PLoS One. 2022 May 4;17(5):e0266003. doi: 10.1371/journal.pone.0266003. eCollection 2022.

ABSTRACT

Why do people prefer one particular COVID-19 vaccine over another? We conducted a pre-registered conjoint experiment (n = 5,432) in France, Germany, and Sweden in which respondents rated the favorability of and chose between pairs of hypothetical COVID-19 vaccines. Differences in effectiveness and the prevalence of side-effects had the largest effects on vaccine preferences. Factors with smaller effects include country of origin (respondents are less favorable to vaccines of Chinese and Russian origin), and vaccine technology (respondents exhibited a small preference for hypothetical mRNA vaccines). The general public also exhibits sensitivity to additional factors (e.g. how expensive the vaccines are). Our data show that vaccine attributes are more important for vaccine preferences among those with higher vaccine favorability and higher risk tolerance. In our conjoint design, vaccine attributes-including effectiveness and side-effect prevalence-appear to have more muted effects among the most vaccine hesitant respondents. The prevalence of side-effects, effectiveness, country of origin and vaccine technology (e.g., mRNA vaccines) determine vaccine acceptance, but they matter little among the vaccine hesitant. Vaccine hesitant people do not find a vaccine more attractive even if it has the most favorable attributes. While the communication of vaccine attributes is important, it is unlikely to convince those who are most vaccine hesitant to get vaccinated.

PMID:35507554 | DOI:10.1371/journal.pone.0266003

Curr Drug Saf. 2022 Apr 29. doi: 10.2174/1574886317666220429111341. Online ahead of print.

ABSTRACT

BACKGROUND: Crohn Disease (CD) is an intestinal inflammatory condition char-acterized by a complex pathogenesis, with elevated levels of inflammatory cytokines. Ada-limumab and certolizumab are two biologic drugs inhibiting TNF-α.

OBJECTIVE: We report the first case of a probable relationship, according to Naranjo causality assessment score, between two consecutive treatments with TNF-α inhibitors and induced erectile dysfunction (ED), that disappeared after switching to another biologic drug (ustekinumab).

CASE PRESENTATION: This case report describes a possible and important association of two TNF-α inhibitors (certolizumab and adalimumab) and ED in a male patient with CD, with resolution after switching to Ustekinumab (anti-interleukin 12 and 23 biologic drug). A 65 years old man experienced erectile dysfunction during treatment with an anti-TNF. The adverse effect disappeared after discontinuation of the drug. All necessary urologic exams were carried out. Adalimumab was replaced by certolizumab and sexual disfunction symptoms appeared again, improving typically at the end of treatment periods and getting worse with each new dose.

RESULTS: Switching to ustekinumab lead to a resolution of the erectile dysfunction.

CONCLUSION: We describe for the first time a sexual dysfunction possibly due to two similar anti TNF drugs and its resolution after the switch to another similar but different drug, highlighting the potential difference between biologic drugs.

PMID:35507800 | DOI:10.2174/1574886317666220429111341

Clin Transl Sci. 2022 May 3. doi: 10.1111/cts.13290. Online ahead of print.

ABSTRACT

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among all infants worldwide and remains a significant cause of morbidity and mortality. To address this unmet medical need, MK-1654, a half-life extended RSV neutralizing monoclonal antibody, is in clinical development for the prevention of RSV disease in infants. This was a phase 1 randomized, placebo-controlled, single-site, double-blind trial of MK-1654 in 44 healthy Japanese adults. The safety, tolerability, pharmacokinetics, anti-drug antibodies (ADA), and serum neutralizing antibody (SNA) titers against RSV were evaluated for one year after a single intramuscular (IM) or intravenous (IV) dose of MK-1654 or placebo in five groups (100 mg IM, 300 mg IM, 300 mg IV, 1000 mg IV or placebo). MK-1654 was generally well tolerated in Japanese adults. There were no serious drug-related adverse events (AEs) reported in any MK-1654 recipient and no discontinuations due to any AEs in the study. The half-life of MK-1654 ranged from 76 to 91 days across dosing groups. Estimated bioavailability was 86% for 100 mg IM and 77% for 300 mg IM. One participant out of 33 (3.0%) developed detectable ADA with no apparent associated AEs. The RSV SNA titers increased in a dose-dependent manner among participants who received MK-1654. These data support the development of MK-1654 for use in Japanese infants.

PMID:35506164 | DOI:10.1111/cts.13290

Aliment Pharmacol Ther. 2022 May 3. doi: 10.1111/apt.16959. Online ahead of print.

ABSTRACT

BACKGROUND: Keverprazan is a novel potassium-competitive acid blocker (P-CAB) with a strong acid-suppressive capacity that may provide clinical benefit in acid-related diseases.

AIMS: This study aimed to explore the non-inferior efficacy and safety of keverprazan to lansoprazole in treating erosive oesophagitis (EO).

METHODS: This was a phase III, randomised, double-blind multicentre study. Patients were randomised to receive keverprazan 20 mg once daily or lansoprazole 30 mg once daily for 4-8 weeks. EO healing rates and adverse events (AEs) were compared between the keverprazan group and the lansoprazole group.

RESULTS: A total of 238 patients comprised the full analysis set (FAS) while 221 patients comprised the per-protocol set (PPS). For FAS analysis, the EO healing rates at week 8 were 95.8% (114/119) and 89.9% (107/119) for keverprazan and lansoprazole respectively. For PPS analysis, the EO healing rates at week 8 were 99.1% (110/111) and 92.7% (102/110) for keverprazan and lansoprazole respectively. Non-inferiority of keverprazan compared with lansoprazole according to EO healing rates at 8 weeks was demonstrated in both FAS (difference: 5.8% [95% CI: -0.6% to 12.3%]; p = 0.081) and PPS (difference: 6.1% [95% CI: 1.1%-11.2%]; p = 0.018) analysis. Drug-related AEs were reported in 34.5% (41/119) patients of the keverprazan group and 25.2% (30/119) patients of the lansoprazole group with no significant difference (p = 0.156). No severe AE happened in the keverprazan group.

CONCLUSIONS: This study demonstrated the non-inferior efficacy of keverprazan to lansoprazole in treating EO. The incidences of drug-related AEs were comparable between keverprazan and lansoprazole.

PMID:35505467 | DOI:10.1111/apt.16959

BMC Cancer. 2022 May 3;22(1):491. doi: 10.1186/s12885-022-09599-w.

ABSTRACT

BACKGROUND: High medication literacy is the basis of rational medication application and is essential for the management of severe adverse drug reactions. The objective of the present study was to assess the level of medication literacy and determine the association between medication literacy and skin adverse drug reactions in non-small-cell lung cancer (NSCLC) patients undergoing targeted epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy.

METHODS: This is a cross-sectional study conducted from May to September 2020. In total, 296 NSCLC patients undergoing targeted EGFR-TKI therapy were recruited from hospitals in Henan, China. Structured questionnaires were used to evaluate skin adverse drug reactions and medication literacy. Pearson correlation analysis and binary logistic regression analysis were carried out to identify the correlations between medication literacy and the severity of skin adverse drug reactions in the recruited patients.

RESULTS: The research sample consisted of 296 patients with a response rate of 92.5%. The mean score of skin adverse drug reactions and the mean score of medication literacy were 1.83 ± 0.91 and 6.54 ± 2.78, respectively. In total, 188 patients (63.5%) were considered to have moderate medication literacy. According to the binary logistic regression analysis, the following factors were associated with severe skin adverse drug reactions: age (B = - 3.929, P = 0.000), sex (B = -4.062, P = 0.000), educational level (B = 2.712, P = 0.002), comorbidity (B = 3.297, P = 0.001), eczema history (B = 2.996, P = 0.001), nutritional status (B = -4.891, P = 0.000), blood interleukin-6 level (B = -2.143, P = 0.013), blood high-sensitivity C-reactive protein level (B = -4.015, P = 0.000), combination of drugs (B = -3.183, P = 0.048) and medication literacy (B = - 1.503, P = 0.000). Subgroup analysis showed that in addition to medication literacy, some other factors including education level, comorbidity, nutritional status, blood interleukin-6 level and combined drug application were common factors that contributed to various adverse skin drug reactions in NSCLC patients under targeted EGFR-TKI therapy.

CONCLUSION: The low medication literacy of the investigated NSCLC patients undergoing targeted EGFR-TKI therapy was correlated with a high proportion of severe skin adverse drug reactions. In addition, factors other than medication literacy including education level, comorbidity, nutritional status, blood interleukin-6 level and the combinatorial application of drugs were also related to the severity of various adverse skin drug reactions. A comprehensive and targeted intervention may be beneficial to improve medication literacy and control severe skin adverse drug reactions in NSCLC patients.

PMID:35505288 | DOI:10.1186/s12885-022-09599-w

Sci Rep. 2022 May 3;12(1):7154. doi: 10.1038/s41598-022-11189-6.

ABSTRACT

Multi-receptor targeting has been proposed as a promising strategy for the development of opioid analgesics with fewer side effects. Cebranopadol and AT-121 are prototypical bifunctional ligands targeting the nociceptin/orphanin FQ peptide receptor (NOP) and µ-opioid receptor (MOP) that elicit potent analgesia in humans and nonhuman primates, respectively. Cebranopadol was reported to produce typical MOP-related side effects such as respiratory depression and reward, whereas AT-121 appeared to be devoid of these liabilities. However, the molecular basis underlying different side effect profiles in opioid analgesics remains unknown. Here, we examine agonist-induced receptor phosphorylation and G protein signaling profiles of a series of chemically diverse mixed MOP/NOP agonists, including cebranopadol and AT-121. We found that these compounds produce strikingly different MOP phosphorylation profiles. Cebranopadol, AT-034 and AT-324 stimulated extensive MOP phosphorylation, whereas AT-201 induced selective phosphorylation at S375 only. AT-121, on the other hand, did not promote any detectable MOP phosphorylation. Conversely, none of these compounds was able to elicit strong NOP phosphorylation and low NOP receptor phosphorylation correlated with partial agonism in a GIRK-channel assay. Our results suggest a close correlation between MOP receptor phosphorylation and side effect profile. Thus, bifunctional MOP/NOP opioid ligands combining low efficacy G protein signaling at both NOP and MOP with no detectable receptor phosphorylation appear to be devoid of side-effects such as respiratory depression, abuse liability or tolerance development, as with AT-121.

PMID:35504962 | DOI:10.1038/s41598-022-11189-6

Drug Des Devel Ther. 2022 Apr 26;16:1191-1198. doi: 10.2147/DDDT.S353898. eCollection 2022.

ABSTRACT

OBJECTIVE: To explore the efficacy and safety of gemcitabine (GEM) combined with cisplatin (DDP) in the treatment of recurrent/metastatic nasopharyngeal carcinoma (NPC).

METHODS: A total of 100 patients with recurrent/metastatic NPC treated in the First Affiliated Hospital, Hengyang Medical School, University of South China from January 2018 to March 2020 were retrospectively enrolled. Based on different chemotherapy schemes, they were assigned to an observation (Obs) group (DDP + GEM, n = 55) and a control (Con) group [DDP + FU (fluorouracil), n = 45]. The two groups were compared regarding the following items: therapeutic efficacy; serum levels of platelet-derived growth factor-BB (PDGF-BB), soluble epithelial cadherin (SE-CAD), and inflammation-related factors before and after treatment; toxic and side effects; 1-year survival rate; and quality of life (QOL) 6 months after treatment.

RESULTS: The Obs group outperformed the Con group in therapeutic efficacy (P < 0.05). There were no significant differences in the levels of PDGF-BB, SE-CAD, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α between the two groups before treatment (P > 0.05). After treatment, better improvements in PDGF-BB, SE-CAD and inflammatory factors were observed in the Obs group (P < 0.05). The toxic and side effects were significantly lower and the 1-year survival rate and patients' QOL after 6 months of treatment were significantly higher in the Obs group compared with the Con group (P < 0.05).

CONCLUSION: GEM combined with DDP can provide more clinical benefits for patients with recurrent/metastatic advanced NPC, with less side effects, high tolerance and significant efficacy, which can be further promoted in clinical use.

PMID:35502425 | PMC:PMC9056024 | DOI:10.2147/DDDT.S353898

BMC Med Inform Decis Mak. 2022 May 2;22(1):118. doi: 10.1186/s12911-022-01832-7.

ABSTRACT

BACKGROUND: Smartphone technology can support paperless reporting of adverse drug reactions (ADRs). The aims of this study were to systematically assess smartphone ADR-reporting applications, understand their qualitative and quantitative impact on ADR reporting, and garner key lessons from owners and developers.

METHODS: This study had three components: (1) An assessment of ADR-reporting apps, (2) an online survey on the impact of app implementation on ADR reporting and the experiences of app developers and owners, and (3) a search of VigiBase, the World Health Organization global database of individual case safety reports (ICSRs), to observe trends in the number of ADR reports targeting countries where the apps were implemented.

RESULTS: Twenty-two apps were included. Eight out of the 22 apps were for countries in the WHO African region. Features observed included E2B data elements (E stands for efficacy) and functions supporting reporting and user engagement. Seventeen app developers and owners answered to the survey and reported overall positive experiences with app features, and post-launch increases in the total number of ICSRs. User type and user environment were cited as factors influencing app use: Respondents said younger people and/or those with an inclination to use technology were more likely to use apps compared to older or more technology-averse people, while respondents in countries with limited internet connectivity reported persistent difficulties in app use.

CONCLUSIONS: Smartphone apps for reporting ADRs offer added value compared to conventional reporting tools. Reporting tools should be selected based on interface features and factors that may influence app usage.

PMID:35501745 | DOI:10.1186/s12911-022-01832-7

Curr Med Res Opin. 2022 May 3:1-31. doi: 10.1080/03007995.2022.2072089. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate analgesic efficacy and safety/tolerability of the nonbenzodiazepine antispasmodic pridinol (PRI) in patients with muscle-related pain.

METHODS: Systematic review and meta-analysis of randomized placebo-controlled trials (RCTs) according to PRISMA guidelines and Cochrane recommendations. Data sources included Google Scholar, Embase, PubMed, ClinicalTrials.gov, EU Clinical Trials Registry, Chinese Clinical Trial Registry, UMIN Clinical Trials Registry, and product manufacturer archives from inception to January 31st, 2022. Eligibility criteria for study selection was randomized, placebo-controlled trials with PRI in adults (≥18 years) with muscle-related pain. Data extraction, synthesis, and analysis carried out by two reviewers independently identified studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. Categorial global response rates (number of patients) based on clinical judgement of study physicians (as primary efficacy endpoint), and response on pain at rest, pain at movement, stiffness, tenderness, and movement restriction (as secondary efficacy endpoints), as well as the number of patients with drug-related adverse events were meta-analytically evaluated using the Review Manager Software 5.4.1.

RESULTS: In total, 38 records were identified, but only two placebo-controlled studies [with 342 patients with mild to moderate acute muscle pain (55.3% female, age 50.6 ± 16.6 years), of whom 173 received pridinol and 169 placebo, each as monotherapy] proved to be suitable for quantitative and qualitative analysis. Treatment with pridinol was (irrespective of its mode of administration as oral tablet or intramuscular injection) associated with a significantly higher global response rate compared to placebo (74.0 vs. 49.7%; OR 2.86, 95%-CI: 1.82-4.51; p < 0.00001; Cohen´s h: 0.506, NNT: 4.1; Chi2 for heterogeneity 1.41 [p = 0.24], I2=29%), and significantly higher response rates were also found for all secondary efficacy endpoints. The safety of pridinol was comparable to that of placebo: DRAEs were only seen in one of the two studies and reported for 13 vs. 10 patients (OR: 0.76 95%-CI: 0.32-18.1; p = 0.54, NNH: 62.6), and related discontinuations were reported for four vs. one patient (2.3 vs. 0.6%; p = 0.231).

CONCLUSION: The results from this meta-analysis as based on two placebo-controlled studies in adult patients with mild to moderate acute muscle pain demonstrate that a 3-week monotherapy with pridinol showed a comparable safety profile, but significantly better analgesic effects and improvements of related impairments such as stiffness, tenderness and movement restrictions compared with placebo - irrespective of its mode of administration.

PMID:35502575 | DOI:10.1080/03007995.2022.2072089

J Infect Public Health. 2022 May;15(5):589-593. doi: 10.1016/j.jiph.2022.04.007. Epub 2022 Apr 20.

ABSTRACT

BACKGROUND: Therapeutic drug monitoring (TDM) has proven effectiveness in maintaining efficacy and reducing toxicities associated with vancomycin. A trough level of (15-20 mg/L) for MRSA serious infections is recommended. Therapeutic failure is of concern due to suboptimal routine vancomycin utilization in clinical practice. This study aims to identify factors of vancomycin TDM practice potentially associated with vancomycin-induced nephrotoxicity and therapeutic failure measured by the need to restart vancomycin therapy within 28-days and all-cause mortality in a tertiary hospital in Oman.

METHODS: A single-center retrospective cohort was conducted in a tertiary care hospital that included all adult patients aged ≥ 18 years treated with IV vancomycin for> 72 h.

RESULTS: Vancomycin therapeutic level was not achieved in 16.8% of the patients, and 47.5% had high levels (>20 mg/L). Vancomycin-induced nephrotoxicity occurred in 31.7% of the patients, it was restarted within 28-days in 18.8% of the patient, and 25.2% of the patients died during the same hospitalization. Univariate analysis showed old age (p < 0.01), higher baseline creatinine reading (p = 0.03), high vancomycin level (p = 0.03), and vancomycin-induced nephrotoxicity (p < 0.01) were associated with increased all-cause mortality. Multivariate analysis identified overweight and vancomycin-induced nephrotoxicity were independent factors associated with increased all-cause mortality (OR:1.04; p = 0.043; 95% CI 1.00-1.08) and (OR:1.96; p = 0.049; 95% CI 1.00-21.61) respectively.

CONCLUSION: Failure to achieve the recommended therapeutic vancomycin level (15-20 mg/L) is common in clinical practice and associated with poor health outcomes; hence, appropriate TDM practice is an essential exercise to improve efficacy, prevent failure and reduce serious toxicities associated with vancomycin therapy.

PMID:35500543 | DOI:10.1016/j.jiph.2022.04.007

Ned Tijdschr Geneeskd. 2022 Mar 2;166:D6502.

ABSTRACT

At several out-of-hours services primary care, a single dose of ondansetron was compared with standard care (oral rehydration solution (ORS)) in young children with gastroenteritis and persistent vomiting. Although vomiting decreased more often in the ondansetron group compared to the control group in the first hours, ondansetron had no effect on ORS use and did not lead to fewer referrals to the hospital. Unfortunately, the outcome measure diarrhoea was missing as a possible adverse effect of ondansetron. Diarrhoea was reported around 2-3 times more often with ondansetron compared to placebo in four of five other studies in children with gastroenteritis and vomiting. It is therefore questionable whether the limited clinical benefit of ondansetron in children with vomiting due to gastroenteritis outweighs the possible (as yet insufficiently investigated) side effect diarrhoea.

PMID:35499602

Dermatol Online J. 2022 Jan 15;28(1). doi: 10.5070/D328157067.

ABSTRACT

Vitiligo is an acquired skin depigmentation disorder related to the destruction of melanocytes. There are a limited number of case reports and studies in current literature that show methotrexate (MTX) is effective in the treatment. A 44-year-old man presented to our clinic with a one-year history of psoriasis. On dermatological examination, there were erythematous, scaly papules and plaques on knees, elbows, gluteal area, and scalp compatible with psoriasis. In addition there was total depigmentation over the body. He had a 30-year history of vitiligo, beginning localized but progressed gradually and covered the entire body surface. Subcutaneous methotrexate 10mg weekly was started for psoriasis. On the 6th week of methotrexate treatment, he presented to our clinic with newly developed brown macules on his face. The result of the punch biopsy taken from a macule was reported as normal skin findings. Because his body was fully depigmented, his brown melanocytic macules on his face were considered as repigmentation associated with MTX treatment. His MTX treatment was stopped by patient request. On his 6-month follow-up, hypopigmentation was observed at prior repigmented macules. Methotrexate can be considered an alternative treatment for vitiligo patients when topical therapy and phototherapy are ineffective or not applicable.

PMID:35499421 | DOI:10.5070/D328157067

Dermatol Online J. 2022 Jan 15;28(1). doi: 10.5070/D328157064.

ABSTRACT

Fixed drug eruption (FDE) is a cutaneous drug reaction that tends to recur in the same area (fixed location) upon re-exposure to the offending agent. We present a 48-year-old woman with FDE being treated for metastatic breast cancer with atezolizumab. We believe this is the first reported case of FDE secondary to atezolizumab.

PMID:35499418 | DOI:10.5070/D328157064

Soc Psychiatry Psychiatr Epidemiol. 2022 May 3. doi: 10.1007/s00127-022-02280-4. Online ahead of print.

ABSTRACT

PURPOSE: People with mental illness are a vulnerable and stigmatised group with poor health outcomes including greater premature mortality. This study aimed to investigate trends and rates of change in unintentional drug-related deaths for people with mental illness, describe types of medicines involved, and identify populations at risk in a cohort from New South Wales, Australia.

METHODS: Features of unintentional drug-related deaths for people with mental illness between 2012 and 2016 were identified in a retrospective review of data from the National Coronial Information System.

RESULTS: A total of 495 unintentional drug-related deaths were identified (1.6 deaths/100,000 population), showing an upward trend (p < 0.01). The most common substance involved was diazepam in both genders (males 135/319, 42%, female 76/176, 43%) and more than one contributory drug was included in 80% of cases. Between 2012 and 2016, amphetamine-related deaths showed the highest increase (3.2-fold), followed by codeine (2.5-fold) and quetiapine (2.5-fold). Males (RR 1.8, 95% CI 1.5-2.2) and people aged 35-44 (RR 1.7, CI 1.3-2.2) were more likely to die from unintentional drug-related deaths compared with the reference (females and people aged 25-34).

CONCLUSION: This study found that the drugs commonly involved in deaths are also the drugs commonly used by and prescribed to people with mental illness. There were also significant differences between gender, age group, and marital status in the trend and rate of unintentional drug-related deaths for people with mental illness. A multifaceted approach encompassing both pharmaceutical prescribing and targeted public health messaging is required to inform intervention and prevention strategies.

PMID:35501478 | DOI:10.1007/s00127-022-02280-4

JAAD Int. 2022 Apr 18;7:144-145. doi: 10.1016/j.jdin.2022.03.010. eCollection 2022 Jun.

NO ABSTRACT

PMID:35497638 | PMC:PMC9043660 | DOI:10.1016/j.jdin.2022.03.010

Cureus. 2022 Mar 26;14(3):e23511. doi: 10.7759/cureus.23511. eCollection 2022 Mar.

ABSTRACT

Renal failure secondary to rhabdomyolysis due to statins is quite rare. We present a case of a 57-year-old patient who developed acute renal failure due to rhabdomyolysis secondary to atorvastatin. Interestingly, this patient had a similar presentation 27 years ago requiring dialysis only once resulting in complete resolution of symptoms. He presented to the hospital generally feeling unwell and then developed generalized body ache. He had an extremely elevated creatinine kinase level of 116,000 and it went up to 145,000. His urine dip was negative for nitrites and was positive for blood and protein. He was commenced on intravenous fluids. He also had a computerized tomographic scan of the kidneys, ureters, and bladder, which showed some fat stranding around both kidneys likely inflammatory in origin. His creatinine level continue to rise despite intravenous fluids and was acidotic on blood gases. He also tested positive for COVID-19 on day 7 of admission and eventually needed dialysis. His renal functions improved to baseline post dialysis and kidney functions returned to normal. His autoimmune screen was negative and his renal functions remained normal on a follow-up visit.

PMID:35494968 | PMC:PMC9037051 | DOI:10.7759/cureus.23511

J Thromb Haemost. 2022 May 1. doi: 10.1111/jth.15744. Online ahead of print.

ABSTRACT

BACKGROUND: Bleeding is a clinically significant issue with all current anticoagulants. Safer antithrombotic strategies are required.

OBJECTIVES: To investigate the safety, pharmacodynamics, and pharmacokinetics of BAY 1831865, a humanized, factor XI (FXI)-directed monoclonal antibody, after single intravenous (i.v.) or subcutaneous (s.c.) doses in healthy volunteers.

PATIENTS/METHODS: In a first-in-human, phase 1 study, 70 volunteers were randomly assigned (4:1) to receive single-dose BAY 1831865 (3.5, 7, 17, 35, 75, or 150 mg i.v. or 150 mg s.c.) or placebo. Adverse events, pharmacodynamics, and pharmacokinetics were evaluated.

RESULTS: In this study, no hemorrhage, or hypersensitivity or infusion-/injection-related reactions were reported. Drug-related adverse events occurred in 3 (5.4%) of 56 volunteers; all were mild and self-limited. Dose-dependent prolongation of activated partial thromboplastin time (aPTT) and inhibition of FXI clotting activity was observed with BAY 1831865 i.v. (geometric mean maximum ratio-to-baseline: aPTT, range, 1.09-3.11 vs 1.05 with placebo; FXI, range, 0.70-0.04 vs 0.91 with placebo). Onset of effect was rapid after i.v. administration, with duration of effect (up to 55 days) determined by dose. BAY 1831865 s.c. had similar pharmacodynamic effects but a slower onset of action. Terminal half-life increased continuously with increasing i.v. dose (range, 28-208 hours), leading to strong and continuous increases in systemic exposure to BAY 1831865. Absolute bioavailability of BAY 1831865 s.c. was 47.2% (95% confidence interval, 30.2-73.7).

CONCLUSIONS: BAY 1831865 i.v. or s.c. was well tolerated, with no evidence of bleeding in healthy volunteers. BAY 1831865 exhibited pronounced, sustained dose-dependent prolongation of aPPT and duration of FXI inhibition.

PMID:35490404 | DOI:10.1111/jth.15744

Anticancer Res. 2022 May;42(5):2737-2741. doi: 10.21873/anticanres.15752.

ABSTRACT

BACKGROUND/AIM: Bendamustine-associated skin damage occurs frequently in Japan and can have a profound impact on health-related quality of life. To our knowledge, there are no reports on the timing of skin damage caused by bendamustine. This study assessed trends in and the time to onset of skin damage caused by bendamustine using the Japanese Adverse Drug Reaction Reporting Database (JADER).

PATIENTS AND METHODS: Data related to skin damage with more than five reported cases from April 2004 to March 2021 were extracted from JADER, and the relative risk of adverse events was estimated using the reporting odds ratio and 95% confidence interval. The data were analyzed for time to onset of skin damage.

RESULTS: JADER included a total of 2,450 reports of adverse drug reactions from bendamustine. Of these, 170 skin ailments of 10 types were reported to be associated with bendamustine. Significant associations for skin damage were found for rash, herpes zoster, and infusion-related reactions. The reporting odds ratios (with 95% confidence interval) for rash, herpes zoster, and infusion-related reaction were 1.63 (1.19-2.21), 3.25 (2.20-4.78), and 7.25 (4.84-10.85), respectively. The median onset (interquartile range) of rash, herpes zoster, and infusion-related reactions caused by bendamustine were 13 (10-28), 60 (28-107), and 6 (1-28) days, respectively.

CONCLUSION: A comprehensive study using a pharmacovigilance approach enabled us to identify that a rash or infusion-related reaction may be expected within 2 weeks of treatment with bendamustine and that the onset of herpes zoster occurs at a median of 2 months after treatment with bendamustine.

PMID:35489764 | DOI:10.21873/anticanres.15752

Anticancer Res. 2022 May;42(5):2553-2565. doi: 10.21873/anticanres.15733.

ABSTRACT

BACKGROUND: Optimal radiation therapy (RT) fractionation in early prostate cancer in elderly patients is controversial. We compared acute toxicities of fractionation schedules: 78/2 Gy, 60/3 Gy and 36.25/7.25 Gy, in this single-centre study. We also evaluated the effect of the rectal immobilization system Rectafix on quality of life (QoL).

PATIENTS AND METHODS: Seventy-three patients with one or two intermediate prostate cancer risk factors according to National Comprehensive Cancer Network criteria were recruited. Twenty-one patients were treated with 78/2 Gy and 60/3 Gy, and 31 patients with 36.25/7.25 Gy. Their QoL data were assessed with regard to genitourinary, gastrointestinal and sexual wellbeing at the beginning and end of RT and at 3 months after treatment. Rectafix was used in the 78/2 Gy and 60/3 Gy groups.

RESULTS: There were no statistically significant QoL differences in between the treatment groups 3 months after RT. The 78/2 Gy group had significantly increased bowel movements between baseline and 3 months after RT (p=0.036). At 3 months after RT, this group also had significantly more erectile dysfunction than the 60/3 Gy group (p=0.025). At the end of RT, the 78/2 Gy group had more symptoms than the 36.25/7.25 Gy group. Rectafix did not reduce acute toxicities in the 78/2 Gy or 60/3 Gy groups.

CONCLUSION: Treatment with the 78/2 Gy schedule is no longer to be recommended due to its increased acute toxicity compared to treatments of 60/3 Gy and 36.25/7.25 Gy. The shortest schedule of 36.25 Gy in five fractions seems to be a convenient treatment option with tolerable acute toxicity.

PMID:35489724 | DOI:10.21873/anticanres.15733

Iran J Kidney Dis. 2022 Mar;16(2):108-114.

ABSTRACT

INTRODUCTION: Geranium has various antioxidant, anti-inflammatory, and anti-microbial effects. Prescribing glutathione probably enhances the protective mechanisms of nephrons against oxidative stresses. This study aimed to evaluate the protective effect of geranium on acetaminophen-induced nephrotoxic rats.

METHODS: In the present study, 70 mice were divided into seven groups. In five groups (T1, T2, T3, T4, and T5), different doses of geranium were given by gavage to the mice for seven days, then on the 8th day, a high dose of acetaminophen was administered intraperitoneally. Group T5 only received geranium extract. The control group received neither acetaminophen nor the extract while the last group received only a toxic dose of acetaminophen. Twenty-four hours after the last drug administration, blood samples were taken to check the levels of uric acid, blood nitrogen, and creatinine. The data were analyzed in SPSS version 25. To investigate the between-group factors' effects, one-way ANOVA with Tukey's post hoc test was performed at the alpha level of < 0.05.

RESULTS: The differences between the levels of blood creatinine, urea, and uric acid were significant (P < .001) among the groups. The mean blood urea for groups T3 and T4 were similar, and they had a significant difference in comparison with the control group (P < .05). The mean creatinine levels were similar between T4, T5, and the control groups and were significantly different from the other groups (P < .05). Blood uric acid for groups T1 and T2 were similar to Group B and higher than the other groups (P < .05).

CONCLUSION: The results showed that by strengthening cell protection mechanisms against oxidative stress, geranium extract reduces the toxic effects of acetaminophen on mice's kidney function and thus ameliorates the damage. As a result, the geranium extract has no adverse effects on kidney function. DOI: 10.52547/ijkd.6679.

PMID:35489079