Sr Care Pharm. 2022 Jul 1;37(7):293-303. doi: 10.4140/TCP.n.2022.293.

ABSTRACT

Objective Evaluate the impact of a telepharmacy service at a geriatrics assessment clinic. Design Retrospective, single-center, nonblinded cohort study. Setting Geriatrics assessment clinic. Patients The intervention/pharmacist and the control/no-pharmacist (provider) group included patients new to the clinic 50 years of age or older from over the span of 4 months. Patients who the pharmacist was unable to reach and those who missed appointments with the provider were excluded. Interventions The pharmacist phoned new patients approximately one week prior and one week after their first appointments with a provider. Main Outcome Measure Primary outcome: number of drug-related problems (DRPs) detected by the pharmacist compared with the provider. Secondary outcomes: number of medication history discrepancies, accepted medication-related recommendations, potentially inappropriate medications (PIMs) deprescribed, and adverse drug reactions (ADRs) detected. Results In the intervention/pharmacist (n = 204) vs control/no pharmacist (n = 200) groups, the number of DRPs was significantly greater (338 vs 218; P = 0.031) and driven by unnecessary drug therapies, doses too high, ADRs, and drug-drug interactions (230 vs 147, P = 0.045; 37 vs 7, P = 0.010; 36 vs 17, P = 0.023; 32 vs 1, P = 0.003, respectively). The difference in number of recommendations made by the pharmacist vs medication changes made by the provider was significant: 457 vs 319, P < 0.001, respectively. Conclusions The addition of a clinical pharmacist conducting telepharmacy at a geriatrics assessment clinic had a positive impact on patient care as it relates to DRPs, deprescribing PIMs, and optimizing medication adherence.

PMID:35752920 | DOI:10.4140/TCP.n.2022.293

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022 May 28;47(5):583-587. doi: 10.11817/j.issn.1672-7347.2022.210393.

ABSTRACT

We reported a case of oxalate crystal-related acute kidney injury caused by orlistat. The patient was admitted for nephrotic syndrome and acute kidney injury. The pathomorphological assessment of renal biopsy showed intratubular oxalate crystals. The patient reported that she had taken orlistat regularly to loss weight for more than a year. This patient had a habit of drinking vegetable soup and strong herbal tea daily. Orlistat, an intestinal lipase inhibitor, may cause secondary hyperoxaluria, that is, intestinal hyperoxaluria. Dietary habits could be a common precipitating factor for orlistat-relevant hyperoxaluria. It was comprehensively considered to be oxalate crystal-related acute renal injury, and the patient's renal function recovered gradually after drug withdrawal. Clinicians should pay attention to screening drug-related acute kidney injury including orlistat when observing patients with unexplained acute kidney injury, and renal biopsy should be performed if necessary. It is also important to warn people who take the orlistat for weight loss about the side effects of this drug so as to adjust the eating habits.

PMID:35753728 | DOI:10.11817/j.issn.1672-7347.2022.210393

Pharmazie. 2022 Jun 1;77(6):207-215. doi: 10.1691/ph.2022.12025.

ABSTRACT

Paediatric patients are more vulnerable to be harmed by medication errors compared to adults due to pharmacokinetic and pharmacodynamic changes in their development, individual dosing calculations, and manipulation of ready to-use products intended for adult patients. According to the Institute of Safe Medication Practices, there are some "drugs that bear a heightened risk of causing significant patient harm when they are used in error"; these drugs are called high-alert medications (HAM). The two-step survey among paediatric clinical expert pharmacists presented here aimed to compile a nation-wide HAM list. To provide detailed guidance, this survey followed a drugbased approach, resulting in specific potential drug related problems (DRPs) and associated recommendations for prevention. In contrast to this approach, in the first round of the survey two drug classes were included that both were rated as HAM (i.e.chemotherapy and parenteral nutrition). Twenty single drugs were identified as HAM, 65% of which were cardiovascular or neurological drugs. The paediatric expert pharmacists mentioned in total 216 potential DRPs; in particular, they identified potential administration-related problems (28% of all DRPs), dosing-related problems (26%), and drug-choice-related problems (18%, e.g.drug confusion and drug monitoring). Moreover, they suggested 275 potential interventions to address these DRPs. Two thirds of all interventions dealt with the preparation by the hospital pharmacy, standardisation of processes (e.g.labelling), and education or training. In conclusion, this survey provided a German paediatric high-alert medication list from a paediatric pharmacist point of view. Moreover, the experts mentioned for the first time specific potential DRPs and associated interventions to guide a local multidisciplinary approach for preventing medication-related harm in children.

PMID:35751160 | DOI:10.1691/ph.2022.12025

Mol Genet Genomic Med. 2022 Jun 24:e1987. doi: 10.1002/mgg3.1987. Online ahead of print.

ABSTRACT

BACKGROUND: In Peru, 32,970 people were diagnosed with tuberculosis (TB) in 2019. Although TB treatment is effective, 3.4%-13% is associated with significant adverse drug reactions (ADR), considering drug-induced liver injury (DILI) as the most prevalent. Among the first-line anti-TB drugs, isoniazid (INH) is primarily responsible for the occurrence of DILI. INH is metabolized in the liver by the enzymes N-acetyltransferase-2 (NAT2) and Cytochrome P450 2E1 (CYP2E1). Based on the previous studies, we hypothesized that the interactions between slow CYP2E1 genotype and NAT2 slow acetylators will induce DILI in TB patients.

METHODS: In this cross-sectional study, all 377 participants completed their anti-TB treatment, and we genotyped SNPs: rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931 for NAT2 and rs3813867 and rs2031920 for CYP2E1.

RESULTS: We found that rapid, intermediate, and slow NAT2 acetylator were 15%, 38%, and 47%, respectively, in the general population. Intermediate NAT2 acetylator is the least prevalent among patients with adverse reactions (p = 0.024). We did not confirm our hypothesis, however, we found that the combination of intermediate NAT2 acetylators and CYP2E1 c1/c1 genotype significantly protected (OR = 0.16; p = 0.049) against the development of DILI in our population.

CONCLUSION: We propose that the presence of NAT2 intermediate and CYP2E1 c1/c1 genotype could help in therapeutic drug monitoring, and optimize its therapeutic benefits while minimizing its risk for side effects or toxicity.

PMID:35751408 | DOI:10.1002/mgg3.1987

PLoS One. 2022 Jun 24;17(6):e0265140. doi: 10.1371/journal.pone.0265140. eCollection 2022.

ABSTRACT

INTRODUCTION: The best way to eradicate corona virus disease (COVID-19) viral infection is mass vaccination. Many studies demonstrate vaccination is associated with some local and systemic side effects. This study aimed to provide evidence on AstraZeneca COVID-19 vaccine side effects.

METHODOLOGY: Institutional based cross-sectional survey was conducted among 254 health workers at Nigist Eleni Mohammed memorial comprehensive specialized hospital (from July 01/ 2021 to July 30/2021). Data were collected consecutively through self-administered online survey created on Google Forms of platform which had been randomly delivered via (Facebook or telegram pages). Demographic data of participants, side effect after first and second dose of vaccine were covered.

RESULT: The prevalence of at least one side effect after first dose was 91.3% and after second dose was 67%. Injection site pain (63.8% vs. 50.4%), headache (48.8% vs. 33.5%), fever (38.8% vs. 20.9%), muscle pain (38.8% vs. 21.7%), fatigue (26% vs. 28.7%, tenderness at the site (27.6% vs. 21.7%), and joint pain (27.6% vs. 20.9%) were the most commonly reported side effects after first and second dose vaccine respectively. Most of participants reported that their symptoms emerged after 6hr of vaccination and only less than 5% of participant's symptoms lasted more than 72hr of post vaccination. The younger age (≤29 year) were more susceptible to at least one side effect (χ 2 = 4.2; p = 0.04) after first dose.

CONCLUSION: The prevalence of side effect after first and second dose vaccine was higher. Most of the symptoms were short lived and mild. This result might help to solve an emerging public health challenge (vaccine hesitancy) nurtured by misinformation related to vaccines safety.

PMID:35749520 | PMC:PMC9232121 | DOI:10.1371/journal.pone.0265140

Molecules. 2022 Jun 13;27(12):3798. doi: 10.3390/molecules27123798.

ABSTRACT

Immunotherapy, which stimulates the body's immune system, has received a considerable amount of press in recent years because of its powerful benefits. Cancer immunotherapy has shown long-term results in patients with advanced disease that are not seen with traditional chemotherapy. Immune checkpoint inhibitors, cytokines like interleukin 2 (IL-2) and interferon-alpha (IFN), and the cancer vaccine sipuleucel-T have all been licensed and approved by the FDA for the treatment of various cancers. These immunotherapy treatments boost anticancer responses by stimulating the immune system. As a result, they have the potential to cause serious, even fatal, inflammatory and immune-related side effects in one or more organs. Immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cell therapy are two immunotherapy treatments that are increasingly being used to treat cancer. Following their widespread usage in the clinic, a wave of immune-related adverse events (irAEs) impacting virtually every system has raised concerns about their unpredictability and randomness. Despite the fact that the majority of adverse effects are minimal and should be addressed with prudence, the risk of life-threatening complications exists. Although most adverse events are small and should be treated with caution, the risk of life-threatening toxicities should not be underestimated, especially given the subtle and unusual indications that make early detection even more difficult. Treatment for these issues is difficult and necessitates a multidisciplinary approach involving not only oncologists but also other internal medicine doctors to guarantee quick diagnosis and treatment. This study's purpose is to give a fundamental overview of immunotherapy and cancer-related side effect management strategies.

PMID:35744922 | PMC:PMC9227460 | DOI:10.3390/molecules27123798

Int J Environ Res Public Health. 2022 Jun 15;19(12):7353. doi: 10.3390/ijerph19127353.

ABSTRACT

Adverse drug reactions (ADRs) are a major health problem in the primary care setting, particularly among the elderly population. While the high frequency of ADRs in the elderly has several causes, a major and common determinant is polypharmacy, which can in turn increase the risk of drug-drug interactions (DDIs). In this paper, we analyzed the drugs prescriptions dispensed to elderly outpatients, to assess changes in the prevalence of selected DDIs in the period 2013-2019. Overall, about 15% of the patients aged &gt;65 years were poly-treated. Among them, a decreasing trend in prevalence was observed for the majority of DDIs during the study period. This trend was particularly noticeable for DDIs involving fluoroquinolones and vitamin K antagonists, where a sharp reduction of over 40% was observed. On the opposite, a small increase in prevalence was observed for the association of antidiabetics and beta-blocking agents and for that of clopidogrel and PPIs. While the occurrence of most of the considered DDIs among poly-treated elderly decreased over time, the prevalence of some of them is still worrying. The complexity of the national drug formularies, as well as the increased number of prescribing actors that are involved, further urges the update of DDI lists to be used to monitor drug appropriateness and reduce avoidable ADRs.

PMID:35742605 | PMC:PMC9224286 | DOI:10.3390/ijerph19127353

Int J Environ Res Public Health. 2022 Jun 9;19(12):7077. doi: 10.3390/ijerph19127077.

ABSTRACT

Iodinated- (ICM) and gadolinium-based (GCM) contrast media are used in radiology imaging techniques, such as computer tomography (CT) and magnetic resonance (MR), respectively. The paper aims to analyze the adverse drug reactions of ICM and GCM on different sites of the body in a highly polluted environment. We analyzed the pharmacovigilance in contrast media on the basis of reports submitted to the Regional Center for Monitoring of Adverse Drug Reactions (ADR) at the Department of Clinical Pharmacology in Wrocław. Safety profiles were compared between different ICM and GCM and at the system organ level using the proportional reporting ratio (PRR). We analyzed 124 reports of adverse reactions related to contrast agents between 2006 and 2021. Our findings revealed that ADR combinations occurred more frequently after the use of iodinated contrast agents (72.08%) than gadolinium contrast agents (27.92%). Iomeprol and Iopromide were identified as the most frequently reported media. Each medium presented a different safety profile. Skin disorders are the most common adverse drug reactions among patients using both iodine- and gadolinium-based contrast media. Gadolinium-based contrast agents are characterized by similar organ toxicity. Conversely, iodine-based contrast agents are more diverse-some of which show tissue specificity, such as Iodixanol for the gastrointestinal system or Iohexol for the respiratory tract. This study shows relatively high occurrence of respiratory tract related ADRs in Wrocław. We also prove that it is possible to choose the most optimal contrast agent for patients with specific organ site problems to omit the possible complications.

PMID:35742323 | PMC:PMC9223239 | DOI:10.3390/ijerph19127077

Int J Environ Res Public Health. 2022 Jun 8;19(12):7014. doi: 10.3390/ijerph19127014.

ABSTRACT

Although it is assumed that loneliness in one relationship might put one at risk of experiencing loneliness in another relationship, this association has rarely been examined as such. In this longitudinal study, we examined the associations between peer- and parent-related loneliness in a sample of 3391 adolescents across three waves (Mage Wave 1 = 14.53; 59.3% female). Using random intercept cross-lagged panel models, parent- and peer-related loneliness were found to be stable over time and were concurrently related to each other. Moreover, the state of peer-related loneliness predicted the state of parent-related loneliness one year later. Thereby, the current study provides limited evidence of a carry-over effect between relation-specific types of loneliness.

PMID:35742263 | PMC:PMC9222296 | DOI:10.3390/ijerph19127014

Res Social Adm Pharm. 2022 Jun 16:S1551-7411(22)00183-8. doi: 10.1016/j.sapharm.2022.06.005. Online ahead of print.

ABSTRACT

BACKGROUND: Drug-related problems (DRPs) lead to substantial morbidity and mortality and increase healthcare costs. Several interventions have been developed to reduce DRPs and improve the outcome of drug therapy.

OBJECTIVE: To investigate DRPs identified through a pharmacist-led intervention and to assess patient satisfaction with the intervention.

METHODS: Patients received two pharmacist consultations 1-2 weeks and 3-5 weeks after collecting a new cardiovascular medicine. Information about patient characteristics, beliefs about medicines (BMQ), DRPs, and patient evaluations were collected using questionnaires.

RESULTS: Pharmacists identified DRPs among 52.4% and 43.1% of the 633 patients at consultation 1 and 2, respectively. Of the DRPs reported in consultation 1, 43.7% were solved at consultation 2. Among patients with side effects, patients who received advice on managing these in consultation 1 where more likely to have solved problems at consultation 2 (61.2% vs. 42.6%, p = 0.008). Female gender, high BMQ concern and the number of new medicines were associated with DRPs. Patients were highly satisfied with the intervention. Predictors of satisfaction were female gender, older age, higher BMQ necessity, face-to-face consultations, longer duration of consultation 1, and solved problems in consultation 2.

CONCLUSIONS: The results indicate that the pharmacist-led follow-up intervention can aid early identification and solving of DRPs in patients prescribed new cardiovascular drugs. Knowledge of factors associated with DRPs and patients' satisfaction may allow further improvement of the intervention.

PMID:35750567 | DOI:10.1016/j.sapharm.2022.06.005

Front Biosci (Landmark Ed). 2022 May 31;27(6):171. doi: 10.31083/j.fbl2706171.

ABSTRACT

In recent years, in-depth research on anti-tumor therapy has brought the emergence of new active chemotherapeutic agents and combination regimens. However, as one of them, taxane drugs are widely used in clinical practice, but it should be noted that many side reactions caused by their application bring some difficulties to routine management. Among the side reactions related to taxane anti-tumor therapy, ocular adverse reactions are occasionally reported and are not life-threatening but may seriously affect patients' life quality. Thus, the continuation, reduction and cessation of taxane chemotherapy still need to be further evaluated by ophthalmologists and oncologists once the side effects show up. To prevent ocular side reactions, close attention should be paid to complications during medication. To facilitate the oncology department and ophthalmologists to comprehensively understand the ophthalmic adverse reactions of taxane drugs and their possible mechanisms and improve drug use efficiency, we collected relevant literature and reviewed and provided some suggestions for the monitoring and managing of ophthalmic toxicity.

PMID:35748247 | DOI:10.31083/j.fbl2706171

Pharmaceutics. 2022 May 30;14(6):1163. doi: 10.3390/pharmaceutics14061163.

ABSTRACT

Angiotensin-converting enzyme inhibitors (ACEI), such as enalapril, are a cornerstone of treatment for pediatric heart failure which is still used off-label. Using a novel age-appropriate formulation of enalapril orodispersible minitablets (ODMTs), phase II/III open-label, multicenter pharmacokinetic (PK) bridging studies were performed in pediatric patients with heart failure due to dilated cardiomyopathy (DCM) and congenital heart disease (CHD) in five participating European countries. Children were treated for 8 weeks with ODMTs according to an age-appropriate dosing schedule. The primary objective was to describe PK parameters (area under the curve (AUC), maximal concentration (Cmax), time to reach maximal concentration (t-max)) of enalapril and its active metabolite enalaprilat. Of 102 patients, 89 patients (n = 26, DCM; n = 63 CHD) were included in the primary PK endpoint analysis. Rate and extent of enalapril and its active metabolite enalaprilat were described and etiology and age could be identified as potential PK modifying factors. The dosing schedule appeared to be tolerated well and did not result in any significant drug-related serious adverse events. The PK analysis and the lack of severe safety events supports the applied age-appropriate dosing schedule for the enalapril ODMTs.

PMID:35745735 | DOI:10.3390/pharmaceutics14061163

J Pers Med. 2022 Jun 15;12(6):974. doi: 10.3390/jpm12060974.

ABSTRACT

Utilizing pharmacogenomics (PGx) and integrating drug-induced phenoconversion to guide opioid therapies could improve the treatment response and decrease the occurrence of adverse drug events. Genetics contribute to the interindividual differences in opioid response. The purpose of this case report highlights the impact of a PGx-informed medication safety review, assisted by a clinical decision support system, in mitigating the drug-gene and drug-drug-gene interactions (DGI and DDGI, respectively) that increase the risk of an inadequate drug response and adverse drug events (ADEs). This case describes a 69-year-old female who was referred for PGx testing for uncontrolled chronic pain caused by osteoarthritis and neuropathy. The clinical pharmacist reviewed the PGx test results and medication regimen and identified several (DGIs and DDGIs, respectively) at Cytochrome P450 (CYP) 2C19 and CYP2D6. The recommendations were to: (1) switch tramadol to buprenorphine transdermal patch, an opioid with lower potential for ADEs, to mitigate a CYP2D6 DDGI; (2) gradually discontinue amitriptyline to alleviate the risk of anticholinergic side effects, ADEs, and multiple DDGIs; and (3) optimize the pregabalin. The provider and the patient agreed to implement these recommendations. Upon follow-up one month later, the patient reported an improved quality of life and pain control. Following the amitriptyline taper, the patient experienced tremors in the upper and lower extremities. When the perpetrator drug, omeprazole, was stopped, the metabolic capacity was no longer impeded; the patient experienced possible amitriptyline withdrawal symptoms due to the rapid withdrawal of amitriptyline, which was reinitiated and tapered off more slowly. This case report demonstrates a successful PGx-informed medication safety review that considered drug-induced phenoconversion and mitigated the risks of pharmacotherapy failure, ADEs, and opioid misuse.

PMID:35743759 | DOI:10.3390/jpm12060974

Ned Tijdschr Geneeskd. 2022 May 5;166:D6199.

ABSTRACT

The Farmacotherapeutisch Kompas (FK) and the KNMP Kennisbank report on side effects of medicinal products, in order of frequency. However, data regarding causality and its assessment are lacking, while this information is crucial when the discontinuation of a drug due to putative side effects is considered. In this article, we describe the role of pharmaceutical companies, the agencies in charge of the evaluation and supervision of medicinal products and Lareb. We also describe how this information is included in the FK and the Kennisbank. Only side effects with a probable causal relation to the drug are registered. However, to err on the side of caution, side effects with a questionable causal relation to the drug are sometimes also registered. It would be helpful for the physician if the FK and the Kennisbank also reported the degree of assessed causality, next to the frequency.

PMID:35736375

Curr Oncol. 2022 Jun 17;29(6):4342-4353. doi: 10.3390/curroncol29060347.

ABSTRACT

INTRODUCTION: With the increasing use of immune checkpoint inhibitors (ICI) for cancer, there is a growing burden on the healthcare system to provide care for the toxicities associated with these agents. Herein, we aim to identify and describe the distribution of encounters seen in an urgent care setting for immune-related adverse events (irAEs) and the clinical outcomes from irAE management.

METHODS: Patient demographics, disease characteristics, and treatment data were collected retrospectively from encounters at an oncology Urgent Care Clinic (UCC) from a single tertiary center for upper aerodigestive malignancies from 1 July 2018 to 30 June 2019. Data were summarized using descriptive statistics with odds ratios for associations between patient features and hospitalization after UCC evaluation.

RESULTS: We identified 494 encounters from 289 individual patients over the study period. A history of ICI therapy was noted in 34% (n = 170/494) of encounters and 29 encounters (29/170, 17%) were confirmed and treated as irAEs. For those treated for irAEs, the majority (n = 19/29; 66%) were discharged home. Having an irAE was associated with an increased risk of hospitalization compared to non-irAEs (OR 5.66; 95% CI 2.15-14.89; p &lt; 0.001).

CONCLUSION: In this single institution experience, the majority of UCC encounters for confirmed irAEs were safely managed within the UCC. In ICI-treated patients, having an irAE was associated with an increased risk of hospitalization versus non-irAEs.

PMID:35735456 | DOI:10.3390/curroncol29060347

J Eur Acad Dermatol Venereol. 2022 Jun;36 Suppl 6:51-58. doi: 10.1111/jdv.18200.

ABSTRACT

Drug-induced photosensitivity is associated with a wide range of anticancer treatments, including conventional chemotherapeutic agents, targeted anticancer therapies, and immune checkpoint inhibitors. These dermatologic adverse events can have a major impact on the well-being and quality of life of cancer patients, leading to dose modifications and interruption or discontinuation of anticancer treatments in severe cases. However, the heterogeneous nature of the photosensitive reactions induced by these agents, as well as the common concomitant use of other potentially photosensitizing drugs (antibiotics, voriconazole, nonsteroidal anti-inflammatory drugs, etc.), can make the diagnosis and, therefore the prevention, of these adverse events particularly challenging. The aim of this review is to describe the most characteristic forms of photosensitivity observed in patients being treated with anticancer treatments, including phototoxicity and photoallergy, and other potentially photo-induced manifestations such as UV recall, exaggerated sunburn reactions associated with treatment-related vitiligo, drug-induced cutaneous lupus erythematosus, and UV-induced hyperpigmentation. We also discuss the photosensitive reactions recently reported with new-generation targeted anticancer therapies and immune checkpoint inhibitors and highlight the importance of continued surveillance to identify photosensitizing agents, and of educating patients on the need for preventive UVA/UVB photoprotective measures.

PMID:35738806 | DOI:10.1111/jdv.18200

Curr Oncol. 2022 May 31;29(6):3996-4011. doi: 10.3390/curroncol29060319.

ABSTRACT

Treatment with bevacizumab is known to cause adverse events such as proteinuria and hypertension, amongst others. However, while bevacizumab-induced hypertension has been linked to increased overall survival (OS), data on proteinuria are controversial. We performed a retrospective analysis to observe the influence of adverse events developed during treatment with bevacizumab and chemotherapy on the OS in patients with metastatic colorectal cancer (mCRC). Kaplan-Meier and log-rank analyses were used to assess differences in OS, and hazard ratios (HR) were estimated using Cox models. Out of the 3497 mCRC patients admitted to our center between 2014 and 2019, 150 met the criteria for inclusion in our analysis. Out of these, 50.7% experienced proteinuria and had reached a longer OS (40 versus 25 months, p = 0.015) and progression-free survival (15 versus 12 months, p = 0.039). The following groups were identified as having a lower risk of death: patients with proteinuria (HR 0.589; 95% CI 0.402-0.863; p = 0.007), one metastatic site (HR 0.533; 95% CI 0.363-0.783; p = 0.001), and non-metastatic stage at diagnosis (HR 0.459; 95% CI 0.293-0.720; p = 0.001). Patients with anemia and diabetes had an increased risk of death. Proteinuria emerges as a useful prognostic factor in mCRC patients undergoing bevacizumab-based systemic therapy, and it could be easily integrated into the decision-making process, thus allowing physicians to further individualize systemic treatments.

PMID:35735428 | DOI:10.3390/curroncol29060319

BMC Complement Med Ther. 2022 Jun 22;22(1):168. doi: 10.1186/s12906-022-03643-9.

ABSTRACT

BACKGROUND: Current therapies for alcohol-induced liver injury are of limited efficacy and associated with significant side effects. With the proposed pathophysiology of alcohol-induced liver injury to be related to deranged gut microbiota, we hypothesized that probiotics would have beneficial effects in attenuating alcohol-induced liver injury.

METHODS: Twenty-four male Sprague-Dawley rats were divided into 4 groups: control group, alcohol group, Lactobacillus plantarum group, and mixed-strain probiotics group. After 4 weeks, all rats were sacrificed, and blood samples were analyzed for ALT, lipopolysaccharide level (LPS), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Liver tissues were processed for histopathology, malondialdehyde (MDA) level and immunohistochemistry for toll-like receptors 4 (TLR-4). Stool samples were collected, and 16S rRNA sequencing was used to analyze the fecal microbiota.

RESULTS: Liver histopathology showed the presence of significant hepatocyte ballooning in the alcohol group as compared with the control group, and the treatment with L. plantarum or mixed-strain probiotics alleviated these changes. Significant elevation of serum ALT, LPS, IL-6, and TNF-α, hepatic MDA levels, and hepatic TLR-4 expression were observed in alcohol-fed rats as compared with control rats. The administration of L. plantarum or mixed-strain probiotics restored these changes to the levels of control rats. The relative abundance of fecal bacteria at genus level showed a significant reduction in Allobaculum, Romboutsia, Bifidobacterium, and Akkermansia in the alcohol group as compared with the control group. In probiotics-treated rats, significant increases in Allobaculum and Bifidobacterium were observed, while the relative abundance of Romboutsia and Akkermansia was unchanged compared to the alcohol group. A reduction in alpha diversity was observed in alcohol-treated rats, whereas the improvement was noted after probiotic treatment.

CONCLUSIONS: The treatment with Lactobacillus, whether as single-, or mixed-strain probiotics, was beneficial in reducing the severity of alcohol-induced liver injury likely through the increase in beneficial bacteria, and the reduction of inflammatory responses, and oxidative stress.

PMID:35733194 | DOI:10.1186/s12906-022-03643-9

Sci Transl Med. 2022 Jun 22;14(650):eabn3353. doi: 10.1126/scitranslmed.abn3353. Epub 2022 Jun 22.

ABSTRACT

Chimeric antigen receptor (CAR) T cell therapies targeting CD19 and CD22 have been successful for treating B cell cancers, but CAR T cells targeting non-B cell cancers remain unsuccessful. We propose that rather than being strictly a side effect of therapy, the large number of CAR interactions with normal B cells may be a key contributor to clinical CAR T cell responses.

PMID:35731887 | DOI:10.1126/scitranslmed.abn3353

Eur Rev Med Pharmacol Sci. 2022 Jun;26(11):4074-4081. doi: 10.26355/eurrev_202206_28977.

ABSTRACT

OBJECTIVE: Atopic dermatitis displays a relevant sleep burden sustained by clinical (i.e., itch), psychological (i.e., inadequate coping strategies) and therapeutic (i.e., frequent loss of drug response) triggers. Dupilumab, the first biologic approved for atopic dermatitis, showed excellent effects on improving pruritus and sleep after only two weeks of treatment but, in some cases, may have paradoxical effects. The rate of sleep-related side-effects remains unknown. More specifically, adverse-drug reactions (ADRs) related to dupilumab have been investigated during the safety phase of randomized clinical trials or in small retrospective epidemiological surveys, but little is known about sleep-related ADRs in real-life settings. Therefore, we took advantage of a global large-scale pharmacovigilance database, carrying out a comprehensive data mining analysis to look at different sleep-related ADRs reported among patients under anti IL-4/13 therapy.

MATERIALS AND METHODS: We analyzed individual case study reports (ICSRs) in VigiBaseTM, the World Health Organization (WHO) global pharmacovigilance database of ADRs collected by national drug authorities in > 140 countries (> 90% of the world population). We looked for patterns of potentially sleep-related ADRs and we applied a disproportionality analysis based on Bayesian Confidence Propagation Neural Network (BCPNN). A meta-analytical approach was used to synthesize the overall effect size of sleep-related ADRs potentially associated to Dupilumab administration.

RESULTS: From inception up to March 9, 2021, 94,065 ADRs from 37,848 unique reports were included and analyzed in the present paper: 1,294 of them (1.4%) concerned sleep disturbances (n=27). Most of sleep-related complaints were generic sleep disorders (n=630), followed by insomnia (n=312), somnolence (n=81), lethargy (n=60), night sweats (n=30), middle insomnia (n=39), hypersomnia (n=25), poor-quality sleep (n=21), initial insomnia (n=17), sleep apnea syndrome (n=13), nightmares (n=11) and sleep deficit (n=11). Interestingly, restlessness and restless leg syndrome, nocturnal dyspnea, narcolepsy and bruxism were reported in 7, 6, 5, 4 and 3 cases, respectively. Only sleep deficit [OR 15.67 (95% CrI 8.61-28.51); IC 3.24 (95% CrI 2.26-3.97)], generic sleep disorder [OR 6.22 (95% CrI 5.74-6.73); IC 2.60 (95% CrI 2.48-2.71)], nocturnal dyspnea [OR 3.68 (95% CrI 1.53-8.87); IC 1.56 (95% CrI 0.03-2.56)] and middle insomnia [OR 1.87 (95% CrI 1.36-2.56); IC 0.88 (95% CrI 0.39-1.30)] achieved the statistical significance threshold.

CONCLUSIONS: In this work, we identified over 37,000 unique case-reports of Dupilumab side-effects reported on the WHO pharmacovigilance database. We specifically categorized those related to sleep issues, which were 1,294. Our findings from large numbers of cases provide data supporting the clinical observations that Dupilumab is usually effective in improving sleep quality and sleep disturbances/impairments, given the lack of statistical significance of several sleep-related ADRs. Further work is needed to closely scrutinize the impact of Dupilumab on sleep, in terms of underlying mechanisms, and to better understand residual sleep disorders in patients with atopic dermatitis and other allergic diseases treated with Dupilumab. Thus, sleep monitoring may be helpful for dermatologists in managing atopic dermatitis patients treated with dupilumab. The limitations of spontaneous reporting systems including underreporting and reporting bias, heterogeneity of sources and impossibility to infer any causal relationship merit consideration and further research is needed.

PMID:35731078 | DOI:10.26355/eurrev_202206_28977