Am J Med Qual. 2024 Jan-Feb 01;39(1):21-32. doi: 10.1097/JMQ.0000000000000161. Epub 2023 Dec 28.

ABSTRACT

Context and implementation approaches can impede the spread of patient safety interventions. The objective of this article is to characterize factors associated with improved outcomes among 9 hospitals implementing a medication safety intervention. Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a pharmacist-driven intervention that led to a sustained reduction in nephrotoxic medication-associated acute kidney injury (NTMx-AKI) at 1 hospital. Using qualitative comparative analysis, the team prospectively assessed the association between context and implementation factors and NTMx-AKI reduction during NINJA spread to 9 hospitals. Five hospitals reduced NTMx-AKI. These 5 had either (1) a pharmacist champion and >2 pharmacists working on NINJA (Scon 1.0, Scov 0.8) or (2) a nephrologist-implementing NINJA with minimal competing organizational priorities (Scon 1.0, Scov 0.2). Interviews identified ways NINJA team leaders obtained pharmacist support or successfully implemented without that support. In conclusion, these findings have implications for future spread of NINJA and suggest an approach to study spread of safety interventions more broadly.

PMID:38127682 | DOI:10.1097/JMQ.0000000000000161

J Med Syst. 2023 Dec 21;48(1):5. doi: 10.1007/s10916-023-02022-2.

ABSTRACT

Physician reviews influence how patients seek care, but dishonest reviews can be detrimental to a physician practice. It is unclear if reviews can be challenged, and processes differ and are not readily apparent. The objective of this observational study was to determine the ability to challenge dishonest negative reviews online. Commonly used websites for physician reviews as of August 2021 were utilized: Healthgrades, Vitals, RateMDs, Zocdoc, Yelp, and Google Business. Each review platform's website was tested for leaving a physician review and process of appeal and possible removal of a negative review. The process for appeal and the steps involved in posting and appealing a review were determined, whether individuals are verified patients and criteria for verification, how physicians can respond, and the process of appealing false or defamatory reviews.Any individual can leave reviews by searching for a physician's name or practice and visiting their profile page and can then provide a rating and written review of their experience with the physician. Many require verification to prevent suspicious activity but not proof of a medical visit, allowing significant potential for inaccurate review postings. Posting a review can be done by anyone without verification of a visit. It is challenging for physicians to remove negative online reviews, as most review platforms have strict policies against. This review concludes that physicians should be aware of their online presence and the steps that can be taken to address issues to mitigate adverse effects on their practices.

PMID:38127210 | DOI:10.1007/s10916-023-02022-2

Cad Saude Publica. 2023 Dec 22;39(12):e00077923. doi: 10.1590/0102-311XPT077923. eCollection 2023.

ABSTRACT

The use of triggers for the active search and detection of adverse drug events (ADEs) has been gaining ground within pharmacovigilance services. Thus, the main objective of the study was to propose a new list of triggers to be used in a center specialized in hematology in Rio de Janeiro, Brazil. The update of the list of triggers consisted of revising the current list, with the exclusion and inclusion of new triggers. To verify the performance of the new list of triggers, a cross-sectional study was conducted in which the new triggers were used to investigate the occurrence of ADEs in patients attended in the emergency unit or hospitalized from January to March 2022. For each suspected ADEs, the patient's profile and adverse drug reactions (ADRs) were characterized regarding causality and severity. The performance of the triggers and their ability to capture ADEs were estimated using the following indicators: frequency of the trigger per 100 medical records, frequency of ADEs per 100 records, and positive predictive value (PPV). To evaluate the overall performance of the proposed new list, the PPV was estimated. A total of 374 prescriptions for triggers were identified in 186 medical records. The most efficient in the detection of possible ADEs were: lidocaine, loperamide, bisacodyl, filgrastim and glycerin clyster. The overall PPV of the new suggested list was 48% versus 10% of the previous list. This study demonstrated the importance of an updated list of triggers for the monitoring of ADEs and improvement of the care provided.

PMID:38126560 | DOI:10.1590/0102-311XPT077923

Int J Surg Case Rep. 2023 Dec 15;114:109157. doi: 10.1016/j.ijscr.2023.109157. Online ahead of print.

ABSTRACT

INTRODUCTION: The management of patients with complex oncological histories poses unique challenges, particularly when they are on targeted chemotherapy agents known for specific side effects. This case report illuminates the multifaceted complexities encountered in such scenarios, with a focus on the rare complications associated with targeted therapies.

CASE PRESENTATION: We present a 50-year-old male with an extensive oncological background, including childhood retinoblastoma and radiation-induced leiomyosarcoma. Recently diagnosed with skull base osteosarcoma, he was undergoing treatment with Regorafenib. Admitted with sepsis due to Pseudomonas aeruginosa-induced community-acquired pneumonia, his clinical course was complicated by lung cavitation leading to a spontaneous pneumothorax. This report highlights the absence of empyema, a crucial differential in the diagnosis.

DISCUSSION: This case unravels the intricate interplay between targeted chemotherapy, concurrent medications like prednisone, and their potential to cause severe complications such as pneumonia and pneumothorax. It delves into the mechanisms by which Regorafenib can lead to lung cavitation and abscess formation, a rare but significant risk. The importance of a multidisciplinary approach for prompt diagnosis and treatment, including surgical intervention, is highlighted. The pathology of the surgically resected lobe revealed metastatic high-grade leiomyosarcoma, adding another layer of complexity to the case.

CONCLUSION: This case serves as a cautionary tale highlighting the need for vigilant monitoring of patients on targeted chemotherapy agents, especially those with complex medical histories. It highlights the importance of considering potential drug-related complications and the rationale behind therapeutic choices, including antibiotic selection and surgical decision-making, in the management of acute medical conditions in these patients.

PMID:38128294 | DOI:10.1016/j.ijscr.2023.109157

J Clin Pharmacol. 2023 Dec 21. doi: 10.1002/jcph.2399. Online ahead of print.

ABSTRACT

The human body is subservient to the age-related changes that affect not only the outer appearance, but also organs and tissues. They also concern the processes of pharmacokinetics and dynamics. This means that the absorption, distribution and metabolism of drugs used by an elderly patient will be slowed down. Therefore, it becomes necessary to prescribe a special dosing regimen for older people. An actual problem is also that with age, many patients require more drugs than young people. This increases the risk of side effects, because many drugs are difficult to combine with each other. Pharmacy of our time is a science that is constantly developing and modernizing, which allows changing therapy for the better: prescribing drugs in smaller quantities, with a smaller range of adverse reactions and a better effect. The aim of the work is to analyze the impact and relationship of older age on the pharmacotherapy of patients, as well as the risks of drug-induced diseases. To carry out this work, such research methods as analysis, synthesis, comparative analysis, classification, analogy, abstraction, induction and generalization were used. The features of the stages of pharmacokinetics and pharmacodynamics in the elderly were considered; studied the data of clinical studies, literature in geriatrics; the effects of a combination or increase in the dosage of drugs have been noted. After the collection of research data and the analysis, it turned out that it is real and necessary to avoid the negative consequences of pharmacotherapy in elderly and senile patients. Considering the natural age-related changes in the condition and functioning of organs and systems, constantly monitoring the effectiveness of drugs and undesirable reactions of the body to them, adjusting treatment protocols will have a favorable result and help optimize pharmacotherapy for the elderly, reduce the risk of side effects and diseases caused by medications. This article is protected by copyright. All rights reserved.

PMID:38129179 | DOI:10.1002/jcph.2399

Pharmacoepidemiol Drug Saf. 2023 Dec 21. doi: 10.1002/pds.5747. Online ahead of print.

ABSTRACT

PURPOSE: Antipsychotic agents, which may increase the risk of infection through dopaminergic dysregulation, are prescribed to a fraction of patients following critical illness. We compared the rate of recurrent sepsis among patients who filled a prescription for antipsychotics with high- or low-D2 affinity.

METHODS: Population-based cohort with active comparator design. We included sepsis survivors older than 65 years with intensive care unit admission and new prescription of antipsychotics in Ontario 2008-2019. The primary outcome were recurrent sepsis episodes within 1 year of follow-up. Patients who filled a prescription within 30 days of hospital discharge for high-D2 affinity antipsychotics (e.g., haloperidol) were compared with patients who filled a prescription within 30 days of hospital discharge for low-D2 affinity antipsychotics (e.g., quetiapine). Multivariable zero-inflated Poisson regression models with robust standard errors adjusting for confounding at baseline were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI).

RESULTS: Overall, 1879 patients filled a prescription for a high-D2, and 1446 patients filled a prescription for a low-D2 affinity antipsychotic. Patients who filled a prescription for a high-D2 affinity antipsychotic did not present a higher rate of recurrent sepsis during 1 year of follow-up, compared with patients who filled a prescription for a low-D2 affinity antipsychotic (IRR: 1.12; 95% CI: 0.94, 1.35).

CONCLUSIONS: We did not find conclusive evidence of a higher rate of recurrent sepsis associated with the prescription of high-D2 affinity antipsychotics (compared with low-D2 affinity antipsychotics) by 1 year of follow-up in adult sepsis survivors with intensive care unit admission.

PMID:38126218 | DOI:10.1002/pds.5747

Medicine (Baltimore). 2023 Dec 15;102(50):e36557. doi: 10.1097/MD.0000000000036557.

ABSTRACT

BACKGROUND: Retinopathy of prematurity (ROP) increases with the survival of late preterm infants, but its relationship with neurodevelopmental outcomes in preterm infants remains controversial. To investigate the relationship between ROP and its severity and adverse neurodevelopmental outcomes in preterm infants.

METHODS: We conducted a meta-analysis. All relevant literature before November 2022 were retrieved from PubMed, Embase, Cochrane Library Web of Science, CNKI, CBM, Wan fang Data, and VIP Database. According to the inclusion criteria and exclusion criteria, eligible literature were included to conduct clinical trial quality assessment, and the Newcastle-Ottawa scale was used to evaluate the quality of evidence. Meta-analysis was performed using RevMan5.3. Data extraction, quality assessment, and meta-analysis were performed independently by 2 people. Mean difference or standardized mean difference of motor, language and cognitive scores (Bayley III or Bayley II) were used as effect sizes for continuous data analysis, all of which were represented by 95% CI. For heterogeneity (I2 ≥ 50% or P < .10), a random effects model was used, otherwise a fixed effects model was used.

RESULTS: A total of 6 literature were included. The results of the ROP group for motor (comprehensive motor, proportional motor, and fine motor), language and cognitive scores were -5.57 (95%CI, -1.43 to 0.04), -0.95 (95%CI, 1.4-0.50), -1.34 (95% CI, 1.77-0.92), -1.75 (95% CI, 2.26-1.24) and -5.56 (95% CI, 9.56-1.57). Additionally, the results of severe ROP group for motor (comprehensive motor, proportional motor, fine motor), language and cognitive scores were -8.32 (95%CI, -8.91 to 7.74), -1.10 (95%CI, -1.83 to -0.36), -1.08 (95%CI, -1.75 to -0.41), -7.03 (95%CI, -7.71 to 6.35), and -7.96 (95%CI, -8.5 to -7.42).

CONCLUSIONS: The Bayley Scale scores of the ROP group were lower than those of the not ROP group, and the scores of the severe ROP were significantly lower than those of the not severe ROP group. These findings suggest that ROP can indeed delay motor, language and cognitive, especially in severe cases.

PMID:38115287 | DOI:10.1097/MD.0000000000036557

BMC Nephrol. 2023 Dec 19;24(1):375. doi: 10.1186/s12882-023-03437-2.

ABSTRACT

BACKGROUND: Kidney dysfunction is a common, progressive condition that is increasingly becoming a global public health issue. Because the kidneys are the major route for drug excretion, impaired renal function can change the pharmacokinetics and pharmacodynamics of drugs that are renally excreted. Additionally, patients with kidney dysfunction often have co-morbidities and the associated use of multiple medications which increases the risk of drug-related problem (DRP) occurrence. This study aimed to determine the prevalence, types, and factors associated with DRPs in patients with kidney dysfunction.

METHOD: We conducted a prospective observational study over 3 months among hospitalized patients diagnosed with acute kidney injury or chronic kidney disease who were hospitalized in the medical ward, and patients attending the renal outpatient clinic at Mbarara Regional Referral Hospital. A total of 183 participants were enrolled through the use of a consecutive sampling technique. DRPs were classified according to the PCNE classification version 9.1. Data analysis was carried out using SPSS version 25.

RESULTS: A total of 174 patients with kidney dysfunction were included in the study with a mean ± SD age of 50.34 ± 18.13 years. A total of 219 DRPs were incurred by 138 (79.3%) study participants. The most common DRPs were 'Untreated symptoms or indication' (35.6%) followed by 'adverse event (possibly) occurring' (28.3%), and 'effect of drug treatment not optimal' (23.3%). Antimicrobials were the most involved drugs in suboptimal drug treatment (31.3%) and unnecessary drug treatment (32.1%). The study showed that length of hospital stay ≥ 5 days (AOR = 6.39, 95% CI: 1.75-23.27; p-value = 0.005) significantly increased the risk of DRP occurrence.

CONCLUSION: The current results, in agreement with previous literature, showed a high burden of DRPs among patients with kidney dysfunction. Antimicrobials were the most involved drugs in suboptimal as well as in unnecessary drug treatment. Longer hospital stay significantly increased the risk of DRPs. The high prevalence of DRPs in patients with kidney dysfunction and the potential impact on antimicrobial resistance underscores the importance of regular medication reviews and close monitoring of patients with renal dysfunction.

PMID:38114948 | PMC:PMC10731752 | DOI:10.1186/s12882-023-03437-2

Drug Ther Bull. 2023 Dec 11:dtb-2023-000069. doi: 10.1136/dtb.2023.000069. Online ahead of print.

NO ABSTRACT

PMID:38123946 | DOI:10.1136/dtb.2023.000069

J Allergy Clin Immunol Pract. 2023 Dec 18:S2213-2198(23)01368-5. doi: 10.1016/j.jaip.2023.12.019. Online ahead of print.

ABSTRACT

BACKGROUND: Berotralstat is a first-line, once-daily oral plasma kallikrein inhibitor approved for prophylaxis of hereditary angioedema (HAE) attacks in patients ≥12 years.

OBJECTIVE: This analysis examined the safety and effectiveness of long-term prophylaxis with berotralstat.

METHODS: APeX-2 was a Phase 3, parallel-group, multicenter trial in patients with HAE caused by C1 inhibitor deficiency (NCT03485911). Part 1 was a randomized, double-blind, placebo-controlled evaluation of 150 and 110 mg berotralstat over 24 weeks. In Part 2, berotralstat-treated patients continued the same treatment and placebo-treated patients were re-randomized to 150 or 110 mg berotralstat for 24 weeks. In Part 3, all patients were treated with open-label berotralstat at 150 mg, which could be continued for up to an additional 4 years. In Part 3, the primary endpoint was long-term safety and tolerability. Secondary endpoints included HAE attack rates and quality of life (QoL).

RESULTS: Eighty-one patients entered Part 3. Treatment-emergent adverse events (TEAEs) occurred in 82.7% of patients, with most being mild or moderate in severity. The most common TEAEs were nasopharyngitis, urinary tract infection, abdominal pain, arthralgia, coronavirus infection, and diarrhea. Drug-related TEAEs occurred in 14.8% of patients, but none were serious. For patients who completed 96 weeks of berotralstat treatment (n=70), mean (standard error) change in attack rate from baseline was -2.21 (0.20) attacks/month. Clinically meaningful improvements in QoL were also observed, with the largest improvements in the functioning domain.

CONCLUSION: Berotralstat was generally well tolerated, provided rapid and sustained reductions in HAE attacks, and improved QoL over 96 weeks.

PMID:38122865 | DOI:10.1016/j.jaip.2023.12.019

Urol Pract. 2024 Jan;11(1):172-178. doi: 10.1097/UPJ.0000000000000470. Epub 2023 Dec 20.

ABSTRACT

INTRODUCTION: Clinical guidelines recommend monitoring for metabolic derangements while on preventive pharmacologic therapy for kidney stone disease. The study objective was to compare the frequency of side effects among patients receiving alkali citrate, thiazides, and allopurinol.

METHODS: Using claims data from working-age adults with kidney stone disease (2008-2019), we identified those with a new prescription for alkali citrate, thiazide, or allopurinol within 12 months after their index stone-related diagnosis or procedure. We fit multivariable logistic regression models, adjusting for cohort characteristics like comorbid illness and medication adherence, to estimate 2-year measured frequencies of claims-based outcomes of acute kidney injury, falls/hip fracture, gastritis, abnormal liver function tests/hepatitis, hypercalcemia, hyperglycemia/diabetes, hyperkalemia, hypokalemia, hyponatremia, and hypotension.

RESULTS: Our cohort consisted of 1776 (34%), 2767 (53%), and 677 (13%) patients prescribed alkali citrate, thiazides, or allopurinol, respectively. Comparing unadjusted rates of incident diagnoses, thiazides compared to alkali citrate and allopurinol were associated with the highest rates of hypercalcemia (2.3% vs 1.5% and 1.0%, respectively, P = .04), hypokalemia (6% vs 3% and 2%, respectively, P < .01), and hyperglycemia/diabetes (17% vs 11% and 16%, respectively, P < .01). No other differences with the other outcomes were significant. In adjusted analyses, compared to alkali citrate, thiazides were associated with a higher odds of hypokalemia (OR=2.01, 95% CI 1.44-2.81) and hyperglycemia/diabetes (OR=1.52, 95% CI 1.26-1.83), while allopurinol was associated with a higher odds of hyperglycemia/diabetes (OR=1.34, 95% CI 1.02-1.75).

CONCLUSIONS: These data provide evidence to support clinical guidelines that recommend periodic serum testing to assess for adverse effects from preventive pharmacologic therapy.

PMID:38117963 | DOI:10.1097/UPJ.0000000000000470

Int J Psychiatry Med. 2023 Nov 21:912174231210567. doi: 10.1177/00912174231210567. Online ahead of print.

ABSTRACT

OBJECTIVE: There is growing evidence that adding non-steroidal anti-inflammatory drugs to some psychopharmacological treatments may help to improve symptoms in patients suffering from major depressive disorder. The present study examined the therapeutic efficacy of adding celecoxib to Ecitalopram and the safety of doing so.

METHOD: In this double-blind randomized controlled trial, 60 patients with major depressive disorder were randomly assigned to either treatment with Ecitalopram plus celecoxib (intervention group) or Ecitalopram and placebo. All patients were evaluated blind to treatment group with the Hamilton Depression Rating Scale (HDRS) before the intervention as well at 4 and 8 weeks after initiating treatment. Chi-square and paired t-test were used to examine between-group differences at those assessment times.

RESULTS: There was no significant difference in depressive symptoms between intervention and placebo groups at baseline. However, at 4 and 8 weeks after the beginning of treatment, there were significant between-group differences in HDRS scores, favoring the intervention group. No between-group differences were found in treatment-related side effects.

CONCLUSIONS: Adding celecoxib to Ecitalopram may effectively improve symptoms of depression in patients suffering major depressive disorder without increasing the risk of drug-related side effects.

PMID:38116669 | DOI:10.1177/00912174231210567

Future Oncol. 2023 Dec 20. doi: 10.2217/fon-2023-0842. Online ahead of print.

ABSTRACT

Aim: To assess the safety and effectiveness of daratumumab monotherapy in Indian patients with relapsed/refractory multiple myeloma. Methods: In this prospective, multicenter, phase IV study, patients (aged ≥18 years) received intravenous daratumumab (16 mg/kg) in six cycles. Safety was the primary end point. Results: Of the 139 patients included, 121 (87.1%) experienced ≥1 treatment-emergent adverse events (TEAEs; 53 [38.1%] drug-related), 32 (23%) had ≥1 serious TEAEs (five [3.6%] drug-related) and 16 (11.5%) deaths were reported (one death [0.7%] was drug-related). Overall response rate was 26.3%; 62.7% of patients had stable disease. Median time to first response and median progression-free survival were 5.2 and 5.9 months, respectively. Functional status and well-being were improved. Conclusion: Daratumumab showed an acceptable and expected safety profile with consistent efficacy, providing a novel therapeutic option for relapsed/refractory multiple myeloma management in India.

PMID:38116642 | DOI:10.2217/fon-2023-0842

Iran J Pharm Res. 2023 Jul 31;22(1):e134722. doi: 10.5812/ijpr-134722. eCollection 2023 Jan-Dec.

ABSTRACT

BACKGROUND: Drug-induced parkinsonism (DIP) is one of the most common movement disorders in approximately 20 - 35% of patients on antipsychotic medications. Managing the symptoms of DIP is challenging due to the limited number of potentially effective medications. On the other hand, this restricted possible treatment could have numerous side effects that ultimately result in patients stopping the medication all at once. The neuroprotective property of Ginkgo biloba extract (EGb) emerged as an effective commodity for the additional treatment of psychiatric disorders.

OBJECTIVES: This study aimed to evaluate the efficacy of EGb in psychiatric patients with symptoms of DIP.

METHODS: A sample of 63 patients who met the inclusion criteria were recruited and randomly assigned to control and experimental groups. Both groups were followed for 3 months. One group received 80 mg of G. biloba three times a day, and the control group received a placebo. The patients were evaluated using the Unified Parkinson's Disease Rating Scale and Montreal Cognitive Assessment.

RESULTS: Ginkgo could change the intensity of rest tremors, the severity of motor symptoms, rigidity, and bradykinesia. Ginkgo biloba might alleviate the severity of parkinsonism and motor symptoms and could lead to changes in the two components of working memory and short-term memory.

CONCLUSIONS: Ginkgo biloba extract can be used as an effective and safe treatment in the management of DIP, whether in patients diagnosed with psychotic disorders or mood disorders.

PMID:38116567 | PMC:PMC10728830 | DOI:10.5812/ijpr-134722

Medicine (Baltimore). 2023 Dec 15;102(50):e36592. doi: 10.1097/MD.0000000000036592.

ABSTRACT

BACKGROUND: Menopause causes a variety of symptoms such as hot flashes and night sweats. While menopausal hormonal therapy has been used for managing postmenopausal vasomotor symptoms (VMS) for quite a while, it has a considerably poor safety profile.

OBJECTIVE: To review and analyze existing data to evaluate the efficacy of the neurokinin-3 antagonist, fezolinetant, in treating postmenopausal VMS and to assess its safety profile.

METHODS: A thorough literature search was performed on PubMed, Cochrane Library, and Google Scholar in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020, to find publications on the efficacy of fezolinetant for postmenopausal VMS. Changes in the frequency and severity scores of moderate/severe VMS and changes in the Hot Flash-Related Daily Interference Scale (HFRDIS), Greene Climacteric Scale (GCS), and Menopause-Specific Quality of Life (MENQoL) were the efficacy outcomes. Adverse events, drug-related treatment-emergent adverse effects (TEAEs), drug-related dropouts, hepatotoxicity, endometrial hyperplasia or tumor, and uterine bleeding were all safety outcomes. We used Review Manager 5.4 for pooling risk ratios (RRs) and mean differences (MDs) for dichotomous and continuous outcomes, respectively. A P value of < .05 was considered significant.

RESULTS: There was a significant reduction in mean daily VMS frequency at weeks 4 and 12 (MD, -2.36; 95% confidence interval [CI], -2.85 to -1.87; P < .00001, for week 12) and also a significant decrease in VMS severity scores in the treatment group. Furthermore, improvements in MENQoL, HFRDIS, and GCS scores were observed. There was no significant difference in adverse events while drug-related TEAEs (RR, 1.21; 95% CI, 0.90-1.63; P = .21) showed a slight increase with fezolinetant. Drug-related dropouts were again similar across the 2 groups. Uterine bleeding had a lower incidence while endometrial events and hepatotoxicity showed a statistically insignificant, increasing trend in the fezolinetant group.

DISCUSSION AND IMPLICATIONS: Fezolinetant can be a treatment option for postmenopausal VMS but warns of a risk increase in endometrial hyperplasia or tumors. The heterogeneity in the data being analyzed, short follow-up period, and small sample size in most of the included randomized controlled trials were the greatest limitations, which must be considered in further research and safety profile exploration.

PMID:38115258 | DOI:10.1097/MD.0000000000036592

Brief Bioinform. 2023 Nov 22;25(1):bbad445. doi: 10.1093/bib/bbad445.

ABSTRACT

In clinical treatment, two or more drugs (i.e. drug combination) are simultaneously or successively used for therapy with the purpose of primarily enhancing the therapeutic efficacy or reducing drug side effects. However, inappropriate drug combination may not only fail to improve efficacy, but even lead to adverse reactions. Therefore, according to the basic principle of improving the efficacy and/or reducing adverse reactions, we should study drug-drug interactions (DDIs) comprehensively and thoroughly so as to reasonably use drug combination. In this review, we first introduced the basic conception and classification of DDIs. Further, some important publicly available databases and web servers about experimentally verified or predicted DDIs were briefly described. As an effective auxiliary tool, computational models for predicting DDIs can not only save the cost of biological experiments, but also provide relevant guidance for combination therapy to some extent. Therefore, we summarized three types of prediction models (including traditional machine learning-based models, deep learning-based models and score function-based models) proposed during recent years and discussed the advantages as well as limitations of them. Besides, we pointed out the problems that need to be solved in the future research of DDIs prediction and provided corresponding suggestions.

PMID:38113076 | DOI:10.1093/bib/bbad445

BMC Infect Dis. 2023 Dec 18;23(1):884. doi: 10.1186/s12879-023-08893-7.

ABSTRACT

INTRODUCTION: Scrub typhus is a bacterial mite-borne disease associated with poor clinical outcomes if not treated adequately. The study aimed to compare the time to defervescence, clinical failure, mortality and treatment-related adverse effects of two common drugs (doxycycline and azithromycin) used for its treatment.

METHODOLOGY: This was a systematic review and meta-analysis. All studies up to 20.03.2023 were screened for eligibility in Pubmed and Embase using a search string containing terms related to scrub typhus, doxycycline and azithromycin. After two phases of screening, all comparative studies where doxycycline and azithromycin were used to treat scrub typhus were included. The studies were critically appraised using standardised tools, and a meta-analysis was performed for time to defervescence (primary outcome), clinical failure, mortality and treatment-related adverse effects.

RESULTS: Of 744 articles from two databases, ten were included in the meta-analysis. All but two studies had a high risk of bias. The meta-analysis for time to defervescence had a high heterogeneity and did not show any significant difference between doxycycline and azithromycin arms [Mean difference of -3.37 hours (95%CI: -10.31 to 3.57), p=0.34]. When the analysis was restricted to studies that included only severe scrub typhus, doxycycline was found to have a shorter time to defervescence [mean difference of -10.15 (95%CI: -19.83 to -0.46) hours, p=0.04]. Additionally, there was no difference between the two arms concerning clinical failure, mortality and treatment-related adverse effects.

CONCLUSION: The current data from studies with a high risk of bias did not find statistically significant differences in clinical outcomes between doxycycline and azithromycin for scrub typhus.

PMID:38110855 | DOI:10.1186/s12879-023-08893-7

Mol Genet Metab. 2023 Dec 13;141(1):108113. doi: 10.1016/j.ymgme.2023.108113. Online ahead of print.

ABSTRACT

Nizubaglustat is a novel, orally available, brain penetrant, potent, and selective dual inhibitor of ceramide glucosyltranferase and non-lysosomal neutral glucosylceramidase (NLGase), which is currently under development for the treatment of subjects with neurological manifestations in primary and secondary gangliosidoses. The objectives of this first-in-human study were to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics (PD) of single oral doses of nizubaglustat after single (1, 3, and 9 mg) and multiple oral doses (9 mg once per day (QD) over 14 days) in healthy adults. Nizubaglustat was rapidly absorbed and systemic exposure was dose-proportional. Steady-state was achieved after three days of QD multiple dosing with minimal accumulation. Renal clearance accounted for around 15% of nizubaglustat elimination. Following multiple dosing, plasma concentrations of glucosylceramide (GlcCer), lactosylceramide (LacCer), and monosialodihexosylganglioside (GM3) decreased to a nadir at Day 10. PD target engagement of GCS inhibition was shown by a median decrease from baseline of plasma concentrations of GlcCer, LacCer, and GM3 ganglioside by 70%, 50%, and 48%, respectively. NLGase inhibition was also manifested by increased concentrations of GlcCer in cerebrospinal fluid from Day 1 to Day 14. Nizubaglustat was safe and well-tolerated at all doses tested. Consistent with the high selectivity, and the absence of intestinal disaccharidases inhibition, no cases of diarrhea were reported. No decreased appetite or weight loss was noted. Only treatment-emergent adverse events with preferred terms belonging to the system organ class skin and subcutaneous disorders of mild intensity were reported as drug-related in the nizubaglustat arm, in line with the pharmacological mechanism targeting glucosylceramide metabolism. Taken together, these data support QD dosing of nizubaglustat and its ongoing development in patients with primary and secondary forms of gangliosidoses.

PMID:38113551 | DOI:10.1016/j.ymgme.2023.108113

Cureus. 2023 Nov 17;15(11):e48955. doi: 10.7759/cureus.48955. eCollection 2023 Nov.

ABSTRACT

Rhabdomyolysis has been reported as a rare side effect of levetiracetam, a first-line anti-epileptic medication. We report the case of a 64-year-old man who presented to the medical center after suffering an unwitnessed seizure. Following the initiation of levetiracetam, the patient's serum creatine kinase (CPK) levels rose rapidly and remained elevated for multiple days. However, the patient did not report any symptoms of acute rhabdomyolysis. Following discontinuation of the medication CPK levels normalized, suggesting that this is a reversible adverse effect of levetiracetam. The patient made a complete recovery and did not display any seizure activity after the initial presentation. This seemingly more common side effect could cause further damage, particularly to the kidneys, and should be monitored closely by prescribing clinicians.

PMID:38111426 | PMC:PMC10726084 | DOI:10.7759/cureus.48955

Mol Imaging Biol. 2023 Dec 18. doi: 10.1007/s11307-023-01878-7. Online ahead of print.

ABSTRACT

PURPOSE: Minzasolmin (UCB0599) is an orally administered, small molecule inhibitor of ASYN misfolding in development as a potential disease-modifying therapy for Parkinson's disease. Here we describe the preclinical development of a radiolabeled tracer and results from a phase 1 study using the tracer to investigate the brain distribution of minzasolmin.

PROCEDURES: In the preclinical study, two radiolabeling positions were investigated on the S-enantiomer of minzasolmin (UCB2713): [11C]methylamine UCB2713 ([11C-N-CH3]UCB2713) and [11C]carbonyl UCB2713 ([11C-CO]UCB2713). Male C57 black 6 mice (N = 10) received intravenous [11C-N-CH3]UCB2713; brain homogenates were assessed for radioactivity and plasma samples analyzed by high-performance liquid chromatography. Positron emission tomography-computed tomography (PET-CT) was used to image brains in a subset of mice (n = 3). In the open-label, phase 1 study, healthy volunteers were scanned twice with PET-CT following injection with [11C]minzasolmin radiotracer (≤ 10 µg), first without, then with oral dosing with non-radiolabeled minzasolmin 360 mg.

PRIMARY OBJECTIVE: to determine biodistribution of minzasolmin in the human brain; secondary objectives included minzasolmin safety/tolerability.

RESULTS: Preclinical data supported the use of [11C]minzasolmin in clinical studies. In the phase 1 study, PET data showed substantial drug signal in the brain of healthy volunteers (N = 4). The mean estimated whole brain total distribution volume (VT) at equilibrium across all regions of interest was 0.512 mL/cm3, no difference in VT was observed following administration of minzasolmin 360 mg. Treatment-emergent adverse events (TEAEs) were reported by 75% (n = 3) of participants. No drug-related TEAEs, deaths, serious adverse events, or discontinuations were reported.

CONCLUSION: Following positive preclinical results with the N-methyl labeled PET tracer, [11C]minzasolmin was used in the phase 1 study, which demonstrated that minzasolmin readily crossed the blood-brain barrier and was well distributed throughout the brain. Safety and pharmacokinetic findings were consistent with previous early-phase studies (such as UP0077, NCT04875962).

PMID:38110790 | DOI:10.1007/s11307-023-01878-7