Identification and validation of diagnostic cut-offs of the ELISpot assay for the diagnosis of invasive aspergillosis in high-risk patients.

OBJECTIVE: We investigated the performance of enzyme linked immunospot (ELISpot) assay for the diagnosis of invasive aspergillosis (IA) in high-risk patients with hematologic malignancies. METHODS: We prospectively enrolled two cohorts of patients undergoing intensive myelosuppressive or immunosuppressive treatments at high risk for IA. ELISpot was performed to detect Aspergillus-specific T cells producing Interleukin-10. RESULTS: In the discovery cohort, a derived cut-off of 40 spot forming cells (SFCs)/106 PBMCs has shown to correctly classify IA cases with a sensitivity and specificity of 89.5% and 88.6%, respectively. This cut-off is lowered to 25 SFC when considering the subset of possible IA patients, with sensitivity and specificity of 76% and 93%, respectively. The application of the 40 SFCs cut-off to the validation cohort resulted in a positivity rate of 83.3% in proven/probable cases and a negativity rate of 92.5% in possible/non-IA cases. Adopting the 25 SCFs cut-off, the assay resulted positive in 83.3% of proven/probable cases while it resulted negative in 66.7% of possible/non-IA cases. CONCLUSIONS: ELISpot shows promises in the diagnosis of IA and the possibility to use two distinct cut-offs with similar diagnostic performances according to patients' different pre-test probability of infection can widen its use in patients at risk.

Cognitive, behavioral and socio-communication skills as predictors of response to Early Start Denver Model: a prospective study in 32 young children with Autism Spectrum Disorder.

Introduction: The effectiveness of early interventions in young autistic children is well established, but there is great interindividual variability in treatment response. Predictors of response to naturalistic developmental behavioral interventions (NDBI), like the Early Start Denver Model (ESDM), are needed. Methods: We conducted an exploratory study to prospectively seek predictors of response in 32 young children treated with ESDM after receiving an ASD diagnosis. All children were less than 39 months old (mean age: 29.7 mo), and received individualized ESDM for nine months. Tests were administered at the beginning, after 4 months, and at the end of treatment. Results: Four children (12.5%) were "strong responders", 8 children (25.0%) were "moderate responders", and 20 children (62.5%) were "poor responders". A more favorable response to ESDM was significantly predicted by higher PEP-3 Expressive Language, Receptive Language, Cognitive Verbal/Preverbal, Visuo-Motor Imitation scores, higher GMDS-ER Personal/Social, and VABS-II Communication scores, by lower ADI-R C restricted/stereotypic behaviors, and by joint attention level. Discussion: Most predictors showed a linear association with increasing response to ESDM, but GMDS-ER Personal-Social and joint attention level predicted strong response, while PEP-3 receptive language equally predicted moderate or strong response. Although larger samples will be necessary to reach definitive conclusions, in conjunction with prior reports our findings begin providing information able to assist clinicians in choosing the most appropriate treatment program for young autistic children.

Role of Body Composition in Patients with Resectable Pancreatic Cancer.

This study investigates the role of body composition parameters in patients with pancreatic cancer undergoing surgical treatment. The research involved 88 patients diagnosed with pancreatic cancer who underwent surgery at the Modena Cancer Center between June 2015 and October 2023. Body composition parameters were obtained from CT scans performed before and after surgery. The percentage of sarcopenic patients at the time of diagnosis of pancreatic cancer is 56.82%. Of the patients who died between the first and second CT evaluated, 58% were sarcopenic, thus confirming the role of sarcopenia on outcome. The study found that all body composition parameters (TAMA, SMI, VFI, and SFI) demonstrated a trend towards reduction between two examinations, indicating an overall depletion in muscle and adipose tissue. We then evaluated the relationships between fat-related parameters (VFI, SFI and VSR) and survival outcomes: overall survival and progression-free survival. Cox univariate regression model show significant parameter related to outcomes was adipose tissue, specifically VFI. The study found that higher VFI levels were associated with greater survival rates. This research holds promise for advancing our understanding of the link between body composition and the prognosis of pancreatic cancer patients.

Physical activity practiced at a young age is associated with a less severe subsequent clinical presentation in facioscapulohumeral muscular dystrophy.

BACKGROUND: In facioscapulohumeral muscular dystrophy (FSHD), it is not known whether physical activity (PA) practiced at young age is associated with the clinical presentation of disease. To assess this issue, we performed a retrospective cohort study concerning the previous practice of sports and, among them, those with medium-high cardiovascular commitment in clinically categorized carriers of a D4Z4 reduced allele (DRA). METHODS: People aged between 18 and 60 were recruited as being DRA carriers. Subcategory (classical phenotype, A; incomplete phenotype, B; asymptomatic carriers, C; complex phenotype, D) and FSHD score, which measures muscle functional impairment, were assessed for all participants. Information on PAs was retrieved by using an online survey dealing with the practice of sports at a young age. RESULTS: 368 participants were included in the study, average age 36.6 years (SD = 9.4), 47.6% male. The FSHD subcategory A was observed in 157 (42.7%) participants with average (± SD) FSHD score of 5.8 ± 3.0; the incomplete phenotype (category B) in 46 (12.5%) participants (average score 2.2 ± 1.7) and the D phenotype in 61 (16.6%, average score 6.5 ± 3.8). Asymptomatic carriers were 104 (subcategory C, 28.3%, score 0.0 ± 0.2). Time from symptoms onset was higher for patients with A (15.8 ± 11.1 years) and D phenotype (13.3 ± 11.9) than for patients with B phenotype (7.3 ± 9.0). The practice of sports was associated with lower FSHD score (-17%) in participants with A phenotype (MR = 0.83, 95% CI = 0.73-0.95, p = 0.007) and by 33% in participants with D phenotype (MR = 0.67, 95% CI = 0.51-0.89, p = 0.006). Conversely, no improvement was observed in participants with incomplete phenotype with mild severity (B). CONCLUSIONS: PAs at a young age are associated with a lower clinical score in the adult A and D FSHD subcategories. These results corroborate the need to consider PAs at the young age as a fundamental indicator for the correct clinical stratification of the disease and its possible evolution.

Effectiveness of patients' involvement in a medical and nursing pain education programme: a protocol for an open-label randomised controlled trial including qualitative data.

INTRODUCTION: Pain is a multidimensional experience that varies among individuals and has a significant impact on their health. A biopsychosocial approach is recommended for effective pain management; however, health professionals' education is weak on this issue. Patient involvement is a promising didactic methodology in developing a more holistic perspective, however there is a lack of reliable evidence on this topic. The aim of the present study is to evaluate the effectiveness of patient involvement in pain education in undergraduate medicine and nursing students. METHODS AND ANALYSIS: An open-label randomised controlled trial including qualitative data will be conducted. After an introductory lesson, each student will be randomly assigned to the intervention group, which includes an educational session conducted by a patient-partner along with an educator, or to the control group in which the session is exclusively conducted by an educator. Both sessions will be carried out according to the Case-Based Learning approach. Primary outcomes will be students' knowledge, attitudes, opinions and beliefs about pain management, whereas the secondary outcome will be students' satisfaction. The Pain Knowledge and Attitudes (PAK) and Chronic Pain Myth Scale (CPMS) will be administered preintervention and postintervention to measure primary outcomes. Students' satisfaction will be measured by a questionnaire at the end of the session. Two focus groups will be conducted to evaluate non-quantifiable aspects of learning. ETHICS AND DISSEMINATION: The protocol of this study was approved by the independent Area Vasta Emilia Nord ethics committee.Adherence to The Declaration of Helsinki and Good Clinical Practice will ensure that the rights, safety and well-being of the participants in the study are safeguarded, as well as data reliability. The results will be disseminated through scientific publications and used to improve the educational offer. A version of the anonymised data set will be released for public access. TRIAL REGISTRATION: Trial was not registered on ClinicalTrials.gov as the interventions being compared only concern educational programmes and the outcomes considered do not refer to any clinical dimension.

Metastatic site patterns by intrinsic subtype and HER2DX in early HER2-positive breast cancer.

BACKGROUND: Even with contemporary treatment strategies, more than 10% of HER2-positive early stage breast cancer patients may experience distant metastasis as first event during follow-up. Tools for predicting unique patterns of metastatic spread are needed to plan personalized surveillance. We evaluated how molecular heterogeneity affects the pattern of distant relapse in HER2-positive breast cancer. METHODS: A total of 677 HER2-positive stage I-III breast cancer patients from ShortHER trial, Cher-LOB trial, and 2 institutional cohorts were included. PAM50 molecular subtypes and research-based HER2DX scores were evaluated. The cumulative incidence of distant relapse as the first event (any site and site specific) was evaluated using competing risk analysis. Median follow-up was 8.4 years. Tests of statistical significance are 2-sided. RESULTS: Stage III and high HER2DX risk score identified patients at the highest risk of distant relapse as first event (10-year incidence 24.5% and 19.7%, respectively). Intrinsic molecular subtypes were associated with specific patterns of metastatic spread: compared with other subtypes, HER2-enriched tumors were more prone to develop brain metastases (10-year incidence 3.8% vs 0.6%, P = .005), basal-like tumors were associated with an increased risk of lung metastases (10-year incidence 11.1% vs 2.6%, P = .001), and luminal tumors developed more frequently bone-only metastases (10-year incidence 5.1% vs 2.0%, P = .042). When added to stage or HER2DX risk score in competing risk regression models, intrinsic subtype maintained an independent association with site-specific metastases. CONCLUSIONS: The integration of intrinsic molecular subtypes with stage or HER2DX risk score predicts site-specific metastatic risk in HER2-positive breast cancer, with potential implications for personalized surveillance and clinical trials aimed at preventing site-specific recurrence.

Low-molecular-weight heparin for the prevention of clinical worsening in severe non-critically ill COVID-19 patients: a joint analysis of two randomized controlled trials.

Coronavirus disease 2019 (COVID-19) carries a high risk of vascular thrombosis. However, whether a specific anticoagulation intensity strategy may prevent clinical worsening in severe COVID-19 patients is still debated. We conducted a joint analysis of two randomized controlled trials, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), to assess the efficacy and safety of two anticoagulant regimens in hospitalized severe COVID-19 patients. Subjects with COVID-19-associated respiratory compromise and/or coagulopathy were randomly assigned to low (4000 IU qd) or high (70 IU Kg-1 every 12 h) enoxaparin dose. The primary efficacy endpoint was clinical worsening within 30 days, defined as the occurrence of at least one of the following events, whichever came first: in-hospital death, evidence of arterial or venous thromboembolism, acute myocardial infarction, need for either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) in patients receiving standard oxygen therapy or none at randomization, and need for mechanical ventilation in any patient. The safety endpoint was major bleeding. We estimated the relative risk (RR) and its 95% confidence interval (CI) for the outcomes. Among 283 patients included in the study (144 in the low-dose and 139 in the high-dose group), 118 (41.7%) were on NIV or CPAP at randomization. 23/139 (16.5%) patients in the high-dose group reached the primary endpoint compared to 33/144 (22.9%) in the low-dose group (RR 0.72, 95% CI 0.45-1.17). No major bleeding was observed. No significant differences were found in the clinical worsening of hospitalized COVID-19 patients treated with high versus low doses of enoxaparin.

Prevalence of co-occurring conditions in children and adults with autism spectrum disorder: A systematic review and meta-analysis.

This systematic review estimates the prevalence of co-occurring conditions (CCs) in children and adults with autism. A comprehensive search strategy consulting existing guidelines, diagnostic manuals, experts, carers, and autistic people was developed. PubMed and PsycInfo databases from inception to May 2022 were searched. PROSPERO registration: CRD42019132347. Two blind authors screened and extracted the data. Prevalence estimates for different CCs were summarized by using random effects models. Subgroup analyses were performed for age groups (children/adolescents vs adults) and study designs (population/registry-based vs clinical sample-based). Of 19,932 studies, 340 publications with about 590,000 participants were included and meta-analyzed to estimate the prevalence of 38-point prevalence, 27-lifetime, and 3 without distinction between point and lifetime prevalence. Point prevalence of developmental coordination disorder, sleep-wake problem, gastrointestinal problem, ADHD, anxiety disorder, overweight/obesity, feeding and eating disorder, elimination disorder, disruptive behavior, and somatic symptoms and related disorder were the most frequent CCs. Prevalence differed depending on the age group and study design. Knowing specific CCs linked to autism helps professional investigations and interventions for improved outcomes.

Weight loss trend after bariatric surgery in a population of obese patients.

BACKGROUND AND AIMS: Bariatric Surgery (BS) is a therapeutic option in patients with severe obesity whose non-surgical techniques have failed. No work has previously explored trajectories of weight loss and how long this was maintained. Aim of study is to describe effect of BS and nutritional intervention on body weight trend in patients with obesity. METHODS: 792 patients who underwent BS from 1996 to 2021 were included. The Protocol provides Laparoscopic Sleeve Gastrectomy (LSG), Vertical Gastroplasty (VBG) and Roux-en-Y Gastric Bypass (GB). %Total Weight Loss (%TWL) and %Excess Weight Loss (%EWL) were evaluated in three cohort of patients. Cumulative incidence of clinical goal after surgery was calculated at two and five years after BS. RESULTS: At two years of follow-up, average %TWL and %EWL were 31.2% (95% CI = 29.0-33.4%) and 71% (95% CI = 65.4-76.5%) for VBG, 34.7% (95% CI = 33.8-35.6%) and 78.0% (95% CI = 75.9-89.1%) for GB and 33.8% (95% CI = 32.5-35.1%) and 68.8% (95% CI = 66.1-71.6%) for LSG. At two years from surgery the cumulative incidence of clinical goal was 70.7% (95% CI = 59.1-79.1%) for VBG, 86.4% (95% CI = 82.4-89.6%) for GB and 83.4% (95% CI = 76.0-87.1%) for LSG. At five years from surgery, average % TWL and % EWL were 22.5% (95% CI = 10.2-34.8%) and 58.2% (95% CI = 28.4-88.1%) for VBG, 31.8% (95% CI = 30.2-33.3%) and 70.8% (95% CI = 67.5-74.1%) for GB and 29.5% (95% CI = 26.2-32.8%) and 62.0% (95% CI = 53.4-70.6%) for LSG respectively. At five years after having reached clinical goal the share of people who were able to maintain their weight was 49.5% (95% CI = 30.8-79.6%) for VBG, 69.5% (95% CI = 58.3-82.8%) for GB and 55.9% (95% CI = 42.1-74.3%) for LSG. The median time of clinical goal maintaining was 4.8 years for VBG (95% CI lower limit = 4.1), 6.6 years for GB (95% CI lower limit = 6.2) and 5.3 years for LSG (95% CI lower limit = 4.8). CONCLUSIONS: Our work confirm effectiveness of BS in patients with obesity and show that who do not reach clinical goal within 2 years, hardly will reach it later and suggest necessity for a medium and long-term follow-up to prevent weight regain.

Early palliative care versus usual haematological care in multiple myeloma: retrospective cohort study.

OBJECTIVES: Although early palliative care (EPC) is beneficial in acute myeloid leukaemia, little is known about EPC value in multiple myeloma (MM). We compared quality indicators for palliative and end-of-life (EOL) care in patients with MM receiving EPC with those of patients who received usual haematological care (UHC). METHODS: This observational, retrospective study was based on 290 consecutive patients with MM. The following indicators were abstracted: providing psychological support, assessing/managing pain, discussing goals of care, promoting advance care plan, accessing home care services; no anti-MM treatment within 14 and 30 days and hospice length of stay >7 days before death; no cardiopulmonary resuscitation, no intubation, <2 hospitalisations and emergency department visits within 30 days before death. Comparisons were performed using unadjusted and confounder-adjusted regression models. RESULTS: 55 patients received EPC and 231 UHC. Compared with UHC patients, EPC patients had a significantly higher number of quality indicators of care (mean 2.62±1.25 vs 1.12±0.95; p<0.0001)); a significant reduction of pain intensity over time (p<0.01) and a trend towards reduced aggressiveness at EOL, with the same survival (5.3 vs 5.46 years; p=0.74)). CONCLUSIONS: Our data support the value of integrating EPC into MM routine practice and lay the groundwork for future prospective comparative studies.

Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis.

In preclinical studies rapamycin was found to target neuroinflammation, by expanding regulatory T cells, and affecting autophagy, two pillars of amyotrophic lateral sclerosis (ALS) pathogenesis. Herein we report a multicenter, randomized, double-blind trial, in 63 ALS patients who were randomly assigned in a 1:1:1 ratio to receive rapamycin 2 mg/m2/day,1 mg/m2/day or placebo (EUDRACT 2016-002399-28; NCT03359538). The primary outcome, the number of patients exhibiting an increase >30% in regulatory T cells from baseline to treatment end, was not attained. Secondary outcomes were changes from baseline of T, B, NK cell subpopulations, inflammasome mRNA expression and activation status, S6-ribosomal protein phosphorylation, neurofilaments; clinical outcome measures of disease progression; survival; safety and quality of life. Of the secondary outcomes, rapamycin decreased mRNA relative expression of the pro-inflammatory cytokine IL-18, reduced plasmatic IL-18 protein, and increased the percentage of classical monocytes and memory switched B cells, although no corrections were applied for multiple tests. In conclusion, we show that rapamycin treatment is well tolerated and provides reassuring safety findings in ALS patients, but further trials are necessary to understand the biological and clinical effects of this drug in ALS.

Impact of Nutritional Status on Postoperative Outcomes in Cancer Patients following Elective Pancreatic Surgery.

BACKGROUND: Pancreatic surgery has been associated with important postoperative morbidity, mortality and prolonged length of hospital stay. In pancreatic surgery, the effect of poor preoperative nutritional status and muscle wasting on postsurgery clinical outcomes still remains unclear and controversial. MATERIALS AND METHODS: A total of 103 consecutive patients with histologically proven carcinoma undergoing elective pancreatic surgery from June 2015 through to July 2020 were included and retrospectively studied. A multidimensional nutritional assessment was performed before elective surgery as required by the local clinical pathway. Clinical and nutritional data were collected in a medical database at diagnosis and after surgery. RESULTS: In the multivariable analysis, body mass index (OR 1.25, 95% CI 1.04-1.59, p = 0.039) and weight loss (OR 1.16, 95% CI 1.06-1.29, p = 0.004) were associated with Clavien score I-II; weight loss (OR 1.13, 95% CI 1.02-1.27, p = 0.027) affected postsurgery morbidity/mortality, and reduced muscle mass was identified as an independent, prognostic factor for postsurgery digestive hemorrhages (OR 0.10, 95% CI 0.01 0.72, p = 0.03) and Clavien score I-II (OR 7.43, 95% CI 1.53-44.88, p = 0.018). No association was identified between nutritional status parameters before surgery and length of hospital stay, 30 days reintervention, 30 days readmission, pancreatic fistula, biliary fistula, Clavien score III-IV, Clavien score V and delayed gastric emptying. CONCLUSIONS: An impaired nutritional status before pancreatic surgery affects many postoperative outcomes. Assessment of nutritional status should be part of routine preoperative procedures in order to achieve early and appropriate nutritional support in pancreatic cancer patients. Further studies are needed to better understand the effect of preoperative nutritional therapy on short-term clinical outcomes in patients undergoing pancreatic elective surgery.

Type of adjuvant endocrine therapy and disease-free survival in patients with early HR-positive/HER2-positive BC: analysis from the phase III randomized ShortHER trial.

The optimal adjuvant endocrine therapy for HR-positive/HER2-positive breast cancer patients is unknown. We included in this analysis 784 patients with HR-positive/HER2-positive BC from the randomized ShortHER trial of adjuvant trastuzumab (1 year vs 9 weeks) + chemotherapy. At a median follow-up of 8.7 years, patients who received AI had a significantly better DFS vs patients who received TAM or TAM-AI: 8-yr DFS 86.4 vs 79.7%, log-rank P = 0.013 (HR 1.52, 95% CI 1.09-2.11). In multivariate analysis, the type of endocrine therapy maintained a significant association with DFS (HR 1.64, 95% CI 1.07-2.52, p = 0.025 for TAM/TAM-AI vs AI). Among premenopausal patients aged ≤45 years, the use of GnRHa was associated with longer DFS: 8-yr DFS rate 85.2 vs 62.6% (log-rank p = 0.019, HR 0.41, 95% CI 0.19-0.88). In this post-hoc analysis of the ShortHER trial adjuvant treatment with AI was independently associated with improved DFS. Subgroup analysis in premenopausal patients suggests benefits with ovarian suppression.Trial registration: NCI ClinicalTrials.gov number: NCT00629278.

Cosmetic Results and Side Effects of Accelerated Partial-Breast Irradiation Versus Whole-Breast Irradiation for Low-Risk Invasive Carcinoma of the Breast: The Randomized Phase III IRMA Trial.

PURPOSE: The results in terms of side effects vary among the published accelerated partial-breast irradiation (APBI) studies. Here, we report the 5-year results for cosmetic outcomes and toxicity of the IRMA trial. METHODS: We ran this randomized phase III trial in 35 centers. Women with stage I-IIA breast cancer treated with breast-conserving surgery, age ≥ 49 years, were randomly assigned 1:1 to receive either whole-breast irradiation (WBI) or external beam radiation therapy APBI (38.5 Gy/10 fraction twice daily). Patients and investigators were not masked to treatment allocation. The primary end point was ipsilateral breast tumor recurrence. We hereby present the analysis of the secondary outcomes, cosmesis, and normal tissue toxicity. All side effects were graded with the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Radiation Morbidity Scoring Schema. Analysis was performed with both intention-to-treat and as-treated approaches. RESULTS: Between March 2007 and March 2019, 3,309 patients were randomly assigned to 1,657 WBI and 1,652 APBI; 3,225 patients comprised the intention-to-treat population (1,623 WBI and 1,602 APBI). At a median follow-up of 5.6 (interquartile range, 4.0-8.4) years, adverse cosmesis in the APBI patients was higher than that in the WBI patients at 3 years (12.7% v 9.2%; P = .009) and at 5 years (14% v 9.8%; P = .012). Late soft tissue toxicity (grade ≥ 3: 2.8% APBI v 1% WBI, P < .0001) and late bone toxicity (grade ≥ 3: 1.1% APBI v 0% WBI, P < .0001) were significantly higher in the APBI arm. There were no significant differences in late skin and lung toxicities. CONCLUSION: External beam radiation therapy-APBI with a twice-daily IRMA schedule was associated with increased rates of late moderate soft tissue and bone toxicities, with a slight decrease in patient-reported cosmetic outcomes at 5 years when compared with WBI, although overall toxicity was in an acceptable range.

Therapeutic hypothermia is associated with changes in prognostic value of general movements.

BACKGROUND AND AIMS: General movements (GMs) have been recognized as the most accurate clinical tools for predicting cerebral palsy (CP). This study aimed to compare the type and prognostic value of abnormal GMs in infants with hypoxic ischemic encephalopathy treated or not with therapeutic hypothermia (TH). MATERIALS AND METHODS: This was a single-center retrospective study. We compared GMs of 55 cooled term infants versus 30 non-cooled term infants with hypoxic ischemic encephalopathy (HIE) and their motor outcome at 24 months of age. We also included data regarding early brain MRI scans. RESULTS: Rates of cerebral palsy was 5.4% and 46.7% in cooled and non-cooled infants respectively (p < 0.001). None of cooled infants showed cramped-synchronized GMs, whereas among non-cooled infants the cramped-synchronized pattern was present in 17.2% and 20% of infants at 1 and 3 months of age respectively. Hypokinesis was never seen in cooled infants and it was present in 23.3% of non-cooled ones. Absent fidgety correlated with CP in 14% and 73% of cooled and non-cooled infants respectively. At brain MRI cooled infants had fewer and less severe cerebral lesions compared to non-cooled infants (p = 0.003). CONCLUSIONS: Abnormal GMs are reduced in infants treated with TH. Hypokinesis and cramped-synchronized GMs are not observed in cooled infants and the associations between absent fidgety movements and CP it is largely abolished. TH is associated with changes in prognostic value of GMs.

Efficacy of a multiple-component and multifactorial personalized fall prevention program in a mixed population of community-dwelling older adults with stroke, Parkinson's Disease, or frailty compared to usual care: The PRE.C.I.S.A. randomized controlled trial.

Background: Fall risk in the elderly is a major public health issue due to the injury-related consequences and the risk of associated long-term disability. However, delivering preventive interventions in usual clinical practice still represents a challenge. Aim: To evaluate the efficacy of a multiple-component combined with a multifactorial personalized intervention in reducing fall rates in a mixed population of community-dwelling elderly compared to usual care. Design: Randomized Controlled Trial (NCT03592420, clinicalTrials.gov). Setting: Outpatients in two Italian centers. Population: 403 community-dwelling elderly at moderate-to-high fall risk, including subjects with Parkinson's Disease and stroke. Methods: After the randomization, the described interventions were administered to the intervention group (n = 203). The control group (n = 200) received usual care and recommendations to minimize fall risk factors. In addition, each participant received a fall diary, followed by 12 monthly phone calls. The primary endpoint was the total number of falls in each group over 12 months, while the secondary endpoints were other fall-related indicators recorded at one year. In addition, participants' functioning was assessed at baseline (T1) and 3-month (T3). Results: 690 falls were reported at 12 months, 48.8% in the intervention and 51.2% in the control group, with 1.66 (± 3.5) and 1.77 (± 3.2) mean falls per subject, respectively. Subjects with ≥ 1 fall and ≥2 falls were, respectively, 236 (58.6%) and 148 (36.7%). No statistically significant differences were observed between groups regarding the number of falls, the falling probability, and the time to the first fall. According to the subgroup analysis, no significant differences were reported. However, a statistically significant difference was found for the Mini-BESTest (p = 0.004) and the Fullerton Advanced Balance Scale (p = 0.006) for the intervention group, with a small effect size (Cohen's d 0.26 and 0.32, respectively), at T1 and T3 evaluations. Conclusions: The intervention was ineffective in reducing the number of falls, the falling probability, and the time to the first fall at 12 months in a mixed population of community-dwelling elderly. A significant improvement for two balance indicators was recorded in the intervention group. Future studies are needed to explore different effects of the proposed interventions to reduce falls and consequences.