Strategia vaccinale in un contesto incerto e in costante evoluzione.

Politics is facing the need to make important decisions about anti-COVID-19 vaccination campaign in uncertain and changing contexts. With reference to the time frame between the administration of the first and second dose, the scientific evidence is still weak and comes from different contexts. New ways to collect and synthesize expert knowledge and opinions are needed with the direct involvement of the citizens in order to explain the uncertainties and maintain trust in institutions and their decisions.

The risk of over-diagnosis in serological testing. Implications for communications strategies.

BACKGROUND: since the beginning of the COVID-19 pandemic, the importance of developing a serological test has emerged and a debate on test accuracy and reliability become an issue widely discussed in the media. The importance of communication during this pandemic has been strongly underlined by public health experts, epidemiologists, media expert, psychologists, sociologists. In the case of serological tests, there are several aspects that have to be considered: why we perform the test, what population is tested, which are the parameters conditioning the results and their interpretation. OBJECTIVES: to show how to quantify the uncertainty related to the validity of the serological test with respect to its predictive value and in particular the positive predictive value. METHODS: the evaluation of a qualitative diagnostic test includes four distinct assessments: accuracy, empirical evidence, practical importance, and prevalence of the pathology. Accuracy is measured by the sensitivity and specificity of the test; empirical evidence is quantified by the likelihood ratio, respectively for a positive and negative test result; the practical importance of the result of a diagnostic test is assessed by the positive or negative predictive value. Prevalence of COVID-19 is substantial uncertainty and it is possible to estimate the apparent prevalence starting from the results obtained with a diagnostic test. RESULTS: at the moment, the knowledge about the accuracy of serological tests is limited and little attention is paid to confidence interval on point estimates. In terms of practical importance of testing at individual level, while negative predictive values are high whatever the level of sensitivity of the test, the interpretation of a positive results is very cumbersome. Positive predictive values above 90% can be reached only by tests with specificity above 99% at the expected prevalence rate of 5%. There is a linear relationship between apparent - testing positive - prevalence and real prevalence. The apparent prevalence in the context of serological test for COVID-19 is always larger than real prevalence. The level of specificity is crucial. CONCLUSIONS: the main applications of the serological test in the epidemic contest are: to study the seroprevalence of the virus antibodies in the general population; to screen the healthcare workers for the early identification of contagious subjects' health care settings and to screen the general population in order to identify new incident cases. In the first two cases, seroprevalence study and screening of a high-risk population, the consequences of the uncertainty associated to the statistics are already accounted for in the first situation, or are overcome by repeating the screening on the healthcare workers, and using the molecular test to verify the presence of the virus in those tested positive. The case of screening of general population is more complex and of major interest for the implication it may have on individual behaviours and on the implementation of public health interventions by the political decision makers. A positive result has, per se, no practical value for individuals since the probability of being really infected by the virus is low. The uncertainty associated with the different estimates (sensitivity, specificity and disease prevalence) play a double role: it is a key factor in defining the informative content of the test result and it might guide the individual actions and the public policy decisions.

A municipality-level analysis of excess mortality in Italy in the period January-April 2020.

BACKGROUND: the first confirmed cases of COVID-19 in WHO European Region was reported at the end of January 2020 and, from that moment, the epidemic has been speeding up and rapidly spreading across Europe. The health, social, and economic consequences of the pandemic are difficult to evaluate, since there are many scientific uncertainties and unknowns. OBJECTIVES: the main focus of this paper is on statistical methods for profiling municipalities by excess mortality, directly or indirectly caused by COVID-19. METHODS: the use of excess mortality for all causes has been advocated as a measure of impact less vulnerable to biases. In this paper, observed mortality for all causes at municipality level in Italy in the period January-April 2020 was compared to the mortality observed in the corresponding period in the previous 5 years (2015-2019). Mortality data were made available by the Ministry of Internal Affairs Italian National Resident Population Demographic Archive and the Italian National Institute of Statistics (Istat). For each municipality, the posterior predictive distribution under a hierarchical null model was obtained. From the posterior predictive distribution, we obtained excess death counts, attributable community rates and q-values. Full Bayesian models implemented via MCMC simulations were used. RESULTS: absolute number of excess deaths highlights the burden paid by major cities to the pandemic. The Attributable Community Rate provides a detailed picture of the spread of the pandemic among the municipalities of Lombardy, Piedmont, and Emilia-Romagna Regions. Using Q-values, it is clearly recognizable evidence of an excess of mortality from late February to April 2020 in a very geographically scattered number of municipalities. A trade-off between false discoveries and false non-discoveries shows the different values of public health actions. CONCLUSIONS: despite the variety of approaches to calculate excess mortality, this study provides an original methodological approach to profile municipalities with excess deaths accounting for spatial and temporal uncertainty.

[Development of a conceptual model for interpretation of monitoring indicators of childhood obesity prevention from the Italian National Prevention Plan]. / Sviluppo di un modello concettuale di riferimento per l'interpretazione degli indicatori di prevenzione dell'obesità infantile e nell'adolescenza nel Piano nazionale della prevenzione.

BACKGROUND: the Italian National Prevention Plan (PNP) posed the standard to be achieved by Regions for the prevention of obesity in childhood and adolescence. The PNP also set up a monitoring system to assess the impact of implemented policies. OBJECTIVES: to develop a conceptual model to facilitate interpretation of variation in outcome indicators. METHODS: after a systematic review, the DPSEEA («Driving forces¼, «Pressures¼, «State¼, «Exposure¼, «Effect¼, «Actions¼) was identified as the more appropriate framework to assess the results of preventive policies. Factors for each component of the framework were identified and indicators that allow measuring the changing of each of these factors were defined. RESULTS: the included «driving forces¼ were related to the profit-led food industry, to the nutrition environment at school, and to household-level factors. Among the «pressures¼, parenting behaviours, food provided by school canteens, sociocultural factors, social context, physical activity (PA), opportunities at school or after-school were included. In the State, the high consumption of processed food, the large quantities of high-calorie food easy available, the consumption of carbonated and sugar-sweetened beverages, the reduced social function of mealtimes in families, the early cessation of breastfeeding, the reduction of outdoors activity, active transportation, and PA at school for children were identified. The «exposure¼ factors were the reduced opportunities of doing PA and the over-consumption of calories that influence the «effect¼, described as the prevalence of children and adolescents affected by obesity. CONCLUSIONS: through the DPSEEA, a conceptual model was set up; it allows to place in the causal chain the «actions¼ and the mechanisms through which these actions should impact on the «exposure¼ (PA and over-consumption of calories), making the rationale of process and impact indicators explicit.

[Development of a conceptual model for interpretation of monitoring indicators of cancer screenings from the Italian National Prevention Plan]. / Sviluppo di un modello concettuale di riferimento per l'interpretazione degli indicatori di monitoraggio degli screening oncologici nel Piano nazionale della prevenzione.

OBJECTIVES: the Italian National Prevention Plan (PNP) posed the standard to be achieved by Italian Regions for the implementation of cervical, breast, and colorectal cancer screening: to invite all of the target populations and to increase the screening uptake up to 50%, 60%, and 50%, respectively, the standard defined by the Essential Levels of Care (LEA). Moreover, for cervical cancer screening, it requires the implementation of HPV-DNA test and, for breast cancer screening, the PNP demands for the definition of diagnostic and follow up pathways for high familial risk women. The PNP also set up a monitoring system to assess the impact of implemented policies. A conceptual model has been defined to facilitate interpretation of variation in outcome indicators. DESIGN: after a systematic review, the DPSEEA (Driving forces, Pressure, State, Exposure, Effect, Actions) was identified as the more appropriate framework to assess the results of preventive policies. Factors for each component of the model were identified and indicators that allow measuring the changing of each of these factors were defined. RESULTS: among the "driving forces", the trust in the health care system and the social capital were included. The presence of opportunistic screening, the competing private clinical activity, the commitment of General Practitioners and "medical" leaders, the attitude to cooperation and to patients' involvement, and the level of agreement between the positions of scientific societies and the recommendations implemented in organized screening programmes were included in the "pressures". In "state", the availability of technological and human resources, the level of management skills and of accessibility were identified. The "exposure" was defined as the coverage of active invitation of the target population and the uptake of screening tests. The "exposure" factors influence the "effect", described as the impact on anticipation of cancer diagnosis, on disease incidence (for cervical and colorectal cancer) and prognosis. The changing in screening programs performance modifies the impact of invitation coverage and test uptake ("exposure"). CONCLUSIONS: through the DPSEEA framework, we set up a logical conceptual model, which includes implementable actions and the mechanisms through which these actions should impact on the "exposure" (invitation coverage and screening uptake) and on the screening performance (quality).

The impact of a pay-for-performance system on timing to hip fracture surgery: experience from the Lazio Region (Italy).

BACKGROUND: A tariff modulation mechanisms has been introduced in some Italian regions with the aim of reducing inappropriate admissions and improving quality of care. In response to a regional act, hospitals in Lazio adopted a clinical pathway for elderly patients with hip fracture and introduced a compensation system based on the quality of health care, as in a pay-for-performance model. The objective of the present study was to compare the proportion of surgery for hip fracture performed within 48 hours of admission among Lazio hospitals according to different payment systems, before and after the implementation of the regional act. METHODS: A retrospective cohort study of patients aged 65 years and over, residing in the Lazio region and admitted to an acute care hospital for hip fracture before (1 July 2008 - 30 June 2009) and after (1 July 2010 - 30 June 2011) the pay-for-performance act. The proportion of surgeries performed within 48 h of hospital arrival was calculated. An adjusted multivariate regression analysis was applied to assess the effect of hospital payment type on the likelihood of surgery within 48 h of hospital arrival. RESULTS: The share of patients with hip fracture that had surgery within 48 hours was 11.7% before the introduction of the pay-for-performance act and 22.2% after. The proportion of early hip fracture operations increased after the pay-for-performance act, regardless of hospital payment type. The largest increase of surgery within 48 h occurred in private hospitals (adjusted Relative Risk = 2.80, p < 0.001). CONCLUSIONS: The introduction of a compensation system based on health care quality is associated with improved quality of care for elderly patients with hip fracture, especially in hospitals that only use the Diagnosis Related Group system.

Health and health service usage outcomes of case management for patients with long-term conditions: a review of reviews.

OBJECTIVE: There have been plenty of articles published in recent decades on patient care in the form of case management (CM), but conclusions regarding health outcomes and costs have often been discordant. The objective of this study was to examine previous systematic reviews and meta-analyses with a view to assessing and pooling the overwhelming amount of data available on CM-based health outcomes and resource usage. METHODS: We conducted a review of reviews of secondary studies (meta-analyses and systematic reviews) addressing the effectiveness of CM compared with usual care (or other organizational models) in adult (18+) with long-term conditions. PubMed, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects (DARE) were searched from 2000 to the end of December 2017. The outcomes of interest are related to process of care, health measures, and resource usage. RESULTS: Twenty-two articles were ultimately considered: 4 meta-analyses and 18 systematic reviews. There is strong evidence of CM increasing adherence to treatment guidelines and improving patient satisfaction, but none of the secondary studies considered demonstrated any effect on patient survival. Based on the available literature, there is contrasting evidence regarding all the other health outcomes, such as quality of life (QOL), clinical outcomes, and functional status. Good-quality secondary studies consistently found nothing to indicate that CM prompts any reduction in the use of hospital resources. CONCLUSION: The source of variability in the literature on the consistency of the evidence for most outcomes is unclear. It may stem from the heterogeneity of CM programs in terms of what their intervention entails, the populations targeted, and the tools used to measure the results. That said, there was consistently strong evidence of CM being associated with a greater adherence to treatment guidelines and higher patient satisfaction, but not with a longer survival or better use of hospital resources.

Physicochemical characterization and cytotoxicity of articaine-2-hydroxypropyl-ß-cyclodextrin inclusion complex.

Articaine (ATC) is one of the most widely used local anesthetics in dentistry. Despite its safety, local toxicity has been reported. This study aimed to develop an ATC-2- hydroxypropyl-ß-cyclodextrin inclusion complex (ATC HPßCD) and to assess its toxicity in vitro. The inclusion complex was performed by solubilization, followed by a fluorimetric and job plot assay to determine the complex stoichiometry. Scanning electron microscopy, DOSY- 1 H-NMR, differential scanning calorimetry (DSC), and sustained release kinetics were used to confirm the inclusion complex formation. In vitro cytotoxicity was analyzed by MTT assay and immunofluorescence in HGF cells. Fluorimetric and job plot assay determined the inclusion complex stoichiometry (ATC:HPßCD = 1:1) and complex formation time (400 min), as indicated by a strong host/guest interaction (Ka = 117.8 M - 1), complexed fraction (f = 41.4%), and different ATC and ATC HPßCD melting points (172 °C e 235 °C, respectively). The mean of cell viability was 31.87% and 63.17% for 20-mM ATC and 20-mM ATC HPßCD, respectively. Moreover, remarkable cell toxicity was observed with free ATC by immunofluorescence. These results indicate the ATC HPßCD complex could be used to improve the safety of ATC. Further research are needed to establish the anesthetic safety and effectiveness in vivo .

Effectiveness of pro-active organizational models in primary care for diabetes patients.

BACKGROUND: Demographic changes and chronicity are posing new challenges to health care systems. Our study aimed to examine how effectively the three different types of proactive primary care models adopted by three different regional health care systems in Italy were improving the quality of diabetes management by general practitioners. METHODS: A coordinated Italian nationwide project to compare systematically the new proactive organizational models implemented at regional and local level (the MEDINA Project) involved several regions and their local health units (LHUs). A quasi-experimental study was conducted on a large dataset obtained by processing administrative databases. A combined indicator was developed to assess the quality of care delivered by primary care physicians, based on adherence to recommendations concerning patient monitoring and treatment. RESULT: The study concerned 602 Italian general practitioners (GPs), 174 of them female, who were caring for a total of 753,366 patients (47,575 of them diabetic). Analyzing a total score, representing global adherence to a quality management of patients with diabetes, confirmed that GPs who had adopted the new model of care for their diabetic patients obtained better results than those who had not, so the new policy was generally effective. CONCLUSION: Our study showed that introducing new, proactive primary care models could sustain efforts made around the world to guarantee good-quality chronic disease management in the primary care setting.

Diabetes management in the primary care setting: a comparison of physicians' performance by gender.

BACKGROUND: A major shift in the gender of the medical-doctor workforce is now underway, and all over the world it is expected that an average 65% of the medical workforce will be women by 2030. In addition, an aging population means that chronic diseases, such as diabetes, are becoming more prevalent and the demand for care is rising. There is growing evidence of female physicians performing better than male physicians.AimOur study aimed to investigate whether any differences in diabetes process indicators are associated with gender, and/or the interaction between gender and different organizational models.Design and settingA population-based cross-sectional analysis was conducted on a large data set obtained by processing the public health administration databases of seven Italian local health units (LHUs). The seven LHUs, distributed all over the Italian peninsula in seven different regions, took part in a national project called MEDINA, with the focus on chronic disease management in primary care (PC). METHODS: A total score was calculated for the average performance in the previously listed five indicators, representing global adherence to a quality management of patients with diabetes. A multilevel analysis was applied to see how LHUs affected the outcome. A quantile regression model was also fitted. RESULTS: Our study included 2287 Italian general practitioners (586 of them female) caring for a total of 2 646 059 patients. Analyzing the performance scores confirmed that female general practitioners obtained better results than males. The differences between males and females were stronger on the 25th and 75th percentiles of the score than on the median values. The interaction between gender and LHU was not significant. CONCLUSION: Our study evidenced that female physicians perform better than males in providing PC for diabetes independently by the different organizational models. Further research to understand the reasons for these gender differences is needed.

Encapsulation of ropivacaine in a combined (donor-acceptor, ionic-gradient) liposomal system promotes extended anesthesia time.

Ropivacaine is a local anesthetic with similar potency but lower systemic toxicity than bupivacaine, the most commonly used spinal anesthetic. The present study concerns the development of a combined drug delivery system for ropivacaine, comprised of two types of liposomes: donor multivesicular vesicles containing 250 mM (NH4)2SO4 plus the anesthetic, and acceptor large unilamellar vesicles with internal pH of 5.5. Both kinds of liposomes were composed of hydrogenated soy-phosphatidylcholine:cholesterol (2:1 mol%) and were prepared at pH 7.4. Dynamic light scattering, transmission electron microscopy and electron paramagnetic resonance techniques were used to characterize the average particle size, polydispersity, zeta potential, morphology and fluidity of the liposomes. In vitro dialysis experiments showed that the combined liposomal system provided significantly longer (72 h) release of ropivacaine, compared to conventional liposomes (~45 h), or plain ropivacaine (~4 h) (p <0.05). The pre-formulations tested were significantly less toxic to 3T3 cells, with toxicity increasing in the order: combined system < ropivacaine in donor or acceptor liposomes < ropivacaine in conventional liposomes < plain ropivacaine. The combined formulation, containing 2% ropivacaine, increased the anesthesia duration up to 9 h after subcutaneous infiltration in mice. In conclusion, a promising drug delivery system for ropivacaine was described, which can be loaded with large amounts of the anesthetic (2%), with reduced in vitro cytotoxicity and extended anesthesia time.

Association of dissatisfaction with care and psychiatric morbidity with poor treatment compliance.

OBJECTIVES: To examine factors associated with compliance with dermatologic treatment. DESIGN: Longitudinal study. Quality of life and psychological well-being were measured before the dermatologic visit with a self-completed questionnaire. Telephone interviews were performed 3 days and 4 weeks after the visit to evaluate patient satisfaction and medication adherence, respectively. SETTING: Outpatient clinics of a large dermatologic hospital in Rome, Italy. PATIENTS: A total of 1389 outpatients were contacted and 722 (52%) agreed to participate. Among them, 424 responded to the inclusion criteria and were enrolled in the study. Of these, 396 (93%) completed the telephone interviews. MAIN OUTCOME MEASURE: Self-reported compliance with dermatologic treatment. RESULTS: The dermatologists' prescriptions were not exactly followed by 44% of patients. In multiple logistic regression analysis, treatment adherence was strongly associated with complete satisfaction. Poor quality of life on the emotions scale (indicating mainly high levels of shame and embarrassment) was also associated with medication adherence. On the contrary, a strong negative association was observed between psychiatric morbidity and compliance. CONCLUSIONS: This is the first longitudinal study on dermatologic patients showing that dissatisfaction with care and psychiatric morbidity are significantly and independently associated with poor medication adherence. To improve medication adherence, particular attention should be dedicated to the physician's interpersonal skills, which emerged as a major component of patient satisfaction. Moreover, our results highlight the need for a timely identification and appropriate management of psychiatric disorders in everyday dermatologic practice.

Postoperative complications in gastrointestinal cancer patients: the joint role of the nutritional status and the nutritional support.

BACKGROUND & AIMS: This study investigated the effects of nutritional support on postoperative complications, in relation with demographic and nutritional factors, intraoperative factors, type and routes of nutritional regimens. METHODS: A series of 1410 subjects underwent major abdominal surgery for gastrointestinal cancer and received various types of nutritional support: standard intravenous fluids (SIF; n=149), total parenteral nutrition (TPN; n=368), enteral nutrition (EN; n=393), and immune-enhancing enteral nutrition (IEEN; n=500). Postoperative complications, considered as major (if lethal or requiring re-operation, or transfer to intensive care unit), or otherwise minor, were recorded. RESULTS: Major and minor complications occurred in 101 (7.2%) and 446 (31.6%) patients, respectively. Factors correlated with postoperative complications at multivariate analysis were pancreatic surgery, (p<0.001), advanced age (p=0.002), weight loss (p=0.019), low serum albumin (p=0.019) and nutritional support (p=0.001). Nutritional support reduced morbidity versus SIF with an increasing protective effect of TPN, EN, and IEEN. This effect remained valid regardless the severity of risk factors identified at the multivariate analysis and it was more evident by considering infectious complications only. CONCLUSIONS: Pancreatic surgery, advanced age, weight loss and low serum albumin are independent risk factors for the onset of postoperative complications. Nutritional support, particularly IEEN, significantly reduced postoperative morbidity.

Correlação entre o desempenho de jogadores de futebol no teste de sprint de 30m e no teste de salto vertical / Correlation between performance of soccer players in the 30-meter sprint test and in the vertical jump test

O objetivo do estudo foi determinar o nível de correlação entre o desempenho nos 10m iniciais, dos 20m finais e no tempo total do teste de sprint de 30m, com o do salto vertical com contra-movimento (CMJ) entre jogadores de futebol. Participaram do estudo 167 jogadores das categorias profissional (N. 94) e júnior (N. 73). Foram determinadas as velocidades dos jogadores em 10m (V10), 20m (V20) e no total de 30m (V30). A habilidade de salto foi avaliada através do CMJ. Para correlacionar os dados, foi utilizado o coeficiente de correlação de Pearson com nível de significância de p<0,05. A categoria júnior apresentou maiores valores de V10 e menores valores de V20 em comparação com a categoria profissional (p<0,05). Os valores de correlação entre o CMJ e os parâmetros de velocidade para a categoria júnior foram; r= 0,239, 0,370, 0,408 para V10, V20 e V30 respectivamente e para a categoria profissional foram; r= 0,381, 0,381 e 0,470 para V10, V20 e V30 respectivamente. Quando as duas categorias foram avaliadas em conjunto os valores de correlação foram; r= 0,293, 0,386 e 0,441 para V10, V20 e V30 respectivamente. Foi encontrada uma fraca correlação entre o CMJ e o V10 da categoria júnior sendo a mesma moderada para os demais parâmetros. A categoria profissional apresentou valores de correlação moderada entre o CMJ e todos os outros parâmetros. Maiores valores de correlação do V10 para a categoria profissional pode ser devido a efeitos específicos do treinamento.

The aim of the present study was to determine the association between the results in the counter movement jump (CMJ) and the results in the first 10 meters, in the final 20 meters and the in the total 30 meters of a 30-meter sprint. One-hundred and sixty seven Soccer players from the professional (N. 93) and under twenty (N. 74) categories, from a Brazilian first division Soccer club participated in the study. The sprint test consisted of a 30-meter run timed at the 10-meter and at the 30-meter marks. The jump capacity was assessed through the CMJ. Pearson’s correlation (r) was used to determine the association between these variables. The significance level adopted was p<.05. The U-20 players presented faster V10 and slower V20 than the professionals (p<.05). The correlation (r) between CMJ and V10, V20 and V30 were .239, .370 and .408, respectively, for the U20 group and .381, .381 and .470, respectively, for the professional group. Evaluating the two categories together the correlation were; r= 0,293, 0,386 and 0,441 to V10, V20 and V30 respectively. The correlation between CMJ and V10 was weak and moderate for V20 and V30. In the professional category the correlation between CMJ and all the other parameters was moderate. It is probable that higher correlation values for CMJ and V10 for the professionals could be attributed to specific training effects.