Understanding Patterns of Adherence to Antifibrotic Treatment in Idiopathic Pulmonary Fibrosis: Insights from an Italian Prospective Cohort Study.

Background: Pirfenidone and Nintedanib have significantly improved the prognosis of patients with idiopathic pulmonary fibrosis (IPF), reducing mortality risk and exacerbations. This study aimed to analyze antifibrotic treatment utilization and its association with clinical outcomes (i.e., acute exacerbation or death) during 2014-2021 in newly diagnosed IPF patients, using Healthcare Utilization Databases of the Marche Region, Italy. Methods: The first 12-month adherence to antifibrotic was estimated using the Proportion of Days Covered (PDC), defining adherence as PDC ≥ 75%. State Sequence Analysis over the initial 52 weeks of treatment was used to identify adherence patterns. The role of adherence patterns on acute exacerbations/death, adjusted by demographic, clinical features, and monthly adherence after the 52-week period (time-dependent variable), was assessed with Cox regression. Results: Among 667 new IPF cases, 296 received antifibrotic prescriptions, with 62.8% being adherent in the first year. Three antifibrotic utilization patterns emerged-high adherence (37.2%), medium adherence (42.5%), and low adherence (20.3%)-with median PDCs of 95.3%, 79.5%, and 18.6%, respectively. These patterns did not directly influence three-year mortality/exacerbation probability, but sustained adherence reduced risk over time. Conclusions: Good adherence was observed in in this population-based study, emphasizing the importance of continuous antifibrotics therapy over time to mitigate adverse outcomes.

Cost-effectiveness of outpatient adherence to recommendations for monitoring of patients hospitalized for heart failure.

AIMS: A set of indicators to assess the quality of care for patients hospitalized for heart failure was developed by an expert working group of the Italian Health Ministry. Because a better performance profile measured using these indicators does not necessarily translate to better outcomes, a study to validate these indicators through their relationship with measurable clinical outcomes and healthcare costs supported by the Italian National Health System was carried out. METHODS AND RESULTS: Residents of four Italian regions (Lombardy, Marche, Lazio, and Sicily) who were newly hospitalized for heart failure (irrespective of stage and New York Heart Association class) during 2014-2015 entered in the cohort and followed up until 2019. Adherence to evidence-based recommendations [i.e. renin-angiotensin-aldosterone system (RAS) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and echocardiograms (ECCs)] experienced during the first year after index discharge was assessed. Composite clinical outcomes (cardiovascular hospital admissions and all-cause mortality) and healthcare costs (hospitalizations, drugs, and outpatient services) were assessed during the follow-up. The restricted mean survival time at 5 years (denoted as the number of months free from clinical outcomes), the hazard of clinical outcomes (according to the Cox model), and average annual healthcare cost (expressed in euros per person-year) were compared between adherent and non-adherent patients. A non-parametric bootstrap method based on 1000 resamples was used to account for uncertainty in cost-effectiveness estimates. A total of 41 406 patients were included in this study (46.3% males, mean age 76.9 ± 9.4 years). Adherence to RAS inhibitors, beta-blockers, MRAs, and ECCs were 64%, 57%, 62%, and 20% among the cohort members, respectively. Compared with non-adherent patients, those who adhered to ECCs, RAS inhibitors, beta-blockers, and MRAs experienced (i) a delay in the composite outcome of 1.6, 1.9, 1.6, and 0.6 months and reduced risks of 9% (95% confidence interval, 2-14%), 11% (7-14%), 8% (5-11%), and 4% (-1-8%), respectively; and (ii) lower (€262, €92, and €571 per year for RAS inhibitors, beta-blockers, and MRAs, respectively) and higher costs (€511 per year for ECC). Adherence to RAS inhibitors, beta-blockers, and MRAs showed a delay in the composite outcome and a saving of costs in 98%, 84%, and 93% of the 1000 bootstrap replications, respectively. CONCLUSIONS: Strict monitoring of patients with heart failure through regular clinical examinations and drug therapies should be considered the cornerstone of national guidelines and audits.

A multi-state analysis of disease trajectories and mental health transitions in patients with type 2 diabetes: A population-based retrospective cohort study utilizing health administrative data.

AIMS: To investigate the risk of major depression and dementia in patients with type 2 diabetes, including dementia resulting from depression, and their impact on diabetes-related complications and mortality. METHODS: We conducted a population-based retrospective cohort study including 11,441 incident cases of diabetes in 2015-2017, with follow-up until 2022. A multi-state survival analysis was performed on a seven-state model with 15 transitions to capture disease progression and onset of mental disorders. RESULTS: Eight-year probabilities of depression, dementia, diabetes-related complications, and death were 9.7% (95% CI 8.7-10.7), 0.9% (95% CI 0.5-1.3), 10.4% (95% CI 9.5-11.4), and 14.8% (95% CI 13.9-15.7), respectively. Depression increased the risk of dementia up to 3.7% (95% CI 2.0-5.4), and up to 10.3% (95% CI 0.3-20.4) if coupled with diabetes complications. Eight-year mortality was 37.5% (95% CI 33.1-42.0) after depression, 74.1% (95% CI 63.7-84.5) after depression plus complications, 76.4% (95% CI 68.8-83.9) after dementia, and 98.6% (95% CI 96.1-100.0) after dementia plus complications. CONCLUSIONS: The interconnections observed across depression, dementia, complications, and mortality underscore the necessity for comprehensive and integrated approaches in managing diabetes. Early screening for depression, followed by timely and targeted interventions, may mitigate the risk of dementia and improve diabetes prognosis.

Genomic Profiling of Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System Suggests Novel Potential Therapeutic Targets.

Primary diffuse large B-cell lymphoma of the primary central nervous system (CNS-DLBCL) is an aggressive disease, with dismal prognosis despite the use of high-dose methotrexate-based polychemotherapy. Our study aimed to expand the biologic profiles of CNS-DLBCL and to correlate them with clinical/imaging findings to gain diagnostic insight and possibly identify new therapeutic targets. We selected 61 CNS-DLBCL whose formalin-fixed paraffin-embedded samples were available at first diagnosis. These were investigated by immunohistochemistry, cMYC rearrangements were explored by fluorescence in situ hybridization, and CNS-DLBCL mutated genes were evaluated by next-generation sequencing. CD10, BCL6, and IRF4 were observed in 16%, 83.6%, and 93% of cases, respectively. As typical of CNS lymphoma, 10 (16.4%) of 61 cases were classified as germinal center (GCB) type and 51 (83.6%) of 61 as non-germinal center (non-GCB) type according to the Hans algorithm. Double-expression status for BCL2 and cMYC was detected in 36 (59%) of 61 cases whereas 25 (41%) of 61 were non-DE. Rearrangement of the cMYC gene was detected in 2 cases, associated with BCL6 translocation only in 1 case MYD88, PIM1, CD79B, and TP53 were mutated in 54.5%, 53.5%, 30.2%, and 18.4% cases, respectively. Novel mutations not previously reported in CNS-DLBCL were found: AIP in 23.1%, PI3KCA in 15%, NOTCH1 in 11.4%, GNAS in 8.1%, CASP8 in 7.9%, EGFR in 6.4%, PTEN in 5.1, and KRAS in 2.6% of cases. Survival was significantly longer for patients with mutated MYD88 (8.7 months vs 1.7 months; log-rank test = 5.43; P = .020) and for patients with mutated CD79B (10.8 months vs 2.5 months; log-rank test = 4.64; P = .031). MYD88 and CD79B predicted a longer survival in patients affected by CNS-DLBCL. Notably, we identified novel mutations that enrich the mutational landscape of CNS-DLBCL, suggest a role of PTEN-PI3K-AKT and receptor tyrosine kinase-RAS-mitogen-activated protein kinase signaling in a subset of CNS-DLBCL, and provide new potential therapeutic targets.

Pramipexole Augmentation for Treatment-Resistant Unipolar and Bipolar Depression in the Real World: A Systematic Review and Meta-Analysis.

BACKGROUND: Pramipexole is a dopamine full agonist approved for the treatment of Parkinson's disease and restless legs syndrome. Its high affinity for the D3 receptor and neuroprotective, antioxidant, and anti-inflammatory activity provides a rationale for the treatment of depression. In this paper, we review studies on the effectiveness and safety of antidepressant pramipexole augmentation in treatment-resistant depression. METHODS: This comprehensive systematic review and meta-analysis of observational studies on pramipexole-antidepressant augmentation included patients with resistant unipolar and bipolar depression. The primary outcome measure was the treatment response, measured at the study endpoint. RESULTS: We identified 8 studies including 281 patients overall, 57% women and 39.5% with bipolar disorder and 60.5% with major depressive disorder. The mean follow-up duration was 27.3 weeks (range 8-69). The pooled estimate of treatment response was 62.5%, without significant differences between unipolar and bipolar depression. Safety was good, with nausea and somnolence the most frequent side effects. CONCLUSIONS: The findings of this systematic review, needing further confirmation, show that off-label use of pramipexole as augmentation of antidepressant treatment could be a useful and safe strategy for unipolar and bipolar treatment-resistant depression.

Assessing attitudes towards insulin pump therapy in adults with type 1 diabetes: Italian validation of the Insulin Pump Attitudes Questionnaire (IT-IPA questionnaire).

AIMS: The aim of the study was to adapt the German version of the insulin pump therapy (IPA) questionnaire to Italian (IT-IPA) and to evaluate its psychometric properties in adults with type 1 diabetes. METHODS: We conducted a cross-sectional study, data were collected through an online survey. In addition to IT-IPA, questionnaires evaluating depression, anxiety, diabetes distress, self-efficacy, and treatment satisfaction were administered. The six factors identified in the IPA German version were assessed using confirmatory factor analysis; psychometric testing included construct validity and internal consistency. RESULTS: The online survey was compiled by 182 individuals with type 1 diabetes: 45.6% continuous subcutaneous insulin infusion (CSII) users and 54.4% multiple daily insulin injection users. The six-factor model had a very good fit in our sample. The internal consistency was acceptable (Cronbach's α = 0.75; 95% IC [0.65-0.81]). Diabetes treatment satisfaction was positively correlated with a positive attitude towards CSII therapy (Spearman's rho = 0.31; p < 0.01), less Technology Dependency, higher Ease of Use, and less Impaired Body Image. Furthermore, less Technology Dependency was associated with lower diabetes distress and depressive symptoms. CONCLUSIONS: The IT-IPA is a valid and reliable questionnaire evaluating attitudes towards insulin pump therapy. The questionnaire can be used for clinical practice during consultations for shared decision-making to CSII therapy.

Prognosis and Survival in Idiopathic Pulmonary Fibrosis in the Era of Antifibrotic Therapy in Italy: Evidence from a Longitudinal Population Study Based on Healthcare Utilization Databases.

The aim was to evaluate the determinants of acute exacerbation (AE) and death in new cases of idiopathic pulmonary fibrosis (IPF) using administrative databases in the Marche Region. Adults at their first prescription of antifibrotics or hospitalization with a diagnosis of IPF occurring in 2014-2019 were considered as new cases. Multiple Cox regression was used to estimate the risk of AE and of all-cause mortality adjusted by demographic and clinical characteristics, stratifying patients according to antifibrotic treatment. Overall, 676 new cases of IPF were identified and 276 deaths and 248 AE events occurred. In never-treated patients, the risk of AE was higher in patients with poor health conditions at diagnosis; the risk of death was higher in males, in patients aged ≥75 and in those with poor health conditions at baseline. The increasing number of AEs increased the risk of death in treated and never-treated patients. Within the limits of an observational study based on secondary data, the combined use of healthcare administrative databases allows the accurate analysis of progression and survival of IPF from the beginning of the antifibrotic therapy era, suggesting that timely and early diagnosis is critical to prescribing the most suitable treatment to increase survival and maintain a healthy life expectancy.

Impact of the COVID-19 Pandemic on the Therapeutic Continuity among Outpatients with Chronic Cardiovascular Therapies.

The COVID-19 pandemic poses major challenges to healthcare systems. We aimed to investigate the impact of the pandemic on prescription and adherence patterns of chronic cardiovascular therapies (lipid-lowering [LL], oral antidiabetic drugs [AD], and antihypertensives [AH]) using administrative pharmaceutical databases. For each treatment, two cohorts of prevalent cases in 2019 and 2020 were compared. We evaluated the percentage change in dispensed packages and treatment adherence as a proportion of days covered (PDC). For all therapies, an increase was observed during March-April 2020 (LL: +4.52%; AD: +2.72%; AH: +1.09%), with a sharp decrease in May-June 2020 (LL: -8.40%; AD: -12.09%; AH: -10.54%) compared to 2019. The impact of the COVID-19 pandemic on chronic cardiovascular treatments appears negligible on adherence: 533,414 patients showed high adherence to LL (PDC ≥ 80%) in January-February 2020, and 2.29% became poorly adherent (PDC < 20%) in the following four-month period (vs. 1.98% in 2019). A similar increase was also observed for AH (1.25% with poor adherence in 2020 vs. 0.93% in 2019). For AD, the increase was restrained (1.55% with poor adherence in 2020 vs. 1.37% in 2019). The rush to supply drugs at the beginning of lockdown preserved the continuity of chronic cardiovascular therapies.

Development and Validation of a Novel Pre-Pregnancy Score Predictive of Preterm Birth in Nulliparous Women Using Data from Italian Healthcare Utilization Databases.

Background: Preterm birth is a major worldwide public health concern, being the leading cause of infant mortality. Understanding of risk factors remains limited, and early identification of women at high risk of preterm birth is an open challenge. Objective: The aim of the study was to develop and validate a novel pre-pregnancy score for preterm delivery in nulliparous women using information from Italian healthcare utilization databases. Study Design: Twenty-six variables independently able to predict preterm delivery were selected, using a LASSO logistic regression, from a large number of features collected in the 4 years prior to conception, related to clinical history and socio-demographic characteristics of 126,839 nulliparous women from Lombardy region who gave birth between 2012 and 2017. A weight proportional to the coefficient estimated by the model was assigned to each of the selected variables, which contributed to the Preterm Birth Score. Discrimination and calibration of the Preterm Birth Score were assessed using an internal validation set (i.e., other 54,359 deliveries from Lombardy) and two external validation sets (i.e., 14,703 and 62,131 deliveries from Marche and Sicily, respectively). Results: The occurrence of preterm delivery increased with increasing the Preterm Birth Score value in all regions in the study. Almost ideal calibration plots were obtained for the internal validation set and Marche, while expected and observed probabilities differed slightly in Sicily for high Preterm Birth Score values. The area under the receiver operating characteristic curve was 60%, 61% and 56% for the internal validation set, Marche and Sicily, respectively. Conclusions: Despite the limited discriminatory power, the Preterm Birth Score is able to stratify women according to their risk of preterm birth, allowing the early identification of mothers who are more likely to have a preterm delivery.

Decision-making and risk-taking in forensic and non-forensic patients with schizophrenia spectrum disorders: A multicenter European study.

Studies of patients with schizophrenia and offenders with severe mental disorders decision-making performance have produced mixed findings. In addition, most earlier studies have assessed decision-making skills in offenders or people with mental disorders, separately, thus neglecting the possible additional contribution of a mental disorder on choice patterns in people who offend. This study aimed to fill this gap by comparing risk-taking in patients with schizophrenia spectrum disorders (SSD), with and without a history of serious violent offending assessing whether, and to what extent, risk-taking represents a significant predictor of group membership, controlling for their executive skills, as well as for socio-demographic and clinical characteristics. Overall, 115 patients with a primary diagnosis of SSD were recruited: 74 were forensic patients with a lifetime history of severe interpersonal violence and 41 were patients with SSD without such a history. No significant group differences were observed on psychopathological symptoms severity. Forensic generally displayed lower scores than non-forensic patients in all cognitive subtests of the Brief Assessment of Cognition in Schizophrenia (except for the "token motor" and the "digit sequencing" tasks) and on all the six dimensions of the Cambridge Gambling Task, except for "Deliberation time", in which forensic scored higher than non-forensic patients. "Deliberation time" was also positively, although weakly correlated with "poor impulse control". Identifying those facets of impaired decision-making mostly predicting offenders' behaviour among individuals with mental disorder might inform risk assessment and be targeted in treatment and rehabilitation protocols.

Clinical determinants of cerebrovascular reactivity in very preterm infants during the transitional period.

BACKGROUND: Preterm infants are at enhanced risk of brain injury due to altered cerebral haemodynamics during postnatal transition. This observational study aimed to assess the clinical determinants of transitional cerebrovascular reactivity and its association with intraventricular haemorrhage (IVH). METHODS: Preterm infants <32 weeks underwent continuous monitoring of cerebral oxygenation and heart rate over the first 72 h after birth. Serial cranial and cardiac ultrasound assessments were performed to evaluate the ductal status and to diagnose IVH onset. The moving correlation coefficient between cerebral oxygenation and heart rate (TOHRx) was calculated. Linear mixed-effect models were used to analyse the impact of relevant clinical variables on TOHRx. The association between TOHRx and IVH development was also assessed. RESULTS: Seventy-seven infants were included. A haemodynamically significant patent ductus arteriosus (hsPDA) (ß = 0.044, 95% CI: 0.007-0.081) and ongoing dopamine treatment (ß = 0.096, 95% CI: 0.032-0.159) were associated with increasing TOHRx, indicating impaired cerebrovascular reactivity. A significant association between TOHRx, mean arterial blood pressure (ß = -0.004, 95% CI: -0.007, -0.001) and CRIB-II score (ß = 0.007, 95% CI: 0.001-0.015) was also observed. TOHRx was significantly higher in infants developing high-grade IVH compared to those without IVH. CONCLUSIONS: Dopamine treatment, low blood pressure, hsPDA and high CRIB-II are associated with impaired cerebrovascular reactivity during postnatal transition, with potential implications on IVH development. IMPACT: The correlation coefficient between cerebral oxygenation and heart rate (TOHRx) provides a non-invasive estimation of cerebrovascular reactivity, whose failure has a potential pathogenic role in the development of IVH in preterm infants. This study shows that cerebrovascular reactivity during the transitional period improves over time and is affected by specific clinical and therapeutic factors, whose knowledge could support the development of individualized neuroprotective strategies in at-risk preterm infants. The evidence of increased TOHRx in infants developing high-grade compared to low-grade or no IVH during the transitional period further supports the role of impaired cerebrovascular reactivity in IVH pathophysiology.

Comparing risk adjustment estimation methods under data availability constraints.

The Italian National Healthcare Service relies on per capita allocation for healthcare funds, despite having a highly detailed and wide range of data to potentially build a complex risk-adjustment formula. However, heterogeneity in data availability limits the development of a national model. This paper implements and ealuates machine learning (ML) and standard risk-adjustment models on different data scenarios that a Region or Country may face, to optimize information with the most predictive model. We show that ML achieves a small but generally statistically insignificant improvement of adjusted R2 and mean squared error with fine data granularity compared to linear regression, while in coarse granularity and poor range of variables scenario no differences were observed. The advantage of ML algorithms is greater in the coarse granularity and fair/rich range of variables set and limited with fine granularity scenarios. The inclusion of detailed morbidity- and pharmacy-based adjustors generally increases fit, although the trade-off of creating adverse economic incentives must be considered.

Occurrence of Idiopathic Pulmonary Fibrosis in Italy: Latest Evidence from Real-World Data.

The aim of the study was to evaluate the trend in the incidence of idiopathic pulmonary fibrosis (IPF) in a real-world setting of the Marche region, a region of Central Italy, between 2014 and 2019. This observational prospective study was based on administrative databases of hospital discharges and drug prescriptions. All adult residents in the Marche Region with a first prescription of antifibrotic drugs, or a first hospitalization with a diagnosis of IPF during the study period, were identified as incident cases of IPF. A multiple Poisson regression analysis was used to estimate the IPF incidence trend, adjusted for age, sex, and health conditions. The mean incidence rate was 9.8 cases per 100,000 person-years. A significant increasing trend of 6% per year was observed. The incidence rates were significantly higher in males than females, older subjects, and those with poorer health conditions. To our knowledge, this is the first study evaluating incidences of IPF over a 6-year period in Italy, combining hospital discharge and drug prescription databases. The study highlights that the combined use of two secondary sources is a reliable strategy to accurately identify new cases of IPF when the appropriate disease registry is lacking.

Serotonin reuptake inhibitor-cognitive behavioural therapy-second generation antipsychotic combination for severe treatment-resistant obsessive-compulsive disorder. A prospective observational study.

INTRODUCTION: Six in ten patients with obsessive-compulsive disorder (OCD) do not respond to the first-line treatments with serotonin reuptake inhibitor (SRI) or cognitive behavioural therapy including exposure and response prevention (CBT/ERP), and several do not respond to second-line treatments, i.e., SRI-second generation antipsychotic (SGA) or SRI-CBT/ERP augmentation. Evidence on third-line treatments is inconsistent. OBJECTIVE: We investigated the 1-year response to SRI-CBT/ERP-SGA combination in patients with severe treatment-resistant OCD, who failed to respond to SRI and to SRI-SGA or SRI-CBT/ERP augmentation. METHODS: Twenty-eight patients were consecutively recruited and treated with SRI (drug(s) and doses previously administered), SGA (risperidone median dosage 1 mg/day in 14 cases, aripiprazole median dosage 3 mg/day in 14 cases) and CBT/ERP (median hours 32.5). Exclusion criteria: mental retardation and organic brain syndrome. RESULTS: The mean Y-BOCS total score reduction at 12 months was 28.2%, 60.7% of patients improved, 46.4% partially responded, 32.1% responded, and 28.6% remitted. Patients previously resistant to SRI-SGA and SRI-CBT/ERP did not significantly differ in the rates of improvement, partial response, response and remission. CONCLUSIONS: This study suggests that SRI-SGA-CBT/ERP combination could be useful for severe treatment-resistant OCD. Small sample size is a limitation.Key pointsUp to 6 in 10 patients with OCD do not respond to first line treatments (CBT/ERP or SRIs) and several to second-line treatments (SRI-SGA or SRI CBT/ERP augmentation).In our study, patients with OCD resistant to the first and the second line treatment improved (61%), partially responded (46%), responded (32%), or remitted (29%) combining SRI, SGA and CBT/ERP.In our patients the SRI-SGA-CBT/ERP augmentation improved working/school, social and family impairment.SRI-SGA-CBT/ERP augmentation is easier to use than other treatments for severe treatment-resistant OCD.

Supply-side solutions targeting demand-side characteristics: causal effects of a chronic disease management program on adherence and health outcomes.

We estimate the effects of a chronic disease management program (CDMP) which adapts various supply-side interventions to specific demand-side conditions (disease-staging) for patients with chronic kidney disease (CKD). Using a unique dataset on the entire population of the Emilia-Romagna region of Italy with hospital-diagnosed CKD, we estimate the causal effects of the CDMP on adherence indicators and health outcomes. As CKD is a progressive disease with clearly-defined disease stages and a treatment regimen that can be titrated by disease severity, we calculate dynamic, severity-specific, indicators of adherence as well as several long-term health outcomes. Our empirical work produces statistically significant and sizeable causal effects on many adherence and health outcome indicators across all CKD patients. More interestingly, we show that the CDMP produces larger effects on patients with early-stage CKD, which is at odds with some of the literature on CDMP that advocates intensifying interventions for high-cost (or late-stage) patients. Our results suggest that it may be more efficient to target early-stage patients to slow the deterioration of their health capital. The results contribute to a small, recent literature in health economics that focuses on the marginal effectiveness of CDMPs after controlling either for supply- or demand-side sources of heterogeneity.

Mortality of patients with bullous pemphigoid in Italy: a retrospective study of a monocentric experience.

BACKGROUND: Mortality of bullous pemphigoid (BP) is a variable parameter, depending especially on the area where the study was conducted. The 1-year mortality rate and the identification of clinic-therapeutic factors with potential prognostic value in patients with BP were evaluated in a cohort from a single referral center. METHODS: We have reviewed medical records of patients with BP diagnosed at the Sant' Orsola-Malpighi Hospital in Bologna (Italy) between 2005 and 2019. Data collected included sex, age at diagnosis, laboratory findings, severity of disease, dosage of systemic treatments, age at death and comorbidities. Only patients who had at least 1 year of follow-up were included. RESULTS: Eighty-five patients were included; the mortality rate was 7.1%. The mortality rate of patients treated with a moderate dosage of corticosteroids was no higher than that of patients treated with a low dosage. The log-rank test showed a statistically significant correlation between mortality and patients aged ≥85, BP230 positive, and CCIS≥4. CONCLUSIONS: Compared with similar studies, our results show a lower 1-year mortality rate. Advanced age at diagnosis and CCIS were confirmed as major independent factors associated with poor prognosis in BP. Administration of moderate dosage of oral corticosteroids seems to have an overall positive benefit-risk ratio, providing a good control of the disease and minimizing the risk of hospitalization, possible related complications and the mortality rate.

Efficacy and safety of 24-week pramipexole augmentation in patients with treatment resistant depression. A retrospective cohort study.

Pramipexole is a dopamine agonist with potential antidepressant, neuroprotective, antioxidant and anti-inflammatory activity. In the present study we investigated the 24 weeks effect and safety of traditional AD augmentation with pramipexole for treatment-resistant depression. The study includes 116 patients, 37 (32%) with bipolar disorders and 79 (68%) with major depressive disorder, who failed to respond to at least 2 ADs trials of different classes and that were treated with AD augmented with pramipexole. Mood stabilizers and/or second-generation antipsychotics were added in patients with bipolar or mixed depression. Exclusion criteria were psychotic depression, rapid cycling bipolar course and previous unsuccessful treatment with pramipexole. After 24 weeks of pramipexole augmentation (median max dose 1.05 mg/day, IQR 0.72-1.08) 74.1% of patients responded (≥50% reduction of baseline Hamilton Depression Rating Scale21 total score) and 66.4% remitted (Hamilton Depression Rating Scale21 total score < 7). Global Assessment of Functioning score significantly increase from 53 (50-60) at baseline to 80 (71-81) at 24 weeks (Wilcoxon signed rank test = 8.174, p < 0.001]. Ten patients (8.6%) dropped out (8 due to side effects and 2 for lack of efficacy) and 1 experienced an induced hypomanic switch. No patient committed a suicide attempt, had suicidal ideation, needed hospitalization, reported lethargy, gambling, hypersexuality and compulsive shopping. The limitations of the study are the observational design, the lack of a control group, the inclusion of outpatients only, the unblinded outcomes assessment, and the flexibility of the add-on schedule. The findings of the present study showed that off-label use of pramipexole as augmentation of traditional AD is an effective and safe 24 weeks treatment of resistant unipolar and bipolar depression. These results need confirmation from randomized clinical trials on larger samples.

Is it time to consider depression as a major complication of type 2 diabetes? Evidence from a large population-based cohort study.

AIMS: Depression in type 2 diabetes may heavily affect the course of the disease. In this study, we investigated, among new cases with type 2 diabetes, the incidence and clinical predictors of depression and determined the extent to which depression constitutes a risk factor for acute and long-term diabetes complications and mortality. METHODS: In this population-based retrospective cohort study, incident cases of type 2 diabetes without a prior history of depression were identified from the administrative databases of the Emilia-Romagna Region, Italy, between 2008 and 2017 and followed up until 2020. Logistic regression models were used to identify the predictors of depression. Cox regression models were used to estimate the risk of acute complications over three years, and the risk of long-term complications and mortality over ten years. RESULTS: Incident cases with type 2 diabetes were 30,815, of whom 5146 (16.7%) developed depression. The predictors of depression onset were as follows: female sex, age > 65 years, living in rural areas and comorbid diseases. Depression in type 2 diabetes was associated with a 2.3-fold risk of developing acute complications, 1.6-fold risk of developing long-term complications and 2.8-fold mortality risk. CONCLUSIONS: Our findings highlight that depression is associated with an increased risk for complications in type 2 diabetes and mortality and should not be neglected. Therefore, it is important to promote screening activities and introduce targeted and personalized treatment for depression in order to reduce the risk of poor short- and long-term outcomes of diabetes.