Pain is one of the most common symptoms in patients with cancer, with cancer-induced bone pain (CIBP) significantly affecting their quality of life. Opioids are commonly used as first-line treatments for cancer pain, but their use requires caution due to non-mechanistic analgesia and significant side effects. As a result, there is a need for new non-opioid drugs that target cancer pain through specific mechanisms. Recent studies on the anticancer effects of lidocaine have highlighted its potential benefits in both treating cancer and alleviating cancer-induced pain. This article discusses the mechanism of action and clinical applications of lidocaine in cancer pain management, and suggests new treatment approaches for patients with CIBP.

Immuno-oncology (IO) agents and pemetrexed are approved for the first-line (1L) maintenance treatment (1LMT) of advanced/metastatic non-small cell lung cancer (a/mNSCLC). This international retrospective chart review assessed real-world treatment patterns and outcomes in patients with a/mNSCLC lacking targetable mutations. Oncologists from seven countries (Canada, France, Germany, Italy, Spain, UK, USA) provided deidentified, medical chart-derived data on randomly selected adults with a/mNSCLC who remained stable or responded to 1L chemotherapy + IO. Treatment patterns, overall survival (OS), progression-free survival (PFS), and healthcare resource utilization (HCRU) were compared by maintenance treatment use following propensity score weighting. The effects of adding pemetrexed to IO-containing 1LMT was investigated in patients with non-squamous/mixed histology. Of 942 patients analyzed, 680 initiated 1LMT. After weighting, 1LMT was associated with longer median PFS (17.7 vs 7.1months; HR [95%CI] 0.63 [0.41-0.85]), similar OS (31.7 vs 31.0months; 0.82 [0.47-1.17]), and fewer mean monthly hospitalizations (0.03 vs 0.1; p < 0.01) versus no 1LMT. Among 469 patients with non-squamous/mixed histology who initiated an IO-containing 1LMT, 283 received IO only while 186 received IO + pemetrexed. Median time to treatment discontinuation (20.0 vs 11.0months; p < 0.001), PFS (21.1 vs 11.1months; HR [95%CI] 0.56 [0.37-0.76]), and OS (35.3 vs 27.3months; 0.70 [0.41-0.98]) were longer for patients receiving IO only versus IO + pemetrexed. Fewer patients administered IO only experienced fatigue (28.3% vs 39.8% [IO + pemetrexed]; p < 0.05) and anemia (16.6% vs 31.2%; p < 0.001). 1LMT was associated with significantly longer PFS and similar OS, without substantially increasing HCRU, among the current study population with a/mNSCLC. Adding pemetrexed to 1LM IO did not confer significant clinical benefit in patients with non-squamous/mixed histology and these patients incurred more adverse events. Additional 1LMT options are needed to further improve clinical outcomes.

The INTEGRATE study aimed to provide information on the use, effectiveness, and safety of esketamine nasal spray (ESK-NS) for the treatment of treatment-resistant depression (TRD) in real-world practice in Spain. This was an observational, cross-sectional, retrospective study conducted in adults aged 18-74years who met the criteria for TRD. The weekly impact of ESK-NS on depressive symptoms was evaluated by clinical judgment using four categories (nonresponse, response, remission, not available). The onset of action 24h after administration was also evaluated. Information on adverse events was collected from the medical records. We included 196 patients, of whom 189 were considered evaluable; the mean (SD) number of previous episodes was 3.7 (3.0). According to the investigator's judgment, 152 (80.4%) of 189 patients were in response or remission in the induction phase, and 54 (90%) of 60 during the maintenance phase. The proportions of patients in remission were 9.5%, 18.7%, and 38.3% during the induction, optimization, and maintenance phases, respectively. Fifty-three (28.0%) patients experienced an improvement in depressive symptoms within the first 24h after the first administration of ESK-NS. Most adverse events reported with ESK-NS were mild and did not require any action with the study drug; the number of adverse events decreased over time, especially during the first 4weeks. Consistent with the available evidence, the results of this study indicate that ESK-NS is an effective and safe option to consider within the therapeutic algorithm for TRD.

This study assessed the effects of astaxanthin supplementation on chronic and acute digital eye strain in school-aged children (10-14years) and evaluated its safety. While previous studies focused on adults, this study examined astaxanthin's effects on developing eyes. A randomized, double-blind, placebo-controlled trial was conducted over 84days involving 64 children engaged in≥4h of screen time daily and experiencing mild to moderate computer vision syndrome (CVS) symptoms as indicated by a CVS-Questionnaire (CVS-Q) score≥8 and<19. Participants received a daily 4-mg astaxanthin soft capsule for 84days. Primary outcomes were measured using CVS-Q, while secondary outcomes included visual fatigue Likert scale (VFLS), visual acuity, spherical equivalence, near point of accommodation, near exophoria, dry eye intensity, pupil size, stereopsis, blinking frequency, immunity, and safety variables. Of the 64 participants (mean age 11.5-11.7years), 35 were male and 29 were female. Astaxanthin supplementation significantly improved CVS-Q scores after 84days (-4.00±4.05 arbitrary units (A.U.) from baseline, p<0.0001) compared to placebo (-1.72±3.61 A.U., p<0.05), a 20% between group difference. The mean VFLS scores were significantly lower in the astaxanthin group (11.55±5.78 A.U.) compared to placebo (15.78±7.12 A.U., p=0.01), showing a 27% improvement after 84days. Stereopsis improved significantly after acute visual load at 28 and 84days (p<0.05, p<0.0001 vs. placebo, respectively), and pupillary light reflex improved after 84days (p<0.05 vs. placebo). Tear production increased after 14, 56, and 84days (p<0.05, p<0.001, and p<0.001 vs. baseline, respectively) in the astaxanthin group, with no significant intergroup difference in the Schirmer I test, visual acuity, spherical equivalence, near point of accommodation, near exphoria, immune markers, or safety variables. Astaxanthin supplementation effectively reduced chronic and acute digital eye strain, while enhancing objective measures of visual performance in school-aged children, underscoring thebenefits of astaxanthin in pediatric visual health and performance. NIH ClinicalTrials.gov (Identifier: NCT05602402); Clinical Trials Registry India (Registration Number: CTRI/2022/10/046606).

The burden of severe asthma on patients, especially on those with concomitant chronic rhinosinusitis with nasal polyps (CRSwNP), is substantial. Treatment intensification with oral corticosteroids is a common strategy for managing severe asthma exacerbations; however, prolonged exposure to systemic corticosteroids is associated with multisystem toxicity. This study aimed to quantify the association between oral corticosteroid use and annual asthma-related costs in patients with severe asthma with or without CRSwNP. This pharmacoeconomic analysis was based on data from the Severe Asthma Network in Italy (SANI) registry. Asthma-related costs were estimated in the context of the Italian healthcare system and included exacerbations requiring treatment intensification, unplanned visits, admissions to hospital and emergency/intensive care units, and lost workdays. For each item, the mean annual cost per patient was estimated based on national tariffs and the frequency of the event. To quantify the association between oral corticosteroid treatment and costs, the study cohort was stratified according to oral corticosteroid use in the 1-year preceding inclusion in the SANI registry. A total of 669 patients from the SANI registry were included in the present analysis, 255 of whom had concomitant CRSwNP. Corticosteroid use was associated with significantly higher annual disease-related costs per patient compared with no corticosteroid use. Compared with the overall study cohort and patients without CRSwNP, patients with CRSwNP had higher disease-related costs (higher by €1307 and €1869, respectively). Use of corticosteroids, in particular systemic corticosteroids, is associated with an increase in asthma-related costs. The concomitant presence of CRSwNP impacts negatively on costs. This study suggests that a thorough analysis of costs, expected benefits, and occurrence of adverse events is required when selecting treatment intensification strategies for managing uncontrolled severe asthma.

IntroductionThe prescription of non-steroidal anti-inflammatory drugs (NSAIDs) covered by the Italian National Health Service is limited to certain pathologies defined in the 2018 update of Note 66 of the Italian Medicines Agency (AIFA), meant to ensure appropriate use of NSAIDs. This analysis was conducted in real clinical practice to describe NSAID utilization from 2019 to 2022 with respect to Note 66 update.MethodsFor this real-world analysis, data were extracted from the administrative databases of healthcare institutions covering ~ 9.1 million citizens. From 2019 to 2022, all subjects with ≥ 1 NSAID prescription were identified. Demographic and clinical characteristics, the proportion of NSAID-treated patients over time, the most prescribed molecules, and drug consumption defined as daily dose (DDD) per 1000 inhabitants/day were recorded.ResultsThe percentage NSAID-treated patients showed a slight increase over time (1.9–3.0%). The most prescribed active ingredients were diclofenac, ketoprofen, nimesulide, etoricoxib, and ibuprofen. NSAID consumption increased from 15.5 to 16.8 DDD/1000 inhabitants/day over 2020–2022, especially in older patients (65–74 years group: 36.2–39.3 DDD/1000 inhabitants/day). From 2019 to 2022, 2,811,910 patients with NSAID prescription(s) in Note 66 were identified, whose average age was 59.7 years. Among them, 0.1–1.0% received NSAIDs for rheumatic diseases and 11.9% in the oncological setting. While diclofenac, etoricoxib, and ketoprofen were commonly prescribed at medium–low dosage as recommended, ibuprofen was used at high dosage (600 mg) in 80% of cases.ConclusionThe analysis showed that patients prescribed with NSAIDs were relatively young (~ 60 years), in contrast with the pathologies covered by Note 66, which typically affect elderly people. Moreover, rheumatic and oncological diseases were poorly represented, thus it is possible that NSAIDs might have been prescribed for indications outside the note. These findings suggest that the use of NSAIDs for pain management in Italy should be optimized, properly weighting their risks and benefits.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-025-03153-3.

IntroductionMirikizumab, a humanized anti-interleukin-23p19 monoclonal antibody, is approved for the treatment of moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD). Two phase 1, open-label, two-arm, randomized studies compared pharmacokinetics and safety of mirikizumab (200 mg, Study AMBW; 300 mg, Study AMBX) to establish bioequivalence. Mirikizumab was administered subcutaneously using an autoinjector or a prefilled syringe (PFS) as a single dose in healthy participants.MethodsParticipants (male and female) were randomized 1:1 to mirikizumab by a PFS (reference) and an autoinjector (test). Participants were sub-randomized (1:1:1) to one of three injection sites (abdomen, arm, thigh) and stratified into one of three weight groups. Primary endpoints were maximum observed drug concentration (Cmax), and area under concentration versus time curves (time zero to infinity [AUC0–∞]; time to last time point with measurable concentration [AUC0–tlast]). Secondary objectives were safety and immunogenicity.ResultsIn Study AMBW, 90% confidence intervals (CIs) for the ratios (autoinjector to PFS) of geometric least squares mean values for Cmax, AUC0–∞, and AUC0–tlast were within prespecified bioequivalence limits (0.80–1.25). Similar results were observed in Study AMBX, after administration of mirikizumab 300 mg, with bioequivalence achieved for AUC0–tlast and AUC0–∞, while the upper bound of the 90% CI of the geometric least squares mean ratio for Cmax was slightly above the bioequivalence upper threshold. Overall safety of mirikizumab was similar between devices in both studies. Immunogenicity was similar overall in Study AMBW, but slightly higher (autoinjector versus PFS) in Study AMBX.ConclusionMirikizumab administered by autoinjector or PFS was considered bioequivalent at the 200-mg UC maintenance dose and the 300-mg CD maintenance dose. Safety and immunogenicity profiles were comparable between autoinjector and PFS. Availability of an autoinjector option may be preferred by some patients and may help improve patient adherence to treatment.Clinical Trial RegistrationClinicalTrials.gov NCT04607733; NCT05069896.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-025-03335-z.

IntroductionAn imbalanced diet is one of the leading causes of metabolic dysfunction-associated steatotic liver disease (MASLD) development. Diet modification remains the leading approach in the disease management. However, the role of minerals in MASLD development and treatment is poorly understood. In this retrospective study we compared minerals intake in patients with MASLD and age- and sex-matched controls, based on the data of a food frequency questionnaire.MethodsA retrospective database search was performed to identify eligible data of the nutritional assessment with software based on a food frequency questionnaire. The institutional medical records of the obtained cohort were then searched for medical conditions in accordance with the inclusion/exclusion criteria. On the basis of the presence of MASLD, the subjects were allocated to either MASLD or the control group. Sex- and age-matched pairs were formed for the analysis. Consumption of major minerals and trace elements was compared using non-parametric statistics.ResultsRecords of 15,862 subjects were screened, and the data of 226 sex- and age-matched pairs of patients with MASLD and controls were selected for the analysis. The absolute average daily intake of most of the minerals, except silicon, cobalt, molybdenum, nickel, and chromium, was greater in the MASLD group than in the control group. However, relative value (per 1000 kcal) analysis revealed that only boron intake was greater in the MASLD group (28.3 ± 38.5 vs 19.5 ± 24.7 μg/day, p = 0.013). Subjects with MASLD exceeded the recommended daily allowance (RDA) for sodium (241% of RDA), phosphorus (211%), vanadium (1576%), manganese (410%), and selenium (197%) intake, but consumed less than the recommended amounts of silicon (5% of the RDA), molybdenum (28%), fluorine (3%), zinc (91%), and chromium (37%).ConclusionPatients with MASLD consumed greater amounts of most minerals than did the control group due to overeating. When diet modification for patients with MASLD is planned, the intake of calcium, zinc, and boron needs to be controlled, and the diet may be modified with food supplements or specific foods rich in these minerals.

IntroductionHypoparathyroidism (HypoPT) is an endocrine disease caused by insufficient levels of parathyroid hormone and is associated with impaired health-related quality of life. This study assessed the clinical burden among individuals with postsurgical chronic HypoPT in Medicare Fee-For-Service.MethodsAdults (aged ≥ 18 years) with newly diagnosed HypoPT (N = 1166) were identified from the Medicare 100% Limited Data Set between July 1, 2017, and March 31, 2020. All had a confirmed diagnosis within 6–12 months after index diagnosis and were required to be continuously enrolled for ≥ 6 months pre index and ≥ 12 months post index. A random sample of non-HypoPT controls (N = 11,258) was synthetically assigned an index date of diagnosis to ensure similar baseline and follow-up periods as individuals with postsurgical chronic HypoPT. The two cohorts were compared before and after matching with respect to the risk of cardiovascular (CV) events, renal complications, urinary tract infections (UTIs), upper respiratory tract infections (URTIs), and mortality.ResultsIndividuals with postsurgical chronic HypoPT were older than non-HypoPT controls (mean age 69 vs. 64 years), more were female (76% vs. 57%), had higher Charlson Comorbidity Index scores (3.24 vs. 0.73), and a higher prevalence of moderate-to-severe renal disease (28.8% vs. 5.6%), nephrocalcinosis (59.9% vs. 0.6%), and nephrolithiasis (8.3% vs. 1.0%). They also had significantly greater mortality (hazard ratio [HR] 2.75). The incident risks of composite CV events (HR 1.35), renal complications (HR 4.92), UTIs (HR 2.09), and URTIs (HR 1.46) were greater in subcohorts without those conditions prior to index. After matching for baseline characteristics, the elevated risk of renal complications, UTIs, and URTIs remained while there was no difference in the risk of CV events or death between individuals with postsurgical chronic HypoPT and controls.ConclusionThe substantial clinical burden of postsurgical chronic HypoPT in Medicare patients highlights the treatment gaps associated with current therapy and the need for parathyroid hormone replacement therapies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-025-03264-x.