The impact of in-hospital cardiac rehabilitation program on medication adherence and clinical outcomes in patients with acute myocardial infarction in the Lazio region of Italy.

BACKGROUND: Medication adherence is a recognized key factor of secondary cardiovascular disease prevention. Cardiac rehabilitation increases medication adherence and adherence to lifestyle changes. This study aimed to evaluate the impact of in-hospital cardiac rehabilitation (IH-CR) on medication adherence as well as other cardiovascular outcomes, following an acute myocardial infarction (AMI). METHODS: This is a population-based study. Data were obtained from the Health Information Systems of the Lazio Region, Italy (5 million inhabitants). Hospitalized patients aged ≥ 18 years with an incident AMI in 2013-2015 were investigated. We divided the whole cohort into 4 groups of patients: ST-elevation AMI (STEMI) and non-ST-elevation AMI (NSTEMI) who underwent or not percutaneous coronary intervention (PCI) during the hospitalization. Primary outcome was medication adherence. Adherence to chronic poly-therapy, based on prescription claims for both 6- and 12-month follow-up, was defined as Medication Possession Ratio (MPR) ≥ 75% to at least 3 of the following medications: antiplatelets, ß-blockers, ACEI/ARBs, statins. Secondary outcomes were all-cause mortality, hospital readmission for cardiovascular and cerebrovascular event (MACCE), and admission to the emergency department (ED) occurring within a 3-year follow-up period. RESULTS: A total of 13.540 patients were enrolled. The median age was 67 years, 4.552 (34%) patients were female. Among the entire cohort, 1.101 (8%) patients attended IH-CR at 33 regional sites. Relevant differences were observed among the 4 groups previously identified (from 3 to 17%). A strong association between the IH-CR participation and medication adherence was observed among AMI patients who did not undergo PCI, for both 6- and 12-month follow-up. Moreover, NSTEMI-NO-PCI participants had lower risk of all-cause mortality (adjusted IRR 0.76; 95% CI 0.60-0.95), hospital readmission due to MACCE (IRR 0.78; 95% CI 0.65-0.94) and admission to the ED (IRR 0.80; 95% CI 0.70-0.91). CONCLUSIONS: Our findings highlight the benefits of IH-CR and support clinical guidelines that consider CR an integral part in the treatment of coronary artery disease. However, IH-CR participation was extremely low, suggesting the need to identify and correct the barriers to CR participation for this higher-risk group of patients.

In-hospital myocardial infarction and adherence to evidence-based drug therapies: a real-world evaluation.

OBJECTIVES: This study aimed to measure adherence to chronic polytherapy following an acute myocardial infarction (AMI) and to find out associations between adherence and the setting of AMI onset (in vs out of hospital) as well as other determinants. DESIGN: Retrospective follow-up study. SETTING: Population living in the Lazio Region, Italy. PARTICIPANTS: This study included 25 779 hospitalised patients with a first diagnosis of AMI in 2012-2016, after the exclusion of those with hospital admission for AMI or related causes in the previous 5 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients were classified as in-hospital AMI (IH-AMI) or out of hospital AMI (OH-AMI) according to present-on-admission codes. Adherence was measured based on prescription claims during a 6-month follow-up after hospital discharge, using medication possession ratio (MPR). Adherence to chronic polytherapy was defined as MPR ≥75% to at least 3 of the following medications: antithrombotics, betablockers, ACE inhibitors/angiotensin receptor blockers and statins. RESULTS: Among the entire cohort, 1 044 (4%) patients suffered IH-AMI. Overall, 15 440 (60%) patients were deemed adherent to chronic polytherapy. Female gender, older age, mental disorders, renal disease, asthma and ongoing concomitant treatments were factors associated with poor adherence. By contrast, patients with more severe AMI and those already taking evidence-based (E-B) drugs were more likely to be adherent. A strong association between the setting of AMI onset and adherence was observed: IH-AMI patients were 46% less likely to be adherent to E-B medications during their 6-month follow-up as compared with OH-AMI patients (OR 0.54; 95% CI 0.47 to 0.62; p<0.001). CONCLUSION: Pharmacotherapy is not consistent with clinical guidelines, especially for IH-AMI patients. Our findings provide evidence on a previously unidentified groups of patients at risk for poor adherence, who might benefit from greater medical attention and dedicated healthcare interventions.

[Covid-19 and clinical-epidemiological research in Italy: proposal of a research agenda on priority topics by the Italian association of epidemiology]. / Covid-19 e ricerca clinico-epidemiologica in Italia: proposta di un'agenda di ricerca su temi prioritari da parte dell'Associazione italiana di epidemiologia.

BACKGROUND: the Covid-19 pandemic has provoked a huge of clinical and epidemiological research initiatives, especially in the most involved countries. However, this very large effort was characterized by several methodological weaknesses, both in the field of discovering effective treatments (with too many small and uncontrolled trials) and in the field of identifying preventable risks and prognostic factors (with too few large, representative and well-designed cohorts or case-control studies). OBJECTIVES: in response to the fragmented and uncoordinated research production on Covid-19, the   italian Association of Epidemiology (AIE) stimulated the formation of a working group (WG) with the aims of identifying the most important gaps in knowledge and to propose a structured research agenda of clinical and epidemiological studies considered at high priority on Covid-19, including recommendations on the preferable methodology. METHODS: the WG was composed by 25 subjects, mainly epidemiologists, statisticians, and other experts in specific fields, who have voluntarily agreed to the proposal. The agreement on a list of main research questions and on the structure of the specific documents to be produced were defined through few meetings and cycles of document exchanges. RESULTS: twelve main research questions on Covid-19 were identified, covering aetiology, prognosis, interventions, follow-up and impact on general and specific populations (children, pregnant women). For each of them, a two-page form was developed, structured in: background, main topics, methods (with recommendations on preferred study design and warnings for bias prevention) and an essential bibliography. CONCLUSIONS: this research agenda represents an initial contribution to direct clinical and epidemiological research efforts on high priority topics with a focus on methodological aspects. Further development and refinements of this agenda by Public Health Authorities are encouraged.

Volume and health outcomes: evidence from systematic reviews and from evaluation of Italian hospital data. / Volumi di attività ed esiti delle cure: prove scientifiche in letteratura ed evidenze empiriche in Italia.

BACKGROUND Improving quality and effectiveness of healthcare is one of the priorities of health policies. Hospital or physician volume represents a measurable variable with an impact on effectiveness of healthcare. An Italian law calls for the definition of «qualitative, structural, technological, and quantitative standards of hospital care¼. There is a need for an evaluation of the available scientific evidence in order to identify qualitative, structural, technological, and quantitative standards of hospital care, including the volume of care above or below which the public and private hospitals may be accredited (or not) to provide specific healthcare interventions. OBJECTIVES To identify conditions/interventions for which an association between volume and outcome has been investigated. To identify conditions/interventions for which an association between volume and outcome has been proved. To analyze the distribution of Italian health providers by volume of activity. To measure the association between volume of care and outcomes of the health providers of the Italian National Health Service (NHS). METHODS Systematic review An overview of systematic reviews was performed searching PubMed, EMBASE, and The Cochrane Library up to November 2016. Studies were evaluated by 2 researchers independently; quality assessment was performed using the AMSTAR checklist. For each health condition and outcome, if available, total number of studies, participants, high volume cut-off values, and metanalysis have been reported. According to the considered outcomes, health topics were classified into 3 groups: positive association: a positive association was demonstrated in the majority of studies/participants and/or a pooled measure (metanalysis) with positive results was reported; lack of association: both studies and/or metanalysis showed no association; no sufficient evidence of association: both results of single studies and metanalysis do not allow to draw firm conclusions on the association between volume and outcome. Analysis of the distribution of Italian hospitals by volume of activity and the association between volume of activity and outcomes: the Italian National Outcome evaluation Programme 2016 The analyses were performed using the Hospital Information System and the National Tax Register (year 2015). For each condition, the number of hospitals by volume of activity was calculated. Hospitals with a volume lower than 3-5 cases/year were excluded. For conditions with more than 1,500 cases/year and frequency of outcome ≥1%, the association between volume of care and outcome was analyzed estimating risk-adjusted outcomes. RESULTS Bibliographic searches identified 80 reviews, evaluating 48 different clinical areas. The main outcome considered was intrahospital/30-day mortality. The other outcomes vary depending on the type of condition or intervention in study. The relationship between hospital volume and outcomes was considered in 47 out of 48 conditions: 34 conditions showed evidence of a positive association; • 14 conditions consider cancer surgery for bladder, breast, colon, rectum, colon rectum, oesophagus, kidney, liver, lung, ovaries, pancreas, prostate, stomach, head and neck; • 11 conditions consider cardiocerebrovascular area: nonruptured and ruptured abdominal aortic aneurysm, acute myocardial infarction, brain aneurysm, carotid endarterectomy, coronary angioplasty, coronary artery bypass, paediatric heart surgery, revascularization of lower limbs, stroke, subarachnoid haemorrhage; • 2 conditions consider orthopaedic area: knee arthroplasty, hip fracture; • 7 conditions consider other areas: AIDS, bariatric surgery, cholecystectomy, intensive care unit, neonatal intensive care unit, sepsis, and traumas; for 3 conditions, no association was demonstrated: hip arthroplasty, dialysis, and thyroidectomy. for the remaining 10 conditions, the available evidence does not allow to draw firm conclusions about the association between hospital volume and considered outcomes: surgery for testicular cancer and intracranial tumours, paediatric oncology, aortofemoral bypass, cardiac catheterization, appendectomy, colectomy, inguinal hernia, respiratory failure, and hysterectomy. The relationship between volume of clinician/surgeon and outcomes was assessed only through the literature re view; to date, it is not possible to analyze this association for Italian health provider hospitals, since information on the clinician/surgeon on the hospital discharge chart is missing. The literature found a positive association for 21 conditions: 9 consider surgery for cancer: bladder, breast, colon, colon rectum, pancreas, prostate, rectum, stomach, and head and neck; 5 consider the cardiocerebrovascular area: ruptured and nonruptured abdominal aortic aneurysm, carotid endarterectomy, paediatric heart surgery, and revascularization of the lower limbs; 2 consider the orthopaedic area: knee and hip arthroplasty; 5 consider other areas: AIDS, bariatric surgery, hysterectomy, intensive care unit, and thyroidectomy. The analysis of the distribution of Italian hospitals concerned the 34 conditions for which the systematic review has shown a positive volume-outcome association. For the following, it was possible to conduct the analysis of the association using national data: unruptured abdominal aortic aneurysm, coronary angioplasty, hip arthroplasty, knee arthroplasty, coronary artery bypass, cancer surgery (colon, liver, breast, pancreas, lung, prostate, kidney, and stomach), laparoscopic cholecystectomy, hip fracture, stroke, acute myocardial infarction. For these conditions, the association between volume and outcome of care was observed. For laparoscopic cholecystectomy and surgery of the breast and stomach cancer, the association between the volume of the discharge (o dismissal) operating unit and the outcome was analyzed. The outcomes differ depending on the condition studied. The shape of the relationship is variable among different conditions, with heterogeneous slope of the curves. DISCUSSION For many conditions, the overview of systematic reviews has shown a strong evidence of association between higher volumes and better outcomes. The quality of the available reviews can be considered good for the consistency of the results between the studies and for the strength of the association; however, this does not mean that the included studies are of good quality. Analyzing national data, potential confounders, including age and comorbidities, have been considered. The systematic review of the literature does not permit to identify predefined volume thresholds. The analysis of national data shows a strong improvement in outcomes in the first part of the curve (from very low to higher volumes) for most conditions. In some cases, the improvement in outcomes remains gradual or constant with the increasing volume of care; in other, the analysis could allow the identification of threshold values beyond which the outcome does not further improve. However, a good knowledge of the relationship between effectiveness of treatments and costs, the geographical distribution and the accessibility to healthcare services are necessary to choose the minimum volumes of care, under which specific health procedures could not been provided in the NHS. Some potential biases due to the use of information systems data should also be considered. The different way of coding among hospitals could lead to a different selection of cases for some conditions. Regarding the definition of the exposure (volume of care), a possible bias could result from misclassification of health providers with high volume of activity. Performing the intervention in different departments/ units of the same hospital would result in an overestimation of the volume of care measured for hospital rather than for department/unit. For the conditions with a further fragmentation within the same structure, the association between volumes of discharge department and outcomes has also been evaluated. In this case, the two curves were different. The limit is to attribute the outcome to the discharge unit, which in case of surgery may not be the intervention unit. A similar bias could occur if the main determinant of the outcome of treatment was the caseload of each surgeon. The results of the analysis may be biased when different operators in the same hospital/unit carried out the same procedure. In any case, the observed association between volumes and outcome is very strong, and it is unlikely to be attributable to biases of the study design. Another aspect on which there is still little evidence is the interaction between volume of the hospital and of the surgeon. A MEDICARE study suggests that in some conditions, especially for specialized surgery, the effect of the surgeon's volume of activity is different depending on the structure volume, whereas it would not differ for some less specialized surgery conditions. The data here presented still show extremely fragmented volumes of both clinical and surgical areas, with a predominance of very low volume structures. Health systems operate, by definition, in a context of limited resources, especially when the amount of resources to allocate to the health system is reduced. In such conditions, the rationalization of the organization of health services based on the volume of care may make resources available to improve the effectiveness of interventions. The identification and certification of services and providers with high volume of activity can help to reduce differences in the access to non-effective procedures. To produce additional evidence to guide the reorganization of the national healthcare system, it will be necessary to design further primary studies to evaluate the effectiveness and safety of policies aimed at concentrating interventions in structures with high volumes of activity.

Patient-reported outcomes in head and neck and thyroid cancer randomised controlled trials: A systematic review of completeness of reporting and impact on interpretation.

AIM: To determine the completeness of reporting of patient-reported outcomes (PROs) of head and neck cancer (HNC) and thyroid cancer randomised-controlled trials (RCTs) and identify PRO measures used. METHODS: A systematic literature search was conducted for HNC and thyroid cancer RCTs with PRO end-points (January 2004-June 2015). Two investigators independently extracted data, assessed adherence to the International Society for Quality of Life Research (ISOQOL) PRO reporting standards and concordance between hypotheses and PRO measures used. Data were entered into the Patient-Reported Outcomes Measurements Over Time in Oncology (PROMOTION) Registry. RESULTS: Sixty-six RCTs were included, 56 (85%) HNC and 10 (15%) thyroid cancer. Twenty-two (33%) included a primary and 44 (67%) included a secondary PRO end-point. A total of 40 unique PRO measures were used. Adherence to the ISOQOL PRO reporting standards was higher for RCTs with primary PRO end-points than for secondary PRO end-points: (mean adherence of 43% and 29% respectively). Completeness of PRO reporting did not improve with time: r = .13, p = .31. ISOQOL checklist items poorly reported included: PRO hypothesis (reported for eight RCTs, 12%), justification chosen of PRO measures (n = 16, 24%), rates of missing PRO data (n = 19, 29%), and generalisability of results (n = 12, 18%). Encouragingly, PROs were identified in 55 RCT abstracts (83%) and PRO results interpreted for 30 RCTs (45%). CONCLUSIONS: Reporting of PRO end-points was more comprehensive in RCTs with primary rather than secondary PRO end-points. Improvement is needed in the transparent reporting of PRO studies, particularly regarding data collection, analyses and generalisability of PRO results.

Predicting survival in advanced hematologic malignancies: do patient-reported symptoms matter?

OBJECTIVE: To investigate whether patient-reported symptoms provide independent prognostic information for survival in patients with hematological malignancies. STUDY DESIGN AND SETTING: Overall 119 patients with various diagnoses were recruited in an observational study and symptoms were assessed with the M.D. Anderson Symptom Inventory (MDASI). Key potential socio-demographic, biomedical, and physician-reported prognostic candidates were also considered. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. Additional sensitivity analysis, based on 500 bootstrap-generated simulation datasets, was also performed to confirm the results obtained with the Cox regression model. RESULTS: The median survival of the entire cohort was 4.8 months (range 0-28 months). The MDASI was completed at baseline by 91% of patients. The final multivariate model retained two parameters as independent prognostic factors for survival: clinical prognostic group and patient's self-reported severity of drowsiness. The following hazard ratios (HR) were found for curable vs. terminal: 0.055 (95% CI, 0.022-0.136; P < 0.001) and 0.193 (95% CI, 0.103-0.362: P < 0.001) for advanced vs. terminal. Patient's self-reported severity of drowsiness independently predicted survival with a HR of 1.801 (95% CI, 1.044-3.107; P = 0.033). Additional sensitivity analysis confirmed the independent prognostic value of variables identified in this study. CONCLUSION: The results suggest that patients' self-reporting of symptoms provides independent prognostic information for survival in patients with hematologic malignancies. These findings underscore the value of collecting patient-reported symptom data in routine clinical practice.