Excess of health care use in general practice and of comorbid chronic conditions in cancer patients compared to controls

<p>Abstract</p> <p>Background</p> <p>The number of cancer patients and the number of patients surviving initial treatments is expected to rise. Traditionally, follow-up monitoring takes place in secondary care. The contribution of general practice is less visible and not clearly defined.</p> <p>This study aimed to compare healthcare use in general practice of patients with cancer during the follow-up phase compared with patients without cancer. We also examined the influence of comorbid conditions on healthcare utilisation by these patients in general practice.</p> <p>Methods</p> <p>We compared health care use of N=8,703 cancer patients with an age and gender-matched control group of patients without cancer from the same practice. Data originate from the Netherlands Information Network of General Practice (LINH), a representative network consisting of 92 general practices with 350,000 enlisted patients. Health care utilisation was assessed using data on contacts with general practice, prescription and referral rates recorded between 1/1/2001 and 31/12/2007. The existence of additional comorbid chronic conditions (ICPC coded) was taken into account.</p> <p>Results</p> <p>Compared to matched controls, cancer patients had more contacts with their GP-practice (19.5 vs. 11.9, p<.01), more consultations with the GP (3.5 vs. 2.7, p<.01), more home visits (1.6 vs. 0.4, p<.01) and they got more medicines prescribed (18.7 vs. 11.6, p<.01) during the follow-up phase. Cancer patients more often had a chronic condition than their matched controls (52% vs. 44%, p<.01). Having a chronic condition increased health care use for both patients with and without cancer. Cancer patients with a comorbid condition had the highest health care use.</p> <p>Conclusion</p> <p>We found that cancer patients in the follow-up phase consulted general practice more often and suffered more often from comorbid chronic conditions, compared to patients without cancer. It is expected that the number of cancer patients will rise in the years to come and that primary health care professionals will be more involved in follow-up care. Care for comorbid chronic conditions, communication between specialists and GPs, and coordination of tasks then need special attention.</p

Family physicians' perspectives on practice guidelines related to cancer control

BACKGROUND: Family physicians (FPs) play an important role in cancer control. While FPs' attitudes towards, and use of guidelines in general have been explored, no study has looked at the needs of FPs with respect to guidelines for the continuum of cancer control. The objective of this study was to understand which guideline topics FPs consider important. METHODS: Five group interviews were conducted by telephone with FPs from across Ontario, Canada. Transcripts were analyzed inductively. Content analysis identified emergent themes. Themes are illustrated by representative quotes taken from the transcripts. RESULTS: The main areas where FPs felt guidelines were needed most included screening – a traditional area of responsibility for FPs – and treatment and follow-up – areas where they felt they lacked the knowledge to best support patients. Confusion over best practice when faced with conflicting guidelines varied according to disease site. FPs defined good guideline formats; the most often cited forms of presentation were tear-off sheets to use interactively with patients, or a binder. Computer-based dissemination was acknowledged as the best way of widely distributing material that needs frequent updates. However, until computer use is a common aspect of practice, mail was considered the most viable method of dissemination. Guidelines designed for use by patients were supported by FPs. CONCLUSIONS: Preferred guideline topics, format, dissemination methods and role of patient guidelines identified by FPs in this study reflect the nature of their practice situations. Guideline developers and those supporting use of evidence-based guidelines (e.g., Canadian Strategy for Cancer Control) have a responsibility to ensure that FPs are provided with the resources they identify as important, and to provide them in a format that will best support their use

Association of rare variants in<i>ARSA</i>with Parkinson’s disease

AbstractBackgroundSeveral lysosomal genes are associated with Parkinson’s disease (PD), yet the association between PD andARSA, which encodes for the enzyme arylsulfatase A, remains controversial.ObjectivesTo evaluate the association between rareARSAvariants and PD.MethodsTo study possible association of rare variants (minor allele frequency&lt;0.01) inARSAwith PD, we performed burden analyses in six independent cohorts with a total of 5,801 PD patients and 20,475 controls, using optimized sequence Kernel association test (SKAT-O), followed by a meta-analysis.ResultsWe found evidence for an association between functionalARSAvariants and PD in four independent cohorts (P≤0.05 in each) and in the meta-analysis (P=0.042). We also found an association between loss-of-function variants and PD in the UKBB cohort (P=0.005) and in the meta-analysis (P=0.049). However, despite replicating in four independent cohorts, these results should be interpreted with caution as no association survived correction for multiple comparisons. Additionally, we describe two families with potential co-segregation of theARSAvariant p.E384K and PD.ConclusionsRare functional and loss-of-functionARSAvariants may be associated with PD. Further replication in large case-control cohorts and in familial studies is required to confirm these associations.</jats:sec

<i>GALC</i>variants affect galactosylceramidase enzymatic activity and risk of Parkinson’s disease

AbstractThe association between glucocerebrosidase (GCase), encoded byGBA, and Parkinson’s disease highlights the role of the lysosome in Parkinson’s disease pathogenesis. Genome-wide association studies (GWAS) in Parkinson’s disease have revealed multiple associated loci, including theGALClocus on chromosome 14.GALCencodes the lysosomal enzyme galactosylceramidase (GalCase), which plays a pivotal role in the glycosphingolipid metabolism pathway. It is still unclear whetherGALCis the gene driving the association in the chromosome 14 locus, and if so, by which mechanism.We first aimed to examine whether variants in theGALClocus and across the genome are associated with GalCase activity. We performed a GWAS in two independent cohorts from a)Columbia University and b)the Parkinson’s Progression Markers Initiative study, followed by a meta-analysis with a total of 976 Parkinson’s disease patients and 478 controls with available data on GalCase activity. We further analyzed the effects of commonGALCvariants on expression and GalCase activity using genomic colocalization methods. Mendelian randomization was used to study whether GalCase activity may be causal in Parkinson’s disease. To study the role of rareGALCvariants we analyzed sequencing data from 5,028 Parkinson’s disease patients and 5,422 controls. Additionally, we studied the functional impact ofGALCknock-out on alpha-synuclein accumulation and on GCase activity in neuronal cell models and performedin silicostructural analysis of commonGALCvariants associated with altered GalCase activity.The top hit in Parkinson’s disease GWAS in theGALClocus, rs979812, is associated with increased GalCase activity (b=1.2; se=0.06; p=5.10E-95). No other variants outside theGALClocus were associated with GalCase activity. Colocalization analysis demonstrated that rs979812 was also associated with increased GalCase expression. Mendelian randomization suggested that increased GalCase activity may be causally associated with Parkinson’s disease (b=0.025, se=0.007, p=0.0008). We did not find an association between rareGALCvariants and Parkinson’s disease.GALCknockout using CRISPR-Cas9 did not lead to alpha-synuclein accumulation, further supporting that increased rather than reduced GalCase levels may be associated with Parkinson’s disease. The structural analysis demonstrated that the common variant p.I562T may lead to improper maturation of GalCase affecting its activity.Our results nominateGALCas the gene associated with Parkinson’s disease in this locus and suggest that the association of variants in theGALClocus may be driven by their effect of increasing GalCase expression and activity. Whether altering GalCase activity could be considered as a therapeutic target should be further studied.</jats:p