Hidradenitis Suppurativa in a Large Cohort of Italian Patients: Evaluation of the Burden of Disease.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually occurs after puberty with painful, deep-seated, inflamed nodules and sinus tracts in the apocrine gland-bearing areas of the body, most commonly the axillae and inguinal and anogenital regions, with a relevant impact on patients' quality of life (QoL). OBJECTIVE: To evaluate how the burden of HS disease impacts on patient well-being and working activities in a large Italian population over a period of 9 months. METHODS: A multicenter, prospective, epidemiologic cohort study was conducted in adult Italian patients with HS. HS severity was assessed through Hurley stage and HS Physician's Global Assessment (HS-PGA), clinical improvement by HS Clinical Response (HiSCR) and partial response, and disease burden through QoL questionnaires (HIDRAdisk, Skindex-16, Dermatology Life Quality Index [DLQI]), and Work Productivity and Activity Impairment - General Health (WPAI:GH). RESULTS: A total of 308 patients (56.2% women; mean age 35.2 ± 12.9 years) were enrolled in 27 dermatologic clinics. Men were older (37.4 years vs. 33.5), more smoking addicted (74.1% vs. 60.1%), and alcohol consumer (34.1% vs. 13.9%), while more women were obese (34.10% vs. 22.22%). At baseline, most patients had a Hurley severity stage of 2 (43.9%), a moderate HS-PGA score (57.1%), and poor QoL (HIDRAdisk: 65.7 ± 23.3, Skindex-16: 60.3 ± 26.9, and DLQI: 10.8 ± 8.1). Patients with more severe disease showed worse QoL. Mean values for the variables related to HS severity decreased during the study period. The achievement of HiSCR and partial response increased during the study. CONCLUSION: This study offers insight into the disease burden of HS in an Italian population. Our results underline the impact of QoL evaluation, also with the use of the HIDRAdisk, in clinical routine as a support to validated severity clinical and instrumental indexes for a "360-degree" assessment of HS patient's burden of disease.

The multifaceted spectrum of liver cirrhosis in older hospitalised patients: analysis of the REPOSI registry.

BACKGROUND: Knowledge on the main clinical and prognostic characteristics of older multimorbid subjects with liver cirrhosis (LC) admitted to acute medical wards is scarce. OBJECTIVES: To estimate the prevalence of LC among older patients admitted to acute medical wards and to assess the main clinical characteristics of LC along with its association with major clinical outcomes and to explore the possibility that well-distinguished phenotypic profiles of LC have classificatory and prognostic properties. METHODS: A cohort of 6,193 older subjects hospitalised between 2010 and 2018 and included in the REPOSI registry was analysed. RESULTS: LC was diagnosed in 315 patients (5%). LC was associated with rehospitalisation (age-sex adjusted hazard ratio, [aHR] 1.44; 95% CI, 1.10-1.88) and with mortality after discharge, independently of all confounders (multiple aHR, 2.1; 95% CI, 1.37-3.22), but not with in-hospital mortality and incident disability. Three main clinical phenotypes of LC patients were recognised: relatively fit subjects (FIT, N = 150), subjects characterised by poor social support (PSS, N = 89) and, finally, subjects with disability and multimorbidity (D&M, N = 76). PSS subjects had an increased incident disability (35% vs 13%, P < 0.05) compared to FIT. D&M patients had a higher mortality (in-hospital: 12% vs 3%/1%, P < 0.01; post-discharge: 41% vs 12%/15%, P < 0.01) and less rehospitalisation (10% vs 32%/34%, P < 0.01) compared to PSS and FIT. CONCLUSIONS: LC has a relatively low prevalence in older hospitalised subjects but, when present, accounts for worse post-discharge outcomes. Phenotypic analysis unravelled the heterogeneity of LC older population and the association of selected phenotypes with different clinical and prognostic features.

Secukinumab Exhibits Sustained and Stable Response in Patients with Moderate-to-Severe Psoriasis: Results from the SUPREME Study.

Secukinumab, a fully human monoclonal antibody, neutralizes interleukin-17A, a cornerstone cytokine driving the multiple manifestations of psoriasis. This post-hoc analysis of the SUPREME study was performed to determine the sustainability of response to secukinumab in terms of Psoriasis Area and Severity Index (PASI) 90 in patients with moderate-to-severe plaque psoriasis. Based on PASI 90 response at week 16, patients were stratified as PASI 90 responders (PASI90R, n = 337) or non-responders (PASI90NR, n = 72). At week 20, 94.2% (n = 295/313) achieved PASI 90/100 response in PASI90R, with response maintained through week 48 (89.6%, n = 189/211). An increased proportion of patients achieved PASI 90/100 response in PASI90NR (week 20: 29.9%, n = 20/67; week 48: 57.1%, n = 20/35). Overall, 64.4% patients achieved absolute PASI score = 0 at week 24 with response sustained to week 48 (66.9%). Secukinumab showed sustained and stable efficacy in maintaining PASI 90 response in patients with moderate-to-severe plaque psoriasis up to week 48.

Relationship between FEV1 and arterial stiffness in elderly people with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is highly prevalent in the elderly, and both COPD and age per se are associated with cardiovascular morbidity. AIMS: We tested the hypothesis that in elderly COPD patients airflow limitation is associated with arterial stiffness and the relationship, if any, is related to endothelial function and systemic inflammation. METHODS: We evaluated lung function, augmentation index (AIx), flow-mediated dilation (FMD), Interleukin-6 (IL-6), and asymmetric dymethilarginine (ADMA) levels in 76 subjects (mean age 73.9 years, SD 6.2) attending a geriatric outpatient clinic. RESULTS: Participants with COPD (N = 41) and controls (N = 35) did not differ in terms of AIx (30 vs 28.2 %, P = 0.30) and FMD (14.2 vs 12.3 %, P = 0.10). Similarly, the two groups did not differ with respect to mean concentrations of inflammation markers (IL-6 and C-reactive protein) and ADMA. Among COPD participants there was an inverse correlation between AIx and Forced Expiratory Volume in the first second (r = -0.349, P = 0.02). This relationship remained significant after correction for potential confounders, including markers of inflammation and ADMA levels (ß = -0.194, P = 0.001). DISCUSSION: According to the results of this study, among COPD patients, bronchial patency and AIx are inversely related, and the relationship is explained neither by endothelial function nor by systemic inflammation. CONCLUSIONS: In elderly COPD people, increased arterial stiffness is related to reduced pulmonary function and it seems worth testing as a potential marker of higher cardiovascular risk.

Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials.

Flow-mediated dilation (FMD) of the brachial artery reflects endothelium-dependent vasodilator function; since it correlates with coronary endothelial function, its reduction could predict cardiovascular events. Several studies have investigated the potential impact of fibrates therapy on endothelial function, but clinical findings have not been fully consistent. We aimed to conduct a meta-analysis of randomized placebo-controlled trials in order to clarify whether fibrate therapy could improve endothelial function. A systematic search in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases was performed to identify randomized placebo-controlled trials investigating the effect of fibrates on endothelial function as estimated by FMD. A random-effects model and generic inverse variance method were used for meta-analysis. Sensitivity analysis, risk of bias evaluation, and publication bias assessment were carried out using standard methods. Random-effects meta-regression was used to evaluate the impact of treatment duration on the estimated effect size. Fifteen trials with a total of 556 subjects met the eligibility criteria. Fibrate therapy significantly improves FMD (weighted mean difference [WMD]: 1.64%, 95% CI: 1.15, 2.13, p<0.001) and the result was confirmed in both subgroups with treatment durations ≤8 weeks (WMD: 1.35%, 95% CI: 0.85, 1.86, p<0.001) and >8 weeks (WMD: 2.55%, 95% CI: 1.21, 3.89, p<0.001). When the analysis was stratified according to the fibrate type, a significant effect was observed with fenofibrate but not with gemfibrozil, though difference between the two subgroups was not significant. Meta-analysis of data from trials where nitrate mediated dilation (NMD) was available did not suggest a significant change in NMD following treatment with fibrates. The results of this meta-analysis suggest that fibrates may exert beneficial effects on endothelial function, even over a short-term treatment course.

Anti-inflammatory properties of low and high doxycycline doses: an in vitro study.

Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. High dose administration (100 or 200 mg/day) is often responsible for development of bacterial resistances and endogenous flora alterations, whereas low doses (20-40 mg/day) do not alter bacteria susceptibility to antibiotics and exert anti-inflammatory activities. In this study, we wanted to assess the efficacy of both low and high doxycycline doses in modulating IL-8, TNF-α, and IL-6 gene expression in HaCaT cells stimulated with LPS. Three experimental settings were used, differing in the timing of doxycycline treatment in respect to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low doses were more effective than high doses in modulating gene expression of LPS-induced proinflammatory cytokines (IL-8, TNF-α, and IL-6), when added before (pretreatment) or after (posttreatment) LPS stimulation. This effect was not appreciated when LPS and doxycycline were simultaneously added to cell cultures: in this case high doses were more effective. In conclusion, our in vitro study suggests that low doxycycline doses could be safely used in chronic or acute skin diseases in which the inflammatory process, either constantly in progress or periodically recurring, has to be prevented or controlled.

Lack of evidence of viral reactivation in HBsAg-negative HBcAb-positive and HCV patients undergoing immunosuppressive therapy for psoriasis.

BACKGROUND: HBV and HCV reactivation have been widely reported in patients undergoing immunosuppressive therapy (IT); however, few data are available on the risk of reactivation in patients with psoriasis receiving IT. The aim of our study was to assess the prevalence of HBV and HCV infection in patients with psoriasis and to evaluate the effects of IT during the course of the infection. METHODS: The study included psoriatic patients who attended an Italian tertiary referral hospital from 2009 to 2012. A total of 224 patients were enrolled. We evaluated: HBV and HCV markers, type of IT and the occurrence of viral reactivation. The observational period ranged from the beginning of IT to the last visit, with a mean follow-up period of 54 months. RESULTS: Two hundred and twenty patients (135 males and 89 females; mean age 59 years; range 18-86 years) with psoriasis, with or without psoriatic arthritis, receiving conventional IT and/or biological drugs were tested for markers of infection. We identified 23/224 patients (10.2%) with isolated positivity for HBcAb positivity, 36/224 (16%) with positivity for HBsAb/HBcAb, and 15/224 (6.6%) with positivity for HCV-Ab. No patient was HBsAg positive, none of them underwent pre-emptive therapy with lamivudine or other antiviral drugs and no one showed episodes of viral reactivation. CONCLUSIONS: The prevalence of HBsAg in patients with psoriasis is lower than that observed in the general population. The prevalence of isolated positivity for HBcAb and of combined positivity for HBcAb and HBsAb is 10.2% and 16%, respectively. The prevalence of HCV infection (HCV-RNA+) is 4%. In patients with psoriasis and HCV-Ab or HBcAb positivity, the IT seems to be safe, regardless of the type of drugs.

Real-Life Effectiveness and Safety of Guselkumab in Patients with Psoriasis Who Have an Inadequate Response to Ustekinumab: A 3-Year Multicenter Study.

Background: Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of IL23. Its effectiveness and safety were widely reported by clinical trials. However, these results must be confirmed in real life since its safety deals with more complicated subjects with respect to trials. Currently, real-life data on the use of guselkumab following treatment failure with ustekinumab are limited, and existing studies usually show a small cohort and/or a reduced follow-up period. In this context, the aim of our study was to evaluate the use of guselkumab in patients who previously did not respond to ustekinumab after up to 3 years of treatment. Methods: A multicenter retrospective study was performed. The study enrolled patients affected by moderate-to-severe plaque psoriasis undergoing treatment with guselkumab who were attending the Psoriasis Center of nine different centers in the Campania region of Italy. Demographic and clinical features were collected for each patient at baseline. Moreover, data on psoriasis severity and adverse events (AEs) were collected at each follow-up visit (week (W)16-W36-W52-W104-W156). Results: A total of 112 patients (70 male, 62.5%; mean age 54.8 ± 11.7 years old) were enrolled. Of these, 48 (42.9%), 34 (30.4%), and 16 (14.3%) reached 1, 2, and 3 years, respectively, of follow-up under guselkumab. A statistically significant clinical improvement was observed since W16, and sustained effectiveness was reported at each timepoint up to W156. No serious AEs were collected. Moreover, a sub analysis on the body mass index, involvement of difficult-to-treat areas, and presence of psoriatic arthritis (PsA) showed that the presence of PsA or palmoplantar psoriasis was associated with a reduced clinical improvement at W16 and W36, without differences from W52. In contrast, the efficacy of guselkumab does not seem to be affected by the BMI, involvement of fingernails, or location in the genital or scalp area. Conclusions: To sum up, our long-term real-life multicenter retrospective study confirmed the efficacy and safety of guselkumab following ustekinumab discontinuation up to 156 weeks of treatment.

Efficacy of Secukinumab in Psoriasis: Post Hoc Gender-Wise Analysis of the SUPREME Study.

Purpose: Psoriasis, a common systemic inflammatory disorder, presents with gender-related differences in the quality of life (QoL) and treatment outcomes. This post hoc analysis from the Phase 3b SUPREME study explored gender-related differences in patient characteristics and efficacy of secukinumab 300 mg on Psoriasis Area and Severity Index (PASI) 75/90/100 and impact on QoL using the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis through week 24. Patients and Methods: The proportion of patients achieving PASI 75/90/100 was computed using a nonresponder imputation approach. Differences between cohorts were analyzed using a logistic regression model. The mean change from baseline in DLQI was computed using the Wilcoxon test. Results: Among the 433 patients (males: 71.6%), females had a higher DLQI than males at baseline (13.1 vs 9.5; P<0.0001). Males had a slightly higher response for PASI 90 than females at week 16 (80.7% vs 78.1%; P=0.0779) and 24 (83.2% vs 79.7%; P=0.0319). No differences were observed between genders in PASI 100/75 responses at week 24. Both genders showed an improvement in DLQI with secukinumab at week 24 (-10.9 vs -8.1, respectively, in females vs males; P=0.0004). Conclusion: In summary, secukinumab was effective in the treatment of psoriasis, irrespective of gender.

Psoriatic disease and tuberculosis nowadays.

Psoriasis is a chronic, relapsing and remitting inflammatory skin and joint disease that has a prevalence of 2-3% in the world's population, whereas of 1-2% in Europe. The traditional concept of psoriasis as the "healthy people's" disease has been recently revised because of ever-increasing reports of associations with various pathological conditions (hypertension, Crohn's disease, type II diabetes mellitus, obesity, dyslipidemia, metabolic syndrome, infectious conditions). Particularly, advances in psoriasis therapies have introduced biologic agents. All the tumor necrosis factor-alpha inhibitors are associated with an increased risk of developing active disease in patients with latent tuberculosis infection, because of TNF-α key role against Mycobacterium tuberculosis. For this reason, exclusion of active tuberculosis and treatment of latent tuberculosis infection are clinical imperatives prior to starting this therapy. Moreover active surveillance for a history of untreated or partially treated tuberculosis or latent form has already been shown to be effective in reducing the number of incident tuberculosis cases.

In vitro ultraviolet A irradiation decreases both release ability and gene-expression of vascular endothelial growth factor-A from mast cells.

Ultraviolet A (UVA) rays penetrate the dermis, influencing the function of different cells, including mast cells, able to produce angiogenic factors. We investigated vascular endothelial growth factor (VEGF) release and gene-expression from mast cells (MCs), after UVA irradiation in vitro. The release of VEGF-A by Human MCs-1 (HMC-1) was induced by calcium ionophore A23187 and phorbol 12 myristate 13 acetate (PMA). Half of the cells received increasing doses of UVA (5, 25 and 50 J/cm(2)), the unirradiated HMC-1 served as controls. VEGF release and VEGF's messenger ribonucleic acid (mRNA) were detected respectively by enzyme-linked immunoabsorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Results showed a UVA dose-dependent inhibitory effect on VEGF-A release from HMC-1. In particular, the release ability was reduced by 71.2% with 5 J/cm(2); 85% with 25 J/cm(2) and 86.3% with 50 J/cm(2). The VEGF-A RNA expression was reduced after UVA irradiation with 5 J/cm(2). We speculated that, at least in vitro and at our experimental conditions, UVA irradiation decreases mast cells-VEGF release and gene-expression.

A multidisciplinary care unit approach for the management of psoriatic arthritis: an Italian experience.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease that can produce disabling joint symptoms, adding significantly to the physical and psychosocial burden of psoriasis. Early detection is important to allow the development of an appropriate care plan to delay the onset of PsA and maximize the patient's quality of life. Our aim was to present the criteria, based on evidence and expert opinion, for a multidisciplinary approach to the management of PsA in a patient already characterized by skin manifestation. METHODS: An expert panel from the principal psoriatic care units of the Campania region of Italy met to discuss their mutual experience of the multidisciplinary approach to the management of psoriatic disease and to describe an integrated dermatologic/rheumatologic approach focused on the early diagnosis, management, and treatment of PsA. RESULTS: Two types of consultation modalities were considered most relevant to the care of patients with psoriatic disease in Italy: the parallel approach and the face-to-face care unit approach. Screening criteria for multidisciplinary care unit admission were described, with dermatologists, as the primary managers of the majority of patients with psoriasis, playing a critical role in introducing patients early on to therapy. CONCLUSIONS: An integrated management approach may enhance patient care by ensuring early diagnosis and treatment, with the potential to achieve better outcomes for both skin and musculoskeletal manifestations of psoriasis. The multidisciplinary care unit model is an effective and satisfying collaborative approach, not only optimizing outcomes and satisfaction for the patient but strengthening collaboration between the specialties.

Polymorphous light eruption and benign summer light eruption in Italy.

BACKGROUND/PURPOSE: Polymorphous light eruption (PLE) heterogeneity has been postulated, but the existence of benign summer light eruption (BSLE) is controversial. We studied the prevalence of the clinical patterns, criteria distinguishing BSLE from PLE, and diagnostic usefulness of phototest. METHODS: Five Italian Photodermatology Centres recruited retrospectively 346 patients with typical clinical history and/or presentation of PLE. Age, gender, skin type, family history and presence of atopy were considered. UVA and UVB MEDs and provocative phototests with UVA and UVB were obtained with a standardized procedure. Photopatch tests were applied according to the IRCDG rules. ANA were assessed by indirect immunofluorescence. RESULTS: Four criteria (predominance of women, shorter latency, uninvolvement of the face and absence of relapse during summer) identified BSLE in only 6.1% of cases. All had positive phototests, mostly with UVA. Uninvolvement of face, short latency and no seasonal relapses identified 11.7% patients, mostly with positive phototests to UVA. Short latency and no seasonal relapses in women identified 11.2% patients. Uninvolvement of face and no seasonal relapses in women identified 8.1% of patients. Uninvolvement of face and short latency in women identified 17.6% of patients. CONCLUSION: Criteria diagnosed BSLE in only a minority of patients, who were positive at phototesting, mostly with UVA.

Skin needling in the treatment of the aging neck.

The aim of this study was to estimate the efficacy of skin needling in the treatment of the aging neck. Eight patients with aging necks were included in the study. Each patient was treated with 2 sessions of needling. The evaluation of treatment effectiveness was based on changes from baseline on the Global Aesthetic Improvement Scale, the Wrinkle Severity Rating Scale, photographic and ultrasonographic images, and silicone rubber microrelief impressions of a selected neck region before and after therapy. Analysis of the photographs, the degree of irregularity of the surface microrelief, and the ultrasound images showed that, after 2 sessions, the lesions' severity grade was reduced in almost 90% of the patients. The present study presents evidence for the efficacy of skin needling for the aging neck.

Defining Resilience in Older People: Does a Subjective Definition of Stressor Work?

BACKGROUND: The operational definition of resilience is elusive and resilient people are difficult to identify. We used self-reported "major health event" (srMHE) to identify resilience and evaluate the functional and mortality trajectories associated with this condition. METHOD: We selected from the InCHIANTI study persons aged 65 or older who could perform the Short Physical Performance Battery at baseline and attended the 3 years follow-up visit. We identified 4 groups: Controls: no srMHE and no decline in physical function; Decliners: no srMHE and decline in physical function; Resilient: srMHE and no decline in physical function; and Non-resilient: srMHE and decline in physical function. Linear mixed models and Cox regression were used to analyze changes in activities of daily living (ADL) score over 9- and 10-year mortality across groups, respectively. RESULTS: The 313 participants that reported a srMHE had worse perceived health status and higher number of GP visits and prescribed drugs at baseline. Of these, 78 were Resilient and 235 Non-resilient; of the remaining, 136 were Controls and 277 Decliners. Compared to the Controls, Resilient had similar change of ADL score over time (ß: -.03, p = .92) and mortality (hazard ratio: 1.31, 95% confidence interval: 0.76-2.23), while Decliners and Non-resilient showed significantly higher mortality and, the latter, worsening of ADL score. Additional srMHE during follow-up affected the rate of change of ADL score and mortality more in the Controls group than in the Resilient group. CONCLUSIONS: A srMHE along with repeated evaluation of physical function may be used to identify resilience in older people, and may complement the standard functional evaluation of geriatric patients.

Impact of Low Muscle Mass and Low Muscle Strength According to EWGSOP2 and EWGSOP1 in Community-Dwelling Older People.

BACKGROUND: A universal definition of sarcopenia is still lacking. Since the European criteria have been recently revised, we aimed at studying prevalence of low muscle strength (LMS) and low muscle mass (LMM), as defined according to the European Working Group of Sarcopenia in Older People (EWGSOP) 2 and 1 definitions, and their individual contribution toward mortality and incident mobility disability in a cohort of community-dwelling older people. METHODS: Longitudinal analysis of 535 participants of the InCHIANTI study. LMS and LMM were defined according to the criteria indicated in the EWGSOP2 and 1. Cox and log-binomial regressions were used to examine association with mortality and 3-year mobility disability (inability to walk 400 m). RESULTS: We observed a lower prevalence of the combination LMM/LMS according to EWGSOP2 compared to EWGSOP1 (3.2% vs 6.2%). Using the new criteria, all sarcopenia components were associated with mortality, although the hazard ratio [HR] for the group LMM/LMS was no longer significant after adjustment for confounders (LMM: HR 2.69, 95% confidence interval [CI] 1.04-6.94; LMS: HR 3.18, 95% CI 1.44-7.01; LMM/LMS: HR 2.95, 95% CI 0.86-10.16). Using EWGSOP1, LMS alone was independently associated with mortality (HR 4.43, 95% CI 1.85-10.57). None of the sarcopenia components conferred a higher risk of mobility disability. CONCLUSIONS: The EWGSOP2 algorithm leads to a reduction in the estimated prevalence of sarcopenia defined as combination of LMM/LMS. The finding that, independent of the adopted criteria, people with LMS and normal mass have a higher mortality risk compared to robust individuals, confirms that evaluation of muscle strength has a central role for prognosis evaluation.

Potentially Inappropriate Medications, Drug-Drug Interactions, and Anticholinergic Burden in Elderly Hospitalized Patients: Does an Association Exist with Post-Discharge Health Outcomes?

BACKGROUND: Polypharmacy is very common in elderly patients and is associated with detrimental outcomes. OBJECTIVE: Our objective was to evaluate the associations between a large panel of therapy quality indicators, including explicit lists of potentially inappropriate medications (PIMs; Beers criteria and Screening Tool of Older Persons' potentially inappropriate Prescriptions [STOPP] criteria), the Anticholinergic Cognitive Burden (ACB) score, and the number of drug-drug interactions (DDIs), with respect to mortality, rehospitalization, and physical function decline within 3 months from hospital discharge in a cohort of hospitalized elderly patients. METHODS: We studied 2631 individuals aged ≥ 65 years (median age 79.6; males 48.6%) enrolled in the REPOSI registry. The relationships with mortality and rehospitalization were evaluated using Cox regressions, and relationships with functional status change (as percentage variation of Barthel Index [BI]) were evaluated using mixed linear models. RESULTS: None of the studied indicators was associated with mortality and rehospitalization. Conversely, only ACB was associated with physical function decline, even after correction for confounders (adjusted mean BI variation of - 7.55%; 95% confidence interval [CI] - 12.37 to - 2.47). The number of medications at discharge, particularly polypharmacy (more than five drugs daily), were the only therapy-related factors associated with mortality (adjusted hazard ratio [aHR] 1.05 [95% CI 1.01-1.10] and 1.70 [95% CI 1.12-2.58], respectively) and rehospitalization (aHR 1.05 [95% CI 1.01-1.08] and 1.31 [95% CI 1.01-1.71], respectively). CONCLUSION: Polypharmacy, a very simple measure, outperformed sophisticated PIM and DDI indicators of quality of therapy as a correlate of primary clinical outcomes, whereas ACB was associated with physical function decline. Thus, innovative approaches to the definition and research of PIMs and DDIs are eagerly awaited from the perspective of averaging the quantitative burden and qualitative interaction of drugs.

Differential diagnosis of psoriasis.

Psoriasis is a common chronic skin disorder estimated to affect about 2% of the Western population. The disease creates a significant stigma for patients and is a major economic burden. Psoriasis has a large spectrum of clinical features and evolution. Clinical features of chronic psoriasis are generally sufficient to make the diagnosis. Diagnostic doubts, however, may arise in several clinical variants and atypical cases or when the psoriatic lesions are localized in particular sites.

Predictive Capacity of Frailty Phenotype Toward Patterns of Disability Identified Using Latent Class Analysis.

OBJECTIVES: Frailty phenotype (FP) has low sensitivity toward the identification of older people who will lose 1 or more activities of daily living. Nevertheless, the definition of disability in terms of activities of daily living may not resemble the pattern of functional impairment occurring during aging. The aim of this study was to examine the discriminative capacity of the FP toward the identification of patterns of disabilities in an extended list of tasks, identified among community-dwelling older people. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: We included 997 persons age 65 years and older selected from the Invecchiare in Chianti (InCHIANTI) Study population. MEASURES: Using latent class analysis, we assessed the pattern of 3-year changes in 24 functional tasks. Then, we calculated the discriminative capacity of the FP for each pattern of disability. Analyses were stratified by sex. RESULTS: In both men and women, we recognized 3 classes: stable function; disability in complex tasks; and global functional disability. Among women, ability of FP to identify persons in global functional disability showed sensitivity = 0.42, specificity = 0.98, positive and negative predictive values 0.75 and 0.91; the corresponding values for prediction of disability in complex tasks were 0.13, 0.98, 0.68, and 0.75. Similar results were obtained among men. CONCLUSIONS/IMPLICATIONS: Over 3 years, older people of the InCHIANTI population remained largely functional stable, some persons developed deficiency in complex tasks, and a minority developed global functional disability. Trying to predict these 3 patterns may be useful for the care of older people in order to promote individualized interventions to reduce the burden of disabilities and their consequences. To this purpose, FP showed a fairly good capacity to identify people at risk of functional decline, but further studies are needed to identify instruments with better prognostic capacity.

Possible role of BMP-4 in the hyper-pigmentation of psoriatic plaques after anti-TNF-α treatment.

Psoriasis over-expresses several inflammatory mediators, which impacts the activity of melanocytes. Tyrosinase (Tyr) and microphthalmia-associated transcription factor (MITF) are the primary regulators of melanogenesis. Furthermore, bone morphogenetic proteins (BMPs) modulate various pathobiologic processes including inflammation, melanogenesis and melanomagenesis. To determine the association between psoriasis and melanogenesis, psoriatic lesional skin was screened through gene expression, immunohistochemistry, immunogold staining and melanin content assays. The present study detected a decreased expression of Tyr, MITF and BMP-4 in psoriatic lesional skin compared with healthy skin. Tyr, BMP-4 and melanin content were also evaluated in the psoriatic lesional skin of patients receiving adalimumab therapy, before and after 16 weeks of treatment. TNF-α blockade modulated the Tyr, BMP-4 and melanin content of the patient skin lesions, which supported the hypothesis that hyper-pigmentation may occur in areas of psoriatic plaque after biological treatment. The present study confirmed the influence of the psoriatic pro-inflammatory network on melanogenesis, exerting an inhibitory effect mediated by TNF-α. Furthermore, the results regarding BMP-4 in the present study add another important element to the mechanism of psoriasis.