Platelets accumulate in lung lesions of tuberculosis patients and inhibit T-cell responses and Mycobacterium tuberculosis replication in macrophages.

Platelets regulate human inflammatory responses that lead to disease. However, the role of platelets in tuberculosis (TB) pathogenesis is still unclear. Here, we show that patients with active TB have a high number of platelets in peripheral blood and a low number of lymphocytes leading to a high platelets to lymphocytes ratio (PL ratio). Moreover, the serum concentration of different mediators promoting platelet differentiation or associated with platelet activation is increased in active TB. Immunohistochemistry analysis shows that platelets localise around the lung granuloma lesions in close contact with T lymphocytes and macrophages. Transcriptomic analysis of caseous tissue of human pulmonary TB granulomas, followed by Gene Ontology analysis, shows that 53 platelet activation-associated genes are highly expressed compared to the normal lung tissue. In vitro activated platelets (or their supernatants) inhibit BCG-induced T- lymphocyte proliferation and IFN-γ production. Likewise, platelets inhibit the growth of intracellular macrophages of Mycobacterium (M.) tuberculosis. Soluble factors released by activated platelets mediate both immunological and M. tuberculosis replication activities. Furthermore, proteomic and neutralisation studies (by mAbs) identify TGF-ß and PF4 as the factors responsible for inhibiting T-cell response and enhancing the mycobactericidal activity of macrophages, respectively. Altogether these results highlight the importance of platelets in TB pathogenesis.

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

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

Diagnostic issues faced by a rare disease healthcare network during Covid-19 outbreak: data from the Campania Rare Disease Registry.

BACKGROUND: The aims of this study were: to investigate the capacity of the rare disease healthcare network in Campania to diagnose patients with rare diseases during the outbreak of Covid-19; and to shed light on problematic diagnoses during this period. METHODS: To describe the impact of the Covid-19 pandemic on the diagnosis of patients with rare diseases, a retrospective analysis of the Campania Region Rare Disease Registry was performed. A tailored questionnaire was sent to rare disease experts to investigate major issues during the emergency period. RESULTS: Prevalence of new diagnoses of rare disease in March and April 2020 was significantly lower than in 2019 (117 versus 317, P < 0.001 and 37 versus 349, P < 0.001, respectively) and 2018 (117 versus 389, P < 0.001 and 37 versus 282, P < 0.001, respectively). Eighty-two among 98 rare disease experts completed the questionnaire. Diagnostic success (95%), access to diagnosis (80%) and follow-up (72%), lack of Personal Protective Equipment (60%), lack of Covid-19 guidelines (50%) and the need for home therapy (78%) were the most important issues raised during Covid-19 outbreak. CONCLUSIONS: This study describes the effects of the Covid-19 outbreak on the diagnosis of rare disease in a single Italian region and investigates potential issues of diagnosis and management during this period.

HLA-E-restricted CD8+ T Lymphocytes Efficiently Control Mycobacterium tuberculosis and HIV-1 Coinfection.

We investigated the contribution of human leukocyte antigen A2 (HLA-A2) and HLA-E-restricted CD8+ T cells in patients with Mycobacterium tuberculosis and human immunodeficiency virus 1 (HIV-1) coinfection. HIV-1 downregulates HLA-A, -B, and -C molecules in infected cells, thus influencing recognition by HLA class I-restricted CD8+ T cells but not by HLA-E-restricted CD8+ T cells, owing to the inability of the virus to downmodulate their expression. Therefore, antigen-specific HLA-E-restricted CD8+ T cells could play a protective role in Mycobacterium tuberculosis and HIV-1 coinfection. HLA-E- and HLA-A2-restricted Mycobacterium tuberculosis-specific CD8+ T cells were tested in vitro for cytotoxic and microbicidal activities, and their frequencies and phenotypes were evaluated ex vivo in patients with active tuberculosis and concomitant HIV-1 infection. HIV-1 and Mycobacterium tuberculosis coinfection caused downmodulation of HLA-A2 expression in human monocyte-derived macrophages associated with resistance to lysis by HLA-A2-restricted CD8+ T cells and failure to restrict the growth of intracellular Mycobacterium tuberculosis. Conversely, HLA-E surface expression and HLA-E-restricted cytolytic and microbicidal CD8 responses were not affected. HLA-E-restricted and Mycobacterium tuberculosis-specific CD8+ T cells were expanded in the circulation of patients with Mycobacterium tuberculosis/HIV-1 coinfection, as measured by tetramer staining, but displayed a terminally differentiated and exhausted phenotype that was rescued in vitro by anti-PD-1 (programmed cell death protein 1) monoclonal antibody. Together, these results indicate that HLA-E-restricted and Mycobacterium tuberculosis-specific CD8+ T cells in patients with Mycobacterium tuberculosis/HIV-1 coinfection have an exhausted phenotype and fail to expand in vitro in response to antigen stimulation, which can be restored by blocking the PD-1 pathway using the specific monoclonal antibody nivolumab.

Fourth Ventricle Outlet Obstruction and Diverticular Enlargement of Luschka Foramina in a Child with Down Syndrome.

INTRODUCTION: Hydrocephalus is not usually part of Down syndrome (DS). Fourth ventricle outlet obstruction is a rare cause of obstructive hydrocephalus, difficult to diagnose, because tetraventricular dilatation may suggest a communicant/nonobstructive hydrocephalus. CASE PRESENTATION: We describe the case of a 6-year-old boy with obstructive tetraventricular hydrocephalus, caused by Luschka and Magen-die foramina obstruction and diverticular enlargement of Luschka foramina (the so-called fourth ventricle outlet obstruction) associated with DS. He was treated with endoscopic third ventriculostomy (ETV) without complications, and a follow-up MRI revealed reduction of the ventricles, disappearance of the diverticula, and patency of the ventriculostomy. CONCLUSION: Diverticular enlargement of Luschka foramina is an important radiological finding for obstructive tetraventricular hydrocephalus. ETV is a viable option in tetraventricular obstructive hydrocephalus in DS.

Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study.

BACKGROUND: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. OBJECTIVES: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. METHODS: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. RESULTS: A total of 12 143 users were registered. A total of 6 949 users reported at least one VAS data recording. Among them, 1 887 users reported ≥7 VAS data. About 1 195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR ≥70% and PDC ≤1.25), 51 (4.23%) were partly adherent (MPR ≥70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. CONCLUSION AND CLINICAL RELEVANCE: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.

ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy": AIRWAYS ICPs initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration project.

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.

Can causality assessment fulfill the new European definition of adverse drug reaction? A review of methods used in spontaneous reporting.

Causality assessment is a fundamental biomedical technique for the signal detection performed by Pharmacovigilance centers in a Spontaneous reporting system. Moreover, it is a crucial and important practice for detecting preventable adverse drug reactions. Among different methods for causality assessment, algorithms (such as the Naranjo, or Begaud Methods) seem for their operational procedure and easier applicability one of the most commonly used methods. With the upcoming of the new European Pharmacovigilance legislation including in the definition of the adverse event also effects resulting from abuse, misuse and medication error, all well-known preventable causes of ADRs, there was an emerging need to evaluate whether algorithms could fulfill this new definition. In this review, twenty-two algorithmic methods were identified and none of them seemed to fulfill perfectly the new criteria of adverse event although some of them come close. In fact, several issues were arisen in applying causality assessment algorithms to these new definitions as for example the impossibility to answer the rechallenge question in case of medication error or AEFI (Adverse Event Following Immunization). Moreover, the exact conditions at which events occurred, as for example dosage or mode of administration should be considered to better assess causality in conditions of abuse/overdose, or misuse as well as in conditions of lack of expected efficacy reports for biotechnological drugs and adverse event occurring after mixing of vaccines. Therefore, this review highlights the need of updating algorithmic methods to allow a perfect applicability in all possible clinical scenarios accordingly or not with the terms of marketing authorization.

Differences in drug use between men and women: an Italian cross sectional study.

BACKGROUND: Drugs are the most important treatment option for most diseases, and the majority of medical consultations result in a prescription. Women and men receive different drug prescriptions and differ in therapeutic response to pharmacological therapy. This disparity is due to biological factors (sex differences) or/and behavior, lifestyle and life experience (gender differences). Sex differences in drug use have been demonstrated in several therapeutic areas; however, there is a lack of overviews on sex and gender differences of drug use in an entire population. METHODS: We conducted a descriptive cross - sectional drug use study, involving the entire Italian population in 2012, aimed at showing and analyzing differences between men and women as regards their exposure to drugs. The data source was IMS LifeLink Treatment DynamicsTMLRx Database and it included all prescribed drugs reimbursed by the Italian National Healthcare System in 2012 and covered 90% of the entire Italian population. The information about the prescriptions was stratified by men and women and age. Drug consumption was expressed as DDD/ 1000 ab die. Exposure to drug prescriptions was expressed as period prevalence (the proportion of the population dispensed ≥1 prescription in 2012 per 1000 inhabitants). Differences of prevalence between men and women were expressed as crude and age adjusted risk ratios with 95% CI. RESULTS: Our findings suggested that the largest differences in drug prescriptions regarded drugs affecting bone structure and mineralization (RR 15.9), calcium (RR 8.6) and thyroid therapy (RR 5.4), dispensed more to women than men. Otherwise ACE inhibitors were more commonly used in men. CONCLUSIONS: This is the first study exploring difference in drug use between men and women and carried out on the entire Italian population. Our findings showed substantial differences between men and women in term of prevalence of drug prescriptions. Some differences in drug use may be explained by sex differences (variations in disease prevalence and severity, pathophysiology, or by other biological differences), other differences need further investigation to explain the apparent lack of a rational medical explanation for some findings. The findings may subsequently be used to plan future studies to address differences suggesting inequity in treatment approaches.

Italian translation and cultural adaptation of the communication assessment tool in an outpatient surgical clinic.

BACKGROUND: The aim of the study is to translate and cross-culturally adapt, for use in the Italian context, the Communication Assessment Tool (CAT) developed by Makoul and colleagues. METHODS: The study was performed in the out-patient clinic of the Surgical Department of Cardarelli Hospital in Naples, Italy. It involved a systematic, standardized, multi-step process adhering to internationally accepted and recommended guidelines. Corrections and adjustments to the translation addressed both linguistic factors and cultural components. RESULTS: The CAT was translated into Italian by two independent Italian mother-tongue translators. The consensus version was then back-translated by an English mother-tongue translator. This translation process was followed by a consensus meeting between the authors of translation and investigators, and then by two comprehension tests on a total of 65 patients. CONCLUSIONS: Results of the translation and cross-cultural adaptation were satisfactory and indicate that the Italian translation of the CAT can be used with confidence in the Italian context.

Rates and reasons for lack of persistence with anti-osteoporotic drugs: analysis of the Campania region database.

Subjects with chronic diseases are more likely to be nonpersistent to pharmacological treatment. Lack of persistence is common among subjects using oral anti-osteoporotic drugs, and leads to increased risk of fragility fracture. The aim of our retrospective study is to analyze the rates and reasons for discontinuation of anti-osteoporotic drugs in the Campania Region. Subjects aged over 40 years were included if they had received at least one prescription for any anti-osteoporotic drugs. Data were obtained from an administrative database of regional data on outpatient drug prescriptions reimbursed by the National Health Service. Patients were followed until the discontinuation of anti-osteoporotic therapy or until the end of the observation period. A total of 30,048 were incident users of anti-osteoporotic drugs: 28,317 (94.2%) females. The mean age of the cohort was 69.0±10.0 years. Weekly bis-phosphonates (51.1%) were the most commonly prescribed drugs. In the overall population, persistence rates were 34.8% after 6 months and 13.4% at one year. A multivariate Cox proportional hazard analysis showed that daily regimen (HR 1.9) treatments remained at higher risk of early discontinuation compared to weekly regimen therapies. Our data showed that the persistence to osteoporosis therapy is significantly worse than reported in literature.

Investigating the Generalizability of Economic Evaluations Conducted in Italy: A Critical Review.

OBJECTIVES: To assess the methodological quality of Italian health economic evaluations and their generalizability or transferability to different settings. METHODS: A literature search was performed on the PubMed search engine to identify trial-based, nonexperimental prospective studies or model-based full economic evaluations carried out in Italy from 1995 to 2013. The studies were randomly assigned to four reviewers who applied a detailed checklist to assess the generalizability and quality of reporting. The review process followed a three-step blinded procedure. The reviewers who carried out the data extraction were blind as to the name of the author(s) of each study. Second, after the first review, articles were reassigned through a second blind randomization to a second reviewer. Finally, any disagreement between the first two reviewers was solved by a senior researcher. RESULTS: One hundred fifty-one economic evaluations eventually met the inclusion criteria. Over time, we observed an increasing transparency in methods and a greater generalizability of results, along with a wider and more representative sample in trials and a larger adoption of transition-Markov models. However, often context-specific economic evaluations are carried out and not enough effort is made to ensure the transferability of their results to other contexts. In recent studies, cost-effectiveness analyses and the use of incremental cost-effectiveness ratio were preferred. CONCLUSIONS: Despite a quite positive temporal trend, generalizability of results still appears as an unsolved question, even if some indication of improvement within Italian studies has been observed.

Polypharmacy Management in Chronic Conditions: A Systematic Literature Review of Italian Interventions.

Background: Potentially inappropriate polypharmacy (PIP) is among the major factors leading to adverse drug reactions, increased healthcare costs, reduced medication adherence, and worsened patient conditions. This study aims to identify existing interventions implemented to monitor and manage polypharmacy in the Italian setting. Methods: A systematic literature review (PROSPERO: CRD42023457049) was carried out according to the PRISMA statement guidelines. PubMed, Embase, ProQuest, and Web of Science were queried without temporal constraints, encompassing all published papers until October 2023. Inclusion criteria followed the PICO model: patients with polypharmacy; interventions to monitor/manage polypharmacy regimen versus no/any intervention; outcomes in terms of intervention effectiveness and cost variation. Results: After duplicate deletion, 153 potentially relevant publications were extracted. Following abstract and full-text screenings, nine articles met the inclusion criteria. Overall, 78% (n = 7) were observational studies, 11% (n = 1) were experimental studies, and 11% (n = 1) were two-phase studies. A total of 44% (n = 4) of the studies involved patients aged ≥ 65 years, while 56% (n = 5) were disease-specific. Monitoring was the most prevalent choice of intervention (67%; n = 6). Outcomes were mainly related to levels of polypharmacy (29%; n = 6) and comorbidities (29%; n = 6), effectiveness rates (14%; n = 3), and avoidable costs (9%; n = 2). Conclusions: This review outlines that Italy is still lacking in interventions to monitor/manage PIP, addressing an unmet need in developing patient-tailored strategies for reducing health-system burden.

Respiratory Syncytial Virus (RSV) Hospitalizations in the Elderly in a Tertiary Care Hospital in Southern Italy as a Useful Proxy for Targeting Vaccine Preventive Strategies.

RSV infection causes severe respiratory illness and mortality in the elderly, especially in the presence of comorbidities. Early identification of infection would result in appropriate clinical-therapeutic management, avoiding hospitalizations, the risk of healthcare-associated infections, and inappropriate antibiotic prescriptions, thus reducing healthcare costs and fighting antimicrobial resistance. The aim of this study was to assess RSV hospitalizations in subjects >64 years hospitalized in a large tertiary care hospital in Southern Italy, in order to assess their usefulness as a proxy for targeting a potential vaccination strategy. Fifty-two RSV-positive patients were identified from the 2014-2015 to the 2022-2023 seasons. RSV type B was found in 71.2% of cases. The median age was 78 years (IQR: 72-84) and 40.4% of the subjects had at least one comorbidity; 5.8% needed intensive care. The use of combined rapid tests for SARS-CoV-2/influenza/RSV identification in primary care settings may contribute to an improved definition of the burden of RSV in the elderly. The implementation of an anti-RSV vaccination strategy in the elderly population would reduce direct and indirect infection costs. More robust epidemiological data in Italy are needed for targeted preventive strategies.

Cost-Effectiveness of Treatment Optimisation with Biomarkers for Immunotherapy in Solid Tumours: A Systematic Review.

This study investigated the health economic evaluations of predictive biomarker testing in solid tumours treated with immune checkpoint inhibitors (ICIs). Searching PubMed, EMBASE, and Web of Science from June 2010 to February 2022, 58 relevant articles were reviewed out of the 730 screened. The focus was predominantly on non-small cell lung cancer (NSCLC) (65%) and other solid tumours (40%). Among the NSCLC studies, 21 out of 35 demonstrated cost-effectiveness, notably for pembrolizumab as first-line treatment when preceded by PD-L1 assessment, cost-effective at a threshold of $100,000/QALY compared to the standard of care. However, for bladder, cervical, and triple-negative breast cancers (TNBCs), no economic evaluations met the affordability threshold of $100,000/QALY. Overall, the review highlights a certain degree of uncertainty about the cost-effectiveness of ICI. In particular, we found PD-L1 expression associated with ICI treatment to be a cost-effective strategy, particularly in NSCLC, urothelial, and renal cell carcinoma. The findings suggest the potential value of predictive biomarker testing, specifically with pembrolizumab in NSCLC, while indicating challenges in achieving cost-effectiveness for certain other solid tumours.

Neutrophil-to-Eosinophil Ratio Predicts the Efficacy of Avelumab in Patients With Advanced Urothelial Carcinoma Enrolled in the MALVA Study (Meet-URO 25).

BACKGROUND: Neutrophil-to-eosinophil ratio (NER) has been described to be associated with outcomes to immune checkpoint inhibitors (ICI) in several tumor types, but less is known about its role of in the response to avelumab in advanced urothelial cancer (aUC). Thus, we reported outcomes by NER of aUC patients treated with avelumab as maintenance after initial response to platinum-based chemotherapy and enrolled in the Maintenance with AVeLumAb ([MALVA] in advanced urothelial neoplasms in response to first-line chemotherapy: an observational retrospective study) study (Meet-URO 25). PATIENTS AND METHODS: Median NER at baseline and after 3 cycles of avelumab were calculated. Progression-free survival (PFS) and overall survival (OS) by NER were reported. RESULTS: At the cutoff date (April 15, 2023), a total of 109 patients were included. The median NER was 28.05 at baseline and 24.46 after 3 cycles of avelumab, respectively. Median PFS was not reached for patients with baseline NER less than the median (

Differentiation, phenotype, and function of interleukin-17-producing human Vγ9Vδ2 T cells.

In healthy adults, the major peripheral blood γδ T-cell subset expresses the Vγ9Vδ2 TCR and displays pleiotropic features. Here we report that coculture of naive Vγ9Vδ2 T cells with phosphoantigens and a cocktail of cytokines (IL-1-ß, TGF-ß, IL-6, and IL-23), leads to selective expression of the transcription factor RORγt and polarization toward IL-17 production. IL-17(+) Vγ9Vδ2 T cells express the chemokine receptor CCR6 and produce IL-17 but neither IL-22 nor IFN-γ; they have a predominant terminally differentiated (CD27(-)CD45RA(+)) phenotype and express granzyme B, TRAIL, FasL, and CD161. On antigen activation, IL-17(+) Vγ9Vδ2 T cells rapidly induce CXCL8-mediated migration and phagocytosis of neutrophils and IL-17-dependent production of ß-defensin by epithelial cells, indicating that they may be involved in host immune responses against infectious microorganisms. Accordingly, an increased percentage of IL-17(+) Vγ9Vδ2 lymphocytes is detected in the peripheral blood and at the site of disease in children with bacterial meningitis, and this pattern was reversed after successful antibacterial therapy. Most notably, the phenotype of IL-17(+) Vγ9Vδ2 T cells in children with meningitis matches that of in vitro differentiated IL-17(+) Vγ9Vδ2 T cells. Our findings delineate a previously unknown subset of human IL-17(+) Vγ9Vδ2 T lymphocytes implicated in the pathophysiology of inflammatory responses during bacterial infections.

Osteoporosis drugs in real-world clinical practice: an analysis of persistence.

The aim of our retrospective cohort study is to analyze the persistence rates in relation to antiosteoporotic drugs using administrative databases in the Campania Region. Patients, aged ≥40 years, were included if at least one prescription for any antiosteoporotic drugs had been filled in between January 1, 2009 and December 31, 2009. Overall, 37,594 patients were incident users of antiosteoporotic drugs. Among them, 15,978 patients had undergone spot-therapies. A total of 2,618 (14.1%) were classified as switchers. Switching rates were highest for patients taking Alendronate 18.9 or Strontium Ranelate 15.0 and lower for patients taking Ibandronate 12.8 or Risedronate 10.8. In the overall population, 33.5% of subjects were still on therapy after 6 months. At 1 year, persistence rates were: Ibandronate 21.6%, Risedronate 15.8%, Alendronate + Vitamin D 15.7%, Raloxifene 14.3%, Alendronate 12.6% and Strontium Ranelate 5.0%.

Challenges in the management of advanced NSCLC among Italian oncologists: a 2019 national survey unfolds regional disparities.

BACKGROUND: Molecular testing is crucial for the implementation of personalized therapy in patients with lung cancer. Whether routine biomarker testing and access to personalized therapies are limited in some Italian regions is unclear. PATIENTS AND METHODS: We conducted a national cross-sectional survey between April and June 2019 among Italian oncologists to determine differences in biomarker testing and access to personalized therapies for lung cancer. RESULTS: Based on GIMBE report n. 3/2018, 32 respondents (37.6%) were defined as belonging to budget deficit regions (BDRs) while 53 (62.4%) were from balanced/positive budget regions (BPRs). Diagnostic assays for EGFR/ALK/ROS1 and PD-L1 were reported to be available in 47/53 (88.7%) and 22/32 (68.85%) centers from BPRs and BDRs, respectively (p=0.04).Liquid biopsy accessibility was wider in BPRs than in BDRs (75.5% (40/53) vs. 50% (16/32), respectively; p=0.03). 84/85 (98.8%) oncologists reported that ⩾75% of eligible patients received first-line targeted therapies. Reason for not administering first-line targeted therapies was defined as clinically-unrelated (molecular testing not available or incomplete, pharmacoeconomic issues) by 25/42 (59.5%) of respondents from BPRs and 21/26 (80.6%) from BDRs (p=0.12). Reason for not administering first-line pembrolizumab was defined as clinically-unrelated by 8/43 (18.6%) of respondents from BPRs and 10/22 (45.4%) from BDRs (p=0.039). CONCLUSION: Disparities in access to diagnostic assay and first line immunotherapy exist between BPRs and BDRs.

Longitudinal Trajectory Modeling to Assess Adherence to Sacubitril/Valsartan among Patients with Heart Failure.

Medication adherence in chronic conditions is a long-term process. Modeling longitudinal trajectories using routinely collected prescription data is a promising method for describing adherence patterns and identifying at-risk groups. The study aimed to characterize distinct long-term sacubitril/valsartan adherence trajectories and factors associated with them in patients with heart failure (HF). Subjects with incident HF starting sac/val in 2017-2018 were identified from the Campania Regional Database for Medication Consumption. We estimated patients' continuous medication availability (CMA9; R package AdhereR) during a 12-month period. We selected groups with similar CMA9 trajectories (Calinski-Harabasz criterion; R package kml). We performed multinomial regression analysis, assessing the relationship between demographic and clinical factors and adherence trajectory groups. The cohort included 4455 subjects, 70% male. Group-based trajectory modeling identified four distinct adherence trajectories: high adherence (42.6% of subjects; CMA mean 0.91 ± 0.08), partial drop-off (19.6%; CMA 0.63 ± 0.13), moderate adherence (19.3%; CMA 0.54 ± 0.11), and low adherence (18.4%; CMA 0.17 ± 0.12). Polypharmacy was associated with partial drop-off adherence (OR 1.194, 95%CI 1.175-1.214), while the occurrence of ≥1 HF hospitalization (OR 1.165, 95%CI 1.151-1.179) or other hospitalizations (OR 1.481, 95%CI 1.459-1.503) were associated with low adherence. This study found that tailoring patient education, providing support, and ongoing monitoring can boost adherence within different groups, potentially improving health outcomes.