Study rationale and design of the PEOPLHE trial.

PURPOSE: Lung cancer screening (LCS) by low-dose computed tomography (LDCT) demonstrated a 20-40% reduction in lung cancer mortality. National stakeholders and international scientific societies are increasingly endorsing LCS programs, but translating their benefits into practice is rather challenging. The "Model for Optimized Implementation of Early Lung Cancer Detection: Prospective Evaluation Of Preventive Lung HEalth" (PEOPLHE) is an Italian multicentric LCS program aiming at testing LCS feasibility and implementation within the national healthcare system. PEOPLHE is intended to assess (i) strategies to optimize LCS workflow, (ii) radiological quality assurance, and (iii) the need for dedicated resources, including smoking cessation facilities. METHODS: PEOPLHE aims to recruit 1.500 high-risk individuals across three tertiary general hospitals in three different Italian regions that provide comprehensive services to large populations to explore geographic, demographic, and socioeconomic diversities. Screening by LDCT will target current or former (quitting < 10 years) smokers (> 15 cigarettes/day for > 25 years, or > 10 cigarettes/day for > 30 years) aged 50-75 years. Lung nodules will be volumetric measured and classified by a modified PEOPLHE Lung-RADS 1.1 system. Current smokers will be offered smoking cessation support. CONCLUSION: The PEOPLHE program will provide information on strategies for screening enrollment and smoking cessation interventions; administrative, organizational, and radiological needs for performing a state-of-the-art LCS; collateral and incidental findings (both pulmonary and extrapulmonary), contributing to the LCS implementation within national healthcare systems.

Impact on Prehospital Delay of a Stroke Preparedness Campaign: A SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial).

BACKGROUND AND PURPOSE: Public campaigns to increase stroke preparedness have been tested in different contexts, showing contradictory results. We evaluated the effectiveness of a stroke campaign, designed specifically for the Italian population in reducing prehospital delay. METHODS: According to an SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial) design, the campaign was launched in 4 provinces in the northern part of the region Emilia Romagna at 3-month intervals in randomized sequence. The units of analysis were the patients admitted to hospital, with stroke and transient ischemic attack, over a time period of 15 months, beginning 3 months before the intervention was launched in the first province to allow for baseline data collection. The proportion of early arrivals (within 2 hours of symptom onset) was the primary outcome. Thrombolysis rate and some behavioral end points were the secondary outcomes. Data were analyzed using a fixed-effect model, adjusting for cluster and time trends. RESULTS: We enrolled 1622 patients, 912 exposed and 710 nonexposed to the campaign. The proportion of early access was nonsignificantly lower in exposed patients (354 [38.8%] versus 315 [44.4%]; adjusted odds ratio, 0.81; 95% confidence interval, 0.60-1.08; P=0.15). As for secondary end points, an increase was found for stroke recognition, which approximated but did not reach statistical significance (P=0.07). CONCLUSIONS: Our campaign was not effective in reducing prehospital delay. Even if some limitations of the intervention, mainly in terms of duration, are taken into account, our study demonstrates that new communication strategies should be tested before large-scale implementation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01881152.

Real-life clinical practice results with vinflunine in patients with relapsed platinum-treated metastatic urothelial carcinoma: an Italian multicenter study (MOVIE-GOIRC 01-2014).

BACKGROUND: Vinflunine is the only chemotherapeutic agent shown to improve survival in platinum-refractory patients with metastatic transitional cell carcinoma of the urothelium (TCCU) in a phase III clinical trial, which led to product registration for this indication in Europe. The aim of this study was to assess the efficacy of vinflunine and to evaluate the prognostic significance of risk factors in a large, unselected cohort of patients with metastatic TCCU treated according to routine clinical practice. METHODS: This was a retrospective multicenter study. Italian cancer centers were selected if, according to the Registry of the Italian Medicines Agency (AIFA), at least four patients had been treated with vinflunine between February 2011 and June 2014, after first- or second-line platinum-based chemotherapy. The primary objective was to test whether the efficacy measured by overall survival (OS) in the registration study could be confirmed in routine clinical practice. Multivariate analysis was carried out using Cox proportional hazard model. RESULTS: A total of 217 patients were treated in 28 Italian centers. Median age was 69 years (IQR 62-76) and 84% were male; Eastern Cooperative Oncology Group performance status (ECOG PS) was ≥ 1 in 53% of patients. The median number of cycles was 4 (IQR 2-6); 29%, 35%, and 36% received an initial dose of 320 mg/m2, 280 mg/m2 or a lower dose, respectively. Median progression-free survival (PFS) and OS for the entire population was 3.2 months (2.6-3.7) and 8.1 months (6.3-8.9). A complete response was observed in six patients, partial response in 21, stable disease in 60, progressive disease in 108, with a disease control rate of 40%. Multivariate analysis showed that ECOG PS, number of metastatic sites and liver involvement were unfavorable prognostic factors for OS. Toxicity was mild, and grade 3-4 adverse effects were mainly: neutropenia (9%), anemia (6%), asthenia/fatigue (7%) and constipation (5%). CONCLUSIONS: In routine clinical practice the results obtained with VFL seem to be better than the results of the registration trial and reinforce evidence supporting its use after failure of a platinum-based chemotherapy.

Development of an education campaign to reduce delays in pre-hospital response to stroke.

BACKGROUND: Systematic reviews call for well-designed trials with clearly described intervention components to support the effectiveness of educational campaigns to reduce patient delay in stroke presentation. We herein describe the systematic development process of a campaign aimed to increase stroke awareness and preparedness. METHODS: Campaign development followed Intervention Mapping (IM), a theory- and evidence-based tool, and was articulated in two phases: needs assessment and intervention development. In phase 1, two cross-sectional surveys were performed, one aiming to measure stroke awareness in the target population and the other to analyze the behavioral determinants of prehospital delay. In phase 2, a matrix of proximal program objectives was developed, theory-based intervention methods and practical strategies were selected and program components and materials produced. RESULTS: In phase 1, the survey on 202 citizens highlighted underestimation of symptom severity, as in only 44% of stroke situations respondents would choose to call the emergency service (EMS). In the survey on 393 consecutive patients, 55% presented over 2 hours after symptom onset; major determinants were deciding to call the general practitioner first and the reaction of the first person the patient called. In phase 2, adult individuals were identified as the target of the intervention, both as potential "patients" and witnesses of stroke. The low educational level found in the patient survey called for a narrative approach in cartoon form. The family setting was chosen for the message because 42% of patients who presented within 2 hours had been advised by a family member to call EMS. To act on people's tendency to view stroke as an untreatable disease, it was decided to avoid fear-arousal appeals and use a positive message providing instructions and hope. Focus groups were used to test educational products and identify the most suitable sites for message dissemination. CONCLUSIONS: The IM approach allowed to develop a stroke campaign integrating theories, scientific evidence and information collected from the target population, and enabled to provide clear explanations for the reasons behind key decisions during the intervention development process. TRIAL REGISTRATION: NCT01881152 . Retrospectively registered June 7 2013.

A method for measuring individual research productivity in hospitals: development and feasibility.

BACKGROUND: Research capacity is a prerequisite for any health care institution intending to provide high-quality care, yet, few clinicians engage in research, and their work is rarely recognized. To make research an institutional activity, it could be helpful to measure health care professionals' research performance. However, a comprehensive approach to do this is lacking. METHODS: We conducted a literature analysis to determine how best to assess research performance. Our method was not restricted to bibliometric and citation parameters, as is usually the case, but also including "hidden" activities, generally not considered in research performance evaluations. RESULTS: A set of 12 easily retrievable indicators was used and corresponding points assigned according to a weighting system intended to reflect the effort estimated to perform each activity. We observed a highly skewed score distribution, with a minority of health care professionals performing well across the indicators. The highest score was recorded for scientific papers (768/1098 points, 70%). Twenty percent of researchers at our institution generated 50% of points. CONCLUSIONS: We develop a simple method for measuring research performance, which could be rapidly implemented in health care institutions. It is hoped that the proposed method might be useful for promoting research and guiding resource allocation, although further evaluations are needed to confirm the method's utility.

Reducing unnecessary hospital days to improve quality of care through physician accountability: a cluster randomised trial.

BACKGROUND: Over 20% of hospital bed use is inappropriate, implying a waste of resources and the increase of patient iatrogenic risk. METHODS: This is a cluster, pragmatic, randomised controlled trial, carried out in a large University Hospital of Northern Italy, aiming to evaluate the effect of a strategy to reduce unnecessary hospital days. The primary outcome was the percentage of patient-days compatible with discharge. Among secondary objectives, to describe the strategy's effect in the long-term, as well as on hospital readmissions, considered to be a marker of the quality of hospital care. The 12 medical wards with the longest length of stay participated. Effectiveness was measured at the individual level on 3498 eligible patients during monthly index days. Patients admitted or discharged on index days, or with stay >90 days, were excluded. All ward staff was blinded to the index days, while staff in the control arm and data analysts were blinded to the trial's objectives and interventions. The strategy comprised the distribution to physicians of the list of their patients whose hospital stay was compatible with discharge according to a validated Delay Tool, and of physician length of stay profiles, followed by audits managed autonomously by the physicians of the ward. RESULTS: During the 12 months of data collection, over 50% of patient-days were judged to be compatible with discharge. Delays were mainly due to problems with activities under medical staff control. Multivariate analysis considering clustering showed that the strategy reduced patient-days compatible with discharge by 16% in the intervention vs control group, (OR=0.841; 95% CI, 0.735 to 0.963; P=0.012). Follow-up at 1 year did not yield a statistically significant difference between the percentages of patient-days judged to be compatible with discharge between the two arms (OR=0.818; 95% CI, 0.476 to 1.405; P=0.47). There was no significant difference in 30-day readmission and mortality rates for all eligible patients (N=3498) between the two arms. CONCLUSIONS: Results indicate that a strategy, involving physician direct accountability, can reduce unnecessary hospital days. Relatively simple interventions, like the one assessed in this study, should be implemented in all hospitals with excessive lengths of stay, since unnecessary prolongation may be harmful to patients. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01422811.

Cultural adaptation of the Italian version of the Patient-Reported Outcomes Common Terminology Criteria for Adverse Event (PRO-CTCAE®).

INTRODUCTION: US National Cancer Institute's (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) is a library of 78 symptom terms and 124 items enabling patient reporting of symptomatic adverse events in cancer trials. This multicenter study used mixed methods to develop an Italian language version of this widely accepted measure, and describe the content validity and reliability in a diverse sample of Italian-speaking patients. METHODS: All PRO-CTCAE items were translated in accordance with international guidelines. Subsequently, the content validity of the PRO-CTCAE-Italian was explored and iteratively refined through cognitive debriefing interviews. Participants (n=96; 52% male; median age 64 years; 26% older adults; 18% lower educational attainment) completed a PRO-CTCAE survey and participated in a semi-structured interview to determine if the translation captured the concepts of the original English language PRO-CTCAE, and to evaluate comprehension, clarity and ease of judgement. Test-retest reliability of the finalized measure was explored in a second sample (n=135). RESULTS: Four rounds of cognitive debriefing interviews were conducted. The majority of PRO-CTCAE symptom terms, attributes and associated response choices were well-understood, and respondents found the items easy to judge. To improve comprehension and clarity, the symptom terms for nausea and pain were rephrased and retested in subsequent interview rounds. Test-retest reliability was excellent for 41/49 items (84%); the median intraclass correlation coefficient was 0.83 (range 0.64-0.94). DISCUSSION: Results support the semantic, conceptual and pragmatic equivalence of PRO-CTCAE-Italian to the original English version, and provide preliminary descriptive evidence of content validity and reliability.

Evaluation of a pilot surgical adverse event detection system for Italian hospitals.

OBJECTIVE: To devise an adverse event (AE) detection system and assess its validity and utility. DESIGN: Observational, retrospective study. SETTING: Six public hospitals in Northern Italy including a Teaching Hospital. PARTICIPANTS: Eligible cases were all patients with at least one admission to a surgical ward, over a 3-month period. INTERVENTIONS: Computerized screening of administrative data and review of flagged charts by an independent panel. MAIN OUTCOME MEASURES: Number of records needed to identify an AE using this detection system. RESULTS: Out of the 3310 eligible cases, 436 (13%) were extracted by computerized screening. In addition, out of the 2874 unflagged cases, 77 randomly extracted records (3%) were added to the sample, to measure unidentified cases. Nursing staff judged 108 of 504 (21%) charts positive for one or more criteria; surgeons confirmed the occurrence of AEs in 80 of 108 (74%) of these. Compared with random chart review, the number of cases needed to detect an AE, with the computerized screening suggested by this study, was reduced by two-thirds, although sensitivity was low (41%). CONCLUSIONS: This approach has the potential to allow the timely identification of AEs, enabling to quickly devise interventions. This detection system could be of true benefit for hospitals that intend assessing their AEs.

Levothyroxine-induced serum free thyroxine response following radioactive iodine administration in patients thyroidectomized for differentiated thyroid cancer: A randomized controlled trial.

PURPOSE: Patients undergoing thyroidectomy for differentiated thyroid cancer (DTC) may require 131-radioactive iodine (RAI) administration for remnant ablation or disease treatment. After ingestion, RAI resides within the gastrointestinal tract potentially leading to mucosal damage and abnormalities in the absorption of levothyroxine (LT4). The aim of this study was to evaluate whether serum FT4 peak, induced by a LT4 challenge, changes according to the LT4 formulation (solid or liquid) in both RAI and non-RAI-treated DTC patients. METHODS: This was a monocentric controlled clinical trial, with a parallel two-groups (1:1) randomization of sequence of LT4 formulation. Patients received 200 mcg LT4 orally administered at 08:00 h, in both solid and liquid formulation, at one-week interval, at baseline and after 1, 3, and 6 months from RAI administration. At each time-point, circulating FT4 was evaluated both before LT4 assumption as well as after 1 and 3 h. FT4 increments were evaluated as area under the curve response (AUC). Analogous protocol with the same time-intervals was followed for non-RAI patients. RESULTS: The trial included 29 consecutive DTC patients, nineteen of whom were submitted to RAI. In RAI subjects, we observed an overall significant reduction in serum FT4 increments with the most relevant decrease at the 1-month time-point, (FT4 AUC: 4.46 ± 0.72 (M ± SD) vs 4.07 ± 0.63 in baseline vs 1-month, P = 0.001) without any difference between the two LT4 formulations. No difference in serum FT4 AUC was found in non-RAI subjects. CONCLUSION: LT4-induced serum FT4 responses are reduced following RAI administration in thyroidectomized DTC patients.

Effectiveness of a Psychosocial Care Quality Improvement Strategy to Address Quality of Life in Patients With Cancer: The HuCare2 Stepped-Wedge Cluster Randomized Trial.

Importance: Many patients with cancer who would benefit from psychosocial care do not receive it. Implementation strategies may favor the integration of psychosocial care into practice and improve patient outcomes. Objective: To evaluate the effectiveness of the Humanization in Cancer Care (HuCare) Quality Improvement Strategy vs standard care as improvement of at least 1 of 2 domains (emotional or social function) of patient health-related quality of life at baseline and 3 months. A key secondary aim included investigation of the long-term effect. Design, Setting, and Participants: HuCare2 was a multicenter, incomplete, stepped-wedge cluster randomized clinical trial, conducted from May 30, 2016, to August 28, 2019, in three 5-center clusters of cancer centers representative of hospital size and geographic location in Italy. The study was divided into 5 equally spaced epochs. Implementation sequence was defined by a blinded statistician; the nature of the intervention precluded blinding for clinical staff. Participants included consecutive adult outpatients with newly diagnosed cancer of any type and stage starting medical cancer treatment. Interventions: The HuCare Quality Improvement Strategy comprised (1) clinician communication training, (2) on-site visits for context analysis and problem-solving, and (3) implementation of 6 evidence-based recommendations. Main Outcomes and Measures: The primary outcome was the difference between the means of changes of individual scores in emotional or social functions of health-related quality of life detected at baseline and 3-month follow-up (within each group) and during the postintervention epoch compared with control periods (between groups). Long-term effect of the intervention (at 12 months) was assessed as a secondary outcome. Intention-to-treat analysis was used. Results: A total of 762 patients (475 [62.3%] women) were enrolled (400 HuCare Quality Improvement Strategy and 362 usual care); mean (SD) age was 61.4 (13.1) years. The HuCare Quality Improvement Strategy significantly improved emotional function during treatment (odds ratio [OR], 1.13; 95% CI, 1.04-1.22; P = .008) but not social function (OR, 0.99; 95% CI, 0.89-1.09; P = .80). Effect on emotional function persisted at 12 months (OR, 1.05; 95% CI, 1.00-1.10; P = .04). Conclusions and Relevance: In this trial, the HuCare Quality Improvement Strategy significantly improved the emotional function aspect of health-related quality of life during cancer treatment and at 12 months, indicating a change in clinician behavior and in ward organization. These findings support the need for strategies to introduce psychosocial care; however, more research is needed on factors that may maximize the effects. Trial Registration: ClinicalTrials.gov Identifier: NCT03008993.

Implementation of a strategy involving a multidisciplinary mobile unit team to prevent hospital admission in nursing home residents: protocol of a quasi-experimental study (MMU-1 study).

INTRODUCTION: Nursing home residents represent a particularly vulnerable population experiencing high risk of unplanned hospital admissions, but few interventions have proved effective in reducing this risk. The aim of this research will be to verify the effects of a hospital-based multidisciplinary mobile unit (MMU) team intervention delivering urgent care to nursing home residents directly at their bedside. METHODS AND ANALYSIS: Four nursing homes based in the Parma province, in Northern Italy, will be involved in this prospective, pragmatic, multicentre, 18-month quasiexperimental study (sequential design with two cohorts). The residents of two nursing homes will receive the MMU team care intervention. In case of urgent care needs, the nursing home physician will contact the hospital physician responsible for the MMU team by phone. The case will be triaged as (a) manageable by phone advice, (b) requiring urgent assessment by the MMU team or (c) requiring immediate emergency department (ED) referral. MMU team is composed of one senior physician and one emergency-medicine resident chosen within the staff of Internal Medicine and Critical Subacute Care Unit of Parma University-Hospital, usually with different specialty background, and equipped with portable ultrasound, set of drugs and devices useful in urgency. The MMU visits patients in nursing homes, with the mission to stabilise clinical conditions and avoid hospital admission. Residents of the other two nursing homes will receive usual care, that is, ED referral in every case of urgency. Study endpoints include unplanned hospital admissions (primary), crude all-cause mortality, hospital mortality, length of stay and healthcare-related costs (secondary). ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Area Vasta Emilia Nord (Emilia-Romagna region). Informed consent will be collected from patients or legal representatives. The results will be actively disseminated through peer-reviewed journals and conference presentations, in compliance with the Italian law. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04085679); Pre-results.

[The strategic research areas of a University Hospital: proposal of a quali-quantitative method.] / Le linee di ricerca strategiche di un'azienda ospedaliero-universitaria: proposta di un metodo quali-quantitativo.

This work aimed to objectively identify the main research areas at the University Hospital of Parma. To this end, a multidisciplinary working group, comprising clinicians, researchers, and hospital management, was formed to develop a shared quali-quantitative method. Easily retrievable performance indicators were selected from the literature (concerning bibliometric data and grant acquisition), and a scoring system developed to assign weights to each indicator. Subsequently, Research Team Leaders were identified from the hospital's "Research Plan", a document produced every three years which contains information on the main research themes carried out at each Department, involved staff and available resources, provided by health care professionals themselves. The selected performance indicators were measured for each Team Leader, and scores assigned, thus creating a ranking list. Through the analyses of the research themes of top Team Leaders, the Working Group identified the following five strategic research areas: (a) personalized treatment in oncology and hematology; (b) chronicization mechanisms in immunomediate diseases; (c) old and new risk factors for cardiovascular diseases; (d) nutritional disorders, metabolic and chronic-degenerative diseases; (e) molecular diagnostic and predictive markers. We have developed an objective method to identify a hospital's main research areas. Its application can guide resource allocation and can offer ways to value the work of professionals involved in research.

Effectiveness of the HuCare Quality Improvement Strategy on health-related quality of life in patients with cancer: study protocol of a stepped-wedge cluster randomised controlled trial (HuCare2 study).

INTRODUCTION: Our group previously demonstrated the feasibility of the HuCare Quality Improvement Strategy (HQIS), aimed at integrating into practice six psychosocial interventions recommended by international guidelines. This trial will assess whether the introduction of the strategy in oncology wards improves patient's health-related quality of life (HRQoL). METHODS AND ANALYSIS: Multicentre, incomplete stepped-wedge cluster randomised controlled trial, conducted in three clusters of five centres each, in three equally spaced time epochs. The study also includes an initial epoch when none of the centres are exposed to the intervention, and a final epoch when all centres will have implemented the strategy. The intervention is applied at a cluster level, and assessed at an individual level with cross-sectional model. A total of 720 patients who received a cancer diagnosis in the previous 2 months and about to start medical treatment will be enrolled. The primary aim is to evaluate the effectiveness of the HQIS versus standard care in terms of improvement of at least one of two domains (emotional and social functions) of HRQoL using the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items) questionnaire, at baseline and at 3 months. This outcome was chosen because patients with cancer generally exhibit low HRQoL, particularly at certain stages of care, and because it allows to assess the strategy's impact as perceived by patients themselves. The HQIS comprises three phases: (1) clinician training-to improve communication-relational skills and instruct on the project; (2) centre support-four on-site visits by experts of the project team, aimed to boost motivation, help with context analysis and identification of solutions; (3) implementation of Evidence-Based Medicine (EBM) recommendations at the centre. ETHICS AND DISSEMINATION: Ethics committee review approval has been obtained from the Ethics Committee of Parma. Results will be disseminated at conferences, and in peer-reviewed and professional journals intended for policymakers and managers. TRIAL REGISTRATION NUMBER: NCT03008993; Pre-results.

The role of GP's compensation schemes in diabetes care: evidence from panel data.

We investigate the impact of the implementation of Diabetes Management Programs with financial incentives in the Italian Region Emilia-Romagna between 2003 and 2005. We focus on avoidable hospitalisations for diabetic patients for whom GPs receive additional payments exceeding capitation. We estimate a panel count data model to test the hypothesis that those patients under the responsibility of GPs receiving a higher share of their income through ad-hoc payments, are less likely to experience avoidable hospitalisations. Our findings indicate that financial transfers may help improve the quality of care, even when they are not based on the ex-post verification of performance. The estimated effect indicates that, at sample averages, an increase of 100 Euros of the financial incentives paid to GPs (around 17% of the yearly payment received by GPs for diabetes programmes) is expected to reduce the number of diabetic ACSCs by 1%, around 100 cases when projected on the entire region.

Incentives in primary care and their impact on potentially avoidable hospital admissions.

Financial incentives in primary care have been introduced with the purpose of improving appropriateness of care and containing demand. We usually observe pay-for-performance programs, but alternatives, such as pay-for-participation in improvement activities and pay-for-compliance with clinical guidelines, have also been implemented. Here, we assess the influence of different programs that ensure extra payments to GPs for containing avoidable hospitalisations. Our dataset covers patients and GPs of the Italian region Emilia-Romagna for the year 2005. By separating pay-for-performance from pay-for-participation and pay-for-compliance programs, we estimate the impact of different financial incentives on the probability of avoidable hospitalisations. As dependent variable, we consider two different sets of conditions for which timely and effective primary care should be able to limit the need for hospital admission. The first is based on 27 medical diagnostic related groups that Emilia-Romagna identifies as at risk of inappropriateness in primary care, while the second refers to the internationally recognised ambulatory care-sensitive conditions. We show that pay-for-performance schemes may have a significant effect over aggregate indicators of appropriateness, while the effectiveness of pay-for-participation schemes is adequately captured only by taking into account subpopulations affected by specific diseases. Moreover, the same scheme produces different effects on the two sets of indicators used, with performance improvements limited to the target explicitly addressed by the Italian policy maker. This evidence is consistent with the idea that a "tunnel vision" effect may occur when public authorities monitor specific sets of objectives as proxies for more general improvements in the quality of health care delivered.