Synthesis Strategy of Tetrapyrrolic Photosensitizers for Their Practical Application in Photodynamic Therapy

This review presents a wide range of tetrapyrrole photosensitizers used for photodynamic therapy (PDT), antimicrobial photodynamic therapy, photoinactivation of pathogens. Methods of synthesis and design of new photosensitizers with greater selectivity of accumulation in tumor tissue and increased photoinduced antitumor activity are considered. The issues of studying the properties of new photosensitizers, their photoactivity, the ability to generate singlet oxygen, and the possibility of using targeted photodynamic therapy in clinical practice are discussed. The review examines the work on PDT by national and foreign researchers.

Aspects of Antiviral Strategies Based on Different Phototherapy Approaches: Hit by the Light.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which caused the COVID-19 pandemic spreading around the world from late 2019, served as a ruthless reminder of the threat viruses pose to global public health. The synthesis of new antiviral drugs, as well as repurposing existing products, is a long-term ongoing process which has challenged the scientific community. One solution could be an effective, accessible, and rapidly available antiviral treatment based on phototherapy (PT). PT has been used to treat several diseases, and relies on the absorption of light by endogenous molecules or exogenous photosensitizers (PS). PT has often been used in cancer treatment and prophylaxis, and as a complement to established chemotherapy and immunotherapy in combined therapeutic strategy. Besides significant applications in anticancer treatment, studies have demonstrated the beneficial impact of PT on respiratory, systemic, emerging, and oncogenic viral infections. The aim of this review was to highlight the potential of PT to combat viral infections by summarizing current progress in photodynamic, photothermal, and photoacoustic approaches. Attention is drawn to the virucidal effect of PT on systemic viruses such as the human immunodeficiency virus and human herpes viruses, including the causative agent of Kaposi sarcoma, human herpes virus (HHV8). PT has good potential for disinfection in anti-norovirus research and against pandemic viruses like SARS-CoV-2.

Comparison of Healthcare Resource Utilization Between Patients Who Engaged or Did Not Engage With a Prescription Digital Therapeutic for Opioid Use Disorder.

BACKGROUND: A prescription digital therapeutic (PDT) (reSET-O®) may expand access to behavioral treatment for patients with opioid use disorder (OUD) treated with buprenorphine, but long-term data on effectiveness are lacking. OBJECTIVE: To compare real-world healthcare resource utilization (HCRU) among patients who engaged with reSET-O and buprenorphine compared to similar patients in recovery treated with buprenorphine who did not fill their reSET-O script or engage with the PDT beyond week one. METHODS: A retrospective analysis of facility and clinical service claims data was conducted in adults with PDT initiation and between 12 weeks and 9 months of continuous enrollment in a health plan after initiation. Patients who filled their prescription and engaged with the therapeutic were compared to patients who filled the prescription but did not engage beyond week one (NE), and patients who did not fill the prescription (NR) (the latter two groups combined into one group hereafter referred to as "non-engagers"). Comparisons were analyzed using a repeated-measures negative binomial model of encounters/procedures, adjusted for number of days in each period. Associated cost trends assessed using current Medicare reimbursement rates. RESULTS: A total of 444 patients redeemed a prescription and engaged with the PDT (mean age 37.5 years, 63.1% female, 84% Medicaid), and 64 patients did not engage with the PDT (mean age 39.5 years, 32.8% female, 73.4% Medicaid). Total cost of hospital facility encounters was $2693 for engaged patients vs $6130 for non-engaged patients. Engaged patients had somewhat higher rates of certain clinician services. Total facility and clinician services costs for engaged vs non-engaged patients were $8733 vs $11,441, for a net cost savings over 9 months of $2708 per patient who engaged with reSET-O. CONCLUSION: Patients who engaged with an OUD-specific PDT had a net cost reduction for inpatient and outpatient services of $2708 per patient over 9 months compared to patients who did not engage with the PDT, despite similar levels of buprenorphine adherence.

Early percutaneous tracheostomy in COVID19 patients with failed intubation: A case series.

INTRODUCTION: COVID19 and pulmonary dysfunction leading to acute respiratory distress syndrome (ARDS). CASE STUDY PRESENTATION: Herein we presented the cases of failed intubation that was replaced by early percutaneous dilational tracheostomy. The procedure is safe for the patients, doctors and clinical staff. CONCLUSION: Additionally, we report mucormycosis after COVID19 treatment that was potentially due to immunosuppressive drugs.

Is haem the real target of COVID-19?

Although a vaccination campaign has been launched in many countries, the COVID-19 pandemic is not under control. The main concern is the emergence of new variants of SARS-CoV-2; therefore, it is important to find approaches to prevent or reduce the virulence and pathogenicity of the virus. Currently, the mechanism of action of SARS-CoV-2 is not fully understood. Considering the clinical effects that occur during the disease, attacking the human respiratory and hematopoietic systems, and the changes in biochemical parameters (including decreases in haemoglobin [Hb] levels and increases in serum ferritin), it is clear that iron metabolism is involved. SARS-CoV-2 induces haemolysis and interacts with Hb molecules via ACE2, CD147, CD26, and other receptors located on erythrocytes and/or blood cell precursors that produce dysfunctional Hb. A molecular docking study has reported a potential link between the virus and the beta chain of haemoglobin and attack on haem. Considering that haem is involved in miRNA processing by binding to the DGCR8-DROSHA complex, we hypothesised that the virus may check this mechanism and thwart the antiviral response.

Photodynamic Therapy and Photobiomodulation on Oral Lesion in Patient with Coronavirus Disease 2019: A Case Report.

Objective: This article reports the case of a patient with oral manifestation of coronavirus disease 2019 (COVID-19) treated with photobiomodulation (PBM) and photodynamic therapy (PDT). Background: Some dermatological and oral mucosal lesions have recently been linked to severe acute respiratory syndrome coronavirus 2 infection. Methods: A 65-year-old female patient with a confirmed real-time reverse transcriptase-polymerase chain reaction diagnosis of COVID-19 presented with dry edematous lips, edema with mucosal desquamation, ulceration and blood crust on the inner aspect of the lips, gingival petechiae and erythematous and pseudomembranous lesions on the dorsum of the tongue. The treatment protocol was three sessions of antimicrobial PDT (aPDT) (660 nm diode laser + methylene blue) to the lips and tongue, every 24 h to control contamination, followed by PBM (low-power laser, 100 mW, 2 J/point) to the lips, tongue, and oral mucosa for additional four sessions every 24 h. Results: Therapy association promoted pain control and healing of oral mucosal lesions in 7 days of treatment. Conclusions: PBM and aPDT could be an interesting approach to manage COVID-19 patients.

Evaluation of the cost-utility of a prescription digital therapeutic for the treatment of opioid use disorder.

Background: The opioid epidemic continues to generate a significant mental and physical health burden on patients, and claims the life of almost 150 Americans daily. Making matters worse, an increase in relapses and/or opioid-related deaths has been reported in more than 40 U.S. states since the start of the COVID-19 pandemic. Opioid use disorder (OUD) is one of the single most expensive disorders in the United States, generating average medical costs of $60B from just 2 million Americans diagnosed with the disorder. In commercial use since 2019, reSET-O is a non-drug, prescription digital therapeutic (PDT) that delivers evidence-based neurobehavioral treatment for OUD and helps overcome the barriers associated with access to care, stigma, and social distancing. Although shown to be cost effective and efficacious in clinical trials and real-world evidence studies, respectively, information on its value for money from a health utilities and cost per quality-adjusted life-year is needed to inform policy discussions.Objectives: To evaluate the impact of reSET-O on health utilities and assess its overall cost per quality-adjusted life year (QALY) gained vs. treatment-as-usual (TAU).Methods: Decision analytic model comparing reSET-O plus TAU to TAU alone (i.e. buprenorphine, face-to-face counseling, and contingency management) over 12 weeks. Clinical effectiveness data (abstinence and health utility) were obtained from a clinical trial, and resource utilization and cost data were adapted from a recent claims data analysis to reflect less frequent face-to-face counseling with the therapeutic.Results: The addition of reSET-O to TAU decreases total health care costs by -$131 and resulted in post-treatment utility values within population norms, with a corresponding gain of 0.003 QALYs. reSET-O when used adjunctively to TAU was economically dominant (less costly, more effective) vs. TAU alone.Conclusion: reSET-O is an economically-dominant adjunctive treatment for OUD and is associated with an overall reduction in total incremental cost vs TAU.

Profile of Somryst Prescription Digital Therapeutic for Chronic Insomnia: Overview of Safety and Efficacy.

Introduction: Prescription digital therapeutics (PDTs) represent a new class of software-based medical devices authorized by the Food and Drug Administration (FDA) to treat disease. Somryst™, the first PDT for treating chronic insomnia, delivers cognitive behavioral therapy for insomnia (CBT-I) via a mobile application. CBT-I is the guideline-recommended, first-line treatment for chronic insomnia, but availability of CBT-I therapists is limited. Somryst addresses this need by providing asynchronous access to CBT-I treatment. As a contactless therapeutic medium, Somryst is also an ideal option when face-to-face therapy is not available or recommended for safety reasons (e.g. because of possible exposure to the SARS-CoV-2 virus). Areas covered: This review summarizes the mechanisms of action and technical features of Somryst, and describes safety and effectiveness data from the randomized trials on which FDA clearance was based. Expert opinion: Somryst demonstrates robust clinical efficacy with a favorable benefit-to-risk profile for treating adults with chronic insomnia. FDA clearance was based on data from 2 clinical trials of the first-generation web-based CBT-I platform Sleep Healthy Using the Internet (SHUTi). Somryst, and PDTs in general, are promising devices to address the need for greater accessibility to effective therapies.

Understanding COVID-19 Pandemic: Molecular Mechanisms and Potential Therapeutic Strategies. An Evidence-Based Review.

Initially, the SARS-CoV-2 virus was considered as a pneumonia virus; however, a series of peer reviewed medical papers published in the last eight months suggest that this virus attacks the brain, heart, intestine, nervous and vascular systems, as well the blood stream. Although many facts remain unknown, an objective appraisal of the current scientific literature addressing the latest progress on COVID-19 is required. The aim of the present study was to conduct a critical review of the literature, focusing on the current molecular structure of SARS-CoV-2 and prospective treatment modalities of COVID-19. The main objectives were to collect, scrutinize and objectively evaluate the current scientific evidence-based information, as well to provide an updated overview of the topic that is ongoing. The authors underlined potential prospective therapies, including vaccine and phototherapy, as a monotherapy or combined with current treatment modalities. The authors concluded that this review has produced high quality evidence, which can be utilized by the clinical scientific community for future reference, as the knowledge and understanding of the SARS-CoV-2 virus are evolving, in terms of its epidemiological, pathogenicity, and clinical manifestations, which ultimately map the strategic path, towards an effective and safe treatment and production of a reliable and potent vaccine.

Does PDT have potential in the treatment of COVID 19 patients?

The corona virus pandemic has ignited a proliferation of research aimed at prevention of spread, early diagnosis and treatment. Coincidentally, in recent years the Yorkshire Laser Centre has been engaged in developing the methodology of applying PDT in chronic bronchiectasis. Our methodology is based on Methylene Blue (MB) mediated PDT used topically within the airway. The novelty of the method is the use of a nebulizer to deliver the photosensitizer. We suggest that our protocol and methodology could be modulated for use in respiratory infections of COVID -19.