PROTAC—From Bench to Bed

A special issue of Medicines (ISSN 2305-6320).

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 89245

Special Issue Editors

Memorial Sloan Kettering Cancer Center (MSKCC), 1275 York Ave., New York, NY 10065, USA
Interests: medicinal chemistry; chemical biology; organic chemistry
Molecular, Cellular and Developmental Biology, Yale University, 260 Whitney Ave., New Haven, CT 06511, USA
Interests: proteolysis targeting chimera

Special Issue Information

Dear Colleagues,

Proteolysis targeting chimera (PROTAC) technology was developed to artificially induce the degradation of a given protein of interest by hijacking the ubiquitin–proteasome system through a bifunctional molecule. PROTACs were first reported in 2001 and have witnessed rapid development in the past two decades. Many of those bifunctional molecules have been utilized to uncover biology mechanisms as probes, and several Phase I clinical trials have been launched to evaluate the most advanced PROTAC molecules against cancer-related diseases. Compared to traditional small molecules, PROTACs can be more selective with equal potency. However, due to the chemical nature of the protein degrader, achieving molecules with satisfied DMPK properties remains a challenge. This Special Issue will tap into the cutting-edge research development of PROTACs on new targets and PROTACs showing good DMPK properties or animal study results. Biological mechanistic studies using PROTACs as a probe or research studies focusing on PROTAC druggability optimization and pharmacology studies are also welcome.

Dr. Deyao Li
Dr. Ke li
Guest Editors

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Keywords

  • PROTAC technology
  • ubiquitination
  • protein degradation
  • degrader
  • drug development
  • pharmacology
  • clinical research

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Published Papers (13 papers)

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Research

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15 pages, 1391 KiB  
Article
Preclinical Trial of Traditional Plant Remedies for the Treatment of Complications of Gestational Malaria
by Peter Uchenna Amadi, Emmanuel Nnabugwu Agomuo, Chinyere Nneka Ukaga, Uche Chinedu Njoku, Joy Adaku Amadi and Chinweuba Godswill Nwaekpe
Medicines 2021, 8(12), 79; https://doi.org/10.3390/medicines8120079 - 17 Dec 2021
Cited by 1 | Viewed by 2644
Abstract
Background: Most pregnant women living in high malaria endemic regions of Nigeria use herbal remedies for the management of malaria-in-pregnancy, rather than the commonly prescribed drugs. Remedies common to this area involve a suspension of A. indica (AI) leaves and in some cases, [...] Read more.
Background: Most pregnant women living in high malaria endemic regions of Nigeria use herbal remedies for the management of malaria-in-pregnancy, rather than the commonly prescribed drugs. Remedies common to this area involve a suspension of A. indica (AI) leaves and in some cases, a suspension containing a mixture of AI and D.edulis (PS). Aim: This study examined the therapeutic efficacies of AI, PS, or a combination of AI and PS in a pregnant rat model for exoerythrocytic stages of Plasmodium falciparum parasite. Method: A predetermined sample size of 30 dams was used (for a power level and confidence interval of 95%), and divided equally into six groups made up of non-malarous dams, untreated malarous dams, and malarous dams either treated exclusively with 1 mL of 3000 mg/kg b.w AI, 1000 mg/kg b.w PS, AI + PS (50% v/v), or 25 mg/kg b.w CQ. Result: No maternal mortality was recorded. AI significantly improved maternal weight gain from 32.4 to 82.2 g and placental weight from 0.44 to 0.53 g. In the curative test, AI and AI + PS significantly reduced the average percentage parasitemia (APP) in the pregnant rats from >80% to <20%. No significant difference in the APP was found between the pregnant rats treated with any of CQ or AI during the suppressive test. Results for the prophylactic test of the study groups showed that the APP was significantly reduced from 24.69% to 3.90% when treated with AI and 3.67% when combined with PS. AI + PS reduced diastolic blood pressure from 89.0 to 81.0 mm/Hg and compared with that of the non malarous dams. AI or AI + PS significantly increased the platelet counts (103 µL) from 214.1 to 364.5 and 351.2, respectively. AI and AI + PS improved birth weight from 2.5 to 3.9 g and crown rump length from 2.6 to 4.1 cm. For biomarkers of preeclampsia, combining AI and PS led to the reversal of the altered levels of creatine kinase, lactate dehydrogenase, cardiac troponin, soluble Fms-Like Tyrosine Kinase-1, and placental growth factor. Conclusions: This study validates the use of A. indica for the treatment of gestational malaria due to its antiplasmodial and related therapeutic effects and in combination with pear seeds for the management of malaria-in-pregnancy-induced preeclampsia. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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15 pages, 1402 KiB  
Article
Neuron-Specific Enolase (NSE) Predicts Long-Term Mortality in Adult Patients after Cardiac Arrest: Results from a Prospective Trial
by Jonas Müller, Benjamin Bissmann, Christoph Becker, Katharina Beck, Nina Loretz, Sebastian Gross, Simon A. Amacher, Chantal Bohren, Hans Pargger, Kai Tisljar, Raoul Sutter, Stephan Marsch and Sabina Hunziker
Medicines 2021, 8(11), 72; https://doi.org/10.3390/medicines8110072 - 17 Nov 2021
Cited by 10 | Viewed by 4361
Abstract
Background: We investigated whether Neuron-specific enolase (NSE) serum concentration predicts long-term mortality and poor neurological outcome in adult cardiac arrest patients. Methods: Within this prospective observational study, we included consecutive adult patients admitted to the intensive care unit (ICU) after cardiac arrest. NSE [...] Read more.
Background: We investigated whether Neuron-specific enolase (NSE) serum concentration predicts long-term mortality and poor neurological outcome in adult cardiac arrest patients. Methods: Within this prospective observational study, we included consecutive adult patients admitted to the intensive care unit (ICU) after cardiac arrest. NSE was measured upon ICU admission and on days 1, 2, 3, 5 and 7. Results: Of 403 patients, 176 (43.7%) survived. Median follow-up duration was 43.7 months (IQR 14.3 to 63.0 months). NSE levels on day 3 were increased more than threefold in non-survivors compared to survivors (median NSE (ng/mL) 19.8 (IQR 15.7 to 27.8) vs. 72.6 (IQR 26 to 194)) and showed the highest prognostic performance for mortality compared to other days of measurement, with an AUC of 0.81 and an adjusted hazard ratio of 1.55 (95% CI 1.41 to 1.71, p < 0.001). Subgroup analysis showed an excellent sensitivity and negative predictive value of 100% of NSE in patients <54 years of age. Conclusion: NSE measured three days after cardiac arrest is associated with long-term mortality and neurological outcome and may provide prognostic information that improves clinical decision making. Particularly in the subgroup of younger patients (<54 years), NSE showed excellent negative predictive value. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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19 pages, 16606 KiB  
Article
Feature Importance of Acute Rejection among Black Kidney Transplant Recipients by Utilizing Random Forest Analysis: An Analysis of the UNOS Database
by Charat Thongprayoon, Caroline C. Jadlowiec, Napat Leeaphorn, Jackrapong Bruminhent, Prakrati C. Acharya, Chirag Acharya, Pattharawin Pattharanitima, Wisit Kaewput, Boonphiphop Boonpheng and Wisit Cheungpasitporn
Medicines 2021, 8(11), 66; https://doi.org/10.3390/medicines8110066 - 2 Nov 2021
Cited by 8 | Viewed by 3593
Abstract
Background: Black kidney transplant recipients have worse allograft outcomes compared to White recipients. The feature importance and feature interaction network analysis framework of machine learning random forest (RF) analysis may provide an understanding of RF structures to design strategies to prevent acute [...] Read more.
Background: Black kidney transplant recipients have worse allograft outcomes compared to White recipients. The feature importance and feature interaction network analysis framework of machine learning random forest (RF) analysis may provide an understanding of RF structures to design strategies to prevent acute rejection among Black recipients. Methods: We conducted tree-based RF feature importance of Black kidney transplant recipients in United States from 2015 to 2019 in the UNOS database using the number of nodes, accuracy decrease, gini decrease, times_a_root, p value, and mean minimal depth. Feature interaction analysis was also performed to evaluate the most frequent occurrences in the RF classification run between correlated and uncorrelated pairs. Results: A total of 22,687 Black kidney transplant recipients were eligible for analysis. Of these, 1330 (6%) had acute rejection within 1 year after kidney transplant. Important variables in the RF models for acute rejection among Black kidney transplant recipients included recipient age, ESKD etiology, PRA, cold ischemia time, donor age, HLA DR mismatch, BMI, serum albumin, degree of HLA mismatch, education level, and dialysis duration. The three most frequent interactions consisted of two numerical variables, including recipient age:donor age, recipient age:serum albumin, and recipient age:BMI, respectively. Conclusions: The application of tree-based RF feature importance and feature interaction network analysis framework identified recipient age, ESKD etiology, PRA, cold ischemia time, donor age, HLA DR mismatch, BMI, serum albumin, degree of HLA mismatch, education level, and dialysis duration as important variables in the RF models for acute rejection among Black kidney transplant recipients in the United States. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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12 pages, 696 KiB  
Article
Seroprevalence of the Serological Markers of Transfusion-Transmissible Infections among Volunteer Blood Donors of Kosti Obstetrics and Gynecology Hospital
by Babiker Saad Almugadam, Omer Mohammed Ali Ibrahim and Yousif Mousa Alobaid Ahmed
Medicines 2021, 8(11), 64; https://doi.org/10.3390/medicines8110064 - 29 Oct 2021
Cited by 3 | Viewed by 2946
Abstract
Background: Transfusion-transmissible infections are well-known global health challenges. The present study is proposed to investigate the seropositivity of anti-HIV1/2, anti-HCV, HBsAg, and anti-T.pallidum among volunteer blood donors of Kosti Obstetrics and Gynecology Hospital. Methods: Our study was conducted in a cross-sectional retrospective [...] Read more.
Background: Transfusion-transmissible infections are well-known global health challenges. The present study is proposed to investigate the seropositivity of anti-HIV1/2, anti-HCV, HBsAg, and anti-T.pallidum among volunteer blood donors of Kosti Obstetrics and Gynecology Hospital. Methods: Our study was conducted in a cross-sectional retrospective manner. The data of donors who attended Kosti Obstetrics and Gynecology Hospital throughout 2016 to 2018 were reviewed and retrieved manually from blood bank records. Results: Out of 8139 donors, 22.52% were seropositive for serological markers of TTIs and 1.67% were seropositive for at least two serological markers of TTIs. The overall seropositivity rate of anti-HIV1/2, HBsAg, anti-HCV, and anti-T.pallidum was 1.77%, 6.07%, 1.14%, and 11.87%, respectively (p < 0.000). Anti-T.pallidum was the most frequently detected (p < 0.05) marker across all study variables. TTIs seroprevalence was significantly (p < 0.05) varied according to the age, residence, occupations, and blood groups. Notably, there was a rising trend in the rate of anti-HIV1/2 and seropositivity for more than one marker with age (p < 0.000). Regionally, rural area residents had a higher rate of anti-HIV1/2 (2.20%), HBsAg (6.31%), anti-HCV (1.42%), anti-T.pallidum (18.38%), and multiple markers seropositivity (2.28%) compared to urban areas. Between occupations, the highest rate of anti-HIV1/2 (p = 0.483), HBsAg (p = 0.003), anti-HCV (p = 0.408), anti-T.pallidum (p < 0.000), and multiple markers seropositivity (p < 0.000) were detected in farmers. Regarding the screening, we also found that the frequency of anti-T.pallidum was significantly (p = 0.003) higher in donors who carry the AB+ve blood group, whereas anti-HCV (1.83%) was more frequent in donors carry O−ve blood group (p = 0.255). As seen, anti-T.pallidum+HBsAg was the most frequently (1.22%) co-occurring markers. In contrast, anti-T.pallidum+anti-HIV1/2+HBsAg was the lowest frequency one (p < 0.000). Conclusions: The study showed an alarming rate of TTIs, which suggests the requirement for comprehensive surveillance and health education programs. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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8 pages, 1360 KiB  
Article
Clinical Outcome of Patients Submitted to Liver Resection in the Context of Metastatic Breast Cancer: A Study of a Tertiary Hospital Center
by Jorge Nogueiro, Vitor Devezas, Fabiana Sousa, Cristina Fernandes, Fernando Osório, Susy Costa, André Magalhães, Henrique Mora, Diana Gonçalves, Hugo Santos-Sousa, André Costa Pinho, Luís Graça, José Luís Fougo and Elisabete Barbosa
Medicines 2021, 8(11), 61; https://doi.org/10.3390/medicines8110061 - 20 Oct 2021
Viewed by 3337
Abstract
Introduction: Breast cancer is the most incident cancer in the world, accounting for 25% of new cancers per year in females. It is the most frequent malignancy in women, being the fifth cause of death from cancer worldwide. Approximately 5 to 10% of [...] Read more.
Introduction: Breast cancer is the most incident cancer in the world, accounting for 25% of new cancers per year in females. It is the most frequent malignancy in women, being the fifth cause of death from cancer worldwide. Approximately 5 to 10% of patients already present with metastases at diagnosis, and the liver is the site of metastases in half of these cases. Liver metastasis (LM) resection, performed after neoadjuvant systemic treatment, has been reported to increase median overall survival in this population. Aim: The aim of this analysis is to assess the outcomes of patients undergoing breast cancer liver metastasis surgical resection, including impact on survival, compared to patients where metastasectomy was not performed. Methods: retrospective review of 55 female patients with breast cancer liver metastases, diagnosed and treated in a single tertiary university hospital from January 2011 to December 2016 was performed. Results: In 32/55 patients (58.2%), multi-organ metastases were identified (the most common sites being bone, lungs, and lymph nodes). Of the remaining 23 patients, the liver was the unique metastatic site; thirteen patients had diffuse bilobar hepatic metastases. The remaining ten patients were proposed for surgical treatment; three of them had peritoneal carcinomatosis identified during surgery, and no hepatic metastasectomy was performed. As a result, only seven (12.7%) patients underwent liver metastasectomy. Overall survival was higher in patients who had LM surgery (65 months [Interquartile Range (IQR) 54–120]), in comparison to those diagnosed with diffuse bilobar hepatic metastases (17.5 months [IQR 11–41]), and with those showing concurrent liver and bone metastases (16.5 months [IQR 6–36]) (p = 0.012). In univariable analysis, the latter two groups showed worse overall survival outcomes (Hazard Ratio (HR) = 3.447, 95%CI: 1.218–9.756, p = 0.02 and HR = 3.855, 95% Confidence Interval (CI): 1.475–10.077, p = 0.006, respectively) when compared to patients with LM. Conclusion: In our series, patients submitted to metastasectomy had a median overall survival after diagnosis of LM three times greater than the non-operated patients with isolated LM, or concurrent LM and bone metastases (65 vs. 17.5 and 16.5 months, respectively). As is vastly known for colorectal cancer liver metastasis, resection of breast cancer liver metastasis may reduce tumor burden, and therefore may improve patient outcome. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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8 pages, 1850 KiB  
Article
Incidence of Screw Loosening in Cortical Bone Trajectory Fixation Technique between Single- and Dual-Threaded Screws
by Chao-Hsuan Chen, Chih-Hsiu Tu, Der-Cherng Chen, Hsiang-Ming Huang, Hao-Yu Chuang, Der-Yang Cho, Da-Tian Bau and Han-Chung Lee
Medicines 2021, 8(9), 50; https://doi.org/10.3390/medicines8090050 - 2 Sep 2021
Cited by 1 | Viewed by 3185
Abstract
Purpose: This study aims to elucidate the radiological outcome after Cortical bone trajectory (CBT) screw fixation and whether dual-threaded (DT) screws should be used in the fusion surgery. Methods: 159 patients with degenerative lumbar disorder who had undergone midline lumbar inter-body fusion surgery [...] Read more.
Purpose: This study aims to elucidate the radiological outcome after Cortical bone trajectory (CBT) screw fixation and whether dual-threaded (DT) screws should be used in the fusion surgery. Methods: 159 patients with degenerative lumbar disorder who had undergone midline lumbar inter-body fusion surgery by CBT screw-fixation technique (2014 to 2018). Patient subgroups were based on single-threaded (ST) or DT screw, fixation length, as well as whether fixation involved to sacrum level (S1). Serial dynamic plain films were reviewed and an appearance of a halo phenomenon between screw–bone interfaces was identified as a case of screw loosening. Results: 29 patients (39.7%) in ST group and 10 patients (11.6%) in DT group demonstrated a halo phenomenon (p < 0.0001 ****). After subgrouping with fixation length, the incidence rates of a halo phenomenon in each group were 11.1%:3% (ST-1L vs. DT-1L), 37%:13.8% (ST-2L vs. DT-2L), and 84.2%:23.5% (ST-3L vs. DT-3L). Among the 85 patients with a fixation involved in S1, 26 patients (52%) with single-threaded screw (STS group) and 8 patients (22.8%) with dual-threaded screw (DTS group) demonstrated a halo appearance (p = 0.0078 **). After subgrouping the fixation level, the incidence of a halo appearance in each group was 25%:0% (STS-1L vs. DTS-1L), 40.9%:26.3% (STS-2L vs. DTS-2L), and 87.5%: 30% (STS-3L vs. DTS-3L). Conclusion: Both fixation length and whether fixation involved to S1 contribute to the incidence of screw loosening, the data supports clinical evidence that DT screws had greater fixation strength with an increased fixative stability and lower incidence of screw loosening in CBT screw fixation compared with ST screws. Level of evidence: 2. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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13 pages, 831 KiB  
Article
Psychometric Properties of the Greek Version of the Medical Office on Patient Safety Culture in Primary Care Settings
by Ioannis Antonakos, Kyriakos Souliotis, Theodora Psaltopoulou, Yannis Tountas, Athanasios Papaefstathiou and Maria Kantzanou
Medicines 2021, 8(8), 42; https://doi.org/10.3390/medicines8080042 - 26 Jul 2021
Cited by 2 | Viewed by 3022
Abstract
Background: Safety culture is considered one of the most crucial premises for further development of patient care in healthcare. During the eight-year economic crisis (2010–2018), Greece made significant reforms in the way the primary health care system operates, aiming at the more efficient [...] Read more.
Background: Safety culture is considered one of the most crucial premises for further development of patient care in healthcare. During the eight-year economic crisis (2010–2018), Greece made significant reforms in the way the primary health care system operates, aiming at the more efficient operation of the system without degrading issues of safety and quality of the provided health services. In this context, this study aims to validate a specialized tool—the Medical Office Survey on Patient Safety Culture (MOSPSC)—developed by the Agency for Healthcare Research and Quality (AHRQ) to evaluate primary care settings in terms of safety culture and quality. Methods: Factor analysis determined the correlation of the factor structure in Greek data with the original questionnaire. The relation of the factor analysis with the Cronbach’s coefficient alpha was also determined, including the construct validity. Results: Eight composites with 34 items were extracted by exploratory factor analysis, with acceptable Cronbach’s alpha coefficients and good construct validity. Consequently, the composites jointly explained 62% of the variance in the responses. Five items were removed from the original version of the questionnaire. As a result, three out of the eight composites were a mixture of items from different compounds of the original tool. The composition of the five factors was similar to that in the original questionnaire. Conclusions: The MOSPSC tool in Greek primary healthcare settings can be used to assess patient safety culture in facilities across the country. From the study, the patient safety culture in Greece was positive, although few composites showed a negative correlation and needed improvement. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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8 pages, 489 KiB  
Article
Comparison of G8 and ISAR Screening Results in Geriatric Urology
by Jobar Bouzan, Boris Stoilkov, Spyridon Nellas and Marcus Horstmann
Medicines 2021, 8(8), 40; https://doi.org/10.3390/medicines8080040 - 22 Jul 2021
Cited by 6 | Viewed by 4943
Abstract
Background: The G8 and ISAR scores are two different screening tools for geriatric risk factors and frailty. The aim of this study was to compare the G8 and ISAR screening results in a cohort of urogeriatric patients to help clinicians to better understand [...] Read more.
Background: The G8 and ISAR scores are two different screening tools for geriatric risk factors and frailty. The aim of this study was to compare the G8 and ISAR screening results in a cohort of urogeriatric patients to help clinicians to better understand and choose between the two tests. Methods: We retrospectively evaluated 100 patients at the age of 75 and above who were treated for different urological conditions. All routinely and prospectively underwent G8 and ISAR screening tests. A G8 score ≤ 14 and an ISAR score > 2 were considered positive. The results for the two tests were compared and correlated to clinical data. Results: The mean age of the patients was 83 y (min. 75–max. 101); 78 of the patients were male, while 22 were female; 58 of the patients were G8-positive, while 42 were G8-negative; and 24 were ISAR-positive, while 76 ISAR were negative. All the ISAR-positive patients were also G8-positive. There was a significant negative correlation between the G8 and ISAR scores (r = −0.77, p < 0.001). Both tests correlated significantly with the Charlson comorbidity index, length of stay, number of coded diagnosis, and Braden score (p < 0.05). Conclusion: Both tests are significantly correlated with each other and to clinical data related to geriatric frailty. However, the G8 score has a much higher rate of positive tests, which limits its use in daily routine, and the ISAR score is therefore preferable. For “fit” geriatric patients, however, a negative G8 score can be of great use as a confirmatory test for further decision making. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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Review

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8 pages, 499 KiB  
Review
Natural Products Induce Lysosomal Membrane Permeabilization as an Anticancer Strategy
by Reginald Halaby
Medicines 2021, 8(11), 69; https://doi.org/10.3390/medicines8110069 - 10 Nov 2021
Viewed by 3876
Abstract
Cancer is a global health and economic issue. The majority of anticancer therapies become ineffective due to frequent genomic turnover and chemoresistance. Furthermore, chemotherapy and radiation are non-specific, killing all rapidly dividing cells including healthy cells. In this review, we examine the ability [...] Read more.
Cancer is a global health and economic issue. The majority of anticancer therapies become ineffective due to frequent genomic turnover and chemoresistance. Furthermore, chemotherapy and radiation are non-specific, killing all rapidly dividing cells including healthy cells. In this review, we examine the ability of some natural products to induce lysosomal-mediated cell death in neoplastic cells as a way to kill them more specifically than conventional therapies. This list is by no means exhaustive. We postulate mechanisms to explain lysosomal membrane permeabilization and its role in triggering cell death in cancer cells. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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8 pages, 306 KiB  
Review
Clinical Trials, Potential Mechanisms, and Adverse Effects of Arnica as an Adjunct Medication for Pain Management
by Amanda G. Smith, Victoria N. Miles, Deltrice T. Holmes, Xin Chen and Wei Lei
Medicines 2021, 8(10), 58; https://doi.org/10.3390/medicines8100058 - 9 Oct 2021
Cited by 8 | Viewed by 14403
Abstract
Arnica has traditionally been used in treating numerous medical conditions, including inflammation and pain. This review aims to summarize the results of studies testing Arnica products for pain management under different conditions, including post-operation, arthritis, low back pain, and other types of musculoskeletal [...] Read more.
Arnica has traditionally been used in treating numerous medical conditions, including inflammation and pain. This review aims to summarize the results of studies testing Arnica products for pain management under different conditions, including post-operation, arthritis, low back pain, and other types of musculoskeletal pain. Based on data from clinical trials, Arnica extract or gel/cream containing Arnica extract shows promising effects for pain relief. These medical benefits of Arnica may be attributed to its chemical components, with demonstrated anti-inflammatory, antioxidant, anti-microbial, and other biological activities. In conclusion, Arnica could be an adjunct therapeutical approach for acute and chronic pain management. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
12 pages, 425 KiB  
Review
The Effective Strategies to Avoid Medication Errors and Improving Reporting Systems
by Abbas Al Mutair, Saad Alhumaid, Abbas Shamsan, Abdul Rehman Zia Zaidi, Mohammed Al Mohaini, Alya Al Mutairi, Ali A. Rabaan, Mansour Awad and Awad Al-Omari
Medicines 2021, 8(9), 46; https://doi.org/10.3390/medicines8090046 - 27 Aug 2021
Cited by 23 | Viewed by 25391
Abstract
Background: Population-based studies from several countries have constantly shown excessively high rates of medication errors and avoidable deaths. An efficient medication error reporting system is the backbone of reliable practice and a measure of progress towards achieving safety. Improvement efforts and system changes [...] Read more.
Background: Population-based studies from several countries have constantly shown excessively high rates of medication errors and avoidable deaths. An efficient medication error reporting system is the backbone of reliable practice and a measure of progress towards achieving safety. Improvement efforts and system changes of medication error reporting systems should be targeted towards reductions in the likelihood of injury to future patients. However, the aim of this review is to provide a summary of medication errors reporting culture, incidence reporting systems, creating effective reporting methods, analysis of medication error reports, and recommendations to improve medication errors reporting systems. Methods: Electronic databases (PubMed, Ovid, EBSCOhost, EMBASE, and ProQuest) were examined from 1 January 1998 to 30 June 2020. 180 articles were found and 60 papers were ultimately included in the review. Data were mined by two reviewers and verified by two other reviewers. The search yielded 684 articles, which were then reduced to 60 after the deletion of duplicates via vetting of titles, abstracts, and full-text papers. Results: Studies were principally from the United States of America and the United Kingdom. Limited studies were from Canada, Australia, New Zealand, Korea, Japan, Greece, France, Saudi Arabia, and Egypt. Detection, measurement, and analysis of medication errors require an active rather than a passive approach. Efforts are needed to encourage medication error reporting, including involving staff in opportunities for improvement and the determination of root cause(s). The National Coordinating Council for Medication Error Reporting and Prevention taxonomy is a classification system to describe and analyze the details around individual medication error events. Conclusion: A successful medication error reporting program should be safe for the reporter, result in constructive and useful recommendations and effective changes while being inclusive of everyone and supported with required resources. Health organizations need to adopt an effectual reporting environment for the medication use process in order to advance into a sounder practice. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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Other

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9 pages, 2106 KiB  
Case Report
Effects of Systemic Enzyme Supplements on Symptoms and Quality of Life in Patients with Pulmonary Fibrosis—A Pilot Study
by Neha Shah
Medicines 2021, 8(11), 68; https://doi.org/10.3390/medicines8110068 - 5 Nov 2021
Cited by 3 | Viewed by 11752
Abstract
Current FDA-approved antifibrotic treatments for Idiopathic Pulmonary Fibrosis slow down disease progression but have little impact on symptoms or quality of life in patients. This study was conducted to evaluate the effects of systemic enzymes in relieving symptoms associated with PF and improving [...] Read more.
Current FDA-approved antifibrotic treatments for Idiopathic Pulmonary Fibrosis slow down disease progression but have little impact on symptoms or quality of life in patients. This study was conducted to evaluate the effects of systemic enzymes in relieving symptoms associated with PF and improving quality of life. Methods: an open-label, prospective study on subjects with a confirmed diagnosis of PF was conducted as proof-of-concept. The subjects (n = 13) received the oral systemic enzyme supplements Serracor-NK and Serra Rx for 12 weeks and completed Health-Related Quality of Life (HRQL) questionnaires. The effect of this regimen was examined by comparing the end-of-treatment questionnaire scores with baseline values. Results: significant improvement was seen in 61.5% of subjects, as assessed by the WHO well-being index; an improvement in scores was seen in 84.6% of the subjects, as assessed by the UCSD Shortness of Breath Questionnaire, with 38.4% of the subjects showing minimal clinically important difference; the supplementation was found to be efficacious in 69.2%, 84.6%, 69.2% and 61.5% of the subjects, as assessed by the Saint George’s Respiratory Questionnaire total, symptom, activity, and impact scores, respectively. Conclusions: Serracor-NK and Serra Rx improve symptoms, as well as mental and physical wellbeing and HRQL in patients with PF. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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9 pages, 1902 KiB  
Case Report
A Rare Case of Recurrent Generalized Peritonitis Caused by Spontaneous Urinary Bladder Rupture after Radiotherapy: A Case Report and Literature Review
by Yusuke Watanabe, Shun Yamazaki, Hanako Yokoyama, Shunta Yakubo, Akihiko Osaki, Kenichi Takaku, Munehiro Sato, Nobuo Waguri and Shuji Terai
Medicines 2021, 8(11), 67; https://doi.org/10.3390/medicines8110067 - 5 Nov 2021
Cited by 2 | Viewed by 4250
Abstract
Since generalized peritonitis is a fatal disease, accurate diagnosis and treatment are important. In this paper, we report a case of recurrent generalized peritonitis associated with spontaneous urinary bladder rupture (SBR). A 65 year old woman, who underwent radiotherapy 21 years prior, was [...] Read more.
Since generalized peritonitis is a fatal disease, accurate diagnosis and treatment are important. In this paper, we report a case of recurrent generalized peritonitis associated with spontaneous urinary bladder rupture (SBR). A 65 year old woman, who underwent radiotherapy 21 years prior, was diagnosed with generalized peritonitis. Although the cause of the generalized peritonitis could not be identified, the patient recovered with conservative treatment in short period. However, recurrent episodes of generalized peritonitis occurred four times. We diagnosed the patient with urinary ascites due to SBR, based on a history of radiotherapy and dysuria. No recurrence of generalized peritonitis had occurred after accurate diagnosis and treatment with long-term bladder catheter placement. Since SBR often occurs as a late complication after radiotherapy, it is difficult to diagnose SBR, which leads to delayed treatment. This case and literature review of similar cases suggest that the information of the following might be helpful in the diagnosis of SBR: (i) history of recurrent generalized peritonitis, (ii) pseudo-renal failure, (iii) history of radiotherapy, (iv) dysuria, and (v) increase or decrease of ascites in a short period. It is important to list SBR in the differential diagnosis by knowing the disease and understanding its clinical features. This case and literature review will serve as a reference for future practices. Full article
(This article belongs to the Special Issue PROTAC—From Bench to Bed)
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