Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

Lung dismissal of HIPDM: a new index of lung disfunction for clinical experimental studies.

It has been shown that the lung, in addition to its function in the exchange of gases, can play an important non-respiratory role in the uptake and metabolism of many circulating substances such as amines, peptides and pro- staglandins. The uptake and dismissal of cir- culating vasoactive amines, such as noradre- naline and serotonin have been found to be im- paired in the course of several conditions of lung injury 1"3. Moreover, a reduced pul- monary removal of vasoactive amines, as studied in man by indicator dilution methods, was observed after cardiopulmonary bypass and in patients with pulmonary hypertension 4'6. We studied in rabbit and man the pulmonary kinetics of N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-l,3-propanediamine (HIPDM), a tracer currently evaluated for brain perfusion studies7. After intravenous injection, radioiodinated HIPDM is rapidly cleared from the blood and most of the activi- ty is found in the lungs where a fairly homo- geneous distribution, resembling that of lung perfusion is observed8'9. In rabbit, 95% of in- jected HIPDM is kept whithin the lungs and is then released with a mean time (t) of several hours as assessed both in vivo, by gamma camera external counting (n=5; t=7.0 hours), and in vitro, by measuring activity in lung homogenates at various times after injection (n=56; t=7.6 hours). In 10 healthy non smok- ing subjects, t was 6.4 ±1 hours, whereas it was 12.1 ±2 hours in 10 asymptomatic smok- ers of 20 cigarettes/day with normal pulmo- nary function tests. Preliminary clinical studies showed that HIPDM lung dismissal is delayed in non smoking patients with primary pulmonary hypertension (n=4; t=11.5±2 hours), and to a greater extent in patients with adult respiratory dystress syndrome (n=4; t=25.8±5 hours), whereas it was not signi- ficantly affected in patients with cardiogenic pulmonary edema (n=4; 1=8.8 ±2 hours). Results of our study show that both smoke exposure and injury to the lung microcircula- tion may impair HIPDM lung kinetics. HIPDM external counting may therefore provide a new index of lung dysfunction in man. In rabbit, lung kinetics of HIPDM, as assessed by exter- nal counting, is almost identical to that obtain- ed by counting of lung homogenates. Further- more, the mean time of dismissal of HIPDM in rabbit is very similar to that of normal non smoking man. Hence, rabbit can be used as a model to evaluate HIPDM lung kinetics in ex- perimentally induced lung injury

Predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis: a multicentre validation study

Introduction The early detection of systemic sclerosis (SSc) patients at high risk of developing digital ulcers could allow preventive treatment, with a reduction of morbidity and social costs. In 2009, a quantitative score, the capillaroscopic skin ulcer risk index (CSURI), calculated according to the formula 'D×M/N(2'), was proposed, which was highly predictive of the appearance of scleroderma digital ulcers within 3 months of capillaroscopic evaluation.OBJECTIVES: This multicentre study aims to validate the predictive value and reproducibility of CSURI in a large population of SSc patients. METHODS: CSURI was analysed in 229 unselected SSc patients by nailfold videocapillaroscopy (NVC). All patients were re-evaluated 3 months later with regard to the persistence and/or appearance of new digital ulcers. RESULTS: 57 of 229 patients presented with digital ulcers after 3 months. The receiver operating characteristic curve analysis showed an area under the curve of 0.884 (95% CI 0.835 to 0.922), with specificity and sensitivity of 81.4% (95% CI 74.8 to 86.89) and 92.98% (95% CI 83.0 to 98.0), respectively, at the cut-off value of 2.96. The reproducibility of CSURI was validated on a random sample of 81 patients, with a κ-statistic measure of interrater agreement of 0.8514. CONCLUSIONS: The role of CSURI was confirmed in detecting scleroderma patients with a significantly high risk of developing digital ulcers within the first 3 months from NVC evaluation. CSURI is the only method validated to predict the appearance of digital ulcers and its introduction into routine clinical practice might help optimise the therapeutic strategy of these harmful SSc complications

The relationship between cerebral vascular disease and parkinsonism: the VADO study

Background: The observation of gait abnormalities, parkinsonism and vascular lesions in elderly patients is often reported as vascular parkinsonism (VP). However the status of striatal dopamine transporter (DAT) and the effects of brain vascular lesions on motor features and levodopa responsiveness are poorly defined. Methods: We recorded clinical features, chronic response to levodopa and vascular risk factors in a crosssectional cohort of consecutive elderly patients with possible Parkinson’s disease (PD) or VP recruited in 20 centers in Italy. Results: We included a total of 158 patients. Onset of motor symptoms was asymmetric in 93 (59%) and symmetric in 65 patients (41%). Symmetric motor onset was associated with greater disease severity. Chronic levodopa response was positive in 75 (47.8%) and negative in 82 patients (52.2%). A negative response to levodopa was associated with greater frequency of symmetric onset of motor symptoms, worst disease severity, absence of dyskinesia and greater number of vascular risk factors. Frontal lobe showed largest vascular load. Striatal DAT was normal in 48 (30.4%) and abnormal in 110 (69.6%) patients. Patients with normal DAT binding showed higher vascular load at MRI. Significant predictive factors of worst disease severity and negative response to levodopa were hypertension, vascular lesions in basal ganglia/periventricular regions, and normal DAT uptake. Conclusions: Multiple cerebral vascular lesions modify clinical presentation and severity in patients with parkinsonism and this is underlined by specific risk factors primarily hypertension. Striatal DAT assessment is helpful in identifying patients where therapy benefit is less likel

High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7).

OBJECTIVE: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. METHODS: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. RESULTS: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P<0.0001 for both). A BMI of ≤25 kg/m2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P<0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P<0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P<0.0001, OR=6.95). CONCLUSIONS: High GADA titer, BMI ≤ 25, ZnT8 and IA-2IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients