Annu Int Conf IEEE Eng Med Biol Soc. 2023 Jul;2023:1-4. doi: 10.1109/EMBC40787.2023.10340721.

ABSTRACT

Drug-induced liver injury (DILI) is one of the most common and serious adverse drug reactions that can lead to acute liver failure and death. Detection of DILI and causal estimation of drug-hepatotoxicity association are of great importance for patient safety. This paper proposes a framework for causal estimation of post-marketing drugs for DILI from real-world electronic health record (EHR) data. Randomized clinical trials were replicated at scale by automatically generating different user and non-user cohorts for each potential drug, and average treatment effects (ATEs) of drugs were estimated using targeted maximum likelihood estimation. Ten years of real-world EHRs were used to validate the framework. Of all 1199 single-ingredient drugs analyzed, 7 novel and 7 known drug-hepatotoxicity associations were found to be causal.

PMID:38083643 | DOI:10.1109/EMBC40787.2023.10340721

Annu Int Conf IEEE Eng Med Biol Soc. 2023 Jul;2023:1-4. doi: 10.1109/EMBC40787.2023.10340698.

ABSTRACT

Vaccine safety is a critical issue for public health, which has recently become more crucial than ever since COVID-19 started to spread worldwide in 2020. Many COVID-19 vaccines have been developed and used without following the traditional three clinical trial stages. Instead, most COVID-19 vaccines were approved through emergency use approval (EUA) within one year, significantly raising the risk of rare and severe adverse events. Reporting systems like the Vaccine Adverse Event Reporting System (VAERS) have been established worldwide to detect unknown and severe adverse reactions as early as possible. Although experts and researchers have been working hard to find ways to detect adverse vaccine event (AVE) signals from VAERS data, most of the contemporary methods are statistical methods based on measuring the disproportionality between vaccine-induced events and non-vaccine-induced events. This paper proposes a novel ensemble AVE detection method, which adopts a stacking ensemble of various disproportionality indicators, fusing dual-scale contingency values measured in single and cumulative yearly duration, and embraces the concept of feature concatenation. Experiments conducted on US VAERS data to predict AVE caused by COVID-19 vaccines show that our proposed method is effective. We observed that: (1) Stacking ensemble of various disproportionality indicators is superior to any single disproportionality indicator and voting ensemble method; (2) Fusing dual-scale contingency values and feature concatenation brings synergy to our proposed stacking ensemble AVE detection. Compared to the best disproportionality metric in this study, our top-performing ensemble version exhibited a 34% improvement in accuracy, 71% in precision, 29% in recall, and 77% in F-measure, with a slight decrease (8%) in specificity.

PMID:38082660 | DOI:10.1109/EMBC40787.2023.10340698

J Eur Acad Dermatol Venereol. 2023 Dec 12. doi: 10.1111/jdv.19730. Online ahead of print.

ABSTRACT

BACKGROUND: Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex-specific differences in the safety of systemic psoriasis therapies.

OBJECTIVES: To examine the real-world, long-term safety of systemic psoriasis therapies with sex stratification in drug-related adverse events (ADRs).

METHODS: Ten-year data from adults with moderate-to-severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient-years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t-tests to compare treatment groups and sex.

RESULTS: In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2-fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0-fold higher drug-related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non-significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87-9.68) compared to CSTs (7.08, CI 5.39-9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8-fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0-fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug-related discontinuation rates for most CSTs in females.

CONCLUSION: Females were associated with a significantly higher rate of ADRs and drug-related discontinuation rates. Sex stratification should be taken into consideration when designing studies in the patient-tailored management of psoriasis.

PMID:38084852 | DOI:10.1111/jdv.19730

J Natl Compr Canc Netw. 2023 Dec;21(12):1303-1311. doi: 10.6004/jnccn.2023.7100.

ABSTRACT

Patients with relapsed or refractory multiple myeloma (RRMM) that is refractory to a proteasome inhibitor, an immunomodulatory drug (IMiD), and an anti-CD38 antibody (triple-class refractory MM) have poor outcomes. Recently, 2 classes of T-cell engaging therapies-CAR T-cell therapy and bispecific T-cell engaging antibodies (BsAbs)-have resulted in unprecedented response rates and survival outcomes in these heavily pretreated patients. The most common targets are BCMA and GPRC5D, with other targets in development. The main classes of adverse effects include cytokine release syndrome, neurotoxicity, infections, and cytopenias, as well as adverse effects unique to specific products. As of September 2023, 2 BCMA-targeting CAR-T cell products, 2 BCMA-targeting BsAbs, and 1 GPRC5D-targeting BsAb, are FDA-approved for standard-of-care use in patients with RRMM who received at least 4 prior lines of therapy, including prior treatment with a proteasome inhibitor, an IMiD, and an anti-CD38 antibody. Earlier-line use is under investigation and has shown promising results. Several other investigational CAR-T constructs and bispecific antibodies are in clinical development. As these therapies become more widely used, including in earlier-line setting, efforts to understand optimal sequencing and mitigate toxicities remain critical.

PMID:38081142 | DOI:10.6004/jnccn.2023.7100

Cochrane Database Syst Rev. 2023 Dec 11;12(12):CD001909. doi: 10.1002/14651858.CD001909.pub4.

ABSTRACT

BACKGROUND: This is an updated version of a Cochrane Review last updated in 2020. Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. In nearly 30% of cases, epilepsy is resistant to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is a second-generation antiseizure medication. When used as an add-on (in combination with other antiseizure medications), lamotrigine can reduce seizures, but with some adverse effects.

OBJECTIVES: To evaluate the benefits and harms of add-on lamotrigine, compared with add-on placebo or no add-on treatment in people with drug-resistant focal epilepsy.

SEARCH METHODS: For this update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 3 October 2022 with no language restrictions. CRS Web includes randomised and quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups, including Epilepsy.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated add-on lamotrigine versus add-on placebo or no add-on treatment in people of any age with drug-resistant focal epilepsy. We used data from the first period of eligible cross-over trials.

DATA COLLECTION AND ANALYSIS: For this update, two review authors independently selected trials and extracted data. Our primary outcome was 50% or greater reduction in seizure frequency. Our secondary outcomes were treatment withdrawal, adverse effects, cognitive effects, and quality of life. Primary analyses were by intention-to-treat. We performed sensitivity best- and worse-case analyses to account for missing outcome data. We calculated pooled risk ratios (RRs) with 95% confidence intervals (95% Cls) for dichotomous outcomes.

MAIN RESULTS: We identified no new studies for this update, so the results and conclusions of the review are unchanged. We included five parallel-group studies in adults or children, eight cross-over studies in adults or children, and one parallel study with a responder-enriched design in infants. In total, these 14 studies enroled 1806 eligible participants (38 infants, 199 children, 1569 adults). Baseline phases ranged from four to 12 weeks and treatment phases ranged from eight to 36 weeks. We rated 11 studies (1243 participants) at low overall risk of bias and three (697 participants) at unclear overall risk of bias due to lack of information on study design. Four studies (563 participants) reported effective blinding. Lamotrigine compared with placebo probably increases the likelihood of achieving 50% or greater reduction in seizure frequency (RR 1.80, 95% CI 1.45 to 2.23; 12 trials, 1322 participants (adults and children); moderate-certainty evidence). There is probably little or no difference in risk of treatment withdrawal for any reason among people treated with lamotrigine versus people treated with placebo (RR 1.11, 95% CI 0.91 to 1.37; 14 trials; 1806 participants; moderate-certainty evidence). Lamotrigine compared with placebo is probably associated with a greater risk of ataxia (RR 3.34, 99% Cl 2.01 to 5.55; 12 trials; 1525 participants; moderate-certainty evidence), dizziness (RR 1.76, 99% Cl 1.28 to 2.43; 13 trials; 1768 participants; moderate-certainty evidence), nausea (RR 1.81, 99% CI 1.22 to 2.68; 12 studies, 1486 participants; moderate-certainty evidence), and diplopia (RR 3.79, 99% Cl 2.15 to 6.68; 3 trials, 944 participants; moderate-certainty evidence). There is probably little or no difference in the risk of fatigue between lamotrigine and placebo (RR 0.82, 99% CI 0.55 to 1.22; 12 studies, 1552 participants; moderate-certainty evidence).

AUTHORS' CONCLUSIONS: Lamotrigine as an add-on treatment for drug-resistant focal seizures is probably effective for reducing seizure frequency. Certain adverse effects (ataxia, dizziness, diplopia, and nausea) are probably more likely to occur with lamotrigine compared with placebo. There is probably little or no difference in the number of people who withdraw from treatment with lamotrigine versus placebo. The trials were of relatively short duration and provided no long-term evidence. In addition, some trials had few participants. Further trials are needed to assess the long-term effects of lamotrigine and to compare lamotrigine with other add-on drugs.

PMID:38078494 | PMC:PMC10712213 | DOI:10.1002/14651858.CD001909.pub4

World J Clin Cases. 2023 Nov 6;11(31):7583-7592. doi: 10.12998/wjcc.v11.i31.7583.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a common neurosurgical complication after brain tumor resection, and its prophylaxis has been widely studied. There are no effective drugs in the clinical management of venous thromboembolism, and there is an absence of evidence-based medicine concerning the treatment of severe multiple traumas.

AIM: To explore whether ulinastatin (UTI) can prevent VTE after brain tumor resection.

METHODS: The present research included patients who underwent brain tumor resection. Patients received UTIs (400,000 IU) or placebos utilizing computer-based random sequencing (in a 1:1 ratio). The primary outcome measures were the incidence of VTE, coagulation function, pulmonary emboli, liver function, renal function, and drug-related adverse effects.

RESULTS: A total of 405 patients were evaluated between January 2019 and December 2021, and 361 of these were initially enrolled in the study to form intention-to-treat, which was given UTI (n = 180) or placebo (n = 181) treatment in a random manner. There were no statistically significant differences in baseline clinical data between the two groups. The incidence of VTE in the UTI group was remarkably improved compared with that in the placebo group. UTI can improve coagulation dysfunction, pulmonary emboli, liver function, and renal function. No significant difference was identified between the two groups in the side effects of UTI-induced diarrhea, vomiting, hospital stays, or hospitalization costs. The incidence of allergies was higher in the UTI group than in the placebo group.

CONCLUSION: The findings from the present research indicated that UTI can decrease the incidence of VTE and clinical outcomes of patients after brain tumor resection and has fewer adverse reactions.

PMID:38078125 | PMC:PMC10698442 | DOI:10.12998/wjcc.v11.i31.7583

Mol Genet Metab Rep. 2023 Nov 28;38:101030. doi: 10.1016/j.ymgmr.2023.101030. eCollection 2024 Mar.

ABSTRACT

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an inherited disorder of cholesterol biosynthesis associated with congenital malformations, growth delay, intellectual disability and behavior problems. SLOS is caused by bi-allelic mutations in DHCR7, which lead to reduced activity of 7-dehydrocholesterol reductase that catalyzes the last step in cholesterol biosynthesis. Symptoms of SLOS are thought to be due to cholesterol deficiency and accumulation of its precursor 7-dehydrocholesterol (7-DHC) and 8-dehydrocholesterol (8-DHC), and toxic oxysterols. Therapy for SLOS often includes dietary cholesterol supplementation, but lipids are poorly absorbed from the diet, possibly due to impaired bile acid synthesis. We hypothesized that bile acid supplementation with cholic acid would improve dietary cholesterol absorption and raise plasma cholesterol levels.

METHODS: Twelve SLOS subjects (10 M, 2F, ages 2-27 years) who had plasma cholesterol ≤125 mg/dL were treated with cholic acid (10 mg/kg/day) divided twice daily for 2 months. Plasma cholesterol, 7-DHC and 8-DHC were measured by GC-MS. Oxysterols were measured by ultra-high-performance LC-MS/MS. Data were analyzed using paired t-tests.

RESULTS: At baseline, plasma cholesterol was 75 ± 24 mg/dL (mean ± SD; range 43-125, n = 12). After 2 months on cholic acid, mean plasma cholesterol increased to 97 ± 29 mg/dL (p = 0.011). Eleven of 12 subjects showed an increase in plasma cholesterol that varied from 3.8% to 85.7% (mean 38.7 ± 23.3%). 7-Hydroxycholesterol decreased by 20.6% on average (p = 0.013) but no significant changes were seen in 7-DHC or 8-DHC. Mean body weight tended to increase (3.6% p = 0.069). Subjects tolerated cholic acid well and experienced no drug-related adverse events.

CONCLUSIONS: In this pilot study, cholic acid supplementation was well tolerated and safe and resulted in an increase in plasma cholesterol in most SLOS subjects. Further controlled longitudinal studies are needed to look for the sustainability of the biochemical effect and possible clinical benefits.

PMID:38077958 | PMC:PMC10698565 | DOI:10.1016/j.ymgmr.2023.101030

Eur J Case Rep Intern Med. 2023 Oct 30;10(12):004121. doi: 10.12890/2023_004121. eCollection 2023.

ABSTRACT

Acute cholangitis is a critical medical condition requiring prompt intervention. This case report explores the complexities and uncertainties encountered in clinical decision-making when faced with a patient presenting with symptoms suggestive of acute cholangitis. We emphasise the importance of considering individual circumstances and factors in the diagnostic process. A 38-year-old woman with a history of Crohn's colitis presented with abdominal pain, jaundice and leukocytosis. Initial evaluation raised suspicions of acute cholangitis, but unexpected findings of blast cells in the peripheral smear led to a diagnosis of B-lymphoblastic leukaemia with BCR-ABL1 fusion. Treatment with steroids and chemotherapy resulted in the resolution of liver abnormalities. This case underscores the necessity of comprehensive assessments for obstructive jaundice and highlights the potential diagnostic challenges posed by underlying haematologic malignancies. It also raises awareness about drug-induced liver injury, and emphasises the importance of complete blood counts and differentials in the initial workup. Healthcare providers should be vigilant in considering alternative diagnoses when faced with obstructive jaundice, as misdiagnosis can lead to invasive procedures with potential adverse events.

LEARNING POINTS: This case highlights the significance of conducting a thorough initial assessment when a patient presents with symptoms suggestive of liver involvement, such as abdominal pain, jaundice and leukocytosis. In this case, the patient's initial symptoms were initially attributed to potential cholangitis due to her clinical presentation, but a peripheral smear unexpectedly revealed blast cells, leading to a diagnosis of B-lymphoblastic leukaemia.The case demonstrates that haematologic malignancies can manifest with various patterns of hepatic involvement, and their presentation can be diverse. In this instance, obstructive jaundice was caused by leukaemic infiltration of the liver, which is a rare initial presentation of acute lymphoblastic leukaemia (ALL).This demonstrates the diagnostic challenges in identifying rare conditions such as leukaemic infiltration of the liver, emphasising the importance of appropriate investigations and consultation with specialists.

PMID:38077708 | PMC:PMC10705825 | DOI:10.12890/2023_004121

Front Psychiatry. 2023 Nov 23;14:1271152. doi: 10.3389/fpsyt.2023.1271152. eCollection 2023.

ABSTRACT

Psychedelic therapy is, arguably, the next frontier in psychiatry. It offers a radical alternative to longstanding, mainstays of treatment, while exciting a paradigm shift in translational science and drug discovery. There is particular interest in 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)-a serotonergic psychedelic-as a novel, fast-acting therapeutic. Yet, few studies have directly examined 5-MeO-DMT for trauma- or stress-related psychopathology, including post-traumatic stress disorder (PTSD). Herein, we present the first longitudinal case study on 5-MeO-DMT for chronic refractory PTSD, in a 23-year-old female. A single dose of vaporized bufotoxin of the Sonoran Desert Toad (Incilius alvarius), containing an estimated 10-15 mg of 5-MeO-DMT, led to clinically significant improvements in PTSD, with next-day effects. This was accompanied by marked reductions in hopelessness and related suicide risk. Improvements, across all constructs, were sustained at 1-, 3-, 6-, and 12-months follow-up, as monitored by a supporting clinician. The subject further endorsed a complete mystical experience, hypothesized to underly 5-MeO-DMT's therapeutic activity. No drug-related, serious adverse events occurred. Together, results showed that 5-MeO-DMT was generally tolerable, safe to administer, and effective for PTSD; however, this was not without risk. The subject reported acute nausea, overwhelming subjective effects, and late onset of night terrors. Further research is warranted to replicate and extend these findings, which are inherently limited, non-generalizable, and rely on methods not clinically accepted.

PMID:38076677 | PMC:PMC10710141 | DOI:10.3389/fpsyt.2023.1271152

Lancet Reg Health Am. 2023 Nov 24;28:100641. doi: 10.1016/j.lana.2023.100641. eCollection 2023 Dec.

ABSTRACT

BACKGROUND: Hypoglycaemia from diabetes treatment causes morbidity and lower quality of life, and prevention should be routinely addressed in clinical visits.

METHODS: This mixed methods study evaluated how primary care providers (PCPs) assess for and prevent hypoglycaemia by analyzing audio-recorded visits from five Veterans Affairs medical centres in the US. Two investigators independently coded visit dialogue to classify discussions of hypoglycaemia history, anticipatory guidance, and adjustments to hypoglycaemia-causing medications according to diabetes guidelines.

FINDINGS: There were 242 patients (one PCP visit per patient) and 49 PCPs. Two thirds of patients were treated with insulin and 40% with sulfonylureas. Hypoglycaemia history was discussed in 78/242 visits (32%). PCPs provided hypoglycaemia anticipatory guidance in 50 visits (21%) that focused on holding diabetes medications while fasting and carrying glucose tabs; avoiding driving and glucagon were not discussed. Hypoglycaemia-causing medications were de-intensified or adjusted more often (p < 0.001) when the patient reported a history of hypoglycaemia (15/51 visits, 29%) than when the patient reported no hypoglycaemia or it was not discussed (6/191 visits, 3%). Haemoglobin A1c (HbA1c) was not associated with diabetes medication adjustment, and only 5/12 patients (42%) who reported hypoglycaemia with HbA1c <7.0% had medications de-intensified or adjusted.

INTERPRETATION: PCPs discussed hypoglycaemia in one-third of visits for at-risk patients and provided limited hypoglycaemia anticipatory guidance. De-intensifying or adjusting hypoglycaemia-causing medications did not occur routinely after reported hypoglycaemia with HbA1c <7.0%. Routine hypoglycaemia assessment and provision of diabetes self-management education are needed to achieve guideline-concordant hypoglycaemia prevention.

FUNDING: U.S. Department of Veterans Affairs and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

PMID:38076413 | PMC:PMC10701452 | DOI:10.1016/j.lana.2023.100641

JHEP Rep. 2023 Aug 12;5(12):100880. doi: 10.1016/j.jhepr.2023.100880. eCollection 2023 Dec.

ABSTRACT

BACKGROUND & AIMS: There is concern about the burden of liver injury in patients with cancer exposed to immune checkpoints inhibitors (ICIs).

METHODS: In a retrospective cohort study, we evaluated the likelihood of grade 3/4 liver injury, of grade 3/4 cholestatic liver injury, and of liver failure, as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5, following treatment with ICIs. We compared these occurrences with a group of cancer patients who were propensity-matched and treated with conventional chemotherapy. For all ICI patients experiencing grade 3/4 liver injury, we conducted a causality assessment using the RUCAM method and examined patient outcomes.

RESULTS: Among 952 patients (median [IQR] age 66 [57-73] years, 64% males) who were treated with ICI between January 1, 2015, and December 31, 2019, a total of 86 (9%) progressed to grade 3/4 liver injury, and liver failure was not observed. Anti-PD-(L)1/anti-CTLA-4 antibodies combinations (adjusted hazard ratio 3.36 [95% CI: 1.67-6.79]; p <0.001), and chronic hepatitis B (adjusted hazard ratio 5.48 [95% CI: 1.62-18.5]; p = 0.006], were independent risk factors. Liver injury was attributed to ICI treatment in 19 (2.0%) patients. Patients with ICI toxicity typically presented with granulomatous hepatitis or cholangiocyte inflammation. ICI withdrawal was associated with cancer progression and mortality. Re-introduction of ICI was not associated with recurrent grade 3/4 liver injury. Compared with matched patients treated with conventional, non-ICI-based chemotherapy, anti-PD-(L)1/anti-CTLA-4 combinations (p <0.001) and anti-PD-(L)1 monotherapies (p = 0.053) increased the risk of grade 3/4 liver injury and of grade 3/4 cholestatic liver injury, respectively.

CONCLUSIONS: An increased risk of grade 3/4 liver injury under anti-PD-(L)1/anti-CTLA-4 antibodies was observed, whereas no substantial increase in the likelihood of liver failure occurred even after treatment reintroduction.

IMPACT AND IMPLICATIONS: There is concern about liver injury in patients with cancer exposed to immune checkpoints inhibitors (ICIs). We investigated the burden of grade 3/4 liver injury after treatment with ICIs in a multicentric cohort of patients with cancer. Overall, a 9% incidence of grade 3/4 liver injury was detected after ICIs, and direct ICI hepatotoxicity was demonstrated in 2% of patients. Anti-PD-(L)1/Anti-CTLA-4 antibody combinations, and chronic HBV infection were independent risk factors. ICI withdrawal for grade 3/4 liver injury was associated with cancer progression. Re-introduction of ICI treatment was not associated with recurrent grade 3/4 liver injury.

PMID:38074948 | PMC:PMC10701119 | DOI:10.1016/j.jhepr.2023.100880

Cureus. 2023 Nov 7;15(11):e48453. doi: 10.7759/cureus.48453. eCollection 2023 Nov.

ABSTRACT

Durvalumab is an immune checkpoint inhibitor (ICI) belonging to the anti-programmed death-ligand 1 (PD-L1) class, and it is used in the treatment of various end-stage malignancies. Immune checkpoint inhibitors are associated with various systemic and cutaneous adverse events. Psoriasiform drug eruptions have been clinically observed in patients who have a personal history of psoriasis being treated with ICIs. We present a unique case of de novo psoriasis in a patient being treated for poorly differentiated adenocarcinoma of the lung. The patient responded well to topical treatment and did not require discontinuation of durvalumab. Our case highlights the importance of clinician familiarity with psoriasis presentation, its association with durvalumab therapy, and treatment options for durvalumab-induced psoriasis.

PMID:38074037 | PMC:PMC10702810 | DOI:10.7759/cureus.48453

Cureus. 2023 Nov 8;15(11):e48500. doi: 10.7759/cureus.48500. eCollection 2023 Nov.

ABSTRACT

AIMS: The aims were to evaluate rheumatic disorder patients' knowledge of the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs), dosage (from where the knowledge is acquired), contraindications (in pregnancy), and drug interactions (such as drug-related disorders), to improve their knowledge about taking NSAIDs in Saudi Arabia.

STUDY DESIGN: It is a descriptive cross-sectional study.

PLACE AND DURATION OF STUDY: The study was conducted among patients with rheumatic disorder (RD) in Saudi Arabia who were invited to join by completing an online questionnaire, from August to November 2022.

METHODOLOGY: Patients with RD who were 16 years and older, received oral NSAIDs, and agreed to participate were included in the study. The data was collected using an Internet-based questionnaire. The Internet-based questionnaire was designed using the Google Forms (Google LLC, Mountain View, California, United States) online survey platform. A consent form accompanied the questionnaire in a cover letter briefly describing the investigation.

RESULTS: A total of 756 participants answered the questionnaire and participated in the final analysis. Most of the participants (75.93%) were female. The type of NSAID used by the participants was Ibuprofen. The majority (83.41%) reported that they responded to the medication. When asked about the primary source of information about the correct dose of these medications, more than two-thirds (69.32%) reported that physicians are the main source of information. The majority of the participants (83.39%) denied using NSAIDs during pregnancy. Half of the participants (49.22%) said they had discussed these medications' harmful effects with their doctors or pharmacists. The female participants were more knowledgeable about NSAIDs and their side effects than the males.

CONCLUSION: The patient's knowledge related to the use of oral NSAIDs was not that satisfactory. There is an urgent need to educate the public regarding the appropriate use of NSAIDs by healthcare providers, particularly in relation to their proper use, potential side effects, and risks associated with long-term use.

PMID:38073919 | PMC:PMC10704060 | DOI:10.7759/cureus.48500

Eur J Hosp Pharm. 2023 Dec 9:ejhpharm-2023-003937. doi: 10.1136/ejhpharm-2023-003937. Online ahead of print.

ABSTRACT

BACKGROUND: Inhaled antibiotics have achieved or stabilised the clinical condition of patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa infection. We aimed to determine the effectiveness of aztreonam lysine inhaled solution (AZLI) in patients with CF and chronic P. aeruginosa infection.

METHODS: A retrospective observational study was conducted on patients with CF and chronic P. aeruginosa infection who received AZLI between July 2012 and September 2018 inclusive in three Spanish hospitals in a routine clinical practice setting. The primary endpoint was the absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) compared with the previous 12 months, at the start of AZLI treatment and 12 months after starting the drug. Other variables analysed were exacerbations, hospitalisations, type and route of antibiotics prescribed, weight and body mass index (BMI) and adverse drug reactions.

RESULTS: In a cohort of 52 patients, AZLI treatment led to stabilisation of FEV1, changing from a mean (SD) value of 55.60 (21.3)% at the start of treatment to 56.8 (20.4)% after 12 months of treatment (p=0.5296) in patients who had not previously received the drug. In addition, it significantly reduced exacerbations from a median (P25; P75) of 2.0 (1.0; 3.0) in the 12 months prior to AZLI to 1.0 (1.0; 2.0) in the 12 months after treatment initiation (p=0.0350). AZLI also reduced the need for other antibiotics and prevented a decrease in BMI, with an adequate safety profile.

CONCLUSIONS: AZLI achieved stabilisation of lung function measured by FEV1 in patients with CF and chronic P. aeruginosa infection, along with an adequate safety profile.

PMID:38071521 | DOI:10.1136/ejhpharm-2023-003937

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Dec;31(6):1647-1656. doi: 10.19746/j.cnki.issn.1009-2137.2023.06.008.

ABSTRACT

OBJECTIVE: To establish a new digital polymerase chain reaction (dPCR) system for the detection of BCR-ABL fusion gene in patients with chronic myeloid leukemia (CML), and explore its analytical performance and clinical applicability in the detection of BCR-ABLp190/210/230.

METHODS: A new dPCR system for detecting BCR-ABLp190/210/230 was successfully developed, and its sensitivity difference with qPCR and improvement of drug side effects in patients with CML during drug reduction or withdrawal were compared.

RESULTS: Among 176 samples, qPCR and dPCR showed high consistency in the sensitivity of detecting BCR-ABL (82.39%), and the positive rate of dPCR was about 5 times higher that of qPCR (20.45% vs 3.98%). During follow-up, blood routine (25% vs 10%), kidney/liver/stomach (25% vs 20%) and cardiac function (10% vs 0) were significantly improved after drug reduction or withdrawal in patients with initial dPCR negative compared with before drug reduction or withdrawal.

CONCLUSIONS: This new dPCR detection system can be applied to the detection of BCR-ABLp190/210/230. It has better consistency and higher positive detection rate than qPCR. Drug withdrawal or dose reduction guided by dPCR has a certain effect on improving drug side effects.

PMID:38071041 | DOI:10.19746/j.cnki.issn.1009-2137.2023.06.008

Int J Mol Sci. 2023 Nov 28;24(23):16843. doi: 10.3390/ijms242316843.

ABSTRACT

Glucocorticoids (GCs) are widely used to treat inflammatory disorders such as acute lung injury (ALI). Here, we explored inorganic-organic hybrid nanoparticles (IOH-NPs) as a new delivery vehicle for GCs in a mouse model of ALI. Betamethasone (BMZ) encapsulated into IOH-NPs (BNPs) ameliorated the massive infiltration of neutrophils into the airways with a similar efficacy as the free drug. This was accompanied by a potent inhibition of pulmonary gene expression and secretion of pro-inflammatory mediators, whereas the alveolar-capillary barrier integrity was only restored by BMZ in its traditional form. Experiments with genetically engineered mice identified myeloid cells and alveolar type II (AT II) cells as essential targets of BNPs in ALI therapy, confirming their high cell-type specificity. Consequently, adverse effects were reduced when using IOH-NPs for GC delivery. BNPs did not alter T and B cell numbers in the blood and also prevented the induction of muscle atrophy after three days of treatment. Collectively, our data suggest that IOH-NPs target GCs to myeloid and AT II cells, resulting in full therapeutic efficacy in the treatment of ALI while being associated with reduced adverse effects.

PMID:38069173 | PMC:PMC10705980 | DOI:10.3390/ijms242316843

Prague Med Rep. 2023;124(4):392-412. doi: 10.14712/23362936.2023.30.

ABSTRACT

The COVID-19 pandemic generated a great impact on health systems. We compared evolution, polypharmacy, and potential drug-drug interactions (P-DDIs) in COVID-19 and non-COVID-19 hospitalizations during first wave of pandemic. Prescriptions for hospitalized patients ≥ 18 years (COVID-19 and non-COVID-19 rooms) between April and September 2020 were included. The computerized medical decision support system SIMDA and the physician order entry system Hdc.DrApp.la were used. Patients in COVID-19 rooms were divided into detectable and non-detectable, according to real-time reverse transcription polymerase chain reaction (RT-PCR). Number of drugs, prescribed on day 1, after day 1, and total; polypharmacy, excessive polypharmacy, and P-DDIs were compared. 1,623 admissions were evaluated: 881 COVID-19, 538 detectable and 343 non-detectable, and 742 non-COVID-19. Mortality was 15% in COVID-19 and 13% in non-COVID-19 (RR [non-COVID-19 vs. COVID-19]: 0.84 [95% CI] [0.66-1.07]). In COVID-19, mortality was 19% in detectable and 9% in non-detectable (RR: 2.07 [1.42-3.00]). Average number of drugs was 4.54/patient (SD ± 3.06) in COVID-19 and 5.92/patient (±3.24) in non-COVID-19 (p&lt;0.001) on day 1 and 5.57/patient (±3.93) in COVID-19 and 9.17/patient (±5.27) in non-COVID-19 (p&lt;0.001) throughout the hospitalization. 45% received polypharmacy in COVID-19 and 62% in non-COVID-19 (RR: 1.38 [1.25-1.51]) and excessive polypharmacy 7% in COVID-19 and 14% in non-COVID-19 (RR: 2.09 [1.54-2.83]). The frequency of total P-DDIs was 0.31/patient (±0.67) in COVID-19 and 0.40/patient (±0.94) in non-COVID-19 (p=0.022). Hospitalizations in the COVID-19 setting are associated with less use of drugs, less polypharmacy and less P-DDIs. Detectable patients had higher mortality.

PMID:38069645 | DOI:10.14712/23362936.2023.30

Ann Med. 2023;55(2):2288309. doi: 10.1080/07853890.2023.2288309. Epub 2023 Dec 8.

ABSTRACT

Objective: Evaluate the profiles of post-exposure prophylaxis (PEP) adherence, adverse drug reactions (ADRs), and discontinuation associated with ADRs to provide information for further PEP program improvement and increase adherence to PEP.Methods: The Web of Science, PubMed, Embase, and the Cochrane Library were searched for cohort studies reporting data related to PEP adherence or ADRs (PROSPERO, CRD42022385073). Pooled estimates of adherence, the incidence of ADRs and discontinuation associated with ADRs, and their 95% confidence intervals (CI) were calculated separately for the included literature using random effects models. For substantial heterogeneity, meta-regression and subgroup analyses were conducted to explore sources of heterogeneity.Results: Overall adherence was 58.4% (95% CI: 50.9%-65.8%), with subgroup analysis showing differences in adherence across samples, with the highest adherence among men who had sex with men (MSM) (72.4%, 95% CI: 63.4%-81.3%) and the lowest adherence among survivors of sexual assault (SAs) (41.7%, 95% CI: 28.0%-55.3%). The incidence of ADRs was 60.3% (95% CI: 50.3%-70.3%), and the prevalence of PEP discontinuation associated with ADRs was 32.7% (95% CI: 23.7%-41.7%), with subgroup analyses revealing disparities in the prevalence of discontinuation associated with ADRs among samples with different drug regimens. Time trend analysis showed a slight downward trend in the incidence of ADRs and PEP discontinuation associated with ADRs.Conclusion: Adherence to PEP was less than 60% across samples, however, there was significant heterogeneity depending on the samples. SAs had the lowest adherence and the highest incidence of PEP discontinuation. Ongoing adherence education for participants, timely monitoring, and management of ADRs may improve adherence.

PMID:38065681 | DOI:10.1080/07853890.2023.2288309

J Infect Dev Ctries. 2023 Nov 30;17(11):1549-1555. doi: 10.3855/jidc.18041.

ABSTRACT

INTRODUCTION: Favipiravir (FVP) is an antiviral and used to treat COVID-19. We aimed to document the safety and adverse events associated with FVP on the outcome of COVID-19 treatment.

METHODOLOGY: The study included 225 adult patients with moderate COVID-19 infection (World Health Organization scale-5). The adverse events (AEs) were evaluated using a grading scale supported by the Food and Drug Administration. Safety was assessed by the frequency of serious AEs.

RESULTS: The AEs associated with FVP treatment were hepatotoxicity (87/225, 38.7%), weakness (32/225, 14.2%), nephrotoxicity (26/225, 11.6%), nausea (18/225, 8.0%), diarrhea (8/225, 3.6%), vomiting (5/225, 2.2%), and insomnia (4/225, 1.8%); rash was not detected. Hepatotoxicity was observed more frequently in patients who also developed nephrotoxicity (57.7% vs 36.2%, p = 0.03). The deceased patients were significantly older and had higher prevalence of hypertension, congestive heart failure (CHF), coronary artery disease, cancer, nephrotoxicity. and angiotensin- converting enzyme inhibitors/angiotensin receptor blocker use. While male gender (OR: 5.38 CI: 1.64-17.67) and CHF (OR: 6.8 CI: 1.92-24.74) were significantly associated with nephrotoxicity, age (OR: 1.06 CI: 1.02-1.10), cancer (OR: 3.9 CI: 1.10-14.22) and nephrotoxicity (OR: 5.5 CI: 1.74-17.74) were associated with mortality.

CONCLUSIONS: Serious AEs were detected at very low levels that would not require discontinuation of treatment or any AE-related death. Since SARS-CoV-2 itself and drug interactions may differ, FVP-related AEs might vary in COVID-19 patients. Our study shows that FVP can be used safely with a low AE profile. More extensive evidence is required to evaluate the long-term AEs of FVP.

PMID:38064405 | DOI:10.3855/jidc.18041

BMC Pharmacol Toxicol. 2023 Dec 7;24(1):74. doi: 10.1186/s40360-023-00715-5.

ABSTRACT

BACKGROUND: Integrase strand transfer inhibitor (INSTIs)-based combination antiretroviral treatment in people living with HIV (PLWH) has been reportedly correlated with several adverse effects, such as weight gain, fetal defects or psychiatric disorders.

METHODS: To comprehensively understand the adverse effect of INSTIs, our study utilized Caenorhabditis Elegans (C. elegans) as a model to investigate how dolutegravir (DTG) affected its life cycle, growth, reproduction and lifespan.

RESULTS: Our results indicated that DTG enhanced body growth at the early stage of treatment, but no change was detected for long-term treatment. The treatment also influenced the reproductive system, decreased egg-hatching but had no effect on egg-laying. Besides, DTG resulted in lifespan reduction, which is dependent on increased levels of reactive oxidative species (ROS) accumulation. Treatment with N-acetyl-cysteine (NAC) in worms restrained intracellular ROS accumulation and improved DTG-induced lifespan reduction.

CONCLUSIONS: Our study demonstrates for the first time the effect of DTG treatment on life cycle. DTG-induced adverse effects are potentially associated with intracellular ROS accumulation. Quenching ROS accumulation might provide a novel strategy for dealing with the adverse effects of INSTIs.

PMID:38062506 | PMC:PMC10702061 | DOI:10.1186/s40360-023-00715-5