Off-label use of combined antiretroviral therapy, analysis of data collected by the Italian Register for HIV-1 infection in paediatrics in a large cohort of children

Background Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children < 2 years of age and 60% in those aged 2–12 years, due to the lack of adequate paediatric clinical studies on pharmacokinetics, pharmacodynamics and drug safety in children. Methods An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13–5.19; p = 0.024). Moreover, children < 2 years of age were at increased risk for receiving off-label HAART with respect to older children (OR: 3.24; 95% CI 1063–7.3; p = 0.001). Even if our safety data regarding off-label regimens where poor, no adverse event was reported. Conclusion The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.

A Brief Overview of Road Accidents and Recent Preventive Methodologies for Accident Hotspots in the United Arab Emirates

This paper highlights major causes of road accidents in the United Arab Emirates (UAE) and explores the possibility of reducing them through modern in-vehicle control technologies. Mostly, road safety data from the Global Road Safety Facility (GSRF), Road Safety Polices and Regulations for UK and UAE have been reviewed for comparison and analysis. It contains a descriptive analysis of road accident data which was taken from Ministry of Interior (MOI) - UAE website. It shows how the Pareto Principle applies to most of the road accidents in the UAE with young males’ poor driving habits and higher maximum speed limits being the major causes and, a systematic approach as per the Nilsson Power Model, to tackle these issues. It ends with the conclusion that, although high speed limits on urban roads and highways are some of the critical factors in causing dangerous road accidents but, it can be tackled with by implementing strict road safety policies and enforcing them with modern in vehicle technologies.

New Contraception Update — Annovera, Phexxi, Slynd, and Twirla

Purpose of Review In this review, we discuss the efficacy, safety, and benefits of four new contraceptive products available in the USA, specifically Annovera, Phexxi, Slynd, and Twirla. Recent Findings Annovera is a vaginal ring releasing ethinyl estradiol and segesterone acetate that can be used for up to one year (13 cycles), offering patients an effective, user-controlled option that may improve contraceptive access for those in low-resource settings or those with barriers to retrieving monthly prescriptions; however, given limited efficacy and safety data in people with body mass index (BMI) > 29 kg/m2, clinicians may consider whether Annovera is an appropriate contraceptive method for obese patients if there are other acceptable alternatives. Phexxi prescription-only vaginal gel is a user-controlled, non-hormonal, on-demand contraceptive method that represents a novel addition to the market with its additional uses as a personal lubricant and as a potential microbicide for urogenital infection prevention. Slynd, a drospirenone-only pill, provides more flexibility for delayed or missed pills while maintaining efficacy and a more favorable bleeding profile compared with previously available progestin-only pills. Lastly, Twirla is a transdermal patch releasing ethinyl estradiol and levonorgestrel that offers users an additional option for a user-controlled, combined hormonal contraceptive method without daily dosing; however, prescription is limited to patients with BMI < 30 kg/m2 due to decreased efficacy and VTE events in people with obesity. Summary The addition of these products expands the available options for pregnancy prevention to address unmet contraceptive needs.

Six-month therapy of CGRP monoclonal antibodies in real-world clinical practice: an interim analysis of efficacy and safety data

Introduction. Migraine is one of the most common disabling neurological disorders. Recently developed monoclonal antibodies to calcitonin gene-related peptide (CGRP) or its receptor are the first targeted medication for preventive therapy of both episodic and chronic migraine. They have been thoroughly investigated in clinical trials; however, there is little data from real-world clinical practice available to date. The aim of this study is to assess the efficacy and safety of 6 months of treatment with erenumab in real-world clinical practice and investigate the effect of the drug on the patients’ sensitivity to medicines for migraine headaches relief and patient satisfaction after treatment.Materials and methods. Our observational cohort prospective study included patients in our Headache Clinic prescribed monoclonal antibodies blocking the CGRP-receptor – erenumab. During the investigation, we evaluated the previous preventive therapy and its efficacy, the number of days with migraine per month, adverse events occurring during the erenumab treatment, depression and anxiety (HADS), migraine disability (MIDAS), the presence of allodynia (ACS-12) and improved response to acute therapy after treatment. A total of 42 patients participated in the study: 6 men, 36 women, the average age was 43.9 ± 12.2. Of them, 38 patients (90%) had chronic migraine. Thirty-two patients (76%) had previously been prescribed preventive therapy, which proved ineffective, and 10 patients (24%) had not once received any type of migraine prevention.Results. Among our patients, we identified 11 patients with resistant migraine and one patient with refractory migraine. During the study, two patients dropped out due to adverse events (constipation). Thirty patients continued the administration of erenumab 70 mg for at least six months. The average number of migraine days per month before treatment was 22.8, and after six months of treatment, it dropped to 7.3. Twenty-nine patients (72.5%) also noted that the response to acute headache treatment improved after the therapy.Conclusion. The results of our study are consistent with the international experience of using erenumab and confirm its effectiveness for migraine preventive therapy, including difficult-to-treat migraine cases. However, further studies with more participants and evaluation of predictors of successful monoclonal antibody therapy are still needed.

The Burden of COVID-19 in Children and Its Prevention by Vaccination: A Joint Statement of the Israeli Pediatric Association and the Israeli Society for Pediatric Infectious Diseases

As of October 2021, SARS-CoV-2 infections were reported among 512,613 children and adolescents in Israel (~33% of all COVID-19 cases). The 5–11-year age group accounted for about 43% (223,850) of affected children and adolescents. In light of the availability of the Pfizer-BioNTech BNT162b2 vaccine against COVID-19 for children aged 5–11 years, we aimed to write a position paper for pediatricians, policymakers and families regarding the clinical aspects of COVID-19 and the vaccination of children against COVID-19. The first objective of this review was to describe the diverse facets of the burden of COVID-19 in children, including the direct effects of hospitalization during the acute phase of the disease, multisystem inflammatory syndrome in children, long COVID and the indirect effects of social isolation and interruption in education. In addition, we aimed to provide an update regarding the efficacy and safety of childhood mRNA COVID-19 vaccination and to instill confidence in pediatricians regarding the benefits of vaccinating children against COVID-19. We reviewed up-to-date Israeli and international epidemiological data and literature regarding COVID-19 morbidity and its sequelae in children, vaccine efficacy in reducing COVID-19-related morbidity and SARS-CoV-2 transmission and vaccine safety data. We conducted a risk–benefit analysis regarding the vaccination of children and adolescents. We concluded that vaccines are safe and effective and are recommended for all children aged 5 to 11 years to protect them from COVID-19 and its complications and to reduce community transmissions. Based on these data, after weighing the benefits of vaccination versus the harm, the Israeli Ministry of Health decided to recommend vaccination for children aged 5–11 years.

Study of Gemcitabine Plus Nab-Paclitaxel-Based Chemotherapy Regimen as First-Line Treatment in Metastatic Pancreatic Carcinoma

Background The purpose of this study was to study the effectiveness of gemcitabine and nab-paclitaxel combination as first-line chemotherapy regimen for the treatment of metastatic pancreatic cancer. There is scarcity of data regarding efficacy and toxicity profile of this combination in Indian population. Aims and Objectives The primary aim of this study was to assess efficacy of this regimen, for which evaluation done in terms of the objective response rate, progression-free survival (PFS), and overall survival. Safety data were also evaluated. Materials and Methods In this prospective study, gemcitabine plus nab-paclitaxel combination chemotherapy was given as first line in metastatic pancreatic carcinoma patients till progression or appearance of grade 3/4 toxicities with treatment. Results The study was performed in 30 patients comprising 18 (60%) males and 12 (40%) females. The median age was 60 years. Median number of cycles administered were six cycles per patient. Seventeen patients (56.67%) had a partial response and 0% had complete response. A total of seven (23.3%) patients progressed on chemotherapy and six (20%) had stable disease (SD). The disease control rate (responses and SD) was 76.7%. The median PFS was 5.75 months. There was no statistically significant difference in terms of response rates and baseline CA 19-9 levels. Most common toxicities were hematological toxicities with rates of grade 3/4 anemia and neutropenia of 20%. Among nonhematological toxicities, nausea (46.67%) and fatigue (30%) were the commonest. Conclusion Combination of gemcitabine and nab-paclitaxel is active and well tolerated in advanced pancreatic carcinoma. To the best of our knowledge, this is the first such study conducted in India.

Metal Complexes and Their Potential Therapeutic Role Against COVID-19: Recent Developments in Drug Designing

COVID-19 is a global pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Being associated with high mortality rates, this pandemic has forced several countries worldwide to impose complete lockdowns to limit the spread of infection. Despite the development of various vaccines, there is still an urgent need to design novel treatments backed with safety data for fighting SARS-CoV-2 and its various mutants. Currently, scientists are putting their strenuous efforts into finding the best treatment option for COVID-19. In this regard, metal complexes being active antiviral agents and immunity enhancers have great potential against SARS-CoV-2. Herein, metal complexes' therapeutic role and significance against treating SARS-CoV-2 or any of its target proteins are discussed.