The Pharmacology of Botulinum Toxin Type A

The aim of this chapter is to structure current information clarifying the most disputable issues of botulinum neurotoxin type A (BoNT/A) pharmacology after systemic (botulism) impact and local medical application. Botulinum neurotoxin (BoNT) pharmacological features evaluated open ways to study factors affecting its biological activity: to extend/shorten its effect duration, to increase/decrease BoNT sensitivity in specific patient populations. The chapter presents unique molecular mechanisms underlying BoNT/A pharmacokinetics and pharmacodynamics: entering the body, distribution, receptor binding, translocation, mediator release suppression, zinc metabolism as well as factors affecting body sensitivity to BoNT at each of those stages. The specific biological effects of BoNT/A, which may underlie its analgesic, anticancer and anti-inflammatory effects, are described. Botulinum neurotoxin pharmacokinetics and pharmacodynamics features discussed herein represent significant clinical relevance since they determine botulinum treatment safety and effectiveness. And also they open ways to develop both BoNT-based therapies and anti-botulinic agents.

High Participant Satisfaction Achieved Using Cryolipolysis for Fat Reduction of the Abdomen and Flanks

Background Patient-reported outcome (PRO) data evaluating the physical and psychosocial impact of Cryolipolysis (CoolSculpting) treatment are limited. Objectives Assess multidimensional aspects of satisfaction following cryolipolysis treatment of the flanks and abdomen using a combination of PRO instruments. Methods This was a multi-national, prospective, single cohort, interventional study. The primary endpoint was the proportion of Satisfied or Very Satisfied participants with treatment at 12 weeks post final treatment. Secondary endpoints included satisfaction categorized by treatment area, total number of treatment cycles, baseline body mass index (BMI), and fat volume reduction measured by 3D photography at 12 weeks post final treatment. Exploratory endpoints assessed the physical and psychosocial impacts of treatment. Safety was monitored throughout the study. Results Of 112 participants who were treated, 74.1% were female. The mean age and BMI were 42.5 years and 24.9 kg/mg 2, respectively. Of the 106 evaluable participants, 89.6% were Satisfied or Very Satisfied with treatment results. Satisfaction was high regardless of body area(s), total number of treatment cycles, or baseline BMI. Mean (SD) fat volume reduction was 264.8 mL (411.4). Overall, 90.6% reported Noticeable or Very Noticeable fat reduction, 89.6% were Likely or Very Likely to treat additional areas, and 93.4% would recommend cryolipolysis to a friend. 24 (21.4%) participants reported treatment-emergent adverse events (AEs); 23 (20.5%) reported these as Adverse Device Effects (ADE). No serious device-related or unanticipated adverse effects occurred. Conclusions Cryolipolysis (CoolSculpting) for fat reduction of the flanks and/or abdomen was well-tolerated and associated with high levels of satisfaction across multidimensional PROs.

Complete Thoracoscopic Segmentectomy and Pulmonary Lobectomy in the Treatment of Small Pulmonary Nodules

Objective: To compare the clinical effect of complete thoracoscopic segmentectomy and pulmonary lobectomy for pulmonary nodules. Methods: In this study, 176 patients with pulmonary nodules were treated in Changshu Hospital Affiliated to Nanjing University of Chinese Medicine from January 2019 to June 2021; according to the type of surgery, the patients were divided into group A (complete thoracoscopic segmentectomy) and group B (complete thoracoscopic pulmonary lobectomy), and the clinical effects were analyzed. Results: The intraoperative blood loss, postoperative drainage volume, postoperative hospitalization days, and lung function of patients in group A were significantly better than those in group B (P < 0.05), while there was no significant difference in the number of dissected lymph nodes. Conclusion: The clinical effect of complete thoracoscopic segmentectomy for patients with small pulmonary nodules is more significant; it does not only ensure lymph node dissection, but also improve surgical-related indicators and treatment safety as well as speed up the recovery of pulmonary function. Its clinical application value is worthy of key analysis by medical institutions.

PENINGKATAN PERAN TENAGA KESEHATAN DAN MASYARAKAT DALAM MENCEGAH KESALAHAN PENGOBATAN

Providing safe services is important in the implementation of health services. Medication errors are a failure of the treatment process that has the potential to cause harm to patients. The incidence of treatment errors can be prevented through increased understanding of health workers and the community regarding the safety of treatment. The active role of patients and their families during treatment process can minimize harm that may happened. This program aims to increase the knowledge of health workers and community as an important element of health services in order to prevent the occurrence of medication error. Efforts to increase knowledge are carried out through the holding of webinars for the community related to 5 moments for medication safety and treatment safety training activities for health workers. Knowledge change was measured using a pre and posttest questionnaires. The target of activities amounted to 37 people and 15 health workers. The results of the analysis showed positive changes in average knowledge with an increase in community knowledge (97.3%) and health workers (100%). The results of this activity become the provision of the community or health workers to increase their role in the safety of treatment with knowledge that has been obtained during community service activities.Keywords: Medication safety, health workers, community, medication error AbstrakPenyediaan layanan yang aman penting dalam penyelenggaraan pelayanan kesehatan. Kesalahan pengobatan merupakan kegagalan proses pengobatan yang berpotensi menimbulkan bahaya bagi pasien. Insiden kesalahan pengobatan dapat dicegah melalui peningkatan pemahaman tenaga kesehatan dan masyarakat terkait keamanan pengobatan. Peran aktif pasien dan keluarganya dalam pelayanan kesehatan dapat meminimalisir bahaya yang mungkin timbul pada proses pengobatan. Tujuan pengabdian masyarakat ini adalah meningkatkan pengetahuan tenaga kesehatan dan masyarakat sebagai unsur penting pelayanan kesehatan agar dapat mencegah terjadinya kejadian medication error. Upaya peningkatan pengetahuan dilakukan melalui penyelenggaraan webinar bagi masyarakat umum terkait 5 moments for medication safety dan kegiatan pelatihan keamanan pengobatan bagi tenaga kesehatan. Perubahan pengetahuan diukur menggunakan kuesioner pre dan post test. Sasaran kegiatan berjumlah 37 masyarakat dan 15 tenaga kesehatan. Hasil analisis menunjukkan adanya perubahan positif rata-rata pengetahuan dengan peningkatan pengetahuan masyarakat (97,3%) dan tenaga kesehatan (100%). Hasil kegiatan ini menjadi bekal masyarakat ataupun tenaga kesehatan untuk meningkatkan perannya dalam keamanan pengobatan dengan pengetahuan yang telah diperoleh selama kegiatan pengabdian masyarakat dilakukan.Kata kunci: Keamanan pengobatan, tenaga kesehatan, masyarakat, kesalahan pengobatan

Quality of life, burden of treatment, safety, and avoidance of future events (QBSAfe) protocol: a pilot study testing an intervention to shift the paradigm of diabetes care

Background Diabetes care has been traditionally focused on targeting certain levels of glycemic control. This narrow emphasis may impose burdens on patients, including high treatment costs, illness-related work, or side effects from medications, while leaving other patient needs and goals under-addressed. The authors aim to shift the paradigm of care for people with diabetes, to focus on quality of life, burden of treatment, safety, and avoidance of future events: the QBSAfe domains. Methods We describe a single-arm pilot study to assess the feasibility and acceptability of using the QBSAfe agenda setting kit (ASK) during routine clinical visits. The set of 14 conversation aid cards was co-developed with patients, family caregivers, and clinicians. The ASK will be used in the context of a clinic visit, which will be recorded by members of the study team to identify patterns of clinician-patient conversations. Feasibility will be measured by the number of participants recruited, time to goal accrual, and completeness of data collection; acceptability will be assessed using post-visit surveys of patients and clinicians. A subgroup of patients will be invited to participate in post-visit qualitative semi-structured interviews for additional feedback. This study will be conducted across three medical centers in the Midwest and East Coast of the USA. Discussion Current healthcare infrastructure and associated demands and pressures on clinicians make changes in care difficult. However, this intervention has the potential to shift conversations during clinical encounters so they can address and directly respond to patient needs, symptoms, and capacity. As part of the QBSAfe ASK, the authors are also actively collaborating with a variety of stakeholders to create tools to help clinicians respond more effectively to patient concerns as they are raised during the clinical encounters. Additional insights about the use of the QBSAfe approach in the virtual space will be gathered during the process of our study due to restrictions imposed upon face to face visit during the COVID-19 pandemic. Trial registration ClinicalTrials.gov, NCT04514523. Registered 17 August 2020—retrospectively registered.

REcovery and SURvival of patients with moderate to severe acute REspiratory distress syndrome (ARDS) due to COVID-19: a multicentre, single-arm, Phase IV Itolizumab Trial: RESURRECT

Objective: To evaluate safety and efficacy of Itolizumab in hospitalized COVID-19 patients with PaO2/FiO2 ratio (PFR) ≤200 requiring oxygen therapy. Design: A multicentre, single-arm, Phase-4 study with a treatment period of 30-Days and an extended follow-up period of 90-Days. Methods: Hospitalized adult patients (n=300) with SARS-CoV-2 infection, with PFR ≤200, oxygen saturation ≤94% and ≥1 elevated inflammatory markers were included from 17 COVID-19 specific tertiary hospitals in India. Patients received Itolizumab infusion 1.6 mg/kg and were assessed for 1-month and then followed up to Day-90. Results: Day-30 post-treatment safety/efficacy results and Day-90 mortality results are presented. Primary outcome measures: incidence of severe acute infusion-related reactions (IRRs) (≥Grade-3) was 1.3% and mortality rate at 1-month was 6.7% (n=20/300). Key secondary analyses: Mortality rate at Day-90 was 8.0% (24/300). 91.7% patients came off the oxygen therapy within Day-30 of treatment. By Day-7, most patients had stable/improved SpO2 without increasing FiO2. Mean PFR improved by 50% by Day-7 (p<0.001) and the trend remained consistent till Day-30. Median time of recovery was 8 days. Cumulatively, at Day-30, 260(86.7%), 256(85.3%), 132(44.0%), 113(37.6%) and 32(10.7%) patients showed >1-point, >2-point, >3-point, >4-point and 5-point improvement on the modified COVID-19 8-point ordinal scale and worsening of symptoms by >1 point, >2 points and 3-points was seen in 26(8.7%), 20(6.7%) and 6(2.0%) patients, respectively. CRP, D-dimer, LDH and serum ferritin levels significantly decreased (p≤0.01) compared with baseline. IL-6 and TNFα levels also decreased 48-hours post-infusion. Overall, 123 treatment-emergent adverse events (TEAEs) were reported in 63 patients, most being Grades 1-3. Most common TEAEs were IRRs and lymphopenia; most common serious TEAEs were septic shock, worsening of ARDS and respiratory failure. No deaths were attributable to Itolizumab. Conclusion: Itolizumab shows no new safety concerns and suggests a mortality and recovery benefit at 1-month in hospitalized COVID-19 patients requiring oxygen therapy.

The Clinical Effect of Moxifen Tablets Combined with Medroxyprogesterone Acetate Injection on Patients with Endometriosis

Objective: To explore the clinical effect of moxifen tablets combined with medroxyprogesterone acetate injection on patients with endometriosis. Methods: 90 patients with endometriosis from August 2018 to March 2019 were randomly divided into control group and observation group, with 45 cases in each group. The control group was treated with moxifene tablets and the observation group with medroxyprogesterone acetate. The changes of serum sex hormone, P, CA125 levels, adverse reactions and therapeutic effects were compared between the two groups. Result: Before treatment, there was no significant difference in serum sex hormone and P, CA125 levels between the two groups (P > 0.05); after treatment, the indexes of the two groups were reduced, and the LH, E2, FSH, CA125 and P water in the observation group were lower than those in the control group (P < 0.05); the curative effect of the observation group was significantly better than that in the control group (P < 0.05); the incidence of adverse reactions in the observation group was lower than that in the control group (P < 0.05). Conclusion: Moxifene combined with medroxyprogesterone acetate has a significant therapeutic effect on endometriosis. It can significantly reduce the level of serum sex hormone. The incidence of adverse reactions is low and the treatment safety is high. It is worth popularizing.

Ibrutinib plus obinutuzumab as frontline therapy for chronic lymphocytic leukemia is associated with a lower rate of infusion-related reactions and with sustained remissions after ibrutinib discontinuation: a single-arm, open-label, phase 1b/2 clinical trial NCT0231576

Ibrutinib-based therapies are costly and require continuous administration. We hypothesized combining BTK inhibition with anti-CD20 monoclonal antibodies would yield deep remissions allowing discontinuation. We enrolled 32 therapy-naïve CLL patients to receive ibrutinib plus obinutuzumab, followed by single-agent ibrutinib. Patients could discontinue ibrutinib after 36 months with sustained complete response (CR). We evaluated treatment safety, efficacy, and outcomes after ibrutinib discontinuation. The overall response rate was 100%, 28% achieved a CR, and 12.5% achieved bone marrow undetectable minimal residual disease. At a three-year median follow-up, 91% remain in remission with 100% overall survival. Five patients in sustained CR stopped ibrutinib and have not progressed. Eight non-CR patients discontinued for other reasons, with only two progressing. The treatment was safe, with a lower IRR rate. All patients responded to treatment with longer time-to-progression after discontinuation of ibrutinib. Our data support the evaluation of ibrutinib discontinuation strategies in more extensive clinical trials.

Management of Type 2 Diabetes Mellitus in a Patient with COVID-19: The Window of Insulin Glargine U300

Research on pharmacological therapies for the treatment and prevention of Coronavirus Disease 2019 (COVID-19) is limited in patients with Type 2 Diabetes Mellitus (T2DM). In this case, diabetes management of a 51-year-old male patient who was followed up and treated with COVID-19 diagnosis in the pandemic clinic is presented. While metformin (2000 mg/day) oral therapy was continued, insulin glargine U100 (IGlar100) was added to the treatment subcutaneously. In addition, enoxaparin, hydroxychloroquine, azithromycin were started to be administered to the patient. During follow-up, respiratory distress and tachypnea (26 breaths/min), high fever (38.3oC), increased CRP (42 mg/dL), and decreased oxygen saturation (91%) were detected. Favipiravir was added to the treatment, and metformin was stopped due to possible lactic acidosis risk. IGlar300 treatment with more potency effect and lower risk of hypoglycaemia was initiated while IGlar100 was discontinued. In the follow-ups, titration was provided with IGlar300 to keep fasting blood glucose between 100-140 mg/dL and postprandial one between 140-180 mg/dL. In the treatment for this purpose, a maximum of 34 units/day insulin was needed. Capillary blood sugar monitoring was revised every 12 hours and then once a day. As the infection was brought under control, the required dose of IGlar300 decreased to 14 units/day. After diabetes training with a video phonecall, he was discharged with metformin and IGlar300. IGlar300 may be effective against diabetes in the COVID-19 pandemic. In addition, a significant contribution can be made both to the treatment safety of the patient in a glycemic sense and to the safety of contamination by reduced contact of health care professionals.