G.A.J. Fransen

Rupture of infra-renal aortic aneurysm after endovascular repair: a series from EUROSTAR registry.

OBJECTIVES Although small, the risk of rupture after EVAR remains a major concern. The aim of this study was to identify mechanisms of late aneurysm rupture after endovascular repair. METHODS Patients who suffered a proven aneurysm rupture after EVAR were identified from the EUROSTAR (European Collaborators on Stent-graft Techniques for Abdominal Aortic Aneurysm Repair) registry. Complications preceding rupture were studied to identify common patterns and possible mechanisms of late rupture. RESULTS A rupture was documented in 34 patients resulting in death of 21 (62%). Adverse events documented during previous follow-up in these patients included endoleak (30%), migration (18%), limb occlusion (12%) and kinking (12%). The findings at time of rupture were documented in 24 patients and including endoleak: Type III (10), Type I (9), Type II (1); stent-graft disintegration (2) and migration (3). Aneurysm diameter changes could be ascertained in 24 patients and had increased in only seven. CONCLUSION The importance of graft-related endoleak, stent-graft disintegration and migration in the causation of aneurysm rupture was confirmed. Poor compliance with follow-up schedule was also identified as a common feature. However, the absence of complications in some patients, who attended regularly for follow-up, highlights the difficulty of predicting rupture after EVAR.

The significance and management of different types of endoleaks

Development of endovascular abdominal aortic aneurysm repair (EVAR) has been accompanied by previously unencountered complications. The most challenging but least understood of these complications is the incomplete seal of the endovascular graft (endoleak), a phenomenon that has a variety of causes. An important consequence of endoleakage may be persistent pressurization of the aneurysm sac, which may ultimately lead to post-EVAR rupture. Data of 110 European centers were recorded in a central database (EUROSTAR). Patient, anatomic characteristics, and operative and device details were correlated with the occurrence of different types of endoleaks. Outcome events during follow-up, particularly expansion of the aneurysm, incidence of conversion to open repair, and post-EVAR rupture were assessed in the different categories of endoleaks and in a group of patients without any endoleak. Type I and III endoleak were associated with an increased frequency of open conversions or risk of rupture of the aneurysm. Device-related endoleaks also correlated with an increased need for secondary interventions. These types of endoleaks need to be treated without delay, and when no other possibilities are present, an open conversion to avert the risk of rupture should be considered. Type II endoleaks do not pose an indication for urgent treatment. However, they may not be harmless, because there was a frequent association with enlargement of aneurysm and reinterventions. Our findings suggest that more frequent surveillance examinations are indicated than in patients without collateral endoleak. The indication for intervention is primarily dictated by documented expansion of the aneurysm.

Meta-analysis: the diagnostic value of alarm symptoms for upper gastrointestinal malignancy.

Background : With the advent of empirical treatment strategies for patients with dyspeptic symptoms, it becomes increasingly important to select patients with a high risk of having cancer for immediate endoscopy. Usually alarming symptoms are used for this matter, but their diagnostic value is by no means clear.

Pragmatic trials in primary care. Methodological challenges and solutions demonstrated by the DIAMOND-study

BackgroundPragmatic randomised controlled trials are often used in primary care to evaluate the effect of a treatment strategy. In these trials it is difficult to achieve both high internal validity and high generalisability. This article will discuss several methodological challenges in designing and conducting a pragmatic primary care based randomised controlled trial, based on our experiences in the DIAMOND-study and will discuss the rationale behind the choices we made. From the successes as well as the problems we experienced the quality of future pragmatic trials may benefit.DiscussionThe first challenge concerned choosing the clinically most relevant interventions to compare and enable blinded comparison, since two interventions had very different appearances. By adding treatment steps to one treatment arm and adding placebo to both treatment arms both internal and external validity were optimized. Nevertheless, although blinding is essential for a high internal validity, it should be warily considered in a pragmatic trial because it decreases external validity. Choosing and recruiting a representative selection of participants was the second challenge. We succeeded in retrieving a representative relatively large patient sample by carefully choosing (few) inclusion and exclusion criteria, by random selection, by paying much attention to participant recruitment and taking the participants reasons to participate into account. Good and regular contact with the GPs and patients was to our opinion essential. The third challenge was to choose the primary outcome, which needed to reflect effectiveness of the treatment in every day practice. We also designed our protocol to follow every day practice as much as possible, although standardized treatment is usually preferred in trials. The aim of this was our fourth challenge: to limit the number of protocol deviations and increase external validity.SummaryIt is challenging to design and conduct a pragmatic trial. Thanks to thorough preparation, we were able to collect highly valid data. To our opinion, a critical deliberation of where on the pragmatic – explanatory spectrum you want your trial to be on forehand, in combination with consulting publications especially on patient recruitment procedures, has been helpful in conducting a successful trial.

Frequency, Predictive Factors, and Consequences of Stent-Graft Kink following Endovascular AAA Repair

Purpose: To determine from the EUROSTAR registry the incidence of stent-graft kink, predictive factors for kinking, and the consequences of this complication on graft patency and aneurysm exclusion. Methods: From January 1994 to June 2002, 4613 patients who underwent endovascular aneurysm repair were registered in the EUROSTAR registry. Presence of kink was determined according to the information available on the follow-up Case Record Form. The population was divided into those with and without stent-graft kink. Patient characteristics, morphological aneurysm features, team experience, type of device, period of implantation, and outcome were compared between the groups by univariate analysis. Significant factors were subsequently submitted to a multivariate Cox proportional hazard analysis. Results: One hundred seventy (3.7%) patients were reported as having a kink of the stent-graft during a mean follow-up of 21 months (range 1–72). Gender, neck angulation, team experience, period of implantation, ASA classification, and device type were independent predictors of kink. The presence of a kink was significantly associated with type I endoleaks (proximal and distal), type III endoleaks (midgraft), graft stenosis, graft limb thrombosis, graft migration, and conversion to open repair. No relationship was found between a decrease in the aneurysm diameter and the occurrence of stent-graft kink. Conclusions: Kinks of stent-grafts were infrequent events in the intermediate term. Patients most at risk were women with angulated aortic necks treated by a minimally experienced team. Kinks are potentially damaging events because they may lead to delayed device-related endoleaks, graft stenosis, thrombosis, and conversion to open repair. They appear more closely associated to graft migration than to aneurysm diameter reduction.

Psychopathology is associated with dyspeptic symptom severity in primary care patients with a new episode of dyspepsia.

Background  Personality and psychiatric disorders are reported to be more common in dyspeptic patients with severe complaints, but it remains unclear whether this association exists for patients with mild and moderate dyspepsia.

Leefstijladviezen, medicatie-instructies en het belang van therapietrouw bij maagklachten

SamenvattingFransen GAJ, Mesters I, Van Marrewijk CJ, Mujakovic S, Knottnerus JA, Muris JWM. Leefstijladviezen, medicatie-instructies en het belang van therapietrouwe bij maagklachten. Huisarts Wet 2007;50(9):445-52.Inleiding Therapietrouw is essentieel om het effect van een behandeling te kunnen evalueren. Veel patiënten met een eerste episode van maagklachten houden zich echter niet aan medicatie-instructies en zeggen geen leefstijladviezen te hebben gekregen. Hierin kan voorlichting door huisartsen een rol spelen.Doel Met dit onderzoek wilden we inzicht krijgen in de voorlichting door huisartsen over leefstijladviezen, medicatie-instructies en therapietrouw.Methode Vragenlijstonderzoek bij huisartsen (n = 114).Resultaten Huisartsen rapporteren dat ze regelmatig leefstijladviezen geven: respectievelijk 73%, 69% en 60% geeft meestal/altijd adviezen over alcoholgebruik, roken en voeding. Het overgrote deel, 95-99%, zegt meestal/altijd instructies te geven over frequentie, dosering en behandelduur van medicatie. Bij een eerste episode van maagklachten adviseert 76% van de huisartsen zelden of nooit om maagzuurremmers te gebruiken op geleide van klachten. Veertien procent geeft aan doorgaans schriftelijke voorlichtingsmaterialen te gebruiken en 61% vraagt regelmatig na of de patiënt de medicatie volgens voorschrift heeft ingenomen.Conclusie In tegenstelling tot wat patiënten melden, zeggen huisartsen gewoonlijk medicatie-instructies en leefstijladviezen te geven. De voorlichting wordt weinig ondersteund met schriftelijke materiaal, wat wellicht zou kunnen bijdragen aan de lage therapietrouw. Hoewel weinig artsen aanbevelen om op geleide van klachten maagzuurremmers te gebruiken, lijken veel patiënten dit toch te doen. Dit kan betekenen dat de medicatie-instructie en het belang van therapietrouw niet voldoende duidelijk zijn voor patiënten.AbstractFransen GAJ, Mesters I, Van Marrewijk CJ, Mujakovic S, Knottnerus JA, Muris JWM. Lifestyle advice, medication instructions and the importance of adherence in case of dyspepsia. Huisarts Wet 2007;50(9):445-52.Background Dyspepsia is a worldwide problem, often treated with acid-suppressants or by a change in lifestyle. However preliminary results from a large RCT investigating the most effective treatment for dyspepsia indicate that only 11% of patients with a first episode of dyspepsia indicated that they had received lifestyle advice and about 50% fail to follow the correct medication instructions. The aim of this study was to investigate which medication instructions and lifestyle advice GPs normally give to their patients with dyspepsia.Method A questionnaire was sent to 259 Dutch GPs participating in an RCT investigating dyspepsia. The questionnaire could be returned anonymously and free of charge. Two reminders were sent out.Results The questionnaire was returned by 114 GPs, 60% of whom usually or always provided nutritional advice, 68% (almost) always advised the patient to stop smoking, and 72% (almost) always advised a reduction in alcohol consumption. The recommendation regarding raising the head end of the bed was provided less often (35% usually/always). Only 14% of the GPs commonly provided written information to support their lifestyle advice. Most GPs found it fairly to highly important that the patient adhere to doses (93%) and duration (95%) of the treatment; 40% of the GPs found adherence to the daily intake schedule very important. As many as 75% of the GPs seldom or never advised on demand use of medication in cases of a first episode of complaints, 39% of the GPs in cases of persisting complaints and only 7% in cases of relapsing complaints seldom or never advised on demand use.Discussion In contrast to the reports from patients, GPs stated that they frequently made recommendations regarding lifestyle. The instructions were often unsupported by written educational materials, which might contribute to low adherence rates and low recall by patients. Most GPs considered compliance with prescribed medication to be very important, but 20% of the GPs did not commonly check compliance. While patients might take their medication on demand, most GPs did not advise on demand use, especially in cases of a first episode of complaints.

Patient adherence to prescribed medication instructions for dyspepsia: The DIAMOND-study

Background: Insight into patient adherence is needed to enable an effect evaluation of medication for dyspepsia. Objectives: Adherence was explored by investigating two adherence outcome measures (completeness and intake fidelity) using data from the DIAMOND-study. Methods: The DIAMOND-study is a pragmatic RCT comparing a ‘step-up’ with a ‘step-down’ treatment strategy. In step 1 participants (n =653) were instructed to use five pills/day for maximally 30 days: an antacid 4dd plus a placebo 1dd (‘step-up’) or a proton pump inhibitor 1dd plus a placebo 4dd (‘step-down’). If the complaints persisted, step 2 was started (H2-receptor antagonist 2dd), and subsequently step 3 (five pills/day, placebo and verum vice versa from step 1). Completeness was assessed by pill counts, intake fidelity by patient questionnaires measuring the degree to which patients adhered to specific instructions concerning timing, frequency, dose and way of intake. Results: In step 1, patients used on average 3.9 pills/day (78% of the prescribed doses), in step 2, 1.7 pills/day (85%) and in step 3, 3.6 pills/day (72%). For the four times daily pills, half of the patients used less than 80% of the prescribed pills per day. This was one third of the patients for the twice daily pills and one quarter for the once daily pills. There were no completeness differences between active or placebo medication and no differences between the study arms. As regards intake fidelity, 70% of the patients made one or more errors in the medication intake. Conclusion: There is room for improvement in adherence rates for dyspepsia medication.

Zuurremmers: hoog inzetten, of juist laag? Het DIAMOND-onderzoek naar effectiviteit en kosten van de step-up en de step-downbenadering bij maagklachten in de eerste lijn.

SamenvattingVan Marrewijk CJ, Mujakovic S, Fransen GA, Numans ME, De Wit NJ, Muris JW, Van Oijen MG, Jansen JB, Grobbee DE, Knottnerus JA, Laheij RJ. Zuurremmers: hoog inzetten, of juist laag? Het DIAMOND-onderzoek naar effectiviteit en kosten van de stepup- en de step-downbenadering bij maagklachten in de eerste lijn. Huisarts Wet 2009;52(8):374-81.Doel Er zijn weliswaar consensusrichtlijnen over de behandeling van ‘maagklachten’ in de eerste lijn, maar de meest kosteneffectieve strategie moet nog worden bepaald. In het DIAMOND-onderzoek zijn de effectiviteit en de kosten van een step-upbenadering vergeleken met die van een step-downbenadering in de initiële behandeling van patiënten met een nieuwe episode ‘maagklachtenMethode Patiënten van 18 jaar en ouder die met nieuw ontstane maagklachten bij de huisarts kwamen, kregen willekeurig een stapsgewijze behandeling met achtereenvolgens een antacidum, een H2-receptorantagonist en een protonpompremmer (stepup), óf dezelfde geneesmiddelen in omgekeerde volgorde (stepdown). Elke stap in dit dubbelblinde, gerandomiseerde gecontroleerde onderzoek duurde vier weken. Een volgende stap werd alleen genomen als de klachten aanhielden of binnen vier weken terugkwamen. De primaire uitkomsten – symptoomverlichting en kosteneffectiviteit na zes maanden – zijn geanalyseerd op basis van ‘intention-to-treat’.Resultaten Tussen oktober 2003 en januari 2006 wezen wij 664 patiënten gerandomiseerd toe aan de step-upbehandeling (n = 341) of de step-downbehandeling (n = 323). Op korte termijn (binnen een maand) had de step-downbehandeling meer effect, maar na zes maanden waren beide benaderingen even succesvol: de step-upbehandeling bij 238 (72%) patiënten, de step-downbehandeling bij 219 (70%) patiënten (oddsratio 0,92; 95%-betrouwbaarheidsinterval 0,7-1,3). In de step-upgroep waren in die zes maanden echter minder medische kosten – vooral medicijnkosten – gemaakt dan in de step-downgroep (€ 228 tegen € 245; p = 0,0008).Conclusie De step-upbehandeling is bij patiënten met nieuw ontstane maagklachten na zes maanden even effectief als de step-downbehandeling, maar kost minder