Tirzepatide against obesity and insulin-resistance: pathophysiological aspects and clinical evidence.

Obesity is a chronic, multifactorial disease in which accumulated excess body fat has a negative impact on health. Obesity continues to rise among the general population, resulting in an epidemic that shows no significant signs of decline. It is directly involved in development of cardiometabolic diseases, ischemic coronary heart disease peripheral arterial disease, heart failure, and arterial hypertension, producing global morbidity and mortality. Mainly, abdominal obesity represents a crucial factor for cardiovascular illness and also the most frequent component of metabolic syndrome. Recent evidence showed that Tirzepatide (TZP), a new drug including both Glucagon Like Peptide 1 (GLP-1) and Glucose-dependent Insulinotropic Polypeptide (GIP) receptor agonism, is effective in subjects with type 2 diabetes (T2D), lowering body weight, fat mass and glycated hemoglobin (HbA1c) also in obese or overweight adults without T2D. This review discusses the pathophysiological mechanisms and clinical aspects of TZP in treating obesity.

Safety of High-Dose Vitamin C in Non-Intensive Care Hospitalized Patients with COVID-19: An Open-Label Clinical Study.

Background: Vitamin C has been used as an antioxidant and has been proven effective in boosting immunity in different diseases, including coronavirus disease (COVID-19). An increasing awareness was directed to the role of intravenous vitamin C in COVID-19. Methods: In this study, we aimed to assess the safety of high-dose intravenous vitamin C added to the conventional regimens for patients with different stages of COVID-19. An open-label clinical trial was conducted on patients with COVID-19. One hundred four patients underwent high-dose intravenous administration of vitamin C (in addition to conventional therapy), precisely 10 g in 250 cc of saline solution in slow infusion (60 drops/min) for three consecutive days. At the same time, 42 patients took the standard-of-care therapy. Results: This study showed the safety of high-dose intravenous administration of vitamin C. No adverse reactions were found. When we evaluated the renal function indices and estimated the glomerular filtration rate (eGRF, calculated with the CKD-EPI Creatinine Equation) as the main side effect and contraindication related to chronic renal failure, no statistically significant differences between the two groups were found. High-dose vitamin C treatment was not associated with a statistically significant reduction in mortality and admission to the intensive care unit, even if the result was bound to the statistical significance. On the contrary, age was independently associated with admission to the intensive care unit and in-hospital mortality as well as noninvasive ventilation (N.I.V.) and continuous positive airway pressure (CPAP) (OR 2.17, 95% CI 1.41-3.35; OR 7.50, 95% CI 1.97-28.54; OR 8.84, 95% CI 2.62-29.88, respectively). When considering the length of hospital stay, treatment with high-dose vitamin C predicts shorter hospitalization (OR -4.95 CI -0.21--9.69). Conclusions: Our findings showed that an intravenous high dose of vitamin C is configured as a safe and promising therapy for patients with moderate to severe COVID-19.

What Is the Role of Basal Weekly Insulin in Clinical Practice? The State of the Art.

Despite the advent of innovative therapies in the treatment of diabetes, ever-increasing awareness is still directed to the role of insulin since it has continued to be at the centre of diabetes therapy for decades, as a therapeutic integration of innovative agents in type 2 diabetes mellitus (T2DM), as the only replacement therapy in type 1 diabetes mellitus (T1DM) and also in gestational diabetes. In this context, the study of molecules such as weekly basal insulins, both for their technological and pharmacodynamic innovation and their manageability and undoubted benefits in compliance with drug therapy, can only be a turning point in diabetes and for all its phenotypes. This review aims to provide insight into the knowledge of basal weekly insulins and their use in type 1 and 2 diabetes mellitus by examining their safety, efficacy, manageability and increased therapeutic compliance.

The lived experience of mothers living with fibromyalgia syndrome: A phenomenological inquiry.

INTRODUCTION: Fibromyalgia syndrome (FMS) is a complex chronic pain condition that negatively impacts women's daily lives, particularly their roles as mothers and wives. A phenomenological qualitative study was conducted to explore the lived experiences of motherhood and daily life among women diagnosed with fibromyalgia. METHODS: A sample of 10 women affected by FMS was recruited between January and February 2020. Participants were interviewed in a face-to-face, in-depth interview using a semi-structured interview guide. Data were collected until saturation, and Colaizzi's method was used to analyse data. RESULTS: This qualitative analysis identified five themes: A trauma preceding diagnosis, Pervasive feelings of misunderstanding, A struggle to maintain strength among limitations, Challenges in fulfilling maternal roles, and Persistent sexual discomfort. The latter two themes emerged as the most prominent. CONCLUSION: These findings highlight the significant impact of fibromyalgia on women's family lives and suggest the need for a more comprehensive care programme.

Effectiveness and safety of filgotinib in rheumatoid arthritis: a real-life multicentre experience.

OBJECTIVES: We investigated the effectiveness and safety of filgotinib in a real-life multicentre cohort of rheumatoid arthritis (RA) patients. METHODS: RA patients were evaluated at baseline and after 12 and 24 weeks and were stratified based on previous treatments as biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and bDMARD-insufficient responders (IR). Concomitant usage of methotrexate (MTX) and oral glucocorticoids (GC) was recorded. At each timepoint we recorded disease activity, laboratory parameters and adverse events. RESULTS: 126 patients were enrolled. 15.8% were bDMARD-naive (G0), while 84% were bDMARD-IR (G1). In G0, 45% of patients were in monotherapy (G2) and 55% were taken MTX (G3). In G1, 50% of patients were in monotherapy (G4) and 50% used MTX (G5).A significant reduction in all parameters at 12 weeks was observed; in the extension to 24 weeks the significant reduction was maintained for patient global assessment (PGA), examiner global assessment (EGA), visual analogue scale (VAS) pain, VAS fatigue, disease activity score (DAS)28- C-reactive protein (CRP) and CRP values. Filgotinib in monotherapy showed better outcomes in bDMARD-naive patients, with significant differences for patient reported outcomes (PROs) and DAS28-CRP. At 12 weeks, low disease activity (LDA) and remission were achieved in a percentage of 37.2 % and 10.7 % by simplified disease activity index (SDAI), 42.6 % and 5.7 % by clinical disease activity index (CDAI), 26.8 % and 25.2 % by DAS28-CRP, respectively. A significant decrease in steroid dose was evidenced in all patients. We observed a major adverse cardiovascular event in one patient and an increase in transaminase in another. No infections from Herpes Zoster were reported. CONCLUSIONS: Our real-world data confirm the effectiveness and safety of filgotinib in the management of RA, especially in bDMARD-naive patients.

Crucial safety issues on Janus kinase inhibitors in rheumatoid arthritis might be associated with the lack of LDL-cholesterol management: a reasoned literature analysis.

This point of view explores the safety concerns of Janus kinase inhibitors (JAK-Is), used in treating rheumatoid arthritis (RA) and other rheumatologic conditions. Increasing evidence shows that JAK-Is may elevate the risk of venous thromboembolism (VTE), especially pulmonary embolism. This fact has prompted the European Medicines Agency to advise cautious use of these drugs in patients over 65, smokers, and those at risk of cardiovascular issues or cancer. The paper analyses the evidence on the association between VTE risk and RA and whether different JAK-Is pose different risks. It also probes the link between VTE, lipids, and JAK inhibition, noting that JAK-Is can alter HDL and LDL levels. On the other hand, some evidence indicates that tighter LDL-cholesterol control could mitigate VTE risk, particularly pulmonary embolism. Moreover, data from trials show little attention to treating this main cardiovascular and VTE risk factor in rheumatological patients. Although the lipid paradox theory emphasizes the U-shaped relationship between LDL cholesterol and cardiovascular risk in patients with RA, uncontrolled levels of clinically relevant LDL cholesterol remain closely linked to cardiovascular and VTE risk. In conclusion, high-potency statins could help to manage the increased cardiovascular and VTE risk concomitant to JAK-Is treatment in rheumatologic patients without depriving them of the best therapeutic choice and, in addition, reducing the inherent risk associated with the disease.

The Role of Vitamin D and Its Molecular Bases in Insulin Resistance, Diabetes, Metabolic Syndrome, and Cardiovascular Disease: State of the Art.

In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is an essential hormone in regulating calcium/phosphorous balance and in the pathogenesis of inflammation, insulin resistance, and obesity. The main forms of vitamin D, Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) are converted into the active form (1,25-dihydroxyvitamin D) thanks to two hydroxylations in the liver, kidney, pancreas, and immune cells. Some anti-inflammatory cytokines are produced at higher levels by vitamin D, while some pro-inflammatory cytokines are released at lower levels. Toll-Like Receptor (TLR) expression is increased, and a pro-inflammatory state is also linked to low levels of vitamin D. Regardless of how it affects inflammation, various pathways suggest that vitamin D directly improves insulin sensitivity and secretion. The level of vitamin D in the body may change the ratio of pro- to anti-inflammatory cytokines, which would impact insulin action, lipid metabolism, and the development and function of adipose tissue. Many studies have demonstrated an inverse relationship between vitamin D concentrations and pro-inflammatory markers, insulin resistance, glucose intolerance, metabolic syndrome, obesity, and cardiovascular disease. It is interesting to note that several long-term studies also revealed an inverse correlation between vitamin D levels and the occurrence of diabetes mellitus. Vitamin D supplementation in people has controversial effects. While some studies demonstrated improvements in insulin sensitivity, glucose, and lipid metabolism, others revealed no significant effect on glycemic homeostasis and inflammation. This review aims to provide insight into the molecular basis of the relationship between vitamin D, insulin resistance, metabolic syndrome, type 1 and 2 diabetes, gestational diabetes, and cardiovascular diseases.

Physical Exercise and Occupational Therapy at Home to Improve the Quality of Life in Subjects Affected by Rheumatoid Arthritis: A Randomized Controlled Trial.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that affects synovial membranes and typically causes joint pain and swelling. The resulting disability of RA is due to the erosion of cartilage and bone from the inflamed synovial tissue. Occupational therapy is a strategy and technique to minimize the joints' fatigue and effort. At the same time, physical exercise reduces the impact of systemic manifestations and improves symptoms in RA. This study investigates the role of a 30-day joint economy intervention (integration of physical exercise and occupational therapy) at home on the quality of life of subjects with RA. METHODS: One hundred and sixty outpatients with RA were enrolled in a single-center trial with PROBE design and were divided into the intervention group (IG), which combined joint protection movements and physical exercise to maintain muscle tone at home, and the control group (CG). Both groups included 80 patients. In all patients, data from the disease activity score (DAS 28), health assessment questionnaire (HAQ), and short-form health survey (SF-12) "Italian version" were collected. In addition, to IG, a brochure was distributed, and the joint economy was explained, while to CG, the brochure only was distributed. The comparison between groups was made using Fisher's exact test for contingency tables and the z-test for the comparison of proportions. The non-parametric Mann-Whitney U test was used to compare quantitative variables between groups. The Wilcoxon signed-ranked test was used for post-intervention versus baseline comparisons. RESULTS: Among the recruited patients, 54% were female. The mean age was 58.0 (42.4-74.7) for the CG and 54.0 (39.7-68.3) for the IG. Patients included in the IG had a higher cumulative illness rating scale for the evaluation of severity and comorbidity index (2.81 vs. 2.58; 2.91 vs. 2.59, respectively), as well as morning stiffness (33.8 vs. 25.0), even if not significant compared with CG patients. Our results indicate that, after 30 days of joint economy intervention at home, the DAS28 erythrocyte sedimentation rate (esr) and DAS28 C-reactive protein (crp), HAQ, and SF-12 mental component score were significantly improved (p = 0.005, p = 0.004, p = 0.009, and p = 0.010, respectively). CONCLUSIONS: Our findings show that the combination of physical exercise and occupational therapy positively affects patients' quality of life with RA considering disease activity, global health status, and mental health.

Mortality Attributable to Bloodstream Infections Caused by Different Carbapenem-Resistant Gram-Negative Bacilli: Results From a Nationwide Study in Italy (ALARICO Network).

BACKGROUND: Our aim was to analyze mortality attributable to carbapenem-resistant (CR) gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs). METHODS: Prospective multicentric study including patients with GNB-BSI from 19 Italian hospitals (June 2018-January 2020). Patients were followed-up to 30 days. Primary outcomes were 30-day mortality and attributable mortality. Attributable mortality was calculated in the following groups: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales, metallo-ß-lactamases (MBL)-producing Enterobacterales, CR-Pseudomonas aeruginosa (CRPA), CR-Acinetobacter baumannii (CRAB). A multivariable analysis with hospital fixed-effect was built to identify factors associated with 30-day mortality. Adjusted OR (aORs) were reported. Attributable mortality was calculated according to the DRIVE-AB Consortium. RESULTS: Overall, 1276 patients with monomicrobial GNB BSI were included: 723/1276 (56.7%) carbapenem-susceptible (CS)-GNB, 304/1276 (23.8%) KPC-, 77/1276 (6%) MBL-producing CRE, 61/1276 (4.8%) CRPA, and 111/1276 (8.7%) CRAB BSI. Thirty-day mortality in patients with CS-GNB BSI was 13.7% compared to 26.6%, 36.4%, 32.8% and 43.2% in patients with BSI by KPC-CRE, MBL-CRE, CRPA and CRAB, respectively (P < .001). On multivariable analysis, age, ward of hospitalization, SOFA score, and Charlson Index were factors associated with 30-day mortality, while urinary source of infection and early appropriate therapy resulted protective factors. Compared to CS-GNB, MBL-producing CRE (aOR 5.86, 95% CI 2.72-12.76), CRPA (aOR 1.99, 95% CI 1.48-5.95) and CRAB (aOR 2.65, 95% CI 1.52-4.61) were significantly associated with 30-day mortality. Attributable mortality rates were 5% for KPC-, 35% for MBL, 19% for CRPA, and 16% for CRAB. CONCLUSIONS: In patients with BSIs, carbapenem-resistance is associated with an excess of mortality, with MBL-producing CRE carrying the highest risk of death.

Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalization and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis.

BACKGROUND: The COVID-19 pandemic represents one of the world's most important challenges for global public healthcare. Various studies have found an association between severe vitamin D deficiency and COVID-19-related outcomes. Vitamin D plays a crucial role in immune function and inflammation. Recent data have suggested a protective role of vitamin D in COVID-19-related health outcomes. The purpose of this meta-analysis and trial sequential analysis (TSA) was to better explain the strength of the association between the protective role of vitamin D supplementation and the risk of mortality and admission to intensive care units (ICUs) in patients with COVID-19. METHODS: We searched four databases on 20 September 2022. Two reviewers screened the randomized clinical trials (RCTs) and assessed the risk of bias, independently and in duplicate. The pre-specified outcomes of interest were mortality and ICU admission. RESULTS: We identified 78 bibliographic citations. After the reviewers' screening, only five RCTs were found to be suitable for our analysis. We performed meta-analyses and then TSAs. Vitamin D administration results in a decreased risk of death and ICU admission (standardized mean difference (95% CI): 0.49 (0.34-0.72) and 0.28 (0.20-0.39), respectively). The TSA of the protective role of vitamin D and ICU admission showed that, since the pooling of the studies reached a definite sample size, the positive association is conclusive. The TSA of the protective role of vitamin D in mortality risk showed that the z-curve was inside the alpha boundaries, indicating that the positive results need further studies. DISCUSSION: The results of the meta-analyses and respective TSAs suggest a definitive association between the protective role of vitamin D and ICU hospitalization.

Critical importance of patient-reported outcomes for a comprehensive assessment of psoriatic arthritis patients.

Introduction: Psoriatic arthritis (PsA) is a heterogeneous, chronic inflammatory disease that negatively impacts patients' quality of life. Patient-reported outcome measures (PROMs) are used to capture patient perspectives in disease assessment, and physicians use the Disease Activity Index for Psoriatic Arthritis (DAPSA) to evaluate disease activity in PsA. The study aimed to assess the relationship between PROMs and the DAPSA score in consecutive outpatients affected by PsA. Materials and methods: A cross-sectional study was conducted from March 2018 to October 2020 at the PsA clinic of the ARNAS Civico in Palermo (Italy), enrolling outpatients with PsA. Patients were assessed for their disease activity according to the DAPSA score, and PROMs, such as PHQ-9, HAQ, FACIT-F, and PsAID, were evaluated. Linear regression analysis evaluated the relationship between the DAPSA Score and the included PROMs. Results: 158 PsA consecutive peripheral subset psoriatic arthritis outpatients were recruited. The median years of illness was 10.6 (9.3-11.9), and the median DAPSA score was 19.02 (9-33.1). The regression analysis highlighted a strong relationship between the DAPSA score and the PsAID (adjR2 26%, p < 0.0001), the FACIT-F (adjR2 25.4%, p < 0.0001), the HAQ (adjR2 23.7%, p < 0.0001), and PHQ-9 (adjR2 15%, p < 0.0001). Conclusion: PROMs are strongly associated with the DAPSA score, but it allows in-depth evaluation of the impact of the disease on different domains of PsA patients' life.

Clinical complexity and diabetes: a multidimensional approach for the management of cardiorenal metabolic syndrome.

Diabetes mellitus (DM) is one of the fastest-growing health emergencies of the 21st century, and one of the chronic diseases with the highest socio-economic impact on health care systems. DM is the main cause of chronic kidney disease, and is associated with a significant increase in cardiovascular risk and clinical and care complexity. The presence of a constellation of cardiac, metabolic, and renal diseases, in a complex patient with DM, constitutes the CardioRenal Metabolic Syndrome (CRMS). The management of these patients should include a paradigm shift from a reactive strategy to a proactive approach, and the integration of territorial, hospital and social assistance services according to the Chronic Care Model (CCM). Complexity science suggests an alternative model in which disease and health arise from complex, dynamic, and unique interactions among the different components of the overall system. The hospital should be viewed as a highly specialized hub of the chronic care system, which interacts with the outpatient specialist and primary care. In order to create effective communication among territorial care units and highly specialized hospitals, levels of clinical complexity are here proposed and included in a multidimensional management model for the complex patient with diabetes and cardiorenal comorbidity.

Rethinking clinical decision-making to improve clinical reasoning.

Improving clinical reasoning techniques is the right way to facilitate decision-making from prognostic, diagnostic, and therapeutic points of view. However, the process to do that is to fill knowledge gaps by studying and growing experience and knowing some cognitive aspects to raise the awareness of thinking mechanisms to avoid cognitive errors through correct educational training. This article examines clinical approaches and educational gaps in training medical students and young doctors. The authors explore the core elements of clinical reasoning, including metacognition, reasoning errors and cognitive biases, reasoning strategies, and ways to improve decision-making. The article addresses the dual-process theory of thought and the new Default Mode Network (DMN) theory. The reader may consider the article a first-level guide to deepen how to think and not what to think, knowing that this synthesis results from years of study and reasoning in clinical practice and educational settings.

The "Diabetes Comorbidome": A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes.

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes' comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called "Diabetes Comorbidome". (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The "Diabetes Comorbidome" represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes.

GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are highly effective in improving glycaemic control either as monotherapy or in combination with other hypoglycaemic drugs, and have low incidence of side effects, such as hypoglycaemia, nausea and weight gain, thus increasing patients' adherence to therapy. Methods: In this review we report the most recent studies demonstrating the beneficial effects of GLP-1RAs on renal outcomes, and also discuss the direct and indirect mechanisms through which they confer kidney protection. Finally, we discuss the metabolic and anti-inflammatory effects of GLP-1RAs in diabetic patients with COVID-19 disease. Results: GLP-1RAs have a nephroprotective action, which is expressed through both indirect (improvement of blood pressure and glycaemic control, weight loss) and direct (restoration of normal intrarenal haemodynamics, prevention of ischaemic and oxidative damage) effects. They have shown also metabolic and anti-inflammation beneficial effects in patients with COVID-19 disease. Conclusions: GLP-1RAs prevent albuminuria and slow the decline of renal function towards end stage renal disease in patients with diabetic kidney disease. They might be an opportunity to break the typical inflammation processes of COVID-19 disease.

Vitamin D 25OH Deficiency and Mortality in Moderate to Severe COVID-19: A Multi-Center Prospective Observational Study.

Introduction: Several studies and meta-analyses suggested the role of vitamin D 25OH in preventing severe forms of coronavirus disease 2019 (COVID-19). However, the evidence on the clinical benefits of vitamin D 25OH adequacy in patients hospitalized for COVID-19 remain conflicting and speculative. We aimed to investigate the association between vitamin D 25OH serum levels and mortality in hospitalized patients with moderate to severe COVID-19. Method: This prospective observational multicentre study included 361 consecutive patients with moderate to severe COVID-19 admitted to the Italian hospitals involved in the NUTRI-COVID19 trial from March to August 2020. For each patient, serum vitamin D 25OH levels were assessed 48 h since admission and classified as deficient (<20 ng/mL) or adequate (≥20 ng/mL). We built a propensity score for low/adequate vitamin D 25OH levels to balance the clinical and demographic properties of the cohort, which resulted in 261 patients with good common support used for the survival analysis. Results: Two Hundred-seventy-seven (77%) of the 361 enrolled patients (207 [57%] males, median age 73 ± 15.6 years) had vitamin D 25OH deficiency. Fifty-two (20%) of the 261 matched patients died during the hospital stay, corresponding to a hazard ratio of 1.18 for vitamin D 25OH deficiency (95% confidence interval: 0.86-1.62; p = 0.29). Discussion: The prevalence of vitamin D 25OH deficiency was confirmed to be very high in hospitalized patients with COVID-19. The use of a propensity score demonstrate an absence of significant association between vitamin D deficiency and mortality in hospitalized patients.

Lessons From COVID-19: Physical Exercise Can Improve and Optimize Health Status.

The outbreak of Coronavirus Disease 2019 (COVID-19) has caused increasing challenges for healthcare systems globally. The disease spread rapidly from Wuhan to the rest of the world, involving more than 400 million individuals and including more than 5 million deaths. In dealing with the pandemic, China and other countries took protective measures such as promoting social distancing, canceling public gatherings, closing schools, quarantining, and imposing lockdowns. All these measures lead to physical inactivity. Being physically inactive has significant repercussions on the status of physical and mental wellbeing, and it is associated with anxiety, stress, increased chronic disease risk, and worsening of chronic conditions. In this sense, the relevance of maintaining a healthy lifestyle through physical exercise has been outlined by the World Health Organization (WHO). The aim of this mini review is to discuss the importance of physical activity in the context of the COVID-19 pandemic, highlighting the benefits of physical activity and exercise that could be potentially effective treatment strategies for comorbid chronic conditions, long covid syndrome (LCS), and symptoms such as depression and anxiety.

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register.

Beta (ß)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to ß2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective ß1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective ß1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a ß1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations.

The CANOVA Study Real-World Evidence of Biologic Treatments in Moderate-Severe Psoriasis in Italy: A Gender Perspective.

Background: In psoriasis, several studies have indicated sex differences in clinical characteristics, type of treatment, and outcomes. A higher impact of psoriasis on quality of life (QoL) and a lower treatment satisfaction have been reported in women by different authors. Objectives: This article reports the results of a post hoc gender analysis of CANOVA study, aimed at assessing 16/24/52-week effectiveness of biologics in patients with moderate-severe plaque psoriasis. Materials and Methods: CANOVA was a real-world, multicenter, noninterventional, retro-prospective study conducted in 17 Italian hospital dermatology clinics. Results: Of the 669 eligible patients, 63.8% were men. Demographic and baseline characteristics and duration of disease were rather homogeneous between sexes. Slightly more women had been treated with biologics (50.4% vs. 46.5%) and had received ≥2 biologic treatment lines (17.2% vs. 12.4%) before study treatment. The most frequently used biologics were secukinumab, ustekinumab, adalimumab, and ixekizumab in both sexes. At 6 months, Psoriasis Area Severity Index (PASI) 75/90/100 responders were 90.8%/72.3%/45.3% of men and 89.2%/76.6%/48.2% of women. Sustained PASI responders were 79.5% of men and 75.9% of women. Treatment satisfaction was significantly lower in women at enrolment for all subscales, and was still lower at 6 months, no longer significantly. Gender distribution in Dermatology Life Quality Index total score classes showed a significantly greater effect of psoriasis on QoL in women, both at enrolment and at the 6-month follow-up. Conclusions: In conclusion, this gender analysis confirms in both genders the efficacy of biologics in psoriasis. However, women reported a greater impact of the disease on QoL and lower treatment satisfaction.