Nat Commun. 2022 Dec 1;13(1):7394. doi: 10.1038/s41467-022-35269-3.

ABSTRACT

Transfusion of healthy red blood cells (RBCs) is a lifesaving process. However, upon storing RBCs, a wide range of damage-associate molecular patterns (DAMPs), such as cell-free DNA, nucleosomes, free-hemoglobin, and poly-unsaturated-fatty-acids are generated. DAMPs can further damage RBCs; thus, the quality of stored RBCs declines during the storage and limits their shelf-life. Since these DAMPs consist of either positive or negative charged species, we developed taurine and acridine containing electrospun-nanofibrous-sheets (Tau-AcrNFS), featuring anionic, cationic charges and an DNA intercalating group on their surfaces. We show that Tau-AcrNFS are efficient in scavenging DAMPs from stored human and mice RBCs ex vivo. We find that intermittent scavenging of DAMPs by Tau-AcrNFS during the storage reduces the loss of RBC membrane integrity and reduces discocytes-to-spheroechinocytes transformation in stored-old-RBCs. We perform RBC-transfusion studies in mice to reveal that intermittent removal of DAMPs enhances the quality of stored-old-RBCs equivalent to freshly collected RBCs, and increases their shelf-life by ~22%. Such prophylactic technology may lead to the development of novel blood bags or medical device, and may therefore impact healthcare by reducing transfusion-related adverse effects.

PMID:36450757 | PMC:PMC9712616 | DOI:10.1038/s41467-022-35269-3

Biol Pharm Bull. 2022;45(12):1832-1838. doi: 10.1248/bpb.b22-00620.

ABSTRACT

SMTP-7, a fungal metabolite, is reported to have a high degree of availability for the ischemia-reperfusion (IR)-induced acute kidney injury (AKI) model. Cisplatin, a widely used anticancer drug, has serious side effects, such as AKI. Hence, we aimed to examine the effect of SMTP-7 on cisplatin-induced AKI in this study. Significant increases in blood urea nitrogen (BUN) and serum creatinine (Scr) were observed at 72 h after the intravenous infusion of cisplatin (20 mg/kg). Histologically, necrosis and dilatation (hyaline casts) as well as regeneration were observed in proximal tubules. SMTP-7 inhibited the elevation on BUN and Scr caused by cisplatin dose dependently. The efficacy of SMTP-7 was notable when the drug was administered on the day after cisplatin treatment, whereas the repeated administration of the drug did not result in an enhanced efficacy. Moreover, 10 mg/kg of SMTP-7 considerably ameliorated tubular necrosis and dilatation. The cisplatin treatment also caused an up-regulation of tumor necrosis factor-α (TNF-α) mRNA expression prior to the elevation of the levels of BUN and Scr. Administration of SMTP-7 (10 mg/kg) at 24 h after the cisplatin infusion alleviated the up-regulation of TNF-α mRNA expression. These findings suggest that SMTP-7 exhibits a renoprotective effect against cisplatin infusion based on the inhibition of the expression of pro-inflammatory cytokines such as TNF-α and may be expected a new effective drug for the treatment of cisplatin-induced AKI.

PMID:36450536 | DOI:10.1248/bpb.b22-00620

Biol Pharm Bull. 2022;45(12):1805-1811. doi: 10.1248/bpb.b22-00496.

ABSTRACT

Bevacizumab is an inhibitor of vascular endothelial growth factor (VEGF) that prevents tumor growth. While bevacizumab is therapeutically effective, it induces several adverse events. Among these, central nervous system (CNS) ischemia can lead to death or permanent disability. In this study, we reviewed the Japanese Adverse Drug Event Report database to analyze the occurrence of CNS ischemia after bevacizumab administration. Significant associations between the occurrence of CNS ischemia and bevacizumab use were detected (adjusted reporting odds ratios (ROR): 2.68, 95% confidence interval (CI): 2.00-3.59, p < 0.001). Furthermore, an association between diagnosis of glioma and bevacizumab use was also detected (p < 0.001). These events occurred early after the start of treatment and then gradually decreased; however, more than half of CNS ischemia events were reported beyond 30 d after the first administration. In addition, a logistic regression suggested that CNS ischemia caused by bevacizumab was associated with glioma, underlying hypertension and aging. A poor prognosis was reported for several cases occurring in elderly patients (over 60 years of age). Although bevacizumab is a useful pharmacological treatment for cancer, caution should be taken to avoid severe adverse events. Accordingly, the patient's general and medical condition should be carefully examined before initiating treatment, and blood pressure should be continuously assessed throughout treatment with bevacizumab to prevent CNS ischemia.

PMID:36450533 | DOI:10.1248/bpb.b22-00496

Biol Pharm Bull. 2022;45(12):1754-1763. doi: 10.1248/bpb.b22-00398.

ABSTRACT

Pentazocine (PTZ) is a widely used drug for postoperative pain. It should be administered at appropriate dosing intervals not only because of its morphine-like side effects but also because frequent inappropriate dosing can lead to dependence. Although perioperative patients reportedly have nonnegligible effects on placebo drugs and postoperative wound healing, no pharmacokinetic (PK)/pharmacodynamic (PD) model has been established and simulated using real-world data for the perioperative period. This study aimed to perform PTZ modeling and simulation and to establish an indicator of the timing of drug efficacy evaluation in clinical practice. Participants were in-hospital orthopedic surgery patients who received 15 mg of PTZ within 48 h postoperatively. Pain severity was assessed using the numerical rating scale (NRS). A two-compartment model was selected for the population PK model and an indirect response model for the PK/PD model. Using these models, a virtual population of 1000 patients with Painbase NRS of 5 and 6 and body weights of 40, 80, and 120 kg were treated with single and multiple PTZ administrations (4, 8, and 24 h apart) of 15 mg. Simulation results indicate that its analgesic efficacy should be evaluated within 1 h after administration of 15 mg of PTZ. Additional doses should be considered every 8-12 h in postoperative patients with Painbase NRS of 5 weighing 40-80 kg. Simulation using the PK/PD model developed in this study may provide useful information for determining the analgesic effects and timing of the dosing interval after PTZ administration in perioperative patients.

PMID:36450528 | DOI:10.1248/bpb.b22-00398

Yakugaku Zasshi. 2022;142(12):1313-1319. doi: 10.1248/yakushi.22-00122.

ABSTRACT

Photoimmunotherapy (PIT) is a new cancer therapy that uses near-infrared (NIR) light and a conjugate of an antibody and a photosensitizer (IR700). Since both NIR light and the conjugate are not toxic for human, PIT has attracted attention as a promising cancer therapy with less side effects. However, there is no photosensitizer for PIT other than IR700. To improve the therapeutic effect, more light-sensitive dye is needed. To this end, we have studied the cytotoxic mechanism of PIT, showing that the hydrophilic axial ligand cleavage of IR700 by NIR light irradiation is important for the cytotoxicity. Herein, I focused on the triplet state (T1) of IR700 because the light-induced axial ligand cleavage reaction is thought to occur via the T1. First, the quantum yield of intersystem crossing, which is the transition efficiency from the excited singlet state (S1) to T1, was determined by analysis of the T1 kinetics using fluorescence correlation spectroscopy (FCS). Also, I examined whether the cytotoxicity of IR700 can be changed in the presence of a triplet quencher. The findings obtained here will be important information for the design of a new photosensitizer for PIT in the future.

PMID:36450507 | DOI:10.1248/yakushi.22-00122

Einstein (Sao Paulo). 2022 Nov 25;20:eAO0067. doi: 10.31744/einstein_journal/2022AO0067. eCollection 2022.

ABSTRACT

OBJECTIVE: So far, at least 18 different severe acute respiratory syndrome coronavirus-2 vaccines have been approved. Until October 2022, 12.8 billion doses had been administered all over the world. Vaccination of high-risk groups and healthcare professionals was initially prioritized. This cross-sectional survey aimed to investigate the occurrence of vaccine side effects, as well as the incidence of COVID-19 among vaccinated healthcare professionals.

METHODS: A survey was structured and shared with healthcare professionals using a digital platform to collect data between May and June 2021.

RESULTS: This study included 6,115 participants. The most prevalent age group was 30-39 years (31.3%), 67.3% were female and 73.2% accounted for physicians, and nearly half worked in frontline care for COVID-19. Approximately, two-thirds of them were vaccinated with CoronaVac, and about 60% reported at least one side effect following the vaccination. Nevertheless, minor reactions were more frequent, such as pain at site of injection, fatigue, and headache. Our data could be used to inform people on the likelihood of side effects of COVID-19 vaccines, particularly CoronaVac, since this is the largest study about vaccine reactions using this vaccine, to our best knowledge.

CONCLUSION: The incidence of side effects in Brazilian healthcare professionals was 60%, and the most common side effects included local swelling/pain, fatigue/tiredness, fever, headache, and limb pain.

PMID:36449755 | DOI:10.31744/einstein_journal/2022AO0067

PLoS One. 2022 Nov 30;17(11):e0278127. doi: 10.1371/journal.pone.0278127. eCollection 2022.

ABSTRACT

International evidence shows that people approaching end of life (EOL) have high prevalence of polypharmacy, including overprescribing. Overprescribing may have adverse side effects for mental and physical health and represents wasteful spending. Little is known about prescribing near EOL in Ireland. We aimed to describe the prevalence of two undesirable outcomes, and to identify factors associated with these outcomes: potentially questionable prescribing, and potentially inadequate prescribing, in the last year of life (LYOL). We used The Irish Longitudinal Study on Ageing, a biennial nationally representative dataset on people aged 50+ in Ireland. We analysed a sub-sample of participants with high mortality risk and categorised their self-reported medication use as potentially questionable or potentially inadequate based on previous research. We identified mortality through the national death registry (died in <365 days versus not). We used descriptive statistics to quantify prevalence of our outcomes, and we used multivariable logistic regression to identify factors associated with these outcomes. Of 525 observations, 401 (76%) had potentially inadequate and 294 (56%) potentially questionable medications. Of the 401 participants with potentially inadequate medications, 42 were in their LYOL. OF the 294 participants with potentially questionable medications, 26 were in their LYOL. One factor was significantly associated with potentially inadequate medications in LYOL: male (odds ratio (OR) 4.40, p = .004) Three factors were associated with potentially questionable medications in LYOL: male (OR 3.37, p = .002); three or more activities of daily living (ADLs) (OR 3.97, p = .003); and outpatient hospital visits (OR 1.03, p = .02). Thousands of older people die annually in Ireland with potentially inappropriate or questionable prescribing patterns. Gender differences for these outcomes are very large. Further work is needed to identify and reduce overprescribing near EOL in Ireland, particularly among men.

PMID:36449504 | DOI:10.1371/journal.pone.0278127

J Clin Psychiatry. 2022 Nov 30;83(6):22f14722. doi: 10.4088/JCP.22f14722.

ABSTRACT

Three drug dosing strategies can be employed to address dose-dependent drug adverse effects. The usual strategy is to continue the drug but at a lower dose; it would then take 5 half-lives of the drug for the new steady state to be attained and for a dose-dependent adverse effect to correspondingly attenuate. Such slow offset of the adverse effect could be disadvantageous for drugs such as fluoxetine, penfluridol, and cariprazine that have long half-lives. A second strategy is to stop the drug and to resume it at a lower dose when the adverse effect attenuates as the drug blood level falls. This strategy introduces subjectivity in timing the reintroduction of the drug, requires closer patient monitoring, and risks nonadherence and relapse. The third strategy is to stop the drug for a prespecified number of days and to then reintroduce it at a lower dose. From a knowledge of pharmacokinetics, it can be shown that stopping a drug for just 1 half-life and then resuming it at half the dose results in the immediate achievement of steady state; that is, there is no need to wait for 4 additional half-lives as with the usual strategy of dose reduction without dosing interruption. A limitation of this pharmacokinetically driven dosing strategy, however, is that it would work well in the average patient but not in those with outlying pharmacokinetic parameters.

PMID:36449476 | DOI:10.4088/JCP.22f14722

JAMA Netw Open. 2022 Nov 1;5(11):e2244412. doi: 10.1001/jamanetworkopen.2022.44412.

ABSTRACT

IMPORTANCE: Attrition in cancer clinical trials (CCTs) can lead to systematic bias, underpowered analyses, and a loss of scientific knowledge to improve treatments. Little attention has focused on retention, especially the role of perceived benefits and burdens, after participants have experienced the trial.

OBJECTIVES: To examine the association between patients' perceived benefits and burdens of research participation and CCT retention.

DESIGN, SETTING, AND PARTICIPANTS: This survey study was conducted at a National Cancer Institute-designated comprehensive cancer center in the Northeast region of the US. The sample included adult patients with a cancer diagnosis participating in cancer therapeutic trials. Data were collected from September 2015 to June 2019. Analysis of study data was ongoing since November 2019 through October 2022.

EXPOSURES: Self-reported validated survey instrument with a list of 22 benefits and 23 burdens of research participation that can be rated by patients with a 5-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree).

MAIN OUTCOMES AND MEASURES: A primary outcome was actual withdrawal from the CCT, and a composite outcome was composite withdrawal that included both actual withdrawal and thoughts of withdrawing. Bivariate and multivariable logistic regressions were used.

RESULTS: Among the 334 participants in the sample, the mean (SD) age was 61.9 (11.5) years and 174 women (52.1%) were included. Top-cited benefits included both aspirational and action-oriented goals, including helping others (94.2%), contributing to society (90.3%), being treated respectfully (86.2%), and hoping for a cure (86.0%). Worry over receiving a placebo (61.3%), rearranging one's life (41.9%), and experiencing bothersome adverse effects (41.6%) were notable burdens. An increased burden score was associated with a higher probability of actual withdrawal (adjusted odds ratio [OR], 1.86; 95% CI, 1.1-3.17; P = .02) or composite withdrawal (adjusted OR, 3.44; 95% CI, 2.09-5.67; P < .001). An increased benefit score was associated with lower composite withdrawal (adjusted OR, 0.40; 95% CI, 0.24-0.66; P < .001). For participants who reported the benefits as being equal to or greater than the burdens, 13.4% withdrew. For those who perceived the benefits as being less than the burdens, 33.3% withdrew (adjusted OR, 3.38; 95% CI, 1.13-10.14; P = .03). The risk of withdrawal was even higher for the composite outcome (adjusted OR, 7.70; 95% CI, 2.76-21.48; P < .001).

CONCLUSIONS AND RELEVANCE: This survey study found that patients perceived important benefits from CCT participation, and this perception was associated with trial retention, even among those who also perceived substantial burdens. A broader dialogue among stakeholders can inform an ethical and patient-centric focus on benefits throughout the course of a CCT to increase retention.

PMID:36449287 | DOI:10.1001/jamanetworkopen.2022.44412

Cancer Treat Res. 2022;184:141-149. doi: 10.1007/978-3-031-04402-1_10.

ABSTRACT

Adverse drug/device reactions (ADRs) serious enough to lead to box warnings on drug labels or drug withdrawals occur in about one fifth of all new molecular entities.

PMID:36449194 | DOI:10.1007/978-3-031-04402-1_10

Cancer Treat Res. 2022;184:129-140. doi: 10.1007/978-3-031-04402-1_9.

ABSTRACT

Severe adverse drug reactions (sADRs) are important causes of morbidity and mortality. The Southern Network on Adverse Drug Reactions (SONAR), a National Cancer Institute-funded pharmacovigilance program, has outlined a novel 9-stop methodology, termed ANTICIPATE, that has evaluated this methodology, among persons with chronic kidney disease (CKD).

PMID:36449193 | DOI:10.1007/978-3-031-04402-1_9

Cancer Treat Res. 2022;184:87-102. doi: 10.1007/978-3-031-04402-1_6.

ABSTRACT

More than half of all serious adverse drug reactions are identified seven years after FDA approval. One recent and unusual example involves a syndrome initially termed nephrogenic dermatopathic fibrosis, and then called nephrogenic systemic fibrosis (NSF).

PMID:36449190 | DOI:10.1007/978-3-031-04402-1_6

Cancer Treat Res. 2022;184:75-85. doi: 10.1007/978-3-031-04402-1_5.

ABSTRACT

About 1-10% of all serious adverse drug reactions (sADRs) are reported to the Food and Drug Administration (FDA) ( Moore T, Bennett C. Underreporting of Hemorrhagic and Thrombotic Complications of Pharmaceuticals to the U.S. Food and Drug Administration: Empirical Findings for Warfarin, Clopidogrel, Ticlopidine, and Thalidomide from the Southern Network on Adverse Reactions (SONAR). Semin Thromb Hemost. 2012;38(08):905-907. https://doi.org/10.1055/s-0032-1328890 ). Prevailing opinion suggests that low reporting rates reflect time constraints.

PMID:36449189 | DOI:10.1007/978-3-031-04402-1_5

J Int Med Res. 2022 Nov;50(11):3000605221138480. doi: 10.1177/03000605221138480.

ABSTRACT

The combination of sacubitril and valsartan has recently become eligible for reimbursement in Japan for the treatment of hypertension. However, the real-world clinical efficacy of sacubitril/valsartan in patients with hypertension who are taking multiple anti-hypertensive medications remains to be characterized. We treated a man in his late 40s who had undergone a percutaneous coronary intervention and had hypertension that was refractory to multiple anti-hypertensive medications. We initiated sacubitril/valsartan 200 mg/day as an add-on therapy, and 3 months later, his blood pressure had decreased from 154/78 mmHg to 134/70 mmHg, in the absence of any drug-related adverse events. Furthermore, his left ventricular mass index had improved from 135 g/m2 to 112 g/m2. Thus, sacubitril/valsartan might ameliorate hypertrophy in patients with hypertension.

PMID:36448517 | DOI:10.1177/03000605221138480

BMC Health Serv Res. 2022 Nov 28;22(1):1438. doi: 10.1186/s12913-022-08862-x.

NO ABSTRACT

PMID:36443812 | PMC:PMC9706996 | DOI:10.1186/s12913-022-08862-x

J Int Med Res. 2022 Nov;50(11):3000605221138455. doi: 10.1177/03000605221138455.

ABSTRACT

OBJECTIVE: Some drugs have adverse effects on glucose metabolism, but it is unknown whether prescription drugs used prior to conception influence the future risk of gestational diabetes mellitus (GDM). Our study evaluated whether the purchase of prescription drugs 6 months prior to conception was associated with the occurrence of GDM.

METHODS: This cohort study enrolled women with a Finnish background who delivered between 2009 and 2015 in the city of Vantaa, Finland (N = 10,455). Data on maternal characteristics and prescription drug purchases were obtained from national health registers. The use of a unique personal identification number enabled us to combine the register data on an individual level.

RESULTS: Six months prior to conception, women who had pregnancies complicated by GDM purchased more prescription drugs than women without GDM (1.38 ± 2.04 vs. 1.11 ± 1.80). The GDM risk was higher in women with higher numbers of prescription purchases and those with more than three deliveries.

CONCLUSIONS: Multiparous women who purchase several prescription drugs should be given personalized counseling to prevent GDM.

PMID:36446764 | DOI:10.1177/03000605221138455

Neurol Neuroimmunol Neuroinflamm. 2022 Nov 29;10(1):e200058. doi: 10.1212/NXI.0000000000200058. Print 2023 Jan.

ABSTRACT

BACKGROUND AND OBJECTIVES: To clinically characterize post-immune checkpoint inhibitor (ICI) Hu antibody (Ab) neurologic disorders, we analyzed Hu-Ab-positive patients with neurologic immune-related adverse events (n-irAEs) and compared them with patients with other n-irAEs, ICI-naive patients with Hu-Ab paraneoplastic neurologic syndromes (PNSs) identified in the same study center, and those with Hu-Ab n-irAEs reported elsewhere.

METHODS: Patients whose samples were sent to the French reference center for a suspicion of n-irAE (2015-2021) were identified; those with a final diagnosis of n-irAE and Hu-Ab were included. Control groups included patients with a final diagnosis of n-irAE occurring during the same period as the patients included (2018-2021) but without Hu-Ab, and ICI-naive patients with Hu-Ab PNS diagnosed during the same period; a systematic review was performed to identify previous reports.

RESULTS: Eleven patients with Hu-Ab and n-irAEs were included (median age, 66 years, range 44-76 years; 73% men). Ten patients had small cell lung cancer, and 1 had lung adenocarcinoma. The median follow-up from onset was 3 months (range 0.5-18 months). Compared with those with other n-irAEs (n = 63), Hu-Ab-positive patients had more frequently co-occurring involvement of both central and peripheral nervous systems (36% vs 8%, p = 0.02) and limbic (54% vs 14%, p < 0.01), brainstem (27% vs 5%, p = 0.02), and dorsal root ganglia (45% vs 5%, p < 0.01) involvement. The proportion of patients with severe disability (modified Rankin Scale score >3) at diagnosis was higher among Hu-Ab n-irAEs (91% vs 52%, p = 0.02). Patients with Hu-Ab had also poorer outcome (100% vs 28%, p < 0.01) and higher mortality (91% vs 46%, p < 0.01). There was no significant difference in terms of clinical features between Hu-Ab n-irAEs and ICI-naive Hu-Ab PNS (n = 92), but there was a poorer outcome (56/78, 71%, p < 0.01) and higher mortality (26%, p < 0.01) among the former. No significant difference was found between the patients reported herein and those in the literature.

DISCUSSION: The presence of Hu-Ab identifies a subgroup of n-irAEs that consistently reproduce the phenotypes of Hu-Ab-related PNS, supporting the hypothesis of ICI triggering or unmasking PNS. As these patients show high disability and mortality, further studies are required to investigate the underlying immunopathogenic mechanisms and to improve the outcome of Hu-Ab n-irAEs.

PMID:36446613 | PMC:PMC9709718 | DOI:10.1212/NXI.0000000000200058

BMJ Open. 2022 Nov 29;12(11):e065520. doi: 10.1136/bmjopen-2022-065520.

ABSTRACT

INTRODUCTION: Neurodevelopmental disorders are a group of disorders thought to be associated with the functioning of the brain and the nervous system. Children with neurodevelopmental disorders often have sleep-related comorbidities that may negatively affect quality of life for both the children and their families. Melatonin is one of the most used interventions in children with neurodevelopmental disorders and sleep disorders. Previous reviews have investigated the effects of melatonin for sleep disorders in children with neurodevelopmental disorders, but these had important limitations, such as inadequate analysis of adverse effects, small sample sizes and short follow-up.

METHODS AND ANALYSIS: This is a protocol for a systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials. The protocol is reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. We will search for published and unpublished trials in the Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, PsycINFO, ClinicalTrials.gov and the International Clinical Trials Registry Platform. We will search the databases from their inception without language restrictions. We will also request clinical study reports from regulatory authorities and pharmaceutical companies. Review authors working in pairs will screen reports, extract data and conduct risk of bias assessments using the Cochrane Risk of Bias tool. We will include randomised clinical trials comparing melatonin versus placebo or no intervention for sleep disorders in children with neurodevelopmental disorders. Primary outcomes will be total sleep time and adverse effects. Secondary outcomes will be quality of life of the child and caregivers and sleep onset latency. Data will be analysed using random-effects and fixed-effect meta-analyses. Certainty of evidence will be assessed with Grading of Recommendations, Assessment, Development and Evaluation approach.

ETHICS AND DISSEMINATION: Ethical approval was not required for this protocol. The systematic review will be published in a peer-reviewed journal.

PROSPERO REGISTRATION NUMBER: CRD42022337530.

PMID:36446459 | PMC:PMC9710329 | DOI:10.1136/bmjopen-2022-065520

Cutis. 2022 Sep;110(3):E19-E20. doi: 10.12788/cutis.0632.

NO ABSTRACT

PMID:36446123 | DOI:10.12788/cutis.0632

Cutis. 2022 Oct;110(4):201-206. doi: 10.12788/cutis.0627.

ABSTRACT

Glucocorticoids (GCs) are among the most widely prescribed medications in dermatologic practice. Although considered generally safe and efficacious, prolonged use and high dosing regimens may precipitate GC-induced osteoporosis, which contributes to an increased risk for fragility fractures. Dermatologists using and prescribing GCs must be aware of the risk for GC-induced osteoporosis. This review details the risks for osteoporosis and osteoporotic (OP) fractures in the setting of topical, intralesional, intramuscular, and systemic GC treatment, as well as nutritional supplementation recommendations that may reduce the risk of these adverse effects.

PMID:36446101 | DOI:10.12788/cutis.0627