care providers. Results: Compared to psychiatrists, GPs were more reluctant to refer to specialized care, they needed less supplementary information and reached their conclusion in less time. Their processing of information appeared to be more contextual. Psychiatrists used a more stable procedure in which information inspection took place independently of differences in the vignettes. Conclusions: GPs and psychiatrists not only give different answers (treatment advices) because they have different expertise, but also because they have different questions due to other roles, and they use different clinical decision procedures. Insight in these differences can be useful for ameliorating collaborative mental health care.6 p

Persisterende depressie

De persisterende depressie (chronische depressie) is ook vaak een therapieresistente depressie, wat wil zeggen dat er geen verbetering is opgetreden met de gebruikelijke behandelstappen. Dan is het nodig om de diagnostiek te heroverwegen en de behandeling te intensiveren. Rehabilitatie dient ook meegenomen te worden in de behandeling met extra aandacht voor zelfmanagement, omdat klachtvermindering van groot belang is in de aanpak. Er zijn weinig specifieke rehabilitatieprogramma's voor depressie ontwikkeld, maar er is wel een groot aanbod van 'peer support' zowel online als live. Meer onderzoek naar rehabilitatie en herstel bij depressie is gewenst

Stoornis in het gebruik van een middel

Verslaving kan zich ontwikkelen tot een ernstige psychiatrische aandoening. Mensen met EPA hebben vaak een comorbide stoornis in het gebruik van een of meerdere middelen. De symptomatologie is niet altijd eenduidig naar een oorzaak te herleiden vanwege verschil in symptomatologie tijdens acuut en chronisch gebruik en onthouding van middelen, en de overlap en interactie met deze symptomatologie en overige psychische en somatische morbiditeit. Juiste diagnostiek is hierdoor uitdagend en behandeling van deze patiëntengroep is overwegend intensief en zal multidisciplinair uitgevoerd moeten worden. De sterk verhoogde mortaliteit en morbiditeit en het verminderd welzijn bij deze groep onderstreept de noodzaak van een adequate behandelin

Huisarts versus psychiater bij depressieve klachten

Item does not contain fulltextAchtergrond Er is behoefte aan duidelijkheid over de aansluiting tussen de generalistische en de specialistische zorg op het gebied van psychiatrische problematiek. Onderzoek wijst uit dat huisartsen depressieve symptomen minder goed herkennen en de ernst ervan vaak onderschatten. Wij onderzochten op welke manier huisartsen en psychiaters tot hun oordeel komen bij patiënten met depressieve klachten, en voor welke diagnostiek en behandeling zij dan kiezen. Methode Wij vroegen 25 huisartsen en 26 psychiaters om online vier casussen te beoordelen en steeds het best passende beleid te kiezen. Iedere casus bevatte 15 hyperlinks naar verschillende categorieën aanvullende informatie. Door het klikgedrag van de deelnemers te monitoren konden wij nagaan hoe zij tot hun oordeel kwamen. Resultaten De deelnemers waren eensgezind over de ernst van de problematiek, maar de psychiaters kozen vaker voor psychoeducatie en medicatie door een psychiater of klinisch psycholoog, waar de huisartsen vaker kozen voor een huisarts of maatschappelijk werker. De huisartsen hadden voor hun oordeel veel minder tijd nodig dan de psychiaters en klikten veel minder vaak door naar diepere informatielagen. Huisartsen gingen vooral op zoek naar de sociale context, psychiaters naar de symptoomgeschiedenis. Conclusie De huisartsen en psychiaters in ons onderzoek oordeelden inderdaad verschillend over dezelfde depressieve klachten. Deze verschillen zijn echter functioneel en sluiten aan bij de taak die beide disciplines in de zorg vervullen: de generalistische poortwachter versus de specialistische achterwacht. Meer overeenstemming zou de kwaliteit van de zorg niet verbeteren.4 p