The progression trajectory of Bipolar Disorder: results from the application of a staging model over a ten-year observation.

BACKGROUND: Trying to better define Bipolar Disorder (BD) progression, different staging models have been conceptualized, each one emphasizing different aspects of illness. In a previous article we retrospectively applied the main staging models to a sample of 100 bipolar patients at four time points over a ten-year observation. In the present study, focusing on Kupka & Hillegers's model, we aimed to assess the transition of the same sample through the different stages of illness and to explore the potential role of clinical variables on the risk of progression. METHODS: Multistate Model using the mstate package in R and Markov model with stratified hazards were used for statistical analysis. RESULTS: A high hazard of transition from stage 2 to 3 emerged, with a probability of staying in stage 2 decreasing to 14 % after 3 years. BD II was significantly associated with transition from stage 1 to 2, whereas the number of lifetime episodes >3 and the elevated predominant polarity with transition from stage 3 to 4. CONCLUSION: Our results corroborated the evidence on BD progression and contributed to outline its trajectory over time. Further effort may help to define a standardized staging approach towards ever increasing tailored interventions.

Utility, acceptability and applicability of a nucleic acid amplification test in comparison with a syndromic approach in the management of sexually transmitted diseases at Mulago National Referral Hospital in Uganda (ASTRHA): protocol for an open-label, randomised controlled trial.

INTRODUCTION: Sexually transmitted diseases (STDs) are a major cause of long-term disability. Urethral discharge syndrome (UDS), abnormal vaginal discharge (AVD) and genital ulcer disease (GUD) are very common in low-income and middle-income countries (LMICs), where, due to lack of resources, these infections are managed according to a syndromic approach. Although microbiological diagnosis using nuclear acid amplification tests (NAAT) is already a standard to prescribe targeted treatments in industrialised countries, no randomised clinical trials have been conducted to evaluate clinical usefulness and acceptability of NAAT in comparison with syndromic approach in LMICs. The results of this study could inform diagnostic guidelines since they may suggest an update of the current recommendation if microbiological diagnosis using NAAT in the management of STD is demonstrated to be both useful and acceptable in an LMIC context. METHODS AND ANALYSIS: The primary objective of this randomised, open-label trial is to evaluate the clinical usefulness of a NAAT and its acceptability in comparison with a clinical syndromic approach and to explore whether this test could replace the syndromic approach in the management of STDs at a national referral hospital in Uganda. 220 patients presenting to the STD clinic at Mulago Hospital in Kampala, Uganda with AVD, UDS or GUD will be randomised to either standard of care (syndromic management) or NAAT-based treatment with a 1:1 ratio. All the patients will be asked to return after 2 or 3 weeks for a control visit. Primary outcome will be therapeutic appropriateness. ETHICS AND DISSEMINATION: This trial was approved by the Mulago Hospital Research and Ethical Committee (MHREC2023-97) and the Uganda National Council for Science and Technology (HS31000ES). Patients will give informed consent to participate before taking part in the study. Results will be published in peer-reviewed journals in open-access formats and data made available in anonymised form. TRIAL REGISTRATION NUMBER: NCT05994495.

Predictors of Nursing Home Placement in a Cohort of European People with Alzheimer's Disease and Other Dementia Cases Enrolled in SCU-B or Non SCU-B Centers: The RECage Study.

Background: Nursing home placement (NHP) can be the final step of patients with Alzheimer's disease. Objective: We aimed to identify NHP predictors among 508 people with dementia with a 3-year follow-up. Methods: We analyzed data from the international observational RECage study, involving 508 people with especially Alzheimer's disease and comparing a cohort enrolled by five centers with a Special Care Unit for BPSD (behavioral and psychological symptoms of dementia) and another one enrolled by six centers lacking this facility. The tertiary objective of the study was to assess the possible role of the SCU-B in delaying NHP. We assessed the relationship of the baseline characteristics with NHP by means of univariate analysis followed by Cox's multivariate model. Results: Patients' mean age was 78.1 years, 54.9% were women. Diagnosis mean age was 75.4 (±8.32) years; the main diagnosis was Alzheimer's disease (296; 58.4%). During follow-up, 96 (18.9%) patients died and 153 (30.1%) were institutionalized without a statistically significant difference between the two cohorts (p = 0.9626). The mean NHP time was 902 (95% CI: 870-934). The multivariable analysis without death as a competing risk retained four independent predictors of NHP: age increase (hazard ratio (HR) = 1.023, 95% CI: 1.000-1.046), patient education level increase (HR = 1.062, 95% CI: 1.024-1.101), Neuropsychiatric Inventory total increase (HR = 1.018; 95% CI: 1.011-1.026), and total Mini-Mental State Examination as a favorable factor (HR = 0.948, 95% CI: 0.925-0.971). Gender (females versus males: HR = 1.265, 95% CI: 0.899-1.781) was included in the final Cox's model for adjusting the estimates for. Conclusions: Our data partially agree with the predictors of NHP in literature including the effect of high education level. No caregivers' factors were statistically significant. Clinical trial registration: NCT03507504.

Bland and Altman agreement method: to plot differences against means or differences against standard? An endless tale?

OBJECTIVES: In the Bland and Altman analysis of agreement studies, there is some controversy whether "to plot the differences between the Standard/actual measurement method and the test/new measurement method against their mean" or "to plot the differences against the standard method". Of course, this is not just a "graphic dispute" as a regression model is inherent in the graphical choice to test the proportional and systematic biases. METHODS: We revised two relevant papers claiming to plot the differences against the standard and outlined their pitfalls taking into account the underlying statistical methodology. Furthermore, we have considered the conditions (correlation between the two measurement methods and ratio of their variances) leading correlation coefficient and regression slope between differences and means or differences and standard different from zero. RESULTS: We have shown the situations in which the regression slope and the correlation coefficient calculated from the differences and means according to Bland and Altman approach or calculated from the differences and standard are closer to zero giving the minimum possible value of spurious proportional error between the two methods. CONCLUSIONS: We highlighted how the calculation of the expected values of the correlation coefficients and, above all, of the regression slope can be very useful for choosing the statistical model in the context of an agreement study between two measurement methods. Finally, we outlined some recommendations for understanding the real possibility of carrying out agreement or calibration studies.

Respectful Caring for the Agitated Elderly (ReCAGE): A Multicentre, Prospective, Observational Study to Evaluate the Effectiveness of Special Care Units for People with Dementia.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) bring complexity in the clinical management of people with dementia; therefore, it is important to evaluate different models of care, such as Special Care Units (SCU-B).∥Objective:To evaluate the SCU-B effectiveness toward alleviating BPSD and improving the quality of life (QoL) of patients and their caregivers.∥Methods:ReCAGE was a multicenter, controlled, longitudinal study where 508 patients with BPSD were enrolled in two cohorts: 262 patients from centers endowed with a SCU-B, and 246 from centers without SCU-B. Statistical analyses included factorial ANCOVA for comparison among centers. The primary endpoint was effectiveness of the SCU-B, measured through the Neuropsychiatric Inventory (NPI) changes. Secondary endpoints were change in QoL of patients and caregivers, and the tertiary endpoint was time to nursing home admission.∥Results:The NPI scores decreased in both arms, with a statistically significant difference from baseline to 36 months (p < 0.0001) in both cohorts. Over time, NPI decreased more steeply during the first year in the SCU-B arm, but in the following two years the slope was clearly in favor of the control arm. This different pattern of the two cohorts reached statistical significance at the interaction "cohort by time" (p < 0.0001). Conflicting results were found regarding the outcomes of quality of life, while there were no differences in time to institutionalization in both cohorts.∥Conclusion:The RECage study did not confirm the long-term superiority of the pathway comprising a SCU-B. A post-hoc analysis revealed data supporting their acute effectiveness during behavioral crises.

A Confirmatory and an Exploratory Factor Analysis of the Cohen-Mansfield Agitation Inventory (CMAI) in a European Case Series of Patients with Dementia: Results from the RECage Study.

BACKGROUND: One of the most widely used instruments for assessing agitation in dementia patients is the Cohen-Mansfield Agitation Inventory (CMAI), nevertheless no global score has been proposed. The aim of this study is: (a) to conduct a confirmatory (CFA) and exploratory factor analysis (EFA) of CMAI on people with dementia and Psychological and Behavioral Symptoms (BPSD), and (b) to propose an alternative structure, based on clinical criteria including all CMAI items. METHODS: Confirmatory and exploratory factor analyses were carried out on the CMAI 29 items administered at baseline to 505 patients with dementia (PwD) and BPSD enrolled in the international observational RECage study. RESULTS: The three-factor structure has not been confirmed by the CFA, whilst the EFA was carried out respectively on 25 items disregarding 4 items with a prevalence ≤5% and then on 20 items disregarding 9 items with a prevalence ≤10%. The four-factor structure explaining 56% of the variance comprised Physically Aggressive behavior, Verbally Aggressive behavior, Physically non-aggressive behavior, and Physically and verbally aggressive behavior. CONCLUSIONS: A new grouping of all items according to a clinical criterion is proposed, allowing for a more sensible evaluation of the symptoms leading to better differentiation.

Factors influencing the presence of potentially explosive gases during colonoscopy: Results of the SATISFACTION study.

This study tested the hypothesis that bowel preparation with mannitol should not affect the colonic concentration of H2 and CH4 . Therefore, the SATISFACTION study, an international, multicenter, randomized, parallel-group phase II-III study investigated this issue. The phase II dose-finding part of the study evaluated H2 , CH4 , and O2 concentrations in 179 patients randomized to treatment with 50 g, 100 g, or 150 g mannitol. Phase III of the study compared the presence of intestinal gases in 680 patients randomized (1:1) to receive mannitol 100 g in single dose or a standard split-dose 2 L polyethylene glycol (PEG)-Asc preparation (2 L PEG-Asc). Phase II results showed that mannitol did not influence the concentration of intestinal gases. During phase III, no patient in either group had H2 or CH4 concentrations above the critical thresholds. In patients with H2 and/or CH4 levels above detectable concentrations, the mean values were below the risk thresholds by at least one order of magnitude. The results also highlighted the effectiveness of standard washing and insufflation maneuvers in removing residual intestinal gases. In conclusion, bowel cleansing with mannitol was safe as the concentrations of H2 and CH4 were the same as those found in patients prepared with 2 L PEG-Asc. In both groups, the concentrations of gases were influenced more by the degree of cleansing achieved and the insufflation and washing maneuvers performed than by the preparation used for bowel cleansing. The trial protocol was registered with ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04759885) and with EudraCT (eudract_number: 2019-002856-18).

The three facets of the SARS-CoV-2 pandemic during the first two waves in the northern, central, and southern Italy.

BACKGROUND: There is a scarcity of information in literature regarding the clinical differences and comorbidities of patients affected by Coronavirus disease 2019 (COVID-19), which could clarify the different prevalence of the outcomes (composite and only death) between several Italian regions. OBJECTIVE: This study aimed to assess the heterogeneity of clinical features of patients with COVID-19 upon hospital admission and disease outcomes in the northern, central, and southern Italian regions. METHODS: An observational cohort multicenter retrospective study including 1210 patients who were admitted for COVID-19 in Infectious diseases, Pulmonology, Endocrinology, Geriatrics and Internal Medicine Units in Italian cities stratified between north (263 patients); center (320 patients); and south (627 patients), during the first and second pandemic waves of SARS-CoV-2 (from February 1, 2020 to January 31, 2021). The data, obtained from clinical charts and collected in a single database, comprehended demographic characteristics, comorbidities, hospital and home pharmacological therapies, oxygen therapy, laboratory values, discharge, death and Intensive care Unit (ICU) transfer. Death or ICU transfer were defined as composite outcomes. RESULTS: Male patients were more frequent in the northern Italian region than in the central and southern regions. Diabetes mellitus, arterial hypertension, chronic pulmonary and chronic kidney diseases were the comorbidities more frequent in the southern region; cancer, heart failure, stroke and atrial fibrillation were more frequent in the central region. The prevalence of the composite outcome was recorded more frequently in the southern region. Multivariable analysis showed a direct association between the combined event and age, ischemic cardiac disease, and chronic kidney disease, in addition to the geographical area. CONCLUSIONS: Statistically significant heterogeneity was observed in patients with COVID-19 characteristics at admission and outcomes from northern to southern Italy. The higher frequency of ICU transfer and death in the southern region may depend on the wider hospital admission of frail patients for the availability of more beds since the burden of COVID-19 on the healthcare system was less intense in southern region. In any case, predictive analysis of clinical outcomes should consider that the geographical differences that may reflect clinical differences in patient characteristics, are also related to access to health-care facilities and care modalities. Overall, the present results caution against generalizability of prognostic scores in COVID-19 patients derived from hospital cohorts in different settings.

Staging models applied in a sample of patients with bipolar disorder: Results from a retrospective cohort study.

BACKGROUND: Bipolar Disorder (BD) is a life-long illness with compelling evidence of progression. Although different staging models have been proposed to evaluate its course, clinical data remain limited. The aim of the present study was to retrospectively assess applicability of available staging approaches and their pattern of progression in a sample of bipolar patients. METHODS: In a naturalistic sample of 100 BD patients, retrospective assessment of clinical stages was performed at four time points over 10 years, according to four staging models. Staging progression with potential associations between stages and unfavourable illness characteristics were analyzed. RESULTS: A pattern of stage worsening emerged for each model, with a significant increase at every time point. Greater stage increases emerged in patients with lower educational level, age at first elevated episode ≤35 years, duration of illness ≤25 years, and duration of untreated illness ≤5 years. Lower stage values were associated with BD II, no psychiatric hospitalization, depressive onset and predominant polarity, ≤three lifetime episodes, age at first mood stabilizer >40 years, duration of illness ≤25 years, and engaged/employed status. Higher stage values were associated with lower age at first elevated episode and mood stabilizing treatment instead. LIMITATIONS: Naturalistic and retrospective design, recruitment at a 2nd level specialistic clinic. CONCLUSIONS: Reported findings support the progressive nature of BD and the application of staging models for early intervention, suggesting a conceptualization of a standardized approach to better characterize patients, predict their clinical course, and deliver tailored treatment options.

Lessons learned and implications of early therapies for coronavirus disease in a territorial service centre in the Calabria region: a retrospective study.

BACKGROUND: Monoclonal antibodies (mAbs) and antivirals have been approved for early therapy of coronavirus disease (COVID-19), however, in the real-life setting, there are difficulties to prescribe these therapies within few days from symptom onset as recommended, and effectiveness of combined use of these drugs have been hypothesised in most-at-risk patients (such as those immunocompromised) but data supporting this strategy are limited. METHODS: We describe the real-life experience of SARS-CoV-2 antivirals and/or monoclonal antibodies (mAbs) and focus on the hospitalisation rate due to the progression of COVID-19. Clinical results obtained through our risk-stratification algorithm and benefits achieved through a strategic proximity territorial centre are provided. We also report a case series with an in-depth evaluation of SARS-CoV-2 genome in relationship with treatment strategy and clinical evolution of patients. RESULTS: Two hundred eighty-eight patients were analysed; 94/288 (32.6%) patients were treated with mAb monotherapy, 171/288 (59.4%) patients were treated with antivirals, and 23/288 (8%) patients received both mAbs and one antiviral drug. Haematological malignancies were more frequent in patients treated with combination therapy than in the other groups (p = 0.0003). There was a substantial increase in the number of treated patients since the opening of the centre dedicated to early therapies for COVID-19. The provided disease-management and treatment appeared to be effective since 98.6% patients recovered without hospital admission. Moreover, combination therapy with mAbs and antivirals seemed successful because all patients admitted to the hospital for COVID-19 did not receive such therapies, while none of the most-at-risk patients treated with combination therapy were hospitalized or reported adverse events. CONCLUSIONS: A low rate of COVID-19 progression requiring hospital admission was observed in patients included in this study. The dedicated COVID-19 proximity territorial service appeared to strengthen the regional sanitary system, avoiding the overwhelming of other services. Importantly, our results also support early combination therapy: it is possible that this strategy reduces the emergence of escape mutants of SARS-CoV-2, thereby increasing efficacy of early treatment, especially in immunocompromised individuals.

Bone Strain Index: preliminary distributional characteristics in a population of women with normal bone mass, osteopenia and osteoporosis.

PURPOSE: Bone Strain Index (BSI) is a recently developed dual-energy X-ray absorptiometry (DXA) software, applying a finite element analysis on lumbar spine and femoral DXA scans. BSI is a parameter of bone deformation, providing information on bone resistance to applied loads. BSI values indicate the average bone strain in the explored site, where a higher strain (higher BSI values) suggests a higher fracture risk. This study reports the distributional characteristics of lumbar BSI (L-BSI) in women with normal bone mass, osteopenia or osteoporosis and their relationships with BMD, weight, height and BMI. MATERIAL AND METHODS: Two-hundred-fifty-nine consecutive unfractured women who performed DXA were divided into three groups based on BMD T-score: normal bone mass (n = 43, 16.6%), osteopenia (n = 82, 31.7%) and osteoporosis (n = 134, 51.7%). The distribution of L-BSI was evaluated with conventional statistical methods, histograms and by calculating parametric and nonparametric 95% confidence intervals, together with the 90%, 95% and 99% bilateral tolerance limits with a 95% confidence. RESULTS: Ninety percent bilateral tolerance limits with 95% confidence for L-BSI distribution are 1.0-2.40, 0.95-2.63 and 0.84-3.15 in the group of patients with normal bone mass, 1.34-2.78, 1.24-2.95 and 1.05-3.32 in the osteopenic group and 1.68-3.79, 1.58-4.15 and 1.40-4.96 in the osteoporotic group. CONCLUSION: In women without vertebral fractures at baseline, L-BSI values from 1.68 (osteoporotic group) and 2.40 (upper of the normal bone mass group) can be tentatively chosen as a lower and upper threshold to stratify postmenopausal women according to their bone resistance to loads.

Psychological impact of COVID-19 after hospital discharge: A follow-up study on Italian recovered patients.

BACKGROUND: Since COVID-19 outbreak, clinical experience on its management during the acute phase has rapidly grown, including potential effects on the psychopathological dimension. However, still few data are available regarding the impact on survivors' mental health over the long-term. METHODS: A sample of 1457 COVID-19 patients underwent a multidisciplinary follow-up protocol, approximately 3 months after hospital discharge, including a psychological evaluation. The primary outcomes were anxiety, depression, resilience, post-traumatic symptoms, and health-related quality of life. Furthermore, we examined the potential role of hospitalization and delay in the follow-up assessment on the increased burden of illness. RESULTS: Although a general high level of resilience emerged, suggesting most patients relied on their individual and interpersonal resources to face difficulties related to the pandemic, almost one third of the sample reported signs of psychological distress over time, especially post-traumatic symptoms, with anxiety being more represented than depression. Furthermore, hospitalization - regardless of the setting of care - and promptness in follow-up evaluation were found to play a protective role on patients' recovery and mental wellbeing. LIMITATIONS: Selection bias of patients exclusively admitted to the hospital; absence of a control group; psychological assessment relying on self-reported instruments. CONCLUSIONS: The current crisis demands resilience and adjustment resources, either in the acute and post-acute phase. Thus, the clinical effort should aim at relieving the traumatic impact of such condition through timely interventions. Further investigation may address potential predictors of developing a traumatic stress response, in order to identify and promptly treat at-risk subpopulations.

Pharmacokinetics of oral mannitol for bowel preparation for colonoscopy.

This study aimed to define the pharmacokinetics (PKs) of oral mannitol used as an osmotic laxative for bowel preparation for colonoscopy. The PKs of oral mannitol was evaluated in a substudy as part of a phase II dose-finding, international, multicenter, randomized, parallel-group, endoscopist-blinded study. Patients were randomly assigned to take 50, 100, or 150 g mannitol. Venous blood samples were drawn at baseline (T0), 1 h (T1), 2 h (T2), 4 h (T4), and 8 h (T8) after completion of mannitol self-administration. The mean mannitol plasma concentrations (mg/ml) were dose-dependent with a consistent difference among doses. The mean maximum concentration (Cmax) ± SD was 0.63 ± 0.15, 1.02 ± 0.28, and 1.36 ± 0.39 mg/ml, in the three dosage groups, respectively. The mean area under the curve from zero to infinity (AUC0-∞) was 2.667 ± 0.668, 4.992 ± 1.706, and 7.403 ± 3.472 mg/ml*h in the 50, 100, and 150 g mannitol dose groups, respectively. Bioavailability was similar in the three dose groups and was just over 20% (0.243 ± 0.073, 0.209 ± 0.081, and 0.228 ± 0.093 in the 50, 100, and 150 g mannitol dose groups, respectively). The present study showed that the bioavailability of oral mannitol is just over 20% and is similar for the three tested doses (50, 100, and 150 g). The linear increase in Cmax, AUC0-t8, and AUC0-∞ must be considered when choosing the oral mannitol dose for bowel preparation to avoid its systemic osmotic effects.

Factors associated with lifetime suicide attempts in bipolar disorder: results from an Italian nationwide study.

The purpose of the present study was to detect demographic and clinical factors associated with lifetime suicide attempts in Bipolar Disorder (BD). A total of 1673 bipolar patients from different psychiatric departments were compared according to the lifetime presence of suicide attempts on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (presence of suicide attempts) at the univariate analyses, preliminary multiple logistic regression analyses were realized. A final multivariable logistic regression was then performed, considering the presence of lifetime suicide attempts as the dependent variable and statistically significant demographic/clinical characteristics as independent variables. The final multivariable logistic regression analysis showed that an earlier age at first contact with psychiatric services (odds ratio [OR] = 0.97, p < 0.01), the presence of psychotic symptoms (OR = 1.56, p < 0.01) or hospitalizations (OR = 1.73, p < 0.01) in the last year, the attribution of symptoms to a psychiatric disorder (no versus yes: OR = 0.71, partly versus yes OR = 0.60, p < 0.01), and the administration of psychoeducation in the last year (OR = 1.49, p < 0.01) were all factors associated with lifetime suicide attempts in patients affected by BD. In addition, female patients resulted to have an increased association with life-long suicidal behavior compared to males (OR: 1.02, p < 0.01). Several clinical factors showed complex associations with lifetime suicide attempts in bipolar patients. These patients, therefore, require strict clinical monitoring for their predisposition to a less symptom stabilization. Future research will have to investigate the best management strategies to improve the prognosis of bipolar subjects presenting suicidal behavior.

Prevalence of Antibiotic Resistance Over Time in a Third-Level University Hospital.

This study evaluated the spread and possible changes in resistance patterns of ESKAPE bacteria to first-choice antibiotics from 2015 to 2019 at a third-level university hospital after persuasive stewardship measures were implemented. Isolates were divided into three groups (group 1, low drug-resistant; group 2, multidrug/extremely drug-resistant; and group 3, pan-resistant bacteria) and a chi-squared test (χ2) was applied to determine differences in their distributions. Among the 2,521 isolates, Klebsiella pneumoniae was the most frequently detected (31.1%). From 2015 to 2019, the frequency of isolates in groups 2 and 3 decreased from 70.1% to 48.6% (χ2 = 63.439; p < 0.0001). Stratifying isolates by bacterial species, for K. pneumoniae, the frequency of PDR isolates decreased from 20% to 1.3% (χ2 = 15.885; p = 0.003). For Acinetobacter baumannii, a statistically significant decrease was found in groups 2 and 3: from 100% to 83.3% (χ2 = 27.721; p < 0.001). Also, for Pseudomonas aeruginosa and Enterobacter spp., the frequency of groups 2 and 3 decreased from 100% to 28.3% (χ2 = 225.287; p < 0.001) and from 75% to 48.7% (χ2 = 15.408; p = 0.003), respectively. These results indicate that a program consisting of persuasive stewardship measures, which were rolled out during the time frame of our study, may be useful to control drug-resistant bacteria in a hospital setting.

Effect of directly acting antivirals for hepatitis C virus infection on proprotein convertase subtilisin/kexin type 9 level.

BACKGROUND AND AIMS: Eradication of the hepatitis C virus (HCV) may affect proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and cardiovascular risk. However, information regarding PCSK9 level after HCV eradication is lacking. Hence, in this case-control retrospective study, we aimed to evaluate PCSK9 level from pretherapy baseline up to sustained virological response (SVR). METHODS: Eighty-four patients treated with directly acting antivirals (DAAs) between July 2015 and May 2018 were enrolled. Differences in baseline PCSK9 level due to absence/presence of recorded baseline characteristics (covariates) were evaluated. Changes in PCSK9 levels from pretherapy to SVR (ΔPCSK9) and their correlations with the covariates were assessed. The repeated measures analysis of variance was used to investigate the differences in PCSK9 level from the baseline to the achievement of SVR due to absence/presence of any covariate. RESULTS: The mean age of the patients was 67.6 ± 11 years, and 53.6% were males. Baseline PCSK9 levels were statistically lower in patients using statins than in those not using statins (mean, 70.3 ± 43.1 ng/mL vs 271.8 ± 252.2 ng/mL; P = .017). PCSK9 level decreased significantly from baseline to the time of SVR (255 ± 248 ng/mL vs 169 ± 188 ng/mL; P < .001). PCSK9 levels were statistically higher in the HCV-infected patients at baseline than in the control group (255 ± 248 vs 166.3 ± 120.2 ng/mL; P = .020); however, this difference was lost after achieving SVR (mean, 169 ± 188 vs 166.3 ± 120.2 ng/mL; P = .464). Changes in PCSK9 level was not statistically related to any of the recorded covariates. The PCSK9 mean level did not differ significantly with absence/presence of any covariate from pretherapy to SVR. CONCLUSIONS: The reduction in mean PCSK9 level from baseline pretherapy to after HCV eradication was statistically significant. Whether PCSK9 is a new biomarker for cardiovascular risk in these patients remains to be ascertained.

Rationale, Design, and Methodology of a Prospective Cohort Study for Coping with Behavioral and Psychological Symptoms of Dementia: The RECage Project.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are quite challenging problems during the dementia course. Special Care Units for people with dementia (PwD) and BPSD (SCU-B) are residential medical structures, where BPSD patients are temporarily admitted, in case of unmanageable behavioral disturbances at home. OBJECTIVE: RECage (REspectful Caring for AGitated Elderly) aspires to assess the short and long-term effectiveness of SCU-Bs toward alleviating BPSD and improving the quality of life (QoL) of PwD and their caregivers. METHODS: RECage is a three-year, prospective study enrolling 500 PwD. Particularly, 250 community-dwelling PwDs presenting with severe BPSD will be recruited by five clinical centers across Europe, endowed with a SCU-B, for a short period of time; a second similar group of 250 PwD will be followed by six other no-SCU-B centers solely via outpatient visits. RECage's endpoints include short and long-term SCU-B clinical efficacy, QoL of patients and caregivers, cost-effectiveness of the SCU-B, psychotropic drug consumption, caregivers' attitude toward dementia, and time to nursing home placement. RESULTS: PwD admitted in SCU-Bs are expected to have diminished rates of BPSD and better QoL and their caregivers are also expected to have better QoL and improved attitude towards dementia, compared to those followed in no-SCU-Bs. Also, the cost of care and the psychotropic drug consumption are expected to be lower. Finally, PwD followed in no-SCU-Bs are expected to have earlier admission to nursing homes. CONCLUSION: The cohort study results will refine the SCU-B model, issuing recommendations for implementation of SCU-Bs in the countries where they are scarce or non-existent.