Repurposing of parenterally administered active substances used to treat pain both systemically and locally.

Pain is a constant in our lives. The efficacy of drug therapy administered by the parenteral route is often limited either by the physicochemical characteristics of the drug itself or its adsorption-distribution-metabolism-excretion (ADME) mechanisms. One promising alternative is the design of innovative drug delivery systems that can improve the pharmacokinetics |(PK) and/or reduce the toxicity of traditionally used drugs. In this review, we discuss several products that have been approved by the main regulatory agencies (i.e., nano- and microsystems, implants, and oil-based solutions), highlighting the newest technologies that govern both locally and systemically the delivery of drugs. Finally, we also discuss the risk assessment of the scale-up process required, given the impact that this approach could have on drug manufacturing. Teaser: The management of pain by way of the parenteral route can be improved using complex drug delivery systems (e.g., micro- and nanosystems) which require high-level assessment and shorten the regulatory pathway.

Strengths and Challenges of Implementing a Learning Collaborative in the Ryan White HIV/AIDS Program.

Learning collaboratives (LCs) are a popular tool for supporting collaboration and shared learning among health programs. Many variations of LCs have been reported in the literature. However, descriptions of key LC components and implementation lack standardization, making it hard to compare and contrast different LC approaches. To advance the field's understanding of how primary elements of LCs are implemented, we describe the implementation of an LC in the Ryan White HIV/AIDS Program using a recently established taxonomy of four primary elements of LCs-innovation, social systems, communication, and time. Additionally, we explain the strengths and challenges we encountered with regard to each of these elements when implementing this LC. We then offer recommendations to others on how to leverage LC facilitators and mitigate challenges in future projects. This information can guide other programs to replicate beneficial practices and avoid pitfalls in future LC projects.

A Case of Reversible Cerebral Vasoconstriction Syndrome: Postpartum Cerebral Angiopathy in a 32-Year-Old Primigravid Treated with Intravenous Immunoglobulin.

This is a case of a 32-year-old primigravid who developed sudden severe headache on the 7th day postpartum associated with focal neurologic deficits and altered sensorium. She had a GCS score of 6, anisocoric pupils and an NIHSS score of 31. Cranial MRI with MRA showed multifocal hyperacute to acute infarcts on the left occipital lobe, left thalamus, and midbrain which was more prominent on the right. Due to clinical deterioration, a repeat Cranial MRI with MRA was done and showed progression of infarcts involving both thalami and right pons with interval appearance of contour irregularities in the proximal anterior cerebral, posterior cerebral, basilar and internal carotid arteries. Serial transcranial Doppler showed significant distal right middle cerebral artery vasospasm. She was managed as a case of reversible cerebral vasoconstriction syndrome, associated with postpartum cerebral angiopathy. Intravenous pulse methylprednisolone was started subsequently IVIG was initiated. Intravenous immunoglobulin was given for 5 days. The patient gradually improved, underwent rehabilitation therapy, and was discharged stable after 6 weeks.

Google search behavior for meningitis and its vaccines: an infodemiological study.

BACKGROUND: The internet has made significant contributions towards health education. Analyzing the pattern of online behavior regarding meningitis and vaccinations may be worthwhile. It is hypothesized that the online search patterns in meningitis are correlated with its number of cases and the search patterns of its related vaccines. METHODS: This was an infodemiological study that determined the relationship among online search interest in meningitis, its worldwide number of cases and its associated vaccines. Using Google Trends™ Search Volume Indices (SVIs), we evaluated the search queries "meningitis," "pneumococcal vaccine," "BCG vaccine," "meningococcal vaccine" and "influenza vaccine" in January 2021, covering January 2008 to December 2020. Spearman rank correlation was used to determine correlations between these queries. RESULTS: The worldwide search interest in meningitis from 2008 to 2020 showed an average SVI of 46 ± 8.8. The most searched topics were symptoms, vaccines, and infectious agents with SVIs of 100, 52, and 39, respectively. The top three countries with the highest search interest were Ghana, Kazakhstan, and Kenya. There were weak, but statistically significant correlations between meningitis and the BCG (ρ = 0.369, p < 0.001) and meningococcal (ρ = 0.183, p < 0.05) vaccines. There were no statistically significant associations between the number of cases, influenza vaccine, and pneumococcal vaccine. CONCLUSION: The relationships among the Google SVIs for meningitis and its related vaccines and number of cases data were inconsistent and remained unclear. Future infodemiological studies may expand their scopes to social media, semantics, and big data for more robust conclusions.

Gene Therapy.

Gene therapy medicinal products (GTMPs) are one of the most promising biopharmaceuticals, which are beginning to show encouraging results. The broad clinical research activity has been addressed mainly to cancer, primarily to those cancers that do not respond well to conventional treatment. GTMPs to treat rare disorders caused by single-gene mutations have also made important advancements toward market availability, with eye and hematopoietic system diseases as the main applications.Nucleic acid-marketed products are based on both in vivo and ex vivo strategies. Apart from DNA-based therapies, antisense oligonucleotides, small interfering RNA, and, recently, T-cell-based therapies have been also marketed. Moreover, the gene-editing tool CRISPR is boosting the development of new gene therapy-based medicines, and it is expected to have a substantial impact on the gene therapy biopharmaceutical market in the near future.However, despite the important advancements of gene therapy, many challenges have still to be overcome, which are discussed in this book chapter. Issues such as efficacy and safety of the gene delivery systems and manufacturing capacity of biotechnological companies to produce viral vectors are usually considered, but problems related to cost and patient affordability must be also faced to ensure the success of this emerging therapy. Graphical Abstract.

Synchronization matters for motor coordination.

Using electroencephalography and electromyography recordings from healthy participants during a visual-depended bimanual coordination task, de Vries and colleagues showed that functional synchronization is important in motor coordination. The authors reported that higher coordination correlated positively with intermuscular synchrony, but correlated negatively with corticomuscular synchrony. They proposed that these two diverse motor systems operate differently depending on task demands. Similar experimental paradigms could identify motor mechanisms in patients with neurological disorders to design novel rehabilitation strategies.

[Management of NSTEMI in a hospital without interventional cardiology and without use of GRACE score: Does the clinician appreciation match the GRACE score calculated retrospectively for the coronarography delay?] / Prise en charge des syndromes coronaires aigus sans sus décalage du ST dans un hôpital sans cardiologie interventionnelle : l'appréciation du clinicien rejoint-elle le score de GRACE dans le délai de réalisation de la coronarographie ?

PURPOSE: The management of non-ST segment elevation acute coronary syndromes (NSTEACS) remains an issue for mobidity, mortality, and an economic stake. The first aim of the study was to evaluate the additional value of the GRACE score for the compliance with the recommended times to coronary angiography in an hospital without interventional cardiology. We also analysed the in-hospital and 6-month mortality and the predictive factors of compliance for the coronarography delays. METHODS: Retrospective monocenter cross-sectional study including consecutive patients with chest pain suggestive of a NSTEACS during 1 year. Data of the delay to coronarography were collected and GRACE score was calculated a posteriori. RESULTS: The time to perform coronary angiography was non-compliant in 49% of cases (27 patients out of 55). The calculation of the GRACE score would have allowed correcting the delay for two patients of our cohort. Clinical appreciation, troponin elevation, ECG modifications were associated with the delay compliance. Age <75 years predisposed to recommended delays. Renal failure and history of coronaropathy were significantly associated with non compliant delays. A non-compliant delay was significantly associated with higher mortality. CONCLUSION: In our experience, the knowledge of the GRACE score had little impact on the timing of coronary angiography. However, as a predictor of mid and long term mortality, GRACE score remains SCA ST+ useful to intensify surveillance of high-risk patients.

Keratoacanthoma arising after site injection infection of cosmetic collagen filler.

INTRODUCTION: Over one million treatments in more than 40 countries have been administered Zyplast implants. Infections at collagen implant sites have occurred in fewer than one per thousand treated patients. PRESENTATION OF CASE: We present a case report of a 27-year-old man; he developed a severe granulomatous reaction in the site of resolvable collagen filler injection Zyplast, and one month later developed a cutaneous nodular lesion. Histological examination of the lesion revealed Keratoacanthoma (KA) with surgical margins free of tumor. We performed two surgical corrections within a period of six months on multiple hypertrophic skin scars of the face. Two years after the last excision, the patient continued to be free of any recurrence. DISCUSSION: Keratoacanthoma (KA) is a benign skin tumor with a quick growth pattern but may regress spontaneously. Though the exact etiology of KA is uncertain, it is found to be more frequent in elderly people, on photo-exposed skin areas and cutaneous infection site. Bovine collagen intradermal injections, though catabolized over the time in the patient, can raise several complications already described in technical literature, but we want underline that cutaneous infection near filler injection site can develope KA as described in our case report. CONCLUSION: KA must be considered as a new local unforeseeable complication of bovine collagen injection to fill facial soft tissue when occurred a face cutaneous infection. We believe that radical excision is the golden standard.