[Shared decision-making in metaclinical medicine: from informed consent to shared probability]. / Il processo decisionale condiviso nella medicina metaclinica: dal consenso informato alla probabilità condivisa.

At the dawn of "metaclinical medicine" era, shared decision-making represents the overcoming of modern medicine guidelines and classical medicine experience. The patient's life plan, the doctor's health plan, the scientist's evidence-based plan, the administrator's plan and the beliefs of the society for healthcare options should be integrated into the shared decision-making process to avoid patient's unrealistic expectations, doctor's self-referential and defensive medicine, the science without compassion of the scientist, the administered medicine of the politician, the herd mentality of artificial intelligence. For a doctor who must evaluate according to science and conscience, it becomes difficult to make decisions about a patient who thinks that there can be "no decisions about me without me". It risks being a pure declamatory statement in the absence of clinical knowledge and the associated concept of probability. The idea of moving from informed consent to shared probability is convenient for both the doctor and the patient but not for litigation professionals. Even in metaclinical medicine, clinical decision support systems, if well governed, would facilitate the choice of the best treatment according to the definition of absolute risk reduction and the number of patients to be treated to avoid an event, leaving it up to the doctor-patient relationship the narrative and the choice of the most appropriate treatment, which also requires taking care of the emotional and compassionate aspects.

[Process to insulin for type 2 diabetes mellitus therapy]. / Processo all'insulina nella terapia del diabete mellito di tipo 2.

In type 1 diabetes mellitus and in symptomatic and critical hyperglycemic states, insulin is a lifesaving drug; however, its value in long-term type 2 diabetes therapy, which represents more than 90% of diabetes, has not been assessed. This happens despite the fact that, in randomized studies on type 2 diabetes, insulin is used in two-thirds of cases when intensive hypoglycemic treatment is needed and in half of the patients when treatment is the standard one. This is a major issue from a clinical, economic and social-health organization point of view as insulin therapy is expensive and needs a complex organization. Observational and retrospective studies from the scientific literature show that in this type of diabetes insulin treatment is associated with increased cardiovascular and all-cause mortality. It is not clear whether this is due to a greater severity of the clinical picture, to the therapeutic target of blood glucose that may induce hypoglycemia, or to the intrinsic pharmacological activity of the drug that beyond reducing hyperglycemia can cause hypoglycemia, water retention, weight gain and hyperinsulinemia with proatherogenic effects. In particular, in patients with heart failure at high cardiovascular risk or with high insulin resistance, these clues are supported by meaningful data. Although there is no definitive evidence (the so-called "smoking gun") from randomized controlled trials, the high degree of suspicion induces the preferential choice of other drugs such as sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and metformin beyond avoiding glycemic targets that induce hypoglycemia, especially in frail, elderly patients, or patients with cardiovascular diseases. These drugs, for their proven efficacy and the easy use within an outpatient setting (that favors their prescription and improves the inertia of the doctor and the adherence of patients), could help a more effective treatment of patients, both for quality and life expectancy beyond mere glycemic control.

[The patient in clinical research: disposable guinea pig or involved actor?] / Il paziente nella ricerca clinica: cavia a disposizione o attore interessato?

BACKGROUND: The request for informed consent to join a clinical trial often creates mistrust and hesitation in the patient who should be enrolled. In our study, we evaluated the reasons for refusing to participate in a clinical trial. METHODS: In the last 10 years of cardiovascular clinical research, we asked an informed consent to 2586 patients for intervention studies. Overall, 59% agreed to join clinical trials, 40% refused. The 1% initially accepted and then withdrew the consent. Those who refused were more frequently women, relatively younger (mean age 62 ± 5 vs 74 ± 9 years) and had a higher level of education and income. We asked all these patients who refused to answer a brief questionnaire about the reasons for rejection. RESULTS: Of 1031 patients, 629 (61%), accepted to answer the interview; 176 (28%) answered they refused on relatives', friends' or other doctors' advices, or after Internet searches; 157 (25%) answered they did not agree about how the trials were carried out (double-blind control procedure, use of placebo); 126 (20%) did not trust official medicine; 63 (10%) could not guarantee their presence at the follow-up visits; 69 (11%) did not want to undergo additional medical examinations; 31 (5%) had previous bad research experiences (feeling like a guinea pig); 7 (about 1%) refused for other reasons. CONCLUSIONS: Recruitment into clinical research studies is still a major challenge. Patients, due to a prevailing humanistic culture, are not fully aware of the importance of participation in clinical research, which is sometimes considered as exclusive economic or prestige interest. In our experience, people who refused participation in the trials were younger, with a high level of education and income, more frequently women. The researcher's task is to motivate the patient by emphasizing that participating in a study means being the actors of a treatment choice and that one is a guinea pig when taking untested therapies.

[Digitalis, a drug to be scrapped?] / La digitale: un farmaco da rottamare?

We performed a comprehensive review of the scientific literature on the use of digoxin in heart failure and atrial fibrillation. In congestive heart failure (CHF) there is only one randomized trial with a statistical sample sufficiently large. In this trial (DIG trial), which enrolled patients with systolic left ventricular dysfunction in sinus rhythm, digoxin had a neutral action on mortality and modestly reduced the overall need of hospitalization. The study was conducted in the pre-beta-blocker era and, therefore, it has a doubtful application to the current clinical context. There are no randomized trials on atrial fibrillation, either with or without heart failure. Several observational and retrospective studies and meta-analysis have shown an association between the use of digoxin and increased mortality about 20%. Both in the European and American guidelines, even in class I recommendations, evidence is not supported by randomized or observational trials, but just by experts' opinions. Digoxin use in CHF and atrial fibrillation is related to the physician's clinical judgment, based more on consolidated custom that on established scientific evidence. In our opinion, this therapy should be withdrawn until new randomized controlled trials will provide evidence of its efficacy. Two trials have been planned to this aim. Also the issue of toxicity threshold is still unresolved; digoxinemia values should be <1 ng/ml if digoxin is used, to avoid overdosing and toxicity with increased mortality.