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Wielders CC, Boerman AW, Schimmer B, van den Brom R, Notermans DW, van der Hoek W, Schneeberger PM

Persistent high IgG phase I antibody levels against Coxiella burnetii among veterinarians compared to patients previously diagnosed with acute Q fever after three years of follow-up. PLoS One. 2015 Jan 20;10(1):e0116937.

doi: 10.1371/journal.pone.0116937. eCollection 2015.

BACKGROUND: Little is known about the development of chronic Q fever in occupational risk groups. The aim of this study was to perform long-term follow-up of Coxiella burnetii seropositive veterinarians and investigate the course of IgG phase I and phase II antibodies against C. burnetii antigens and to compare this course with that in patients previously diagnosed with acute Q fever. METHODS: Veterinarians with IgG phase I ≥ 1:256 (immunofluorescence assay) that participated in a previous seroprevalence study were asked to provide a second blood sample three years later. IgG antibody profiles were compared to a group of acute Q fever patients who had IgG phase I ≥ 1:256 twelve months after diagnosis. RESULTS: IgG phase I was detected in all veterinarians (n = 76) and in 85% of Q fever patients (n = 98) after three years (p<0.001). IgG phase I ≥ 1:1,024, indicating possible chronic Q fever, was found in 36% of veterinarians and 12% of patients (OR 3.95, 95%

CI: 1.84-8.49). CONCLUSIONS: IgG phase I persists among veterinarians presumably because of continuous exposure to C.

burnetii during their work. Serological and clinical follow-up of occupationally exposed risk groups should be considered.

PMID: 25608699

Hagenaars JC, Wever PC, Shamelian SO, Van Petersen AS, Hilbink M, Renders NH, De Jager-Leclercq GL, Moll FL, Koning OH. Vascular chronic Q fever: quality of life. Epidemiol Infect. 2015 Oct;143(13):2903-9. doi:

10.1017/S0950268814003951. Epub 2015 Jan 22.

The aim of this study was to evaluate the quality of life in patients with vascular chronic Q fever at time of diagnosis and during follow-up. Based upon the SF-36 questionnaire, the mean physical and mental health of each patient were assessed at 3-month intervals for up to 18 months. A total of 26 patients were included in the study. At time of diagnosis, the mean physical health and mental health score was 50•6 [95% confidence interval (CI) 46•7-54•4] and 44•6 (95% CI 41•6-47•5), respectively. During treatment, the mean physical health score declined significantly by 1•7 points each 3 months (P <

0•001) to 40•8 (95% CI 34•4-45•1). The mean mental health score significantly and steadily increased towards 51•2 (95%

CI 46•9-54•3) during follow-up (P = 0•026). A total of 23% of patients were cured after 18 months of follow-up. In con-clusion, quality of life at time of diagnosis for patients with vascular chronic Q fever is lower compared to a similar group of

patients, matched for age and gender, with an aortic abdominal aneurysmal disease, and physical health decreases further after starting treatment. Considering the low percentage of cure, the current treatment of vascular chronic Q fever patients may require a separate strategy from that of endocarditis in order to increase survival.

PMID: 25633758

Poolman RW, Verhaar JA, Schreurs BW, Bom LP, Nelissen RG, Koot HW, Goosen JH, Verheyen CC. Finding the right hip implant for patient and surgeon: the Dutch strategy - empowering patients. Hip Int. 2015 Apr 20;25(2):131-7. doi: 10.5301/hipint.5000209. Epub 2015 Feb 28.

We describe the implementation process of hip prostheses selection in the Netherlands. The recent problems with large head metal-on-metal hip prostheses resulted in substantial damage to the surgeons’ credibility and reputation in the media.

This led to a true sense of urgency among orthopaedic surgeons to increase their activities to secure patient safety. The board of the Dutch Orthopaedic Association (NOV) in the Netherlands established a Dutch Hip Task Force (DHTF) with the explicit assignment of formulating criteria to classify the quality of total hip implants on the Dutch market based on survi-vorship. The aim was to offer unequivocal information enabling a balanced choice of total hip prosthesis. The ultimate goal of the NOV is that all implanted total hip prostheses implanted in the Netherlands are based on reliable clinical evidence. The DHTF decided to adapt the principles of the National Institute for Health and Care Excellence (NICE, UK) (www.nice.org.uk).

The taskforce uses data from the registries as well as the Orthopaedic Data Evaluation Panel (ODEP). If the ODEP guidelines had been chosen as standard alone, one quarter of our listed hip components would not have been included. In our view this underlines the strength in the Dutch approach where high quality registry data and ODEP ratings are complementary and result in a list of reliable hip prostheses. Most importantly we offer patients insights into the known quality of the implants by sharing the results of our implant review. This will facilitate shared decision making by empowering patients in their knowledge on available hip arthroplasties.

PMID: 25636328

Berm EJ, Hak E, Postma M, Boshuisen M, Breuning L, Brouwers JR, Dhondt T, Jansen PA, Kok RM, Maring JG, van Marum R, Mulder H, Voshaar RC, Risselada AJ, Venema H, Vleugel L, Wilffert B. Effects and cost-effectiveness of pharmacogenetic screening for CYP2D6 among older adults starting therapy with

nortriptyline or venlafaxine: study protocol for a pragmatic randomized controlled trial (CYSCEtrial). Trials. 2015 Jan 31;16(1):37. doi:10.1186/s13063-015-0561-0.

BACKGROUND: Nortriptyline and venlafaxine are commonly used antidepressants for treatment of depression in older patients. Both drugs are metabolized by the polymorphic cytochrome P450-2D6 (CYP2D6) enzyme and guidelines for dose adaptations based on the CYP2D6 genotype have been developed. The CYP2D6 Screening Among Elderly (CYSCE) trial is designed to address the potential health and economic value of genotyping for CYP2D6 in optimizing dose-finding of nortriptyline and venlafaxine. METHODS/DESIGN: In a pragmatic randomized controlled trial, patients diagnosed with a major depressive disorder according to the DSM-IV and aged 60 years or older will be recruited from psychiatric centers across the Netherlands. After CYP2D6 genotyping determined in peripheral blood obtained by finger-prick, patients will be grouped into poor, intermediate, extensive, or ultrarapid metabolizers. Patients with deviant genotype (that is poor, intermediate or ultrarapid genotype) will be randomly allocated to an intervention group in which the genotype and dosing advice is communicated to the treating physician, or to a control group in which patients receive care as usual. Additionally, an external reference group of patients with the extensive metabolizer genotype is included. Primary outcome in all groups is time needed to obtain an adequate blood level of the antidepressant drug. Secondary outcomes include adverse drug reactions measured by a shortened Antidepressant Side-Effects Checklist (ASEC), and cost-effectiveness of the screening.

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DISCUSSION: Results of this trial will guide policy-making with regard to pharmacogenetic screening prior to treatment with nortriptyline or venlafaxine among older patients with depression. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01778907 ; registration date: 22 January 2013.

PMID: 25648985

de Vries C, Doggen C, Hilbers E, Verheij R, IJzerman M, Geertsma R, Kusters R. Results of a survey among GP practices on how they manage patient safety aspects related to point-of-care testing in every day practice. BMC Fam Pract. 2015 Feb 5;16(1):9.

BACKGROUND: Point-of-care (POC) tests are devices or test strips that can be used near or at the site where care is delivered to patients, enabling a relatively fast diagnosis. Although many general practitioners (GPs) in the Netherlands are using POC tests in their practice, little is known on how they manage the corresponding patient safety aspects. METHODS:

To obtain information on this aspect, an invitation to participate in a web-based questionnaire was sent to a random sample of 750 GP practices. Of this sample 111 GP practices returned a complete questionnaire. Data was analysed by using des-criptive statistics. RESULTS: Results show that there is not always attention for quality control measures such as checking storage conditions, executing calibration, and maintenance. In addition, universal hygienic measures, such as washing hands before taking a blood sample, are not always followed. Refresher courses on the use of POC tests are hardly organized. Only a few of the GPs contact the manufacturer of the device when a device failure occurs. Well-controlled aspects include patient identification and actions taken when ambiguous test results are obtained. CONCLUSIONS: We observed a number of risks for errors with POC tests in GP practices that may be reduced by proper training of personnel, introduction of standard operating procedures and measures for quality control and improved hygiene. To encourage proper use of POCT in general practices, a national POCT guideline, dedicated to primary care and in line with ISO standards, should be introduced.

PMID: 25652303

Ranschaert ER, Boland GW, Duerinckx AJ, Barneveld Binkhuysen FH. Comparison of European (ESR) and American (ACR) white papers on teleradiology: patient primacy is paramount. J Am Coll Radiol. 2015 Feb;12(2):174-82. doi: 10.1016/j.jacr.2014.09.027.

The ACR and European Society of Radiology white papers on teleradiology propose best practice guidelines for teleradiology, with each body focusing on its respective local situation, market, and legal regulations. The organizations have com-mon viewpoints, the most important being patient primacy, maintenance of quality, and the “supplementary” position of teleradiology to local services. The major differences between the white papers are related mainly to the market situation, the use of teleradiology, teleradiologist credentialing and certification, the principles of “international” teleradiology, and the need to obtain “informed consent” from patients. The authors describe these similarities and differences by highlighting the background and context of teleradiology in Europe and the United States.

PMID: 25652526

Kröger E, Van Marum R, Souverein P, Carmichael PH, Egberts T. Treatment with rivastigmine or galantamine and risk of urinary incontinence: results from a Dutch database study. Pharmacoepidemiol Drug Saf. 2015 Mar;24(3):276-85. doi: 10.1002/pds.3741. Epub 2015 Feb 4.

BACKGROUND: Treatment of Alzheimer disease (AD) with cholinesterase inhibitors (ChEIs) may increase the risk of urinary incontinence (UI). OBJECTIVE: To assess whether ChEI use was associated with the risk of UI among older patients with AD. METHODS: A crossover cohort study using the PHARMO Record Linkage System included 10 years of data on drug

dispensing histories for over two million Dutch residents. Included patients were aged 50 +, free of UI for the last 6 months, received a first ChEI prescription during the study period, had at least 12 months prior drug exposure history and one subsequent prescription of any drug. UI was defined as a first dispensing of a urinary spasmolytic or of incontinence products for at least 30 days. Cox regression with time-varying covariates and multivariate adjustment allowed assessing whether UI incidence was associated with ChEI exposure. RESULTS: Among 3154 patients there were 657 UI cases during a mean follow-up of 5.1 years before a first ChEI dispensing, and 499 cases after ChEI initiation, during a mean follow-up of 2.0 years. Among the 2700 participants free of UI one year before ChEI initiation, the adjusted hazard ratio (HR) for UI was 1.13 (95% CI: 0.97-1.32) when periods with ChEI use were compared to periods without ChEI use. Sensitivity analyses may suggest an increased risk in the 1(st) month after ChEI initiation (HR: 1.72, p = 0.09) CONCLUSION: Worsening AD may increase incidence of UI, but no firm association between ChEI treatment and risk of UI could be shown from these data.

PMID: 25668198

Bakker NE, Kuppens RJ, Siemensma EP, Tummers-de Lind van Wijngaarden RF, Festen DA, Bindels-de Heus GC, Bocca G, Haring DA, Hoorweg-Nijman JJ, Houdijk EC, Jira PE, Lunshof L, Odink RJ, Oostdijk W, Rotteveel J, Van Alfen AA, Van Leeuwen M, Van Wieringen H, Wegdam-den Boer ME, Zwaveling-Soonawala N, Hokken-Koelega AC. Bone mineral density in children and adolescents with Prader-Willi syndrome: a longitudinal study during puberty and 9 years of growth hormone treatment. J. Clin. Endocrinol. Metab. 2015;100: 1609-1618.

CONTEXT: Longitudinal data on bone mineral density (BMD) in children and adolescents with Prader-Willi Syndrome (PWS) during long-term GH treatment are not available. OBJECTIVE: This study aimed to determine effects of long-term GH treatment and puberty on BMD of total body (BMDTB), lumbar spine (BMDLS), and bone mineral apparent density of the lumbar spine (BMADLS) in children with PWS. DESIGN AND SETTING: This was a prospective longitudinal study of a Dutch PWS cohort. PARTICIPANTS: Seventy-seven children with PWS who remained prepubertal during GH treatment for 4 years and 64 children with PWS who received GH treatment for 9 years participated in the study. INTERVENTION: The children received GH treatment, 1 mg/m(2)/day (κ 0.035 mg/kg/d). MAIN OUTCOME MEASURES: BMDTB, BMDLS, and BMADLS was measured by using the same dual-energy x-ray absorptiometry machine for all annual measurements. RESULTS: In the prepubertal group, BMDTB standard deviation score (SDS) and BMDLSSDS significantly increased during 4 years of GH treatment whereas BMADLSSDS remained stable. During adolescence, BMDTBSDS and BMADLSSDS decreased signifi-cantly, in girls from the age of 11 years and in boys from the ages of 14 and 16 years, respectively, but all BMD parameters remained within the normal range. Higher Tanner stages tended to be associated with lower BMDTBSDS (P = .083) and a significantly lower BMADLSSDS (P = .016). After 9 years of GH treatment, lean body mass SDS was the most powerful pre-dictor of BMDTBSDS and BMDLSSDS in adolescents with PWS. CONCLUSIONS: This long-term GH study demonstrates that BMDTB, BMDLS, and BMADLS remain stable in prepubertal children with PWS but decreases during adolescence, parallel to incomplete pubertal development. Based on our findings, clinicians should start sex hormone therapy from the age of 11 years in girls and 14 years in boys unless there is a normal progression of puberty.

PMID: 25688100

Vogelaar FJ, Lips DJ, van Dorsten FR, Lemmens VE, Bosscha K. Impact of anaesthetic technique on survival in colon cancer: a review of the literature. Gastroenterol Rep (Oxf). 2016 Feb;4(1):30-4. doi: 10.1093/gastro/

gov001. Epub 2015 Feb 16. Review.

An oncological surgical resection is the mainstay of treatment for potentially curable colon cancer. At the time of surgery, a large fraction of patients do harbour-although not visibly-minimal residual disease at the time of surgery. The immunosup-pression that accompanies surgery may have an effect on disease recurrence and survival. Regional or neuraxial anaesthetic techniques like epidural anaesthesia may suppress immune function less than opioid analgesia, by reducing stress response

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and significantly reducing exposure to opioids. Consistent with this hypothesis, regional anaesthetic techniques have been as-sociated with lower recurrence rates in breast cancer and prostate cancer. Results for colon cancer, however, are contradictory.

In this review of the literature we describe all studies addressing the association of the use of epidural anaesthesia and survival in colon cancer surgery.

PMID: 25703856

Van Erning FN, Janssen-Heijnen ML, Creemers GJ, Pruijt HF, Maas HA, Lemmens VE. Deciding on adjuvant chemotherapy for elderly patients with stage III colon cancer: A qualitative insight into the perspectives of surgeons and medical oncologists. J Geriatr Oncol. 2015 May;6(3):219-24. doi: 10.1016/j.jgo.2015.02.001. Epub 2015 Feb 20.

OBJECTIVE: The aim of this study is to identify doctor-related factors determining the decision-making for adjuvant chemo-therapy for patients with stage III colon cancer aged ≥75years. MATERIALS AND METHODS: 21 surgeons and 15 medical oncologists from 10 community hospitals were asked to complete a short questionnaire including tick-box questions regarding motives for non-referral/non-treatment, consultation of geriatricians, chemotherapy schemes prescribed and an open ques-tion regarding tolerability of chemotherapy. RESULTS: 29 medical specialists returned a completed quesques-tionnaire (response 81%). The motives for non-referral/non-treatment reported most often were comorbidity/bad general health condition of the patient; surgical complications; and treatment offered but refused by patient/family. 39% of the surgeons and 55% of the medical oncologists reported consultation of a geriatrician in 2-30% of their decisions. CAPOX and capecitabine were reported by medical oncologists as the most frequently prescribed regimens. Factors that influenced the decision for monotherapy or combination therapy were comorbidity; general health condition of the patient; and toxicity profile of the chemotherapeutics.

In general, medical oncologists defined grade ≤2 toxicities as tolerable, with the exception of neuropathy, for which grade ≤1 toxicity was accepted. CONCLUSIONS: In case medical oncologists prescribe adjuvant chemotherapy to elderly patients with stage III colon cancer, the chemotherapy schemes used are in line with clinical guidelines and they agree on acceptable levels of toxicity. However, the variation among surgeons and medical oncologists in motives for non-referral, non-treatment and consultation of geriatricians when deciding on adjuvant chemotherapy for elderly patients with stage III colon cancer, shows the complexity and need for specific knowledge.

PMID: 25722298

Schoffelen T, Ammerdorffer A, Hagenaars JC, Bleeker-Rovers CP, Wegdam-Blans MC, Wever PC, Joosten LA, van der Meer JW, Sprong T, Netea MG, van Deuren M, van de Vosse E. Genetic Variation in Pattern Recognition Receptors and Adaptor Proteins Associated With Development of Chronic Q Fever. J Infect Dis. 2015 Feb 26. pii:

jiv113. [Epub ahead of print]

BACKGROUND: Q fever is an infection caused by Coxiella burnetii. Persistent infection (chronic Q fever) develops in 1%-5% of patients. We hypothesize that inefficient recognition of C. burnetii and/or activation of host-defense in individuals carrying genetic variants in pattern recognition receptors or adaptors would result in an increased likelihood to develop chronic Q fever. METHODS: Twenty-four single-nucleotide polymorphisms in genes encoding Toll-like receptors, nucleotide-binding oligomerization domain-like receptor-2, κvκ3 integrin, CR3, and adaptors myeloid differentiation primary response protein 88 (MyD88), and Toll interleukin 1 receptor domain-containing adaptor protein (TIRAP) were genotyped in 139 patients with chronic Q fever and in 220 controls with cardiovascular risk-factors and previous exposure to C. burnetii. Associations between these single-nucleotide polymorphisms and chronic Q fever were assessed by means of univariate logistic regression models.

Cytokine production in whole-blood stimulation assays was correlated with relevant genotypes. RESULTS: Polymorphisms in TLR1 (R80T), NOD2 (1007fsX1), and MYD88 (-938C>A) were associated with chronic Q fever. No association was observed

for polymorphisms in TLR2, TLR4, TLR6, TLR8, ITGAV, ITGB3, ITGAM, and TIRAP. No correction for multiple testing was per-formed because only genes with a known role in initial recognition of C. burnetii were included. In the whole-blood assays, individuals carrying the TLR1 80R-allele showed increased interleukin 10 production with C. burnetii exposure. CONCLU-SIONS: Polymorphisms in TLR1 (R80T), NOD2 (L1007fsX1), and MYD88 (-938C>A) are associated with predisposition to development of chronic Q fever. For TLR1, increased interleukin 10 responses to C. burnetii in individuals carrying the risk allele may contribute to the increased risk of chronic Q fever.

PMID: 25732130

Jacobs LH, van Borren M, Gemen E, van Eck M, van Son B, Glatz JF, Daniels M, Kusters R. Rapidly rule out acute myocardial infarction by combining copeptin and heart-type fatty acid-binding protein with cardiac troponin. Ann Clin Biochem. 2015 Sep;52(Pt 5):550-61. doi: 10.1177/0004563215578189. Epub 2015 Mar 2.

BACKGROUND: The rapid exclusion of acute myocardial infarction in patients with chest pain can reduce the length of hos-pital admission, prevent unnecessary diagnostic work-up and reduce the burden on our health-care systems. The combined use of biomarkers that are associated with different pathophysiological aspects of acute myocardial infarction could improve the early diagnostic assessment of patients presenting with chest pain. METHODS: We measured cardiac troponin I, copep-tin and heart-type fatty acid-binding protein concentrations in 584 patients who presented to the emergency department with acute chest pain. The diagnostic performances for the diagnosis of acute myocardial infarction and NSTEMI were calculated for the individual markers and their combinations. Separate calculations were made for patients presenting to the emergency department <3 h, 3-6 h and 6-12 h after chest pain onset. RESULTS: For ruling out acute myocardial infarction, the net predictive values (95% CI) of cardiac troponin I, copeptin and heart-type fatty acid-binding protein were 90.4%

(87.3-92.9), 84% (79.8-87.6) and 87% (83.5-90), respectively. Combining the three biomarkers resulted in a net predictive value of 95.8% (92.8-97.8). The improvement was most pronounced in the early presenters (<3 h) where the combined net predictive value was 92.9% (87.3-96.5) compared to 84.6% (79.4-88.9) for cardiac troponin I alone. The area under the receiver operating characteristic for the triple biomarker combination increased significantly (P < 0.05) compared to that of cardiac troponin I alone (0.880 [0.833-0.928] vs. 0.840 [0.781-0.898], respectively). CONCLUSIONS: Combining copeptin, heart-type fatty acid-binding protein and cardiac troponin I measurements improves the diagnostic performance in patients presenting with chest pain. Importantly, in patients who present early (<3 h) after chest pain onset, the combination impro-ves the diagnostic performance compared to the standard cardiac troponin I measurement alone.

(87.3-92.9), 84% (79.8-87.6) and 87% (83.5-90), respectively. Combining the three biomarkers resulted in a net predictive value of 95.8% (92.8-97.8). The improvement was most pronounced in the early presenters (<3 h) where the combined net predictive value was 92.9% (87.3-96.5) compared to 84.6% (79.4-88.9) for cardiac troponin I alone. The area under the receiver operating characteristic for the triple biomarker combination increased significantly (P < 0.05) compared to that of cardiac troponin I alone (0.880 [0.833-0.928] vs. 0.840 [0.781-0.898], respectively). CONCLUSIONS: Combining copeptin, heart-type fatty acid-binding protein and cardiac troponin I measurements improves the diagnostic performance in patients presenting with chest pain. Importantly, in patients who present early (<3 h) after chest pain onset, the combination impro-ves the diagnostic performance compared to the standard cardiac troponin I measurement alone.