BMC Med Educ. 2024 Jan 3;24(1):13. doi: 10.1186/s12909-023-04963-1.

ABSTRACT

Pharmacovigilance stands out for its importance in obtaining existing knowledge about medicine and patient safety and should be recognized as a continuous line of study. It constitutes a highly relevant component in the activities of health professionals, with spontaneous notification of suspected adverse drug reactions being its main emphasis. The underreporting that persists can be overcome through continuous professional development programs, reinforcing theoretical and practical knowledge in the curricular plans of health courses. As a result, more educated professionals will also allow citizens to recognize the importance of pharmacovigilance. The main objective of this study was to describe and characterize the teaching-learning process of pharmacovigilance in Portugal, analyzing the knowledge, perceptions and attitudes of students and health professionals. In total, ninety-three curricular unit forms of the seventeen healthcare courses included were analyzed, among which only three referred to pharmacovigilance as mandatory and thirty-nine did not address any keywords. The questionnaire applied was answered by 650 participants, both students (62%) and professionals (38%). Approximately 84.4% of the students and 54.7% of the professionals affirmed that they had never spontaneously reported an adverse drug reaction. Only 24.6% of the students and 17.8% of professionals referred to the existence of specific course content dedicated to pharmacovigilance in their coursework. In view of these results, it is evident that there is a need for a wider reflection regarding the further training and constant update of practicing professionals as well as in diverse health institutions, investing in the creation of an academic curriculum that integrates pharmacovigilance in healthcare courses.

PMID:38172845 | PMC:PMC10765940 | DOI:10.1186/s12909-023-04963-1

Sante Publique. 2024 Jan 3;35(5):121-132. doi: 10.3917/spub.235.0121.

ABSTRACT

INTRODUCTION: Seasonal malaria chemoprevention (SMC) by mass administration of sulfadoxine pyrimethamine + amodiaquine (SPAQ) reduces the burden of malaria in children aged 3–59 months. The occurrence of adverse drug reaction (ADR) may affect the success of this intervention. There are few studies of SMC adverse event surveillance in sub-Saharan Africa, particularly in Burkina Faso, a highly endemic country. Our main objective was to characterize the ADRs reported during SMC campaigns in Burkina Faso. Secondly, we evaluated the performance of the pharmacovigilance integrated into the SMC program in order to support safe administration of SMC.

METHOD: This was a retrospective descriptive study of SMC individual case safety reports recorded in VigiBase® in Burkina Faso from 2014 to 2021. We used the P-method for the analysis of preventable serious adverse drug reactions and WHO criteria for assessing the performance of pharmacovigilance integrated into the SMC program.

RESULTS: A total of 1,105 SMC individual case safety reports were registered in VigiBase® for 23,311,453 doses of SPAQ given between 2014 and 2021. No pharmacovigilance signal was detected. The number of serious cases was 101, of which 23 (22.8%) were preventable. In 38.1% of children, the occurrence of ADRs led to discontinuation of SMC treatment. Vomiting was the most frequently reported adverse drug reaction (48.0%). The proportion of children whose treatment was discontinued due to vomiting was 42.7%, while the proportion of treatment discontinuation for other ADRs was 32.8% (p = 0.01). The SMC program contributed at 46.2% to the national pharmacovigilance database. The reporting rate was 0.03 per 1,000 exposed children in 2021. The median completeness score of the ICSRs was 0.7 (IQR: 0.5–0.7), and the median time to register the ICSRs in VigiBase® was 204 (IQR: 143–333) days.

CONCLUSIONS: Post-drug administration vomiting may interfere with the purpose of SMC. Measures to manage this adverse drug reaction should be taken to improve the success of the SMC program. Based on the information on reporting time and reporting rate, spontaneous reporting should be supported by active surveillance, including cohort event monitoring, in Burkina Faso.

PMID:38172043 | DOI:10.3917/spub.235.0121

BMC Med. 2024 Jan 2;22(1):5. doi: 10.1186/s12916-023-03213-x.

ABSTRACT

BACKGROUND: Long-term opioid use is associated with dependency, addiction, and serious adverse events. Although a framework to reduce inappropriate opioid prescribing exists, there is no consensus on prescribing indicators for preventable opioid-related problems in patients with chronic pain in primary care in the UK. This study aimed to identify opioid prescription scenarios for developing indicators for prescribing opioids to patients with chronic pain in primary care.

METHODS: Scenarios of opioid prescribing indicators were identified from a literature review, guidelines, and government reports. Twenty-one indicators were identified and presented in various opioid scenarios concerning opioid-related harm and adverse effects, drug-drug interactions, and drug-disease interactions in certain disease conditions. After receiving ethics approval, two rounds of electronic Delphi panel technique surveys were conducted with 24 expert panellists from the UK (clinicians, pharmacists, and independent prescribers) from August 2020 to February 2021. Each indicator was rated on a 1-9 scale from inappropriate to appropriate. The score's median, 30th and 70th percentiles, and disagreement index were calculated.

RESULTS: The panel unanimously agreed that 15 out of the 21 opioid prescribing scenarios were inappropriate, primarily due to their potential for causing harm to patients. This consensus was reflected in the low appropriateness scores (median ranging from 1 to 3). There were no scenarios with a high consensus that prescribing was appropriate. The indicators were considered inappropriate due to drug-disease interactions (n = 8), drug-drug interactions (n = 2), adverse effects (n = 3), and prescribed dose and duration (n = 2). Examples included prescribing opioids during pregnancy, concurrently with benzodiazepines, long-term without a laxative prescription and prescribing > 120-mg morphine milligram equivalent per day or long-term duration over 3 months after surgery.

CONCLUSIONS: The high agreement on opioid prescribing indicators indicates that these potentially hazardous consequences are relevant and concerning to healthcare practitioners. Future research is needed to evaluate the feasibility and implementation of these indicators within primary care settings. This research will provide valuable insights and evidence to support opioid prescribing and deprescribing strategies. Moreover, the findings will be crucial in informing primary care practitioners and shaping quality outcome frameworks and other initiatives to enhance the safety and quality of care in primary care settings.

PMID:38167142 | DOI:10.1186/s12916-023-03213-x

Clin Colorectal Cancer. 2023 Dec 16:S1533-0028(23)00125-1. doi: 10.1016/j.clcc.2023.12.003. Online ahead of print.

ABSTRACT

Immune checkpoint inhibitors have transformed the treatment paradigm for various types of cancer. Nonetheless, with the utilization of these groundbreaking treatments, immune-related adverse events (irAEs) are increasingly encountered. Colonic and hepatic involvement are among the most frequently encountered irAEs. Drug-induced side effects, infectious causes, and tumor-related symptoms are the key differentials for irAE complications. Potential risk factors for the development of irAEs include combination use of immune checkpoint inhibitors, past development of irAEs with other immunotherapy treatments, certain concomitant drugs, and a pre-existing personal or family history of autoimmune illness such as inflammatory bowel disease. The importance of early recognition, timely and proper management cannot be understated, as there are profound clinical implications on the overall cancer treatment plan and prognosis once these adverse events occur. Herein, we cover the clinical management of the well-established gastrointestinal irAEs of enterocolitis and hepatitis, and also provide an overview of several other emerging entities.

PMID:38172003 | DOI:10.1016/j.clcc.2023.12.003

Nat Commun. 2024 Jan 2;15(1):14. doi: 10.1038/s41467-023-44514-2.

ABSTRACT

Cyclic high-dose testosterone administration, known as bipolar androgen therapy (BAT), is a treatment strategy for patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we report the results of a multicenter, single arm Phase 2 study (NCT03554317) enrolling 45 patients with heavily pretreated mCRPC who received BAT (testosterone cypionate, 400 mg intramuscularly every 28 days) with the addition of nivolumab (480 mg intravenously every 28 days) following three cycles of BAT monotherapy. The primary endpoint of a confirmed PSA50 response rate was met and estimated at 40% (N = 18/45, 95% CI: 25.7-55.7%, P = 0.02 one-sided against the 25% null hypothesis). Sixteen of the PSA50 responses were achieved before the addition of nivolumab. Secondary endpoints included objective response rate (ORR), median PSA progression-free survival, radiographic progression-free survival (rPFS), overall survival (OS), and safety/tolerability. The ORR was 24% (N = 10/42). Three of the objective responses occurred following the addition of nivolumab. After a median follow-up of 17.9 months, the median rPFS was 5.6 (95% CI: 5.4-6.8) months, and median OS was 24.4 (95% CI: 17.6-31.1) months. BAT/nivolumab was well tolerated, resulting in only five (11%) drug related, grade-3 adverse events. In a predefined exploratory analysis, clinical response rates correlated with increased baseline levels of intratumoral PD-1 + T cells. In paired metastatic tumor biopsies, BAT induced pro-inflammatory gene expression changes that were restricted to patients achieving a clinical response. These data suggest that BAT may augment antitumor immune responses that are further potentiated by immune checkpoint blockade.

PMID:38167882 | DOI:10.1038/s41467-023-44514-2

BMC Surg. 2024 Jan 2;24(1):3. doi: 10.1186/s12893-023-02293-z.

ABSTRACT

BACKGROUND: Hydromorphone hydrochloride has a satisfactory postoperative analgesic effect for patients with colorectal cancer but is accompanied by a relatively high incidence of adverse events. Low-doses of naloxone combined with opioids for patient-controlled analgesia can reduce the incidence of drug-related adverse events. Nalmefene is a more selective opioid receptor antagonist than naloxone. The aim of this study was to determine the impact of low-doses of nalmefene on the analgesic effect and incidence of adverse events of patients with hydromorphone patient-controlled analgesia (PCA) undergoing colorectal radical surgery.

METHODS: Ninety-nine patients undergoing elective laparoscopic or hand-assisted laparoscopic radical surgery under general anaesthesia were randomly divided into three groups. Group N1 received hydromorphone hydrochloride 0.15 mg/kg + nalmefene 2 µg/kg; Group N2 received hydromorphone hydrochloride 0.15 mg/kg + nalmefene 0.5 µg/kg; and the control group (Group C) received hydromorphone hydrochloride 0.15 mg/kg. All medications were diluted to 100 ml with normal saline. The primary outcome was pain intensity at 12 h after surgery; the secondary outcomes were the occurrence of nausea, vomiting and pruritus and the total analgesic consumption of the PCA pump at 1 h, 6 h, 12 h, 24 and 48 h after surgery.

RESULTS: The NRS scores of Group N1 (2 µg/kg) were significantly lower than those of Group C (P = 0.025), and no difference was found between group N2 and group C (P > 0.05). Among the three groups, the NRS scores of Group N1 (2 µg/kg) were significantly lower than those of Group C at 12 h (P = 0.01) and 48 h (P = 0.01) postoperatively. Compared with 12 h postoperatively, the NRS scores were lower at 24 h postoperatively in Group N1 and Group C (P < 0.05) and significantly lower at 48 h postoperatively in all three groups (P < 0.001). There was a significant difference in the incidence of pruritus among the three groups (P = 0.036).

CONCLUSIONS: Nalmefene at a dosage of 2 µg/kg enhances the postoperative analgesic effect of hydromorphone hydrochloride and reduces the occurrence of postoperative pruritus.

TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR2000033520, date: 03/06/2020).

PMID:38166917 | DOI:10.1186/s12893-023-02293-z

PLoS One. 2024 Jan 2;19(1):e0295208. doi: 10.1371/journal.pone.0295208. eCollection 2024.

ABSTRACT

BACKGROUND: Stroke is a neurological disease and a leading cause of mortality worldwide. Strokes mainly consist of two types: hemorrhage and ischemia. Stroke patients are being administered multiple drug therapy and are at risk of drug-related problems.

AIM: To estimate drug-related problems (DRPs) and clinical end outcomes in hospitalized stroke patients.

METHODS: Current study was a multicenter, cross-sectional prospective observational study including 250 stroke patients admitted to tertiary care hospitals in Karachi, Pakistan. The study included all clinical subtypes of stroke patients i.e. Stroke, Ischemic stroke, Hemorrhagic stroke, CVA, and TIA. Associations among patient-clinical end outcomes and drug therapy-related variables like DRPs, mortality, and morbidity rates were estimated using Pearson's chi-squared test. Statistical analysis was done by using SPSS software, version 25.

RESULTS: A total of 250 patients participated in this study suffering from different clinical subtypes of stroke i.e. Ischemic stroke, hemorrhagic stroke, TIA, and CVA, including 46% male and 54% female patients. The majority of patients' stay at the hospital was between 1-10 days. The overall mortality rate in stroke patients was 51%. HAIs were observed in 70% of patients, HAIs faced by patients were SAP, CAP, UTI, sepsis, and VAP. Drugs were assessed according to NEML i.e. access group antibiotics, watch group antibiotics, reserve group antibiotics, statins, antiepileptics, and proton pump inhibitors. Majorly ceftriaxone was administered to 79% of patients, piperacillin-tazobactam to 52%, and cefixime to 48%, whereas meropenem was administered to 42% of patients along with vancomycin to 39% of total patients. A high mortality rate was observed in the case of Klebsiella pneumoniae and Staphylococcus aureus i.e. 78% and in the case of streptococcus pneumoniae 61% mortality rate was observed. Due to the presence of DRPs and various other clinical factors like comorbidities, DDIs, HAIs, administration of potentially nephrotoxic drugs, and administration of antibiotics without having CST, hospitalized stroke patients faced many problems.

CONCLUSION: This study helped determine DRPs along with various clinical factors affecting the clinical end outcomes of patients suffering from any clinical subtype of stroke. Due to the enhancement in the evidence of the incidence of DRPs in tertiary care hospitals, pharmacist-led drug therapy review by interfering with doctors and other medical professionals at the patient bed site is needed and should be done to avoid any negative end outcomes and serious issues related to DRPs.

PMID:38165875 | DOI:10.1371/journal.pone.0295208

PLoS One. 2024 Jan 2;19(1):e0296450. doi: 10.1371/journal.pone.0296450. eCollection 2024.

ABSTRACT

Drug-induced pseudoaldosteronism is a typical adverse effect of Kampo formulas. Previous research described the potential risks of Kampo formula-linked pseudoaldosteronism. However, few studies assessed the risk factors using a real-world database and a data-mining approach. Using the Japanese Adverse Drug Event Report database, we extracted pseudoaldosteronism reports for 148 Kampo formulas covered by Japanese national health insurance. Adverse events were decided according to the preferred terminology of the Medical Dictionary for Regulatory Activities/Japanese version 25.1. We calculated reporting odds ratio (RORs) and identified Kampo formulas as suspected causes of pseudoaldosteronism. Moreover, we evaluated clinical factors associated with Kampo formula-induced pseudoaldosteronism via logistic regression. From April 2004 to November 2022, 6334 adverse events related to the Kampo formulas were reported. We selected 2471 reports containing complete clinical data, including 210 reports on pseudoaldosteronism. In the pseudoaldosteronism group, 69.0% of patients were female, and 85.2% were ≥70 years old. The formulas most commonly associated with pseudoaldosteronism were Shakuyakukanzoto, Yokukansan, and Ryokeijutsukanto (ROR [95% confidence interval {CI}] = 18.3 [13.0-25.9], 8.1 [5.4-12.0], and 5.5 [1.4-21.9], respectively). Logistic analysis identified female sex (odds ratio [OR] [95% CI] = 1.7 [1.2-2.6]; P = 0.006), older age (≥70, 5.0 [3.2-7.8]; P < 0.001), low body weight (<50 kg, 2.2 [1.5-3.2]; P < 0.001), diuretics usage (2.1 [1.3-4.8]; P = 0.004), hypertension (1.6 [1.1-2.4]; P = 0.014), and dementia (7.0 [4.2-11.6]; P < 0.001) as pseudoaldosteronism-related factors. Additionally, the daily Glycyrrhiza dose (OR = 2.1 [1.9-2.3]; P < 0.001) and duration of administration (>14 days, OR = 2.8 [1.7-4.5]; P < 0.001) were associated with adverse events. We did not observe an interaction between aging and hypertension. Careful follow-up is warranted during long-term Glycyrrhiza-containing Kampo formula use in patients with multiple clinical factors for pseudoaldosteronism.

PMID:38165850 | DOI:10.1371/journal.pone.0296450

West J Emerg Med. 2023 Nov;24(6):1131-1145. doi: 10.5811/westjem.59099.

ABSTRACT

INTRODUCTION: Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration (FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion duration. Recently, simplified, off-label two-bag NAC infusion protocols have become more common. The purpose of this review is to summarize the effectiveness and safety of two-bag NAC.

METHODS: We undertook a comprehensive search of PubMed, EMBASE, and MEDLINE from inception to December 13, 2022, for articles describing human acetaminophen poisonings treated with two-bag NAC, defined as any regimen involving two discrete infusions in two separate bags. Outcomes included effectiveness (measured by incidence of liver injury); incidence of non-allergic anaphylactoid reactions (NAAR); gastrointestinal, cutaneous, and systemic reactions; treatments for NAARs; incidence of NAC-related medication errors; and delays or interruptions in NAC administration.

RESULTS: Twelve articles met final inclusion, 10 of which compared two-bag NAC to the three-bag regimen. Nine articles evaluated the two-bag/20-hour regimen, a simplified version of the FDA-approved three-bag regimen in which the traditional first and second bags are combined into a single four-hour infusion. Nine articles assessed comparative effectiveness of two-bag NAC in terms of liver injury, most commonly assessed for by incidence of hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1,000 international units per liter). No difference in liver injury was observed between two-bag and three-bag regimens. Of nine articles comparing incidence of NAARs, eight demonstrated statistically fewer NAARs with two-bag regimens, and one showed no difference. In seven articles evaluating treatment for NAARs (antihistamines, corticosteroids, epinephrine), all showed that patients received fewer medications for NAARs with two-bag NAC. Three articles evaluated NAC-related medication errors; two demonstrated no difference, while one study evaluating only children showed fewer errors with two-bag NAC. Two studies evaluated delays and/or interruptions in NAC infusions; both favored two-bag NAC.

CONCLUSION: For patients with acetaminophen poisoning, two-bag NAC regimens appear to have similar outcomes to the traditional three-bag regimen in terms of liver injury. Two-bag NAC regimens are associated with fewer adverse events and fewer treatments for those events than the three-bag regimen and fewer interruptions in antidotal therapy.

PMID:38165196 | DOI:10.5811/westjem.59099

Am J Psychiatry. 2024 Jan 1;181(1):81-82. doi: 10.1176/appi.ajp.20230484.

NO ABSTRACT

PMID:38161298 | DOI:10.1176/appi.ajp.20230484

Psychiatry Investig. 2023 Dec;20(12):1112-1125. doi: 10.30773/pi.2022.0216. Epub 2023 Dec 18.

ABSTRACT

OBJECTIVE: To find the safety of long-acting injectable antipsychotics (LAIs) compared to each other, and/or placebo in the treatment of schizophrenia (SCZ) and/or schizoaffective disorder (SZA).

METHODS: We performed a systematic review and a network meta-analysis of randomized controlled trials (RCTs) comparing the safety of LAIs versus other LAIs or placebo in adults diagnosed with SCZ or SZA. The primary outcomes were treatment emergent adverse events (TEAEs), serious treatment emergent adverse events (STEAEs), and deaths. The secondary outcomes included treatment discontinuations due to adverse events and all-cause discontinuations.

RESULTS: Seventeen RCTs were included (n=7,908). There were no significant differences between LAIs and placebo in the risk of presenting TEAEs. LAIs had a significant lower risk of presenting STEAEs except for aripiprazole. No significant differences in deaths were found. LAIs showed a significant protective effect against all-cause discontinuation, except for haloperidol. Only aripiprazole had a significantly lower risk of treatment discontinuation due to adverse events.

CONCLUSION: We found no significant differences in the risk of presenting TEAEs between LAIs and placebo. The majority of LAIs had a significantly lower risk of presenting STEAEs than placebo. Development of international guidelines for the report of safety outcomes related to antipsychotics especially for LAIs in clinical trials could minimize report and interpretation biases and improve the accuracy of posterior meta-analysis.

PMID:38163650 | DOI:10.30773/pi.2022.0216

Cureus. 2023 Dec 30;15(12):e51335. doi: 10.7759/cureus.51335. eCollection 2023 Dec.

ABSTRACT

Background and aim Antidepressant drugs are commonly used to treat depressive disorders and anxiety. However, they can cause side effects, including drug-induced serotonin syndrome, which is a potentially life-threatening condition. It is essential to understand the level of knowledge of healthcare professionals who are likely to prescribe and administer these medications. This article aims to assess the knowledge of Saudi medical, nursing, and pharmacy students and interns regarding antidepressant drugs and drug-induced serotonin syndrome. Methods A cross-sectional survey was conducted among medical, nursing, and pharmacy students and interns in Saudi Arabia. A self-administered questionnaire was used to collect data from participants. The questionnaire consisted of three sections: demographic information, knowledge about antidepressants, and knowledge about serotonin syndrome. Results A total of 425 participants were included in the study. The median knowledge score for antidepressants and serotonin syndrome was moderate to good, with median scores of 18 out of 23 (IQR: 16-20) and eight out of 12 (IQR: 6-10), respectively. However, more than half of the participants had sufficient knowledge about these topics, with only 227 (53.4%) and 264 (62.1%) having sufficient knowledge about antidepressants and serotonin syndrome, respectively. Regarding serotonin syndrome, males had a significantly higher proportion of sufficient knowledge compared to females, 86 (70.5%) out of 122 vs. 178 (58.7%) out of 303 (p=0.024), respectively. Medical students/interns had a significantly higher proportion of sufficient knowledge about antidepressants compared to nursing students/interns. According to the academic year, interns had the highest proportion of sufficient knowledge. Conclusion The current study revealed that Saudi medical, nursing, and pharmacy students and interns had moderate to good levels of knowledge about antidepressants and serotonin syndrome. The participating students had slightly better knowledge about serotonin syndrome in comparison to knowledge about antidepressants. Further research is needed to identify the causes of the knowledge gap and develop targeted interventions to address these causes. Educational efforts to ensure the safe and effective use of antidepressants are needed.

PMID:38161564 | PMC:PMC10757576 | DOI:10.7759/cureus.51335

Sr Care Pharm. 2024 Jan 1;39(1):14-21. doi: 10.4140/TCP.n.2024.14.

ABSTRACT

Background Older people have higher risk of experiencing medication-related problems (MRPs), leading to increased morbidity, health care use, and mortality. Few studies have examined the pathway between limited English proficiency (LEP) among older people and health service use through MRPs. Objective This study aimed to explore the association of LEP among Latino older people with MRPs and their relationship to emergency room (ER) visits. Methods Researchers used secondary enrollment data from a community medication program for older people (N = 180). Researchers conducted linear regression to examine the relationship between ethnicity/English proficiency and MRPs, and logistic regression to explore the association between MRPs and ER visits. Generalized structural equation modeling (GSEM) with bootstrapping was used to test the indirect effect between LEP Latino through MRPs to ER visits. Results The sample included 70% non-Latino participants, 12% English-speaking Latinos, and 18% LEP Latinos. Analysis LEP Latinos were associated with having 3.4 more MRPs than non-Latino participants, after controlling for covariates. Additionally, each additional MRP was associated with a 10% increased probability of having an ER visit. The GSEM results illustrated there was a significant indirect effect between LEP through MRPs to ER visits (β = 0.27, 95% CI 0.07-0.61). Conclusion Though LEP was not directly related to increased ER visits, it may have inhibited the ability of Latinos to read and understand medication instructions, contributing to their elevated risk of experiencing MRPs, thus indirectly increasing potential risks of having ER visits.

PMID:38160237 | DOI:10.4140/TCP.n.2024.14

Ter Arkh. 2023 Aug 17;95(6):494-499. doi: 10.26442/00403660.2023.06.202297.

ABSTRACT

AIM: To evaluate the efficacy and safety of a combination of virus-neutralizing monoclonal antibodies - MAB (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with risk factors in real word settings.

MATERIALS AND METHODS: A non-interventional non-comparative observational study with primary prospective data collection included 108 patients with mild to moderate COVID-19 (mean age 61 years), who had risk factors for developing severe disease. All patients (n=108) were treated with a combination of MAB casirivimab and imdevimab intravenous single infusion 1200 mg (600 mg of each component). The efficacy and safety of MAB were assessed at 7, 14, and 28 days after infusion.

RESULTS: Efficacy. Indications for hospitalization by day 7 from the moment of MAB administration were in 0.9% (n=1), by day 14 - in 1.9% (n=2), by day 28 - in 0.9% of patients; to stay in the intensive care units by the 7th day - in 4.6% (n=5), by the 14th day - in 0.9% (n=1), by the 28th day - in 0.9% (n=1) patients. During 28 days of follow up, the need for mechanical ventilation and extracorporeal membrane oxygenation was registered in 2/108 (1.8%) patients. There were no deaths directly related to COVID-19 in the assessed cohort of patients. Safety. By the 28th day of the follow up, no adverse effects due to MAB therapy were registered.

CONCLUSION: An analysis of the results of a non-interventional observational study summarized in this article showed the high efficacy and safety of virus-neutralizing MAB combination (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with of risk factors for severe COVID-19 in real word settings.

PMID:38158969 | DOI:10.26442/00403660.2023.06.202297

Med Oncol. 2023 Dec 29;41(1):40. doi: 10.1007/s12032-023-02267-4.

ABSTRACT

Efforts in cancer immunotherapy aim to counteract evasion mechanisms and stimulate the immune system to recognise and attack cancer cells effectively. Combination therapies that target multiple aspects of immune evasion are being investigated to enhance the overall efficacy of cancer immunotherapy. PD-1 (Programmed Cell Death Protein 1), CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4), LAG-3 (Lymphocyte-Activation Gene 3), and TIM-3 (T Cell Immunoglobulin and Mucin Domain-Containing Protein3) are all immune checkpoint receptors that play crucial roles in regulating the immune response and maintaining self-tolerance often exploited by cancer cells to evade immune surveillance. Antibodies targeted against immune checkpoint inhibitors such as anti-PD-1 antibodies (e.g., pembrolizumab, nivolumab), anti-CTLA-4 antibodies (e.g., Ipilimumab), and experimental drugs targeting LAG-3 and TIM-3, aim to block these interactions and unleash the immune system's ability to recognise and destroy cancer cells. The US FDA has approved different categories of immune checkpoint inhibitors that have been utilised successfully in some patients with metastatic melanoma, renal cell carcinoma, head and neck cancers, and non-small lung cancer. Although several immune checkpoint inhibitor antibodies have been developed, they exhibited immune-related adverse effects, resulting in hypophysitis, diabetes, and neurological issues. These adverse effects of antibodies can be reduced by developing aptamer against the target. Aptamers offer several advantages over traditional antibodies, such as improved specificity, reduced immunogenicity, and flexible design for reduced adverse effects that specifically target and block protein-protein or receptor-ligand interactions involved in immune checkpoint pathways. The current study aims to review the function of particular immune checkpoint inhibitors along with developed aptamer-mediated antitumor cytotoxicity in cancer treatment.

PMID:38158454 | DOI:10.1007/s12032-023-02267-4

Int J Antimicrob Agents. 2023 Dec 27:107075. doi: 10.1016/j.ijantimicag.2023.107075. Online ahead of print.

ABSTRACT

INTRODUCTION: 9MW1411 is a humanized monoclonal antibody against S. aureus alpha toxin. The safety, pharmacokinetics (PK) and immunogenicity of 9MW1411 should be characterized in humans before further clinical development.

METHODS: A single-centre, randomised, double-blind, placebo-controlled phase I clinical study was conducted in humans for the first time. A total of 42 healthy Chinese subjects were randomised to receive single ascending dose of 9MW1411 (200, 600, 1500, 3000 or 5,000 mg) or placebo. Safety, PK parameters, anti-drug antibody (ADA) were analysed. Monte Carlo simulations (MCS) were performed to predict the probability of target attainment (PTA) after single dose IV administration of 1500, 3000 and 5000 mg of 9MW1411.

RESULTS: Thirty-four subjects received 9MW1411, completed the study, and were included in data analysis. Five cases of drug-related AEs occurred in 4 subjects. All the adverse events (AEs) were mild or moderate. The Cmax, AUC0-t, and AUC0-∞ of 9MW1411 increased with dose after IV administration of 200 to 5000 mg 9MW1411. The mean Cmax increased from 85.40 ± 5.43 to 2082.11 ± 343.10 μg/mL, and AUC0-∞ from 29511.68 ± 5550.91 to 729985.49 ± 124932.18 h·μg/mL. The elimination half-life (T1/2) was 19-23 days. 9MW1411 ADA was positive in 3 subjects. MCS indicated that single dose of 3000 or 5000 mg 9MW1411 could achieve PTA > 90% for S. aureus.

CONCLUSIONS: 9MW1411 has shown a good safety profile in healthy Chinese subjects after single dose up to 5000 mg. Single dose of 3000 mg 9MW1411 is appropriate for use in subsequent studies.

PMID:38157918 | DOI:10.1016/j.ijantimicag.2023.107075

Nagoya J Med Sci. 2023 Nov;85(4):668-681. doi: 10.18999/nagjms.85.4.668.

ABSTRACT

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for treating pain and inflammation. Spontaneous adverse drug reaction (ADR) reports represent a rich data source for the detection of unknown and rare ADRs. This cross-sectional study aimed to analyze the characteristics of ADRs due to NSAIDs in Thailand. All ADR reports of NSAIDs for systemic use from 2015 to 2019 were extracted from the national database in Thailand. Patient characteristics, drug use information, adverse event information, and source of senders in 32,857 reports were analyzed. The annual number of ADR reports due to NSAIDs decreased from 7,008 in 2015 to 5,922 in 2019. The most frequently reported drug was ibuprofen (n=12,645, 38.5%) followed by diclofenac (n=7,795, 23.7%), most patients were 40-59 years old, and the major adverse reaction was angioedema (n=7,513, 22.9%). Serious reactions were recorded in 20.7% (n=6,801) of the total ADRs. Most patients (n=20,593, 62.7%) recovered without sequelae, but there were 5,420 patients (16.5%) who could not recover and 3,109 patients (9.5%) who were recovering. Eight patients (0.02%) died of Stevens-Johnson syndrome (n=3), toxic epidermal necrolysis (n=4), and anaphylactic shock (n=1), which were possibly related to ADRs. The number of ADR reports due to NSAIDs decreased from 2015 to 2019 in Thailand. Serious ADRs and death cases accounted for 20.7% and 0.02%, respectively. Most fatal cases exhibited severe drug-induced skin reactions.

PMID:38155619 | PMC:PMC10751502 | DOI:10.18999/nagjms.85.4.668

Cureus. 2023 Nov 28;15(11):e49548. doi: 10.7759/cureus.49548. eCollection 2023 Nov.

ABSTRACT

Corticosteroid-induced myopathy is the most common drug-induced myopathy and could appear during the treatment of diseases where corticosteroids are the mainstay of treatment. We present a clinical case of a patient treated with corticosteroids who presented with proximal muscle weakness, myalgias, marked elevation of muscle enzymes, and acute kidney injury due to rhabdomyolysis. The definitive diagnosis was only possible through a muscle biopsy.

PMID:38156153 | PMC:PMC10753519 | DOI:10.7759/cureus.49548

BMJ Open. 2023 Dec 28;13(12):e076028. doi: 10.1136/bmjopen-2023-076028.

ABSTRACT

OBJECTIVE: Investigate risk for falls, fractures and syncope in older adult patients treated with nortriptyline compared with paroxetine and alternative medications.

DESIGN: Retrospective cohort study.

SETTING: The electronic medical record and prescription drug database of a large integrated healthcare system in Southern California.

PARTICIPANTS: Ambulatory patients, age ≥65 years diagnosed with depression, anxiety disorder or peripheral neuropathy, dispensed one or more of ten study medications between 1 January 2008 and 31 December 2018.

MAIN OUTCOME MEASURES: HR for falls, fractures and syncope with exposure to study medications adjusted for patient demographic variables and comorbidities.

RESULTS: Among 195 207 subjects, 19 305 falls, 15 088 fractures and 11 313 episodes of syncope were observed during the study period. Compared with the reference medication, nortriptyline, the adjusted HRs (aHRs) for falls were statistically significantly greater for: paroxetine (aHR 1.48, 95% CI 1.39 to 1.57), amitriptyline (1.20, 95% CI 1.08 to 1.33), venlafaxine (1.44, 95% CI 1.34 to 1.56), duloxetine (1.25, 95% CI 1.12 to 1.40), fluoxetine (1.51, 95% CI 1.44 to 1.59), sertraline (1.53, 95% CI 1.44 to 1.62), citalopram (1.61, 95% CI 1.52 to 1.71) and escitalopram (1.37, 95% CI 1.21 to 1.54), but not gabapentin (0.95, 95% CI 0.89 to 1.02). For fractures, compared with nortriptyline, aHRs were significantly greater for: paroxetine, venlafaxine, duloxetine, fluoxetine, sertraline, citalopram, escitalopram and gabapentin, with aHRs ranging from 1.30 for gabapentin to 1.82 for escitalopram; risk was statistically similar for amitriptyline. For syncope, the aHRs were significantly greater for: paroxetine, venlafaxine, fluoxetine, sertraline and citalopram, with aHRs ranging from 1.19 for fluoxetine and paroxetine up to 1.30 for citalopram and sertraline; risk was similar for amitriptyline, duloxetine, escitalopram and gabapentin.

CONCLUSIONS: Compared with therapeutic alternatives, nortriptyline was found to represent a lower risk for falls, fractures and syncope, versus comparator medications, except for a few instances that had equivalent risk. The risk for these adverse events from paroxetine was comparable to the alternative medications.

PMID:38154883 | DOI:10.1136/bmjopen-2023-076028

Support Care Cancer. 2023 Dec 28;32(1):68. doi: 10.1007/s00520-023-08275-4.

ABSTRACT

BACKGROUND: In the field of exercise oncology, there is a need to quantify the potential benefits of moderate, self-directed physical activity during active treatment. In a pooled analysis of three identical single-arm intervention studies, we investigate the association of activity tracker steps with patient-reported toxicities during chemotherapy.

METHODS: Women with early breast cancer who were enrolled in the intervention studies reported their symptom severity every 2-3 weeks throughout chemotherapy, and daily steps were documented through a Fitbit activity tracker. Relative risks (RR) and 95% confidence intervals (CI) were calculated using Poisson regression models with robust variance. For outcomes significant in unadjusted models, adjusted RRs were calculated controlling for race, age, and education level. Tracker step cut point (high step, low step) was determined by the means. Cumulative incidence functions of moderate, severe, and very severe (MSVS) symptoms were estimated using the Kaplan-Meier method and compared using a Cox proportional hazard model.

RESULTS: In a sample of 283 women, mean age was 56 years and 76% were White. Mean tracker-documented steps/week were 29,625, with 55% walking below the mean (low step) and 45% above (high step). In multivariable analysis, high step patients had lower risk for fatigue [RR 0.83 (0.70, 0.99)] (p = 0.04), anxiety [RR 0.59 (0.42, 0.84)] (p = 0.003), nausea [RR 0.66 (0.46, 0.96)] (p = 0.03), depression [RR 0.59 (0.37, 0.03)] (p = 0.02), and ≥ 6 MSVS symptoms [RR 0.73 (0.54, 1.00)] (p = 0.05) and had 36% lower risk for dose reductions [RR 0.64 (95% CI 0.43, 0.97)] (p = 0.03).

CONCLUSION: Self-directed walking at a rate of at least 30,000 steps/week may moderate the severity of treatment side effects during chemotherapy for early breast cancer.

TRIAL NUMBERS: NCT02167932, NCT02328313, NCT03761706.

PMID:38153568 | DOI:10.1007/s00520-023-08275-4