Cancer Invest. 2021 Jul 9:1-23. doi: 10.1080/07357907.2021.1954190. Online ahead of print.

ABSTRACT

The major problems with cancer therapy are drug-induced side effects. There is an urgent need for safe anti-tumor drugs. Artemisinin is a Chinese herbal remedy for malaria with efficacy and safety. However, several studies reported that artemisinin causes neurotoxicity and cardiotoxicity in animal models. Recently, nanostructured drug delivery systems have been designed to improve therapeutic efficacy and reduce toxicity. Artemisinin has been reported to show anticancer properties. The anticancer effects of artemisinin appear to be mediated by inducing cell cycle arrest, promoting ferroptosis and autophagy, inhibiting cell metastasis. Therefore, the review is to concentrate on mechanisms and molecular targets of artemisinin as anti-tumor agents. We believe these will be important topics in realizing the potential of artemisinin and its derivatives as potent anticancer agents.

PMID:34241563 | DOI:10.1080/07357907.2021.1954190

Br J Clin Pharmacol. 2021 Jul 8. doi: 10.1111/bcp.14980. Online ahead of print.

ABSTRACT

AIM: Cabotegravir is an integrase strand transfer inhibitor in clinical development as long-acting (LA) injectable HIV preexposure prophylaxis.

METHODS: This phase I study assessed pharmacokinetics of cabotegravir in plasma and anatomical sites associated with sexual HIV-1 transmission after repeated oral and single intramuscular (IM) LA dosing in healthy adults. Following a 28-day oral lead-in period of cabotegravir 30 mg and a washout period of 14 to 42 days, participants were administered a single ultrasound-guided gluteal IM cabotegravir LA 600-mg injection. The study objective was to characterize cabotegravir concentrations in plasma, cervical, vaginal, and rectal tissues and cervicovaginal and rectal fluids and through Week 12 after IM injection.

RESULTS: Nineteen participants enrolled and 16 completed the study through Week 52. Cabotegravir was detected in plasma and all tissues and fluids. Median plasma cabotegravir concentrations exceeded the in vitro protein-adjusted 90% maximal inhibitory concentration through Week 12. Median tissue- and fluid-to-plasma cabotegravir concentration ratios across all visits were 0.32 for rectal fluid and 0.08 to 0.16 for other tissues and fluids. Adjusted R2 coefficients between cabotegravir concentrations in plasma and cervical, vaginal, and rectal tissues were 0.78, 0.79, and 0.90, respectively. Injection-site reactions were common (88% of participants) and were mostly grade 1 in intensity (82%). Two participants reported 11 non-drug-related serious adverse events.

CONCLUSION: Concentrations of cabotegravir in tissues and fluids were proportional to plasma over time, with strong correlations between tissue and plasma concentrations. Cabotegravir LA tissue-to-plasma ratios may be important for understanding its use as preexposure prophylaxis.

PMID:34240467 | DOI:10.1111/bcp.14980

Front Immunol. 2021 Jun 22;12:695954. doi: 10.3389/fimmu.2021.695954. eCollection 2021.

ABSTRACT

Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to Aspergillus which colonizes the airways of patients with asthma and cystic fibrosis. Its diagnosis could be difficult in some cases due to atypical presentations especially when there is no medical history of asthma. Treatment of ABPA is frequently associated to side effects but cumulated drug toxicity due to different molecules is rarely reported. An accurate choice among the different available molecules and effective on ABPA is crucial. We report a case of ABPA in a woman without a known history of asthma. She presented an acute bronchitis with wheezing dyspnea leading to an acute respiratory failure. She was hospitalized in the intensive care unit. The bronchoscopy revealed a complete obstruction of the left primary bronchus by a sticky greenish material. The culture of this material isolated Aspergillus fumigatus and that of bronchial aspiration fluid isolated Pseudomonas aeruginosa. The diagnosis of ABPA was based on elevated eosinophil count, the presence of specific IgE and IgG against Aspergillus fumigatus and left segmental collapse on chest computed tomography. The patient received an inhaled treatment for her asthma and a high dose of oral corticosteroids for ABPA. Her symptoms improved but during the decrease of corticosteroids, the patient presented a relapse. She received itraconazole in addition to corticosteroids. Four months later, she presented a drug-induced hepatitis due to itraconazole which was immediately stopped. During the monitoring of her asthma which was partially controlled, the patient presented an aseptic osteonecrosis of both femoral heads that required surgery. Nine months after itraconazole discontinuation, she presented a second relapse of her ABPA. She received voriconazole for nine months associated with a low dose of systemic corticosteroid therapy with an improvement of her symptoms. After discontinuation of antifungal treatment, there was no relapse for one year follow-up.

PMID:34239516 | PMC:PMC8259593 | DOI:10.3389/fimmu.2021.695954

Musculoskeletal Care. 2021 Jul 8. doi: 10.1002/msc.1577. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the barriers and facilitators of adherence to methotrexate (MTX) in people with rheumatic diseases and to explore the experience of shared decision-making.

METHODS: A qualitative study was carried out. People diagnosed with inflammatory arthritides or systemic autoimmune diseases and who were treated with MTX were invited to participate in focus groups. The discourse was coded and synthesised with a content analysis approach.

RESULTS: The groups included 12 representative patients (rheumatoid arthritis, spondylarthritis, and systemic lupus erythematosus, taking either oral or subcutaneous MTX). Four main themes were identified: (1) drug-related aspects (package insert, adverse events, administration, and difficulties with treatment); (2) patient-physician relationship; (3) social environment (lack of visibility of rheumatic diseases and the support of patient associations); and (4) medication and medical care practicalities (information, reliable sources, and expanding knowledge in other health areas).

CONCLUSIONS: Aspects identified might help improve adherence, including quality information, especially on adverse events, the role of the setting, and shared decision-making.

PMID:34236743 | DOI:10.1002/msc.1577

Eur J Hosp Pharm. 2021 Jul 7:ejhpharm-2021-002875. doi: 10.1136/ejhpharm-2021-002875. Online ahead of print.

ABSTRACT

In Turkey, diphtheria-tetanus-acellular pertussis-inactivated poliovirus and Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine has been administered to all children in the second, fourth, sixth and 18th months within the scope of the national vaccination programme. Here we present a rare case of fixed drug eruption (FDE) that occurred as a result of the administration of a pentavalent DTaP-IPV-Hib combined vaccine in a 4-month-old girl. There was no history of taking any other medication before or when the lesion appeared. The lesion responded well to 1 week of topical methylprednisolone aceponate cream application and regressed within 1 week, leaving mild hyperpigmentation. Few cases of FDE have been reported occurring after administration of various vaccines and it is extremely rare in children. To our knowledge, this is the first reported case of FDE developing in an infant after the combined pentavalent DTaP-IPV-Hib vaccine.

PMID:34233904 | DOI:10.1136/ejhpharm-2021-002875

Arthritis Res Ther. 2021 Jul 8;23(1):182. doi: 10.1186/s13075-021-02566-z.

ABSTRACT

BACKGROUND: Tapering or stopping biological disease-modifying anti-rheumatic drugs has been proposed for patients with rheumatoid arthritis (RA) in remission, but it frequently results in high rates of recurrence. This study evaluates the efficacy and safety of tacrolimus (TAC) as maintenance therapy in patients with established RA in remission after receiving combination therapy with tumor necrosis factor inhibitor (TNFi) and methotrexate (MTX).

METHODS: This 24-week, prospective, open-label trial included patients who received TNFi and MTX at stable doses for ≥24 weeks and had low disease activity (LDA), measured by Disease Activity Score-28 for ≥12 weeks. Patients selected one of two arms: maintenance (TNFi plus MTX) or switched (TAC plus MTX). The primary outcome was the difference in the proportion of patients maintaining LDA at week 24, which was assessed using a logistic regression model. Adverse events were monitored throughout the study period.

RESULTS: In efficacy analysis, 80 and 34 patients were included in the maintenance and switched arms, respectively. At week 24, LDA was maintained in 99% and 91% of patients in the maintenance and switched arms, respectively (odds ratio, 0.14; 95% confidence interval, 0.01-1.59). Drug-related adverse effects tended to be more common in the switched arm than in the maintenance arm (20.9% versus 7.1%, respectively) but were well-tolerated.

CONCLUSION: This controlled study tested a novel treatment strategy of switching from TNFi to TAC in RA patients with sustained LDA, and the findings suggested that TNFi can be replaced with TAC in most patients without the patients experiencing flare-ups for at least 24 weeks.

TRIAL REGISTRATION: Korea CDC CRIS, KCT0005868 . Registered 4 February 2021-retrospectively registered.

PMID:34233727 | DOI:10.1186/s13075-021-02566-z

Curr Protoc. 2021 Jul;1(7):e189. doi: 10.1002/cpz1.189.

ABSTRACT

Cardiovascular pharmacogenomics is the study and identification of genomic markers that are associated with variability in cardiovascular drug response, cardiovascular drug-related outcomes, or cardiovascular drug-related adverse events. This overview presents an introduction and historical background to cardiovascular pharmacogenomics, and a protocol for designing a cardiovascular pharmacogenomics study. Important considerations are also included for constructing a cardiovascular pharmacogenomics phenotype, designing the replication or validation strategy, common statistical approaches, and how to put the results in context with the cardiovascular drug or cardiovascular disease under investigation. © 2021 Wiley Periodicals LLC. Basic Protocol: Designing a cardiovascular pharmacogenomics study.

PMID:34232575 | DOI:10.1002/cpz1.189

J Pharm Pract. 2021 Jul 7:8971900211028208. doi: 10.1177/08971900211028208. Online ahead of print.

ABSTRACT

BACKGROUND: Tocilizumab is an interleukin-6 receptor antagonist hypothesized to blunt the uncontrolled immune response, cytokine release syndrome, in severe COVID-19 and prevent attributable morbidity and mortality. Objective: The objective of this study was to assess the impact of tocilizumab on clinical outcomes in COVID-19-associated cytokine release syndrome.

METHODS: Single-center, retrospective cohort study assessing sixty-nine adult patients receiving tocilizumab for suspected COVID-19 cytokine release syndrome. The primary outcome was change in WHO clinical status scale on day seven post-dose analyzed using the Wilcoxon signed rank test. Secondary outcomes assessed impact of timing of administration on clinical outcome. Safety analyses included development of neutropenia, thrombocytopenia, transaminitis, and sepsis within 7 days post-dose. Statistical analyses were conducted using Microsoft Excel.

RESULTS: No aggregate clinical change was found between day 0 and day 7. Eleven patients improved, twenty-seven worsened, and thirty-one showed no change. Clinical outcomes were weakly correlated with time from symptom onset (rs = 0.21; p = 0.08) or hospital admission (rs = -0.08; p = 0.49) to dose. In-hospital mortality was 63%. Sepsis was diagnosed in 21 patients, five of which were post-dose. Transaminitis, neutropenia, and thrombocytopenia occurred in seven, one, and six patients, respectively.

CONCLUSION: Tocilizumab did not appear to influence clinical outcomes in our study population, irrespective of timing of administration. Adverse events were not considered drug-related.

PMID:34231415 | DOI:10.1177/08971900211028208

Eur J Ophthalmol. 2021 Jul 7:11206721211023320. doi: 10.1177/11206721211023320. Online ahead of print.

ABSTRACT

PURPOSE: To assess the efficacy and safety of supplementing topical cyclosporine A (CsA) to topical corticosteroids (CS), in the prophylaxis and treatment of corneal graft rejection following penetrating keratoplasty (PK).

METHODS: Meta-analysis. Search was performed in PubMed, CENTRAL, ClinicalTrials.gov, reference lists of articles and conference proceedings. Primary outcomes: 1-year rejection-free survival rate (prophylaxis); resolution rate of rejection episodes (treatment). Secondary outcomes: 6- and 24-month rejection-free graft survival rate, number of rejection episodes during follow-up, time-to-resolution of rejection episode, 12- and 24-months graft survival rate, adverse events. Subgroup analyses were planned for high-risk grafts; primary vs. secondary prophylaxis of graft rejection episodes; and CsA concentrations of 0.05%, 1%, and 2%.

RESULTS: Five studies of moderate methodological quality were included (one retrospective, four RCT), assessing 459 eyes (CS + CsA 226, CS 233). In the prophylaxis setting, supplemental CsA was associated with a higher rejection-free survival rate at 12-months (RR 1.25, 95% CI: 1.00-1.56, p = 0.05) and 24-months post-PK (RR 1.56, 95% CI: 1.15-2.11, p < 0.01), though no differences were found at the 6-months timepoint (p = 0.93). This effect was mostly verified using CsA 2% in the high-risk subset of patients. In the treatment setting, no differences were found in the resolution rate of rejection episodes (p = 0.23). No differences existed on drug-related adverse events.

CONCLUSION: In the prophylaxis of rejection episodes post-PK, the combined regimen of CS + CsA was associated with a higher 1- and 2-year rejection-free graft survival rate. Subgroup analysis mostly supported the use of CsA 2% for high-risk grafts. Further studies are needed to validate these results.

PMID:34231398 | DOI:10.1177/11206721211023320

Eur Rev Med Pharmacol Sci. 2021 Jun;25(12):4418-4421. doi: 10.26355/eurrev_202106_26153.

ABSTRACT

OBJECTIVE: Side effects of vaccines are common, but people react differently to different vaccines. Manufacturers provide lists of the side effects of their products. Adverse reactions are proof of the effectiveness of vaccines and that the immune system is responding. In this study, we compare the side effects of the AstraZeneca and Pfizer vaccines. Our survey results show that the side effects of the first dose of the AstraZeneca vaccine are more common than after the first and second doses of the Pfizer vaccine. Most respondents in our survey reported at least one side-effect after the AstraZeneca and Pfizer vaccine, but these reactions were less common after the Pfizer preparation.

PATIENTS AND METHODS: A survey was distributed via the internet. It was conducted among people vaccinated with Pfizer or AstraZeneca. The respondents were asked about the side effects after the first and second doses of the vaccines, such as injection site pain, arm pain, muscle pain, headache, fever, chills, and fatigue.

RESULTS: The questionnaire was completed by 705 people. 196 of them had been vaccinated with Pfizer and 509 with AstraZeneca. Among those vaccinated with the first dose of the AstraZeneca vaccine, 96.5% reported at least one post-vaccination reaction. 17.1% of respondents reported all the side effects listed in the survey. Among those vaccinated with the first Pfizer dose, vaccine reactions were reported by 93.9% of respondents; 2% of respondents experienced all the side effects mentioned in the survey. The second dose of the Pfizer vaccine caused post-vaccinal reactions in most of the subjects: 54.8% of respondents had more adverse reactions, and 15.8% had fewer adverse reactions than after the first dose of this vaccine; 29.4% experienced the same side effects after the first and second doses of the Pfizer vaccine.

CONCLUSIONS: Side effects as a result of vaccination are not rare and are proof that the immune system is responding. However, severe adverse reactions to vaccines can be dangerous, and they engender fear. Concerns about the side effects and complications of COVID-19 vaccines may eclipse opinions regarding their benefits. This study shows that the first dose of the AstraZeneca vaccine causes side effects more often than either dose of the Pfizer vaccine.

PMID:34227078 | DOI:10.26355/eurrev_202106_26153

Int J Clin Pract. 2021 Jul 6:e14605. doi: 10.1111/ijcp.14605. Online ahead of print.

ABSTRACT

BACKGROUND: The long term control of COVID-19 depends on an effective global vaccination strategy. Protecting healthcare workers (HCWs) from serious infection is critical. Malta, a European country, initiated the vaccination roll-out using Pfizer-BioNTech COVID-19 vaccine targeting HCWs. This study determined vaccination adverse effects (AEs) in this cohort.

METHOD: An online survey was disseminated to all HCWs via work email (29/3/21 to 9/4/21) to gather AEs regarding pain, redness and swelling at injection site, fever, chills, fatigue, muscle/joint pains, headache, vomiting and diarrhoea severity following each dose (Likert scale). Descriptive, comparative and multiple binary regression analyses were performed.

RESULTS: A response of 30.30% (n=1480) was achieved with the commonest AEs being pain at injection site (88.92% CI 95%:87.21-90.42), mostly mild (51%) and moderate (43%). Fatigue was reported by 72.97% (CI 95%:70.65-75.17), 42% were mild and 41% were moderate. Females reported significantly (p=<0.05 respectively) more pain (OR:1.90), redness (OR:2.49), swelling at injection site (OR:1.33), fever (OR:1.74), chills (OR:2.32), fatigue (OR:2.43), muscle (OR:1.54) and joint pains (OR:2.01), headache (OR:2.07) and vomiting (OR:3.43) when adjusted for age and HCW role. Localised AEs were reported following both vaccine doses unlike systemic AEs that were mostly reported after second doses.

CONCLUSION: Vaccination benefits outweigh the minor AEs experienced, with females exhibiting a higher susceptibility. The general low vaccination AEs observed within the HCWs cohort is encouraging and should help in allaying vaccine hesitancy among the population.

PMID:34228863 | DOI:10.1111/ijcp.14605

PLoS Comput Biol. 2021 Jul 6;17(7):e1009053. doi: 10.1371/journal.pcbi.1009053. Online ahead of print.

ABSTRACT

Drug-drug interactions account for up to 30% of adverse drug reactions. Increasing prevalence of electronic health records (EHRs) offers a unique opportunity to build machine learning algorithms to identify drug-drug interactions that drive adverse events. In this study, we investigated hospitalizations' data to study drug interactions with non-steroidal anti-inflammatory drugs (NSAIDS) that result in drug-induced liver injury (DILI). We propose a logistic regression based machine learning algorithm that unearths several known interactions from an EHR dataset of about 400,000 hospitalization. Our proposed modeling framework is successful in detecting 87.5% of the positive controls, which are defined by drugs known to interact with diclofenac causing an increased risk of DILI, and correctly ranks aggregate risk of DILI for eight commonly prescribed NSAIDs. We found that our modeling framework is particularly successful in inferring associations of drug-drug interactions from relatively small EHR datasets. Furthermore, we have identified a novel and potentially hepatotoxic interaction that might occur during concomitant use of meloxicam and esomeprazole, which are commonly prescribed together to allay NSAID-induced gastrointestinal (GI) bleeding. Empirically, we validate our approach against prior methods for signal detection on EHR datasets, in which our proposed approach outperforms all the compared methods across most metrics, such as area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC).

PMID:34228716 | DOI:10.1371/journal.pcbi.1009053

Pharm Pract (Granada). 2021 Apr-Jun;19(2):2360. doi: 10.18549/PharmPract.2021.2.2360. Epub 2021 Jun 14.

ABSTRACT

BACKGROUND: Medication error is a global threat to patient safety, particularly in pediatrics. Yet, this issue remains understudied in this population, in both hospital and community settings.

OBJECTIVES: To characterize medication errors involving pediatrics reported to the French Medication Error Guichet, and compare them with medication errors in adults, in each of the hospital and community settings.

METHODS: This was a retrospective secondary data analysis of medication errors reported throughout 2013-2017. Descriptive and multivariate analyses were performed to compare actual and potential medication error reports between pediatrics (aged <18 years) and adults (aged >18 and <60 years). Two subanalyses of actual medication errors with adverse drug reaction (ADR), and serious ADR were conducted.

RESULTS: We analyzed 4,718 medication error reports. In pediatrics, both in hospital (n=791) and community (n=1,541) settings, antibacterials for systemic use (n=121, 15.7%; n=157, 10.4%, respectively) and wrong dose error type (n=391, 49.6%; n=549, 35.7%, respectively) were frequently reported in medication errors. These characteristics were also significantly more likely to be associated with reported errors in pediatrics compared with adults. In the hospital setting, analgesics (adjusted odds ratio (aOR)=1.59; 95% confidence interval (CI) 1.03:2.45), and blood substitutes and perfusion solutions (aOR=3.74; 95%CI 2.24:6.25) were more likely to be associated with reported medication errors in pediatrics; the latter drug class (aOR=3.02; 95%CI 1.59:5.72) along with wrong technique (aOR=2.28; 95%CI 1.01:5.19) and wrong route (aOR=2.74; 95%CI 1.22:6.15) error types related more to reported medication errors with serious ADR in pediatrics. In the community setting, the most frequently reported pediatric medication errors involved vaccines (n=389, 25.7%). Psycholeptics (aOR=2.42; 95%CI 1.36:4.31) were more likely to be associated with reported medication errors with serious ADR in pediatrics. Wrong technique error type (aOR=2.71; 95%CI 1.47:5.00) related more to reported medication errors with ADR in pediatrics.

CONCLUSIONS: We identified pediatric-specific medication error patterns in the hospital and community settings. Our findings inform focused error prevention measures, and pave the way for interventional research targeting the needs of this population.

PMID:34221205 | PMC:PMC8234707 | DOI:10.18549/PharmPract.2021.2.2360

Rinsho Ketsueki. 2021;62(6):582-591. doi: 10.11406/rinketsu.62.582.

ABSTRACT

After the discovery of driver mutations for myeloproliferative neoplasms (MPN), treatment approach for the disease has achieved tremendous progress. Ruxolitinib, a JAK inhibitor, is now widely used for both patients with myelofibrosis and polycythemia vera in several countries, including Japan. Fedratinib, another JAK inhibitor, has been recently approved in the United States. One of the biggest limitations of treatment with JAK inhibitors is the relatively small proportion of patients who achieve a complete molecular response. Furthermore, most of the patients with myelofibrosis had to discontinue the treatment due to drug-related adverse events or disease progression. Therefore, MPN treatment is still at an early and challenging stage, thereby highlighting the urgent need for establishment of a new and more effective therapeutic strategy. One of the promising candidates for MPN treatment is the use of interferons. Modern forms of interferons demonstrate not only a good hematological response but also a deep molecular response, eradicating abnormal MPN clones harboring driver mutations. A number of new agents targeting molecules outside of the JAK-STAT pathway, PI3kinase, NF-kB, or Bcl-2 family of anti-apoptotic proteins are also being considered and tested in clinical studies as single-agent therapies or in combination with JAK inhibitors.

PMID:34219084 | DOI:10.11406/rinketsu.62.582

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2021 Jun 20;39(6):445-447. doi: 10.3760/cma.j.cn121094-20210108-00010.

NO ABSTRACT

PMID:34218563 | DOI:10.3760/cma.j.cn121094-20210108-00010

Emerg Med Clin North Am. 2021 Aug;39(3):555-571. doi: 10.1016/j.emc.2021.04.007. Epub 2021 Jun 9.

ABSTRACT

Pediatric hematologic and oncologic emergencies are in 3 major categories: complications of hematologic disorders, emergencies associated with the new onset of cancers, and treatment-associated oncologic emergencies. The overall number of these patients remains low; however, the mortality associated with these diseases remains high despite significant advances in management. This article presents a review of the most commonly encountered pediatric hematologic and oncologic complications that emergency physicians and providers need to know.

PMID:34215402 | DOI:10.1016/j.emc.2021.04.007

Infect Chemother. 2021 Jun;53(2):271-283. doi: 10.3947/ic.2021.0051.

ABSTRACT

BACKGROUND: Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for Gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (HABP), and ventilator-associated bacterial pneumonia (VABP).

MATERIALS AND METHODS: We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. We included randomized clinical trials-with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A P-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I² statistic.

RESULTS: The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups.

CONCLUSION: Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, HABP, VABP).

PMID:34216121 | DOI:10.3947/ic.2021.0051

Int J Mol Sci. 2021 Jun 6;22(11):6109. doi: 10.3390/ijms22116109.

ABSTRACT

Acute kidney injury (AKI) is a global health challenge of vast proportions, as approx. 13.3% of people worldwide are affected annually. The pathophysiology of AKI is very complex, but its main causes are sepsis, ischemia, and nephrotoxicity. Nephrotoxicity is mainly associated with the use of drugs. Drug-induced AKI accounts for 19-26% of all hospitalized cases. Drug-induced nephrotoxicity develops according to one of the three mechanisms: (1) proximal tubular injury and acute tubular necrosis (ATN) (a dose-dependent mechanism), where the cause is related to apical contact with drugs or their metabolites, the transport of drugs and their metabolites from the apical surface, and the secretion of drugs from the basolateral surface into the tubular lumen; (2) tubular obstruction by crystals or casts containing drugs and their metabolites (a dose-dependent mechanism); (3) interstitial nephritis induced by drugs and their metabolites (a dose-independent mechanism). In this article, the mechanisms of the individual types of injury will be described. Specific groups of drugs will be linked to specific injuries. Additionally, the risk factors for the development of AKI and the methods for preventing and/or treating the condition will be discussed.

PMID:34204029 | PMC:PMC8201165 | DOI:10.3390/ijms22116109

S Afr Fam Pract (2004). 2021 Jun 28;63(1):e1-e3. doi: 10.4102/safp.v63i1.5278.

ABSTRACT

The use of hand sanitisers is common practice to prevent the spread of coronavirus disease 2019 (COVID-19). However, the safety thereof requires consideration as this may be hazardous in children. Recent studies have shown that the misuse and increased unsupervised availability of alcohol-based hand sanitisers may result in adverse events in children such as skin irritation, dryness, cracking and peeling. Unintentional or intentional ingestion of hand sanitisers in children under the age of 12 years may occur because of the colour, smell and flavour added to it. Consumption of alcohol in children may result in hypoglycaemia, apnoea and acidosis. This allows the invasion of other bacterial and viral infections. Children may also rub their eyes with sanitised hands and cause ocular injury. Therefore, the use of hand sanitisers in general needs to be revised in both children and adults. Other interventions on lowering the risk of adverse events because of misuse of hand sanitiser should be practised more often. These include promoting washing of hands over sanitisers where possible, training children on how to use hand sanitisers and creating awareness of the dangers if ingested or in contact with the eyes.

PMID:34212752 | DOI:10.4102/safp.v63i1.5278

J Basic Clin Physiol Pharmacol. 2021 Jun 25;32(4):473-478. doi: 10.1515/jbcpp-2020-0486.

ABSTRACT

OBJECTIVES: One of the methods used to treat coronary artery disease (CAD) is anticoagulant therapy, which involves administering anticoagulants to patients that inhibit the arrangement and actuation of clotting factors. Anticoagulant therapy in patients with CAD must be monitored and evaluated because its greatest side effect is the risk of bleeding. The research aimed to analyze anticoagulants used in therapy for CAD patients and identify potential adverse drug reactions and adverse drug interactions.

METHODS: This was an observational study which collected data retrospectively at Bhayangkara Hospital Surabaya. Patient data had to meet the requirements for inclusion, which were patients treated for a diagnosis of CAD with anticoagulant therapy and were in conditions with or without complications and comorbid diseases. Data were obtained from 40 patient medical records. The data were then processed descriptively.

RESULTS: Most patients were male (80%) and aged 61-70 years old (37.5%). Fondaparinux was administered to 18 patients at a dose of 1 × 2.5 mg SC. Furthermore, enoxaparin was administered to 15 patients at a dose of 2 × 60 mg SC, and seven patients received warfarin at a dose of 1 × 2-4 mg per oral.

CONCLUSIONS: The anticoagulants used in this study were fondaparinux 1 × 2.5 mg SC (45%), enoxaparin 2 × 60 mg SC (37.5%), and warfarin 1 × 2-4 mg PO (17.5%). Side effects of the anticoagulants were absent. However, drug interactions with aspirin, clopidogrel, and allopurinol increased the risk of bleeding.

PMID:34214300 | DOI:10.1515/jbcpp-2020-0486