Applying Exercise Capacity and Physical Activity as Single vs Composite Endpoints for Trials of Cardiac Rehabilitation Interventions: Rationale, Use-case, and a Blueprint Method for Sample Size Calculation.

OBJECTIVE: To conceptualize a composite primary endpoint for parallel-group RCTs of exercise-based cardiac rehabilitation (CR) interventions and to explore its application and statistical efficiency. DESIGN: We conducted a statistical exploration of sample size requirements. We combined exercise capacity and physical activity for the composite endpoint (CE), both being directly related to reduced premature mortality in patients with cardiac diseases. Based on smallest detectable and minimal clinically important changes (change in exercise capacity of 15 W and change in physical activity of 10 min/day), the CE combines 2 dichotomous endpoints (achieved/not achieved). To examine statistical efficiency, we compared sample size requirements based on the CE to single endpoints using data from 2 completed CR trials. SETTING: Cardiac rehabilitation phase III. PARTICIPANTS: Patients in cardiac rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Exercise capacity (Pmax assessed by incremental cycle ergometry) and physical activity (daily minutes of moderate to vigorous physical activity assessed by accelerometry). RESULTS: Expecting, for example, a 10% between-group difference and improvement in the clinical outcome, the CE would increase sample size by up to 21% or 61%, depending on the dataset. When expecting a 10% difference and designing an intervention with the aim of non-deterioration, the CE would allow to reduce the sample size by up to 55% or 70%. CONCLUSIONS: Trialists may consider the utility of the CE for future studies in exercise-based CR to reduce sample size requirements. However, perhaps surprisingly at first, the CE could also lead to an increased sample size needed, depending on the observed baseline proportions in the trial population and the aim of the intervention.

Study on Bacteria Isolates and Antimicrobial Resistance in Wildlife in Sicily, Southern Italy.

Wild environments and wildlife can be reservoirs of pathogens and antibiotic resistance. Various studies have reported the presence of zoonotic bacteria, resistant strains, and genetic elements that determine antibiotic resistance in wild animals, especially near urban centers or agricultural and zootechnical activities. The purpose of this study was the analysis, by cultural and molecular methods, of bacteria isolated from wild animals in Sicily, Italy, regarding their susceptibility profile to antibiotics and the presence of antibiotic resistance genes. Bacteriological analyses were conducted on 368 wild animals, leading to the isolation of 222 bacterial strains identified by biochemical tests and 16S rRNA sequencing. The most isolated species was Escherichia coli, followed by Clostridium perfringens and Citrobacter freundii. Antibiograms and the determination of resistance genes showed a reduced spread of bacteria carrying antibiotic resistance among wild animals in Sicily. However, since several wild animals are becoming increasingly close to residential areas, it is important to monitor their health status and to perform microbiological analyses following a One Health approach.

Dermo beta brachytherapy with 188-Re in squamous cell carcinoma of the penis: a new therapy.

BACKGROUND: Squamous cell carcinoma of the penis (SCCP) is the most common penis neoplasia, favoured by phimosis, HPV infection and scleroatrophic lichen. The classic therapy is surgical with anatomic demolition, which often causes important psychological problems. Other non-demolitive therapies can be utilized, such as radiotherapy, brachytherapy and topical medical treatment. OBJECTIVES: We propose a new non-invasive therapy called "Dermo beta brachytherapy (DBBT) with 188-Re" in which a synthetic inert resin-matrix containing a radioactive beta-emitting isotope is applied on the surface of the tumor lesion. MATERIALS AND METHODS: A total of 15 patients with a histologically confirmed diagnosis of SCCP were enrolled for treatment (DBBT). RESULTS: Of the 15 patients, 12 healed, 1 was lost at follow-up and 2 did not respond to therapy. CONCLUSION: The results indicate that DBBT is an effective treatment for SCC of the penis, sparing the anatomical integrity of the organ, and allowing normal sexual activity.

Griscelli syndrome type 2: long-term follow-up after unrelated donor bone marrow transplantation.

Griscelli syndrome (GS) is a rare autosomal recessive disease characterized by silvery hair ('partial albinism'). Three forms exist; GS type 2 (GS2), the most common one, is characterized by severe primary immunodeficiency with acute episodes of hemophagocytic lymphohistiocytosis (HLH) which may be fatal in the absence of hematopoietic stem cell transplantation. A 5-year-old boy with HLH was referred to us because of silvery-gray hair present since birth. Abnormal pigment clumps were observed in the medulla of hair shafts on light microscopy. Electron microscopy of a skin biopsy revealed melanosomes in melanocytes, but not in keratinocytes. Leukocytes were devoid of intracytoplasmic granules on blood smear. Neurological signs were absent. Genotyping revealed a homozygous haplotype for polymorphic markers linked to the RAB27A locus, but no RAB27A mutation. A diagnosis of GS2 was established. The patient received bone marrow transplantation (BMT) from an unrelated donor, and after 72 months he did not show relapse of HLH. The long, uneventful follow-up supports the use of BMT from an unrelated donor if transplantation from a relative is not possible.

Treatment of lentigo maligna with tazarotene 0.1% gel.

We report 2 elderly patients with facial lentigo maligna who experienced complete regression, both clinically and histopathologically, after once-daily topical treatment with tazarotene 0.1% gel for 6 to 8 months. After a follow-up period of 18 and 30 months, no recurrence was observed. We believe that tazarotene might be considered as an alternative medical approach in selected patients with lentigo maligna.

High-dose intravenous immunoglobulin for severe drug reactions: efficacy in toxic epidermal necrolysis.

High-dose intravenous immunoglobulin has been proposed as an alternative treatment for several immuno-mediated inflammatory skin diseases, usually at a dosage of 1 - 2 g/kg. We describe the treatment of 10 patients affected by toxic epidermal necrolysis using 400 mg/kg per day on 5 consecutive days--a schedule that is lower than previously reported schedules. According to the SCORTEN, the earlier predicted mortality rate was 35%. After high-dose intravenous immunoglobulin therapy, a mortality rate of 10% and a survival rate of 90% were reached. In particular, nine patients showed a dramatic improvement already after one course of infusion started at an early stage of the disease. It is our experience, and that of others, that high-dose intravenous immunoglobulin can be considered the drug of first choice for toxic epidermal necrolysis, one of the most severe life-threatening dermatological conditions, and a valid alternative therapy for different long-standing chronic dermatological diseases. This therapy can also be effective in avoiding high steroid dosages and consequently steroid-related or immunosuppressive-related side effects. It is therefore reasonable to propose high-dose intravenous immunoglobulin treatment as a valuable therapeutic tool for dermatologists.