Regional variation in breast cancer treatment in the Netherlands and the role of external peer review: a cohort study comprising 63,516 women

Background Treatment variation is an important issue in health care provision. An external peer review programme for multidisciplinary cancer care was introduced in 1994 in the Netherlands to improve the multidisciplinary organisation of cancer care in hospitals. So far the clinical impact of external quality assessment programmes such as external peer review and accreditation remains unclear. Our objective was to examine the degree of variation in treatment patterns and the possible effect of external peer review for multidisciplinary cancer care for breast cancer patients. Methods Patients with breast cancer were included from 23 hospitals from two ‘intervention regions’ with the longest experience with the programme and 7 hospitals that never participated (control group). Data on tumour and treatment characteristics were retrieved from the Netherlands Cancer Registry. Treatment modalities investigated were: the completeness of breast conserving therapy, introduction of the sentinel node biopsy, radiotherapy after breast conserving surgery for ductal carcinoma in situ (DCIS), adjuvant radiotherapy for locally advanced breast cancer (T3/M0 or any T,N2-3/M0), adjuvant chemotherapy for early stage breast cancer (T1-2/N+/M0) and neo-adjuvant chemotherapy for T4/M0 breast cancer. Hospitals from the two intervention regions were dichotomised based on their implementation proportion (IP) of recommendations from the final reports of each peer review (high IP vs. low IP). This was regarded as a measure of how well a hospital participated in the programme. Results 63,516 female breast cancer patients were included (1990-2010). Variation in treatment patterns was observed between the intervention regions and control group. Multidisciplinary treatment patterns were not consistently better for patients from hospitals with a high IP. Conclusions There is no relationship between the external peer review programme for multidisciplinary cancer care and multidisciplinary treatment patterns for breast cancer patients. Regional factors seem to exert a stronger effect on treatment patterns than hospital participation in external peer revie

What drives centralisation in cancer care?

Background: To improve quality of care, centralisation of cancer services in high-volume centres has been stimulated. Studies linking specialisation and high (surgical) volumes to better outcomes already appeared in the 1990’s. However, actual centralisation was a difficult process in many countries. In this study, factors influencing the centralisation of cancer services in the Netherlands were determined. Material and methods: Centralisation patterns were studied for three types of cancer that are known to benefit from high surgical caseloads: oesophagus-, pancreas- and bladder cancer. The Netherlands Cancer Registry provided data on tumour and treatment characteristics from 2000–2013 for respectively 8037, 4747 and 6362 patients receiving surgery. By plotting timelines of centralisation of cancer surgery, relations with the appearance of (inter)national scientific evidence, actions of medical specialist societies, specific regulation and other important factors on the degree of centralisation were ascertained. Results: For oesophagus and pancreas cancer, a gradual increase in centralisation of surgery is seen from 2005 and 2006 onwards following (inter)national scientific evidence. Centralisation steps for bladder cancer surgery can be seen in 2010 and 2013 anticipating on the publication of norms by the professional society. The most influential stimulus seems to have been regulations on minimum volumes. Conclusion: Scientific evidence on the relationship between volume and outcome lead to the start of centralisation of surgical cancer care in the Netherlands. Once a body of evidence has been established on organisational change that influences professional practice, in addition some form of regulation is needed to ensure widespread implementation

A piece of the human heart: variance of protein phosphorylation in left ventricular samples from end-stage primary cardiomyopathy patients

Cardiomyocyte contraction is regulated by phosphorylation of sarcomeric proteins. Throughout the heart regional and transmural differences may exist in protein phosphorylation. In addition, phosphorylation of sarcomeric proteins is altered in cardiac disease. Heterogeneity in protein phosphorylation may be larger in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) as it may be caused by multiple mutations in genes encoding different sarcomeric proteins. Moreover, HCM is characterized by asymmetric remodelling of the heart. In the present study we assessed if local differences in sarcomeric protein phosphorylation are more evident in primary HCM or DCM than in non-failing donors. Thereto, phosphorylation of the two main target proteins of the beta-adrenergic receptor pathway, troponin I (cTnI) and myosin binding protein C (cMyBP-C) was analysed in different parts in the free left ventricular wall of end–stage failing HCM and DCM patients and donors obtained during transplant surgery. Intra-patient variability in protein phosphorylation within tissue samples of approximately 2 g wet weight was comparable between donor, HCM and DCM samples and could partly be attributed to the precision of the technique. Thus, our data indicate that within the precision of the measurements small, biopsy-sized cardiac tissue samples are representative for the region of the free left ventricular wall from which they were obtained

Contractile Dysfunction Irrespective of the Mutant Protein in Human Hypertrophic Cardiomyopathy With Normal Systolic Function

Background-Hypertrophic cardiomyopathy (HCM), typically characterized by asymmetrical left ventricular hypertrophy, frequently is caused by mutations in sarcomeric proteins. We studied if changes in sarcomeric properties in HCM depend on the underlying protein mutation. Methods and Results-Comparisons were made between cardiac samples from patients carrying a MYBPC3 mutation (MYBPC3(mut); n = 17), mutation negative HCM patients without an identified sarcomere mutation (HCM(mn); n = 11), and nonfailing donors (n = 12). All patients had normal systolic function, but impaired diastolic function. Protein expression of myosin binding protein C (cMyBP-C) was significantly lower in MYBPC3(mut) by 33 +/- 5%, and similar in HCM(mn) compared with donor. cMyBP-C phosphory Conclusions-Changes in sarcomere function reflect the clinical HCM phenotype rather than the specific MYBPC3 mutation. Hypocontractile sarcomeres are a common deficit in human HCM with normal systolic left ventricular function and may contribute to HCM disease progression. (Circ Heart Fail. 2012; 5: 36-46.

Myofilament dysfunction in cardiac disease from mice to men

In healthy human myocardium a tight balance exists between receptor-mediated kinases and phosphatases coordinating phosphorylation of regulatory proteins involved in cardiomyocyte contractility. During heart failure, when neurohumoral stimulation increases to compensate for reduced cardiac pump function, this balance is perturbed. The imbalance between kinases and phosphatases upon chronic neurohumoral stimulation is detrimental and initiates cardiac remodelling, and phosphorylation changes of regulatory proteins, which impair cardiomyocyte function. The main signalling pathway involved in enhanced cardiomyocyte contractility during increased cardiac load is the β-adrenergic signalling route, which becomes desensitized upon chronic stimulation. At the myofilament level, activation of protein kinase A (PKA), the down-stream kinase of the β-adrenergic receptors (β-AR), phosphorylates troponin I, myosin binding protein C and titin, which all exert differential effects on myofilament function. As a consequence of β-AR down-regulation and desensitization, phosphorylation of the PKA-target proteins within the cardiomyocyte may be decreased and alter myofilament function. Here we discuss involvement of altered PKA-mediated myofilament protein phosphorylation in different animal and human studies, and discuss the roles of troponin I, myosin binding protein C and titin in regulating myofilament dysfunction in cardiac disease. Data from the different animal and human studies emphasize the importance of careful biopsy procurement, and the need to investigate localization of kinases and phosphatases within the cardiomyocyte, in particular their co-localization with cardiac myofilaments upon receptor stimulation.</p