Implementation of guidelines in primary health care. A challenge for the municipal health centres in Finland

Objective - To assess the implementation of guidelines in Finnish primary health care units. Design - A semi-quantitative analysis of a cross-sectional interview survey. Setting - All municipal health centres in a selected region in Finland. Subjects - Head physicians and head nurses of the 31 participating units. Main outcome measures - Number of guidelines adopted; methods used in the implementation; and the unit's estimated purposefulness in the implementation of guidelines. Results - All health centres had adopted at least one guideline in the defined task areas, but only one-third of the units had implemented several guidelines. The implementation methods utilised were usually directive and passive rather than co-operative and problem-solving. Half of the units used training and methods involving active partici pation of the personnel, and in one-third a multiprofessional approach was applied. Clients' representatives were hardly ever involved in the adaptation of guidelines. A quarter of the health centres were assessed as purposeful in their policy to implement guidelines, the large units being more goal-oriented than the smaller ones. Conclusions - A minority of health centres are goal-oriented in the adoption of guidelines and use versatile methods to support the implementation; this presents an important managerial challenge for national health care development in Finland

Novel APC mutations in Czech and Slovak FAP families: clinical and genetic aspects

BACKGROUND: Germline mutations in the adenomatous polyposis gene (APC) result in familial adenomatous polyposis (FAP). FAP is an autosomal dominantly inherited disorder predisposing to colorectal cancer. Typical FAP is characterized by hundreds to thousands of colorectal adenomatous polyps and by several extracolonic manifestations. An attenuated form of polyposis (AFAP) is characterized by less than 100 adenomas and later onset of the disease. METHODS: Here, we analyzed the APC gene for germline mutations in 59 Czech and 15 Slovak FAP patients. In addition, 50 apparently APC mutation negative Czech probands and 3 probands of Slovak origin were screened for large deletions encompassing the APC gene. Mutation screening was performed using denaturing gradient gel electrophoresis and/or protein truncation test. DNA fragments showing an aberrant electrophoretic banding pattern were sequenced. Screening for large deletions was performed by multiplex ligation dependent probe amplification. The extent of deletions was analyzed using following microsatellite markers: D5S299, D5S82, D5S134 and D5S346. RESULTS: In the set of Czech and Slovak patients, we identified 46 germline mutations among 74 unrelated probands. Total mutation capture is 62,2% including large deletions. Thirty seven mutations were detected in 49 patients presenting a classical FAP phenotype (75,5%) and 9 mutations in 25 patients with attenuated FAP (36%). We report 20 novel germline APC mutations and 3 large deletions (6%) encompassing the whole-gene deletions and/or exon 14 deletion. In the patients with novel mutations, correlations of the mutation localization are discussed in context of the classical and/or attenuated phenotype of the disease. CONCLUSION: The results of the molecular genetic testing are used both in the establishment of the predictive diagnosis and in the clinical management of patients. In some cases this study has also shown the difficulty to classify clinically between the classical and the attenuated form of FAP according to the established criteria. Interfamilial and/or intrafamilial phenotype variability was also confirmed in some cases which did not fit well with predicted genotype-phenotype correlation. All these findings have to be taken into consideration both in the genetic counselling and in the patient care

Consultocracy and its discontents : A critical typology and a call for a research agenda

Peer reviewe

Inactivation of promoter 1B of APC causes partial gene silencing: evidence for a significant role of the promoter in regulation and causative of familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is caused by germline mutations in the adenomatous polyposis coli (APC) gene. Two promoters, 1A and 1B, have been recognized in APC, and 1B is thought to have a minor role in the regulation of the gene. We have identified a novel deletion encompassing half of this promoter in the largest family (Family 1) of the Swedish Polyposis Registry. The mutation leads to an imbalance in allele-specific expression of APC, and transcription from promoter 1B was highly impaired in both normal colorectal mucosa and blood from mutation carriers. To establish the significance of promoter 1B in normal colorectal mucosa (from controls), expression levels of specific transcripts from each of the promoters, 1A and 1B, were examined, and the expression from 1B was significantly higher compared with 1A. Significant amounts of transcripts generated from promoter 1B were also determined in a panel of 20 various normal tissues examined. In FAP-related tumors, the APC germline mutation is proposed to dictate the second hit. Mutations leaving two or three out of seven 20-amino-acid repeats in the central domain of APC intact seem to be required for tumorigenesis. We examined adenomas from mutation carriers in Family 1 for second hits in the entire gene without any findings, however, loss of the residual expression of the deleterious allele was observed. Three major conclusions of significant importance in relation to the function of APC can be drawn from this study; (i) germline inactivation of promoter 1B is disease causing in FAP; (ii) expression of transcripts from promoter 1B is generated at considerable higher levels compared with 1A, demonstrating a hitherto unknown importance of 1B; (iii) adenoma formation in FAP, caused by impaired function of promoter 1B, does not require homozygous inactivation of APC allowing for alternative genetic models as basis for adenoma formation

Greenhouse gas mitigation scenarios for major emitting countries – Analysis of current climate policies and mitigation commitments: 2021 Update

This report by NewClimate Institute, PBL Netherlands Environmental Assessment Agency and the International Institute for Applied Systems Analysis (IIASA) provides an overview of projected greenhouse gas (GHG) emissions in 26 major emitting countries and regions up to 2030 under currently implemented policies. The report shows that emissions are projected to remain above 2005 levels in most countries but concludes that 16 out of the 26 countries and regions analysed are on track or close to achieve the NDC targets they have previously set for themselves. Eight are on track to also meet their updated NDC targets (with another two countries being close). 11 countries are not on track to meet their updated targets, and five of the 26 countries have not submitted an NDC update