J Oncol Pharm Pract. 2024 Apr 5:10781552241245332. doi: 10.1177/10781552241245332. Online ahead of print.

ABSTRACT

INTRODUCTION: Acute pancreatitis (AP) following drug-induced hypertriglyceridemia is a rare clinical phenomenon. Immune checkpoint inhibitors have revolutionized treatment for a variety of solid organ and hematological malignancies. Pembrolizumab is a programmed cell death receptor-1 (PD-1) inhibitor that has shown promising responses in many advanced cancers. However, a constellation of immune-related adverse events has also been described. There are reports of pembrolizumab-induced hypertriglyceridemia, but AP as a result of this side effect remains an exceedingly rare clinical sequela.

CASE REPORT: We delineate a case of a patient with stage IVB non-small-cell lung cancer who developed progressive abdominal pain and nausea following administration of pembrolizumab for four months. Laboratory studies revealed increased serum lipase and triglyceride levels at 12,562 IU/L and 16,901 mg/dL, respectively. The diagnosis of AP was made based on the revised Atlanta classification criteria. After ruling out alternative causes, pembrolizumab-induced hypertriglyceridemia was considered the likely etiology of AP.

MANAGEMENT AND OUTCOME: The patient was transferred to the medical intensive care unit for close monitoring. Treatment was initiated with intravenous fluids, pain medications, and an insulin infusion. However, her hypertriglyceridemia levels remained persistently elevated, necessitating therapeutic apheresis. She recovered well with no complications after triglyceride apheresis.

DISCUSSION: AP following pembrolizumab-associated hypertriglyceridemia remains a rare clinicopathologic entity. Given the widespread clinical use of immune checkpoint inhibitors, knowledge of such rare adverse events is crucial. Evaluation of serum triglyceride levels before and after initiating pembrolizumab therapy may be mandated, especially in patients with metabolic comorbidities.

PMID:38576329 | DOI:10.1177/10781552241245332

Eur J Neurol. 2024 Apr 4:e16275. doi: 10.1111/ene.16275. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Primary mitochondrial diseases (PMDs) are common inborn errors of energy metabolism, with an estimated prevalence of one in 4300. These disorders typically affect tissues with high energy requirements, including heart, muscle and brain. Epilepsy may be the presenting feature of PMD, can be difficult to treat and often represents a poor prognostic feature. The aim of this study was to develop guidelines and consensus recommendations on safe medication use and seizure management in mitochondrial epilepsy.

METHODS: A panel of 24 experts in mitochondrial medicine, pharmacology and epilepsy management of adults and/or children and two patient representatives from seven countries was established. Experts were members of five different European Reference Networks, known as the Mito InterERN Working Group. A Delphi technique was used to allow the panellists to consider draft recommendations on safe medication use and seizure management in mitochondrial epilepsy, using two rounds with predetermined levels of agreement.

RESULTS: A high level of consensus was reached regarding the safety of 14 out of all 25 drugs reviewed, resulting in endorsement of National Institute for Health and Care Excellence guidelines for seizure management, with some modifications. Exceptions including valproic acid in POLG disease, vigabatrin in patients with γ-aminobutyric acid transaminase deficiency and topiramate in patients at risk for renal tubular acidosis were highlighted.

CONCLUSIONS: These consensus recommendations describe our intent to improve seizure control and reduce the risk of drug-related adverse events in individuals living with PMD-related epilepsy.

PMID:38576261 | DOI:10.1111/ene.16275

Epilepsia Open. 2024 Apr 4. doi: 10.1002/epi4.12929. Online ahead of print.

ABSTRACT

OBJECTIVE: Evaluate efficacy, safety, and tolerability of adjunctive brivaracetam (BRV) in adult Asian patients with focal-onset seizures (FOS).

METHODS: Phase III, randomized, double-blind, placebo-controlled study (EP0083; NCT03083665) evaluating BRV 50 mg/day and 200 mg/day in patients (≥16-80 years) with FOS with/without secondary generalization (focal to bilateral tonic-clonic seizures) despite current treatment with 1 or 2 concomitant antiseizure medications. Following an 8-week baseline, patients were randomized 1:1:1 to placebo, BRV 50 mg/day, or BRV 200 mg/day, and entered a 12-week treatment period. Efficacy outcomes: percent reduction over placebo in 28-day FOS frequency (primary); 50% responder rate in FOS frequency; median percent reduction in FOS frequency from baseline; seizure freedom during treatment period (secondary). Primary safety endpoints: incidences of treatment-emergent adverse events (TEAEs); TEAEs leading to discontinuation; serious TEAEs.

RESULTS: In this study, 448/449 randomized patients (mean age, 34.5 years; 53.8% female) received ≥1 dose of study medication (placebo/BRV 50 mg/BRV 200 mg/day: n = 149/151/148). Percent reduction over placebo in 28-day adjusted FOS frequency was 24.5% (p = 0.0005) and 33.4% (p < 0.0001) with BRV 50 mg/day and 200 mg/day, respectively, 50% responder rate was 19.0%, 41.1%, and 49.3% with placebo, BRV 50 mg/day, and BRV 200 mg/day, respectively (p < 0.0001 for both BRV groups vs. placebo). Median percent reduction in FOS frequency from baseline was 21.3%/38.9%/46.7% in patients on placebo/BRV 50 mg/BRV 200 mg/day, respectively. Overall, 0, 7 (4.6%), and 10 (6.8%) patients were classified as seizure-free during the treatment period on placebo, BRV 50 mg/day, and BRV 200 mg/day, respectively (p = 0.0146/p = 0.0017 for BRV 50 mg/200 mg/day vs. placebo, respectively). TEAE incidences were similar between patients on placebo (58.4%) and all patients receiving BRV (58.5%); TEAE incidences for BRV 50 mg/day and BRV 200 mg/day were 57.0% and 60.1%, respectively. Overall, 0.7% of patients on placebo and 2.0% of all patients on BRV reported serious TEAEs (incidences for BRV 50 mg/day and BRV 200 mg/day were 1.3% and 2.7%, respectively), 20.1% of patients on placebo and 33.1% of all patients on BRV reported drug-related TEAEs (incidences for BRV 50 mg/day and BRV 200 mg/day were 26.5% and 39.9%, respectively), and 4.7% of patients on placebo and 3.0% of all patients on BRV discontinued due to TEAEs (discontinuation incidences for BRV 50 mg/day and BRV 200 mg/day were 2.6% and 3.4%, respectively).

SIGNIFICANCE: Adjunctive BRV was efficacious and well tolerated in adult Asian patients with FOS. Efficacy and safety profiles were consistent with BRV studies in predominantly non-Asian populations.

PLAIN LANGUAGE SUMMARY: Brivaracetam is used to treat partial or focal seizures in people with epilepsy. Most studies with brivaracetam tablets have involved people from non-Asian racial backgrounds. In this study, 449 Asian adults with epilepsy took part. One third took 50 mg of brivaracetam, one third took 200 mg of brivaracetam, and one third took a placebo each day for 12 weeks. On average, those who took brivaracetam had fewer seizures than those given the placebo. Most of the side effects were mild and the number and type of side effects seen were as expected for this medication.

PMID:38576178 | DOI:10.1002/epi4.12929

Sci Rep. 2024 Apr 4;14(1):7932. doi: 10.1038/s41598-024-58721-4.

ABSTRACT

Chiang Mai encounters severe pollution during the wildfire season. Wildland firefighters encounter various hazards while engaged in fire suppression operations, which encompass significant exposure to elevated concentrations of air pollutants resulting from combustion, especially particulate matter. The adverse effects of wildfire smoke on respiratory health are a significant concern. The objective of this study was to examine the potential adverse effects of PM2.5 exposure on the respiratory function and DNA damage of wildland firefighters. This prospective cohort study conducted in Chiang Mai from January to May 2022 planned to evaluate the health status of wildland firefighters during the pre-peak, peak, and post-peak ambient air pollution seasons. The measurement of PM2.5 was done at every forest fire station, as well as utilizing data from the Pollution Control Department. Participants received general health examinations, spirometry evaluations, and blood tests for DNA damage analysis. Pair t-tests and multiple regression models were used to examine the connection between pulmonary function parameters (FVC, FEV1) and PM2.5 concentration, with a significance level of P < 0.05. Thirty-three peak-season and twenty-one post-peak-season participants were enrolled. Four pre-peak-season wildland firefighters had FVC and FEV1 declines of > 15%. Multiple regression analysis showed a negative association between PM2.5 exposure and FVC% predicted (- 2.81%, 95% CI - 5.27 to - 0.34%, P = 0.027) and a marginally significant negative correlation with FVC (- 114.38 ml, 95% CI - 230.36 to 1.59 ml, P = 0.053). The remaining pulmonary measures showed a statistically insignificant decline. There were no significant changes in DNA damage detected. Wildland firefighters suffered a significant decline in pulmonary function associated with PM2.5 exposure. Spirometry is crucial for monitoring and promptly identifying respiratory issues that occur during wildfire seasons. Further research is recommended to explore DNA damage alterations and their potential association with PM2.5.

PMID:38575786 | PMC:PMC10994925 | DOI:10.1038/s41598-024-58721-4

JMIR Hum Factors. 2024 Apr 4;11:e54386. doi: 10.2196/54386.

ABSTRACT

BACKGROUND: Approximately 262 million people worldwide are affected by asthma, and the overuse of reliever medication-specifically, short-acting beta2-agonist (SABA) overuse-is common. This can lead to adverse health effects. A smartphone app, the Asthma app, was developed via a participatory design to help patients gain more insight into their SABA use through monitoring and psychoeducation.

OBJECTIVE: This pilot study aims to evaluate the feasibility and usability of the app. The preliminary effects of using the app after 3 months on decreasing asthma symptoms and improving quality of life were examined.

METHODS: A mixed methods study design was used. Quantitative data were collected using the app. Asthma symptoms (measured using the Control of Allergic Rhinitis and Asthma Test) and the triggers of these symptoms were collected weekly. Quality of life (36-Item Short-Form Health Survey) was assessed at baseline and after 3, 6, and 12 months. User experience (System Usability Scale) was measured at all time points, except for baseline. Furthermore, objective user data were collected, and qualitative interviews, focusing on feasibility and usability, were organized. The interview protocol was based on the Unified Theory of Acceptance and Use of Technology framework. Qualitative data were analyzed using the Framework Method.

RESULTS: The baseline questionnaire was completed by 373 participants. The majority were female (309/373, 82.8%), with a mean age of 46 (SD 15) years, and used, on average, 10 SABA inhalations per week. App usability was rated as good: 82.3 (SD 13.2; N=44) at 3 months. The Control of Allergic Rhinitis and Asthma Test score significantly improved at 3 months (18.5) compared with baseline (14.8; β=.189; SE 0.048; P<.001); however, the obtained score still indicated uncontrolled asthma. At 3 months, there was no significant difference in the quality of life. Owing to the high dropout rate, insufficient data were collected at 6 and 12 months and were, therefore, not further examined. User data showed that 335 users opened the app (250/335, 74.6%, were returning visitors), with an average session time of 1 minute, and SABA registration was most often used (7506/13,081, 57.38%). Qualitative data (from a total of 4 participants; n=2, 50% female) showed that the participants found the app acceptable and clear. Three participants stated that gaining insight into asthma and its triggers was helpful. Two participants no longer used the app because they perceived their asthma as controlled and, therefore, did not use SABA often or only used it regularly based on the advice of the pulmonologist.

CONCLUSIONS: The initial findings regarding the app's feasibility and usability are encouraging. However, the notable dropout rate underscores the need for a cautious interpretation of the results. Subsequent studies, particularly those focusing on implementation, should explore the potential integration of the app into standard treatment practices.

PMID:38574348 | DOI:10.2196/54386

Turk Kardiyol Dern Ars. 2024 Apr;52(3):217-219. doi: 10.5543/tkda.2023.22893.

ABSTRACT

Drug-related muscular adverse effects are relatively common among certain groups of drugs, such as statins and steroids. However, these adverse effects are less well-known for angiotensin receptor blockers (ARBs). It is proposed that telmisartan and irbesartan may cause myotoxicity via increased Peroxisome Proliferator-Activated Receptor gamma (PPAR-gamma) activity. Herein, we present two hypertensive patients in whom telmisartan-induced myotoxicity was observed. Therefore, physicians should be aware that telmisartan, along with some other ARBs, can also cause myopathy. Possible drug-drug interactions should be considered in cases of concomitant prescription of these agents with other myopathic drugs.

PMID:38573089 | DOI:10.5543/tkda.2023.22893

Epilepsia Open. 2024 Apr 4. doi: 10.1002/epi4.12936. Online ahead of print.

ABSTRACT

OBJECTIVE: Cenobamate is an antiseizure medication (ASM) associated with high rates of seizure freedom and acceptable tolerability in patients with focal seizures. To achieve the optimal cenobamate dose for maximal potential effectiveness while avoiding or minimizing drug-related adverse events (AEs), the administration of cenobamate with other ASMs must be managed through concomitant ASM load reduction. A panel of Spanish epilepsy experts aimed to provide a Spanish consensus on how to adjust the dose of concomitant ASMs in patients with drug-resistant epilepsy (DRE) in order to improve the effectiveness and tolerability of adjunctive cenobamate.

METHODS: A three-stage modified Delphi consensus process was undertaken, including six Spanish epileptologists with extensive experience using cenobamate. Based on current literature and their own expert opinion, the expert panel reached a consensus on when and how to adjust the dosage of concomitant ASMs during cenobamate titration.

RESULTS: The expert panel agreed that tailored titration and close follow-up are required to achieve the best efficacy and tolerability when initiating cenobamate in patients receiving concomitant ASMs. When concomitant clobazam, phenytoin, phenobarbital, and sodium channel blockers are taken at high dosages, or when the patient is receiving two or more sodium channel blockers, dosages should be proactively lowered during the cenobamate titration period. Other concomitant ASMs should be reduced only if the patient reports a moderate/severe AE at any stage of the titration period.

SIGNIFICANCE: Cenobamate is an effective ASM with a dose-dependent effect. To maximize effectiveness while maintaining the best tolerability profile, co-medication management is needed. The recommendations included herein provide practical guidance for proactive and reactive management of co-medication in cenobamate-treated patients with DRE and a high drug load.

PLAIN LANGUAGE SUMMARY: Patients with epilepsy may continue to have seizures even after treatment with several different antiseizure medications (ASMs). Cenobamate is an ASM that can reduce seizures in these patients. In this study, six Spanish experts in epilepsy discussed the best way to use cenobamate in drug-resistant epilepsy. They provide practical guidance on when and how the dose of other ASMs might be adjusted to reduce side effects and optimize the use of cenobamate.

PMID:38573131 | DOI:10.1002/epi4.12936

JGH Open. 2024 Apr 2;8(4):e13057. doi: 10.1002/jgh3.13057. eCollection 2024 Apr.

ABSTRACT

BACKGROUND AND AIM: This study aimed to clarify the efficacy and safety of 48-week pemafibrate treatment in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) complicated by dyslipidemia.

METHODS: A total of 110 patients diagnosed with MASLD complicated by dyslipidemia received pemafibrate at a dose of 0.1 mg twice daily for 48 weeks.

RESULTS: The participants were 54 males and 37 females, with a median age of 63 (52-71) years. Besides improvement in lipid profile, significant reductions from baseline to 48 weeks of treatment were found in liver-related enzymes, such as aspartate aminotransferase, alanine aminotransferase (ALT), gamma-glutamyl transpeptidase, and alkaline phosphatase (P < 0.001 for all). A significant decrease in the homeostasis model assessment-insulin resistance (HOMA-IR) was observed in patients with insulin resistance (HOMA-IR ≥ 2.5) (4.34 at baseline to 3.89 at Week 48, P < 0.05). Moreover, changes in ALT were weakly correlated with those in HOMA-IR (r = 0.34; p < 0.05). Regarding noninvasive liver fibrosis tests, platelets, Wisteria floribunda agglutinin-positive Mac-2-binding protein, type IV collagen 7s, and the non-alcoholic fatty liver disease fibrosis score significantly decreased from baseline to Week 48. Most adverse events were Grades 1-2, and no drug-related Grade 3 or higher adverse events were observed.

CONCLUSION: This study demonstrated that 48-week pemafibrate administration improved liver-related enzymes and surrogate marker of liver fibrosis in patients with MASLD. The improvement of insulin resistance by pemafibrate may contribute to the favorable effect on MASLD complicated by dyslipidemia.

PMID:38572327 | PMC:PMC10986296 | DOI:10.1002/jgh3.13057

Eur Urol Open Sci. 2024 Mar 25;63:81-88. doi: 10.1016/j.euros.2024.02.019. eCollection 2024 May.

ABSTRACT

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in "real-life" patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.

PMID:38572301 | PMC:PMC10987796 | DOI:10.1016/j.euros.2024.02.019

J Clin Psychiatry. 2024 Apr 2;85(2):24ac15280. doi: 10.4088/JCP.24ac15280.

NO ABSTRACT

PMID:38569179 | DOI:10.4088/JCP.24ac15280

Farm Hosp. 2024 Apr 2:S1130-6343(24)00005-9. doi: 10.1016/j.farma.2024.01.002. Online ahead of print.

ABSTRACT

BACKGROUND: Adalimumab biosimilar MSB11022 (Idacio ®) has been approved for the same indications as its originator (Humira ®), based on findings from clinical trials in plaque psoriasis. Data on its efficacy and safety in inflammatory bowel disease, however, are scarce.

METHODS: Retrospective, observational study of 44 patients with inflammatory bowel disease: 30 were treated with originator adalimumab, 5 were directly started on MSB11022, and 9 switched from originator to biosimilar adalimumab. To evaluate the effectiveness of the use of adalimumab in inflammatory bowel disease, both laboratory markers (fecal calprotectin and C-reactive protein) and scales that measure the activity of inflammatory bowel disease using specific scales (Harvey-Bradshaw Index (HBI) have been usEd.) for Crohn's disease and Mayo Score for Ulcerative Colitis. Efficacy was evaluated by recording the adverse effects that could occur with the administration of adalimumab (original or biosimilar). The success of the switch was determined by analyzing meaningful differences in effectiveness and safety criteria. Concomitant therapy and the need for dose intensification were also analyzed. Objective of this study was to assess the effectiveness and safety of biosimilar adalimumab in adalimumab-naïve patients and patients switched from originator adalimumab.

RESULTS: No significant differences were observed in clinical disease activity (P=.317) or biochemical parameters [fecal calprotectin (P=.445) and C-reactive protein P=.661)] after the switch from the originator adalimumab to MSB11022. There was not a significant reduction in the concomitant use of corticosteroids and thiopurines (P=.157). No emergency room visits or hospitalizations were observed during the study period and none of the patients experienced serious adverse effects.

CONCLUSIONS: Between originator adalimumab and biosimilar-start cohorts, no differences were observed, between originator adalimumab and switch cohorts, no significant differences were found either, and with the pre- and post-switch to biosimilar comparison, 2 of the 9 patients experienced AEs after the switch. The biosimilar showed a favorable safety profile (one patient with a serious adverse effect (rash) with biosimilar discontinued treatment) and no significant changes to clinical or biochemical parameters were observed after the switch.

PMID:38570210 | DOI:10.1016/j.farma.2024.01.002

Int J Radiat Oncol Biol Phys. 2024 Mar 31:S0360-3016(24)00447-4. doi: 10.1016/j.ijrobp.2024.03.033. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to investigate the safety and efficacy of HL301, a standardized combination product of seven medicinal plants, in radiation pneumonitis in patients with unresectable non-small cell lung cancer (NSCLC) undergoing curative concurrent chemoradiotherapy.

METHODS: The target accrual was 87 and a total of 63 patients were enrolled due to poor accrual rate. We randomly assigned the 63 patients to receive a placebo (arm A), or 1200 mg HL301 (arm B), or 1800 mg HL301 (arm C). Patients received weekly paclitaxel and carboplatin concurrently with intensity-modulated radiotherapy at 60-66 Gy in conventional fractionation. Durvalumab was administered as maintenance treatment according to standard clinical practice. HL301 was administered orally, daily for 12 weeks. The primary endpoint was incidence of grade ≥2 radiation pneumonitis at 24 weeks post-chemoradiotherapy.

RESULTS: The baseline characteristics of the patients were well balanced. The drug was tolerable with a compliance rate of 86.6%, 86.2%, and 88.8% in arms A, B, and C, respectively (P = 0.874). None of the patients experienced severe drug-related adverse events. No significant difference in the rate of adverse events were observed between the treatment arms. The incidence of grade ≥2 radiation pneumonitis at 24 weeks post-chemoradiotherapy was 37.5% (95% CI, 18.5-61.4%), 55.6% (95% CI, 33.7-75.4%), and 52.4% (95% CI, 32.4-71.7%) in arms A, B, and C, respectively (P=0.535).

CONCLUSION: This is the first exploratory clinical trial to test the safety and efficacy of HL301 in patients with NSCLC. Safety and feasibility of HL301 were established but no signals of efficacy in reducing RP was observed in this dose level.

PMID:38565405 | DOI:10.1016/j.ijrobp.2024.03.033

Am J Respir Crit Care Med. 2024 Apr 2. doi: 10.1164/rccm.202311-2004OC. Online ahead of print.

ABSTRACT

RATIONALE: Observational studies suggest that high-dose isoniazid may be efficacious in treating multidrug-resistant tuberculosis (MDR-TB). However, its activity against Mycobacterium tuberculosis (M.tb) with katG mutations (which typically confer high-level resistance) is not established.

OBJECTIVE: To characterize early bactericidal activity (EBA) of high-dose isoniazid in patients with tuberculosis caused by katG-mutated M.tb.

METHODS: A5312 was a Phase 2A randomized, open-label trial. Participants with tuberculosis caused by katG-mutated M.tb were randomized to receive 15 or 20 mg/kg isoniazid daily for 7 days. Daily sputum samples were collected for quantitative culture. Intensive PK sampling was performed on day 6. Data were pooled across all A5312 participants for analysis (drug-sensitive, inhA-mutated, and katG-mutated M.tb). EBA was determined using nonlinear mixed-effects modelling.

RESULTS: Of 80 treated participants, 21 had katG-mutated M.tb. Isoniazid PK was best described by a two-compartment model with an effect of NAT2 acetylator phenotype on clearance. Model-derived Cmax and AUC in the 15 and 20 mg/kg groups were 15.0 and 22.1 mg/L and 57.6 and 76.8 mg∙h/L, respectively. Isoniazid bacterial kill was described using an effect compartment and a sigmoidal Emax relationship. Isoniazid potency against katG-mutated M.tb was approximately 10-fold lower than against inhA-mutated M.tb. The highest dose (20 mg/kg) did not demonstrate measurable EBA, except in a subset of slow NAT2 acetylators (who experienced the highest concentrations). There were no grade 3 or higher drug-related adverse events.

CONCLUSIONS: This study found negligible bactericidal activity of high-dose isoniazid (15-20 mg/kg) in the majority of participants with tuberculosis caused by katG-mutated M.tb. Clinical trial registration available at www.

CLINICALTRIALS: gov, ID: NCT01936831.

PMID:38564365 | DOI:10.1164/rccm.202311-2004OC

Front Psychiatry. 2024 Mar 18;15:1349816. doi: 10.3389/fpsyt.2024.1349816. eCollection 2024.

ABSTRACT

INTRODUCTION: Major Depressive Disorder (MDD) is a chronic, recurrent, and highly prevalent disease that is associated with significant functional disability. During pregnancy, the prevalence of the disease is approximately 20%, with 12% of these, requiring treatment to avoid important negative consequences for the mother-baby binomial. Risk-benefit assessment of the use of antidepressants during pregnancy is mandatory, in addition to knowledge of the long-term effects of prenatal exposure to these drugs in the offspring. In this study, we will perform an updated systematic review and meta-analysis to explore the treatment of depression during pregnancy, along with its effectiveness, safety, and possible harm to women and children.

MATERIALS AND METHODS: We will search for publications in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science, Scopus, Lilacs, and PsycINFO. The reference lists of the included studies will be manually reviewed to identify potentially relevant studies. There will be no restrictions on language or date of publication. Quality assessment of the included studies will be performed independently according to the Cochrane Risk of Bias (RoB2) instrument. To assess the certainty of the findings' body of evidence, we will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. This study aimed to ascertain the efficacy and safety of antidepressants in pregnant women and children.

ETHICS AND DISSEMINATION: Ethical approval was not required as individual patient data were not collected. Dissemination: Plan to publish a systematic review in an open-access medical journal at the end of the process.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023447694.

PMID:38563023 | PMC:PMC10982487 | DOI:10.3389/fpsyt.2024.1349816

Am J Psychiatry. 2024 Apr 1;181(4):342-345. doi: 10.1176/appi.ajp.20230553.

NO ABSTRACT

PMID:38557140 | DOI:10.1176/appi.ajp.20230553

Open Forum Infect Dis. 2024 Feb 23;11(4):ofae102. doi: 10.1093/ofid/ofae102. eCollection 2024 Apr.

ABSTRACT

BACKGROUND: Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties.

OBJECTIVE: We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for coronavirus disease 2019 (COVID-19) pneumonia.

METHODS: This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization.

RESULTS: Of 41 patients recruited, 40 were randomized (20 received the study drug and 20 placebo). The median age of the patients was 74 years and 55.0% were male. Omalizumab was associated with a 92.6% posterior probability of a reduction in mechanical ventilation and death on day 14 with an adjusted odds ratio of 0.11 (95% credible interval 0.002-2.05). Omalizumab was also associated with a 75.9% posterior probability of reduced all-cause mortality on day 28 with an adjusted odds ratio of 0.49 (95% credible interval, 0.06-3.90). No statistically significant differences were found for the time to clinical improvement and duration of hospitalization. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events.

CONCLUSIONS: These results suggest that omalizumab could prove protective against death and mechanical ventilation in hospitalized patients with COVID-19. This study could also support the development of a phase III trial program investigating the antiviral and anti-inflammatory effect of omalizumab for severe respiratory viral illnesses requiring hospital admission. ClinicalTrials.gov ID: NCT04720612.

PMID:38560604 | PMC:PMC10977629 | DOI:10.1093/ofid/ofae102

Cureus. 2024 Mar 1;16(3):e55324. doi: 10.7759/cureus.55324. eCollection 2024 Mar.

ABSTRACT

We report the case of a 76-year-old female who presented with a new onset of petechial rash in her lower extremities after the introduction of a new agent, semaglutide. She started taking this medication three months before her presentation at an initial dosage of 0.5 mg subcutaneously every week. She noticed a 15-pound weight loss and debilitating fatigue within that timeframe. She stopped taking the medication due to nontolerance and GI upset (nausea and vomiting) about a week before her hospitalization. She denied the use of any other agents. Initial lab work revealed elevated transaminases, alkaline phosphatase, total bilirubin, and inflammatory markers. A CT of the abdomen revealed mild cirrhosis and hepatosplenomegaly. Other causes for cirrhosis were effectively ruled out with negative viral hepatitis, ceruloplasmin levels, and the HFE gene. An autoimmune panel was conducted, yielding positive antinuclear antibody (ANA), anti-histone antibodies, elevated double-stranded DNA, as well as low complement levels supporting evidence of drug-induced lupus (DIL). Anti-mitochondrial M2 and anti-smooth antibodies were also detected, indicating a possible overlap syndrome with autoimmune hepatitis. Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) and anti-neutrophil cytoplasmic autoantibodies (C-ANCA) were negative and ruled out the possibility of ANCA-associated vasculitis. The patient's condition improved with pulse-dose steroids, leading to an improvement in liver function tests. Consequently, the decision to perform skin and liver biopsies was deferred. She was discharged with a tapering dose of steroids and scheduled for outpatient follow-up to monitor her progress. This case report can offer insights to healthcare providers regarding the potential side effects of GLP-1 RAs in their patient population.

PMID:38559525 | PMC:PMC10981839 | DOI:10.7759/cureus.55324

Cureus. 2024 Feb 27;16(2):e55095. doi: 10.7759/cureus.55095. eCollection 2024 Feb.

ABSTRACT

Daptomycin-induced eosinophilic pneumonia (DIEP) is a rare but serious complication associated with the use of this broad-spectrum antibiotic. We present the case of a teenager with a history of nasopharyngeal cancer who developed DIEP while receiving daptomycin to treat an infection associated with an implanted chamber catheter. Symptoms included recurrent dyspnea and peripheral eosinophilia, with radiological findings consistent with DIEP. The pathophysiology involves an immune response triggered by daptomycin, resulting in eosinophilic pulmonary inflammation. Diagnosis requires a thorough evaluation of medical history, clinical laboratory tests, and radiological findings. The main treatment involves discontinuation of daptomycin and, in severe cases, the use of steroids. It is essential to consider DIEP in patients with respiratory failure and bilateral pulmonary opacities who have used daptomycin and to suspect it in those with blood eosinophilia or in bronchoalveolar lavage.

PMID:38558746 | PMC:PMC10978459 | DOI:10.7759/cureus.55095

J Toxicol Sci. 2024;49(4):175-191. doi: 10.2131/jts.49.175.

ABSTRACT

The Hippo pathway plays an important role in the growth, development, and regeneration of cells and organs. Transcriptional enhanced associate domain (TEAD), a transcription activator of the Hippo pathway, forms the complex with a transcriptional coactivator yes-associated protein (YAP) or a transcriptional coactivator PDZ-binding motif (TAZ). Their excessive activations are involved in carcinogenesis such as malignant pleural mesothelioma (MPM), and thus inhibition of the TEAD complex is expected to have potent anticancer activity against MPM. On the other hand, YAP or TAZ conditional knockout mice have been reported to show abnormal findings in various tissues, including the kidney, liver, and lung. In the present study, we evaluated the systemic toxicity of K-975, a novel TEAD inhibitor, in rats. When K-975 was administered orally to rats for 1 week, proteinuria suggestive of nephrotoxicity was observed. Electron microscopy revealed that K-975 at 300 mg/kg induced glomerular podocyte foot process effacement. After a 2-week recovery period, proteinuria with foot process effacement was recovered completely. Urinalysis and urinary biomarker evaluation suggested that the urinary albumin index (urinary albumin/urinary creatinine) was the most sensitive marker for detecting K-975-induced nephrotoxicity. After 3 cycles of 1-week administration followed by 2-week recovery periods, nephrotoxicity was reversible; however, incomplete reversibility was observed in rats with severe proteinuria. In conclusion, this study revealed that in rats, oral K-975 treatment induced severe proteinuria by podocyte foot process effacement, which was reversible and monitorable by the urinary albumin index, suggesting important information for developing K-975 as an anticancer drug.

PMID:38556354 | DOI:10.2131/jts.49.175

Sci Rep. 2024 Mar 29;14(1):7489. doi: 10.1038/s41598-024-57909-y.

ABSTRACT

This study aims to evaluate the safety of Alprazolam by analyzing the FAERS database, provide data analysis for monitoring adverse drug reactions. This research encompasses adverse event (AE) reports related to Alprazolam from the first quarter of 2004 to the second quarter of 2023. Four signal mining and analysis methods were utilized, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). Further exploration was conducted regarding patient characteristics and types of AEs. A total of 23,575 AE reports in which Alprazolam was the primary suspect drug were collected, identifying 347 Preferred Term (PT) signals and 27 System Organ Classes (SOCs). The number of AE reports increased annually, especially in 2015, 2018, 2019, and 2020. The main affected groups were females and the age range of 18 to 45. Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders were the most common the organ system in which the AEs occurred. There is a certain risk of drug abuse and suicide with Alprazolam. Most notably, several AEs not recorded in the Alprazolam leaflet appeared among the top 30 PTs in signal strength, including but not limited to Benzodiazepine drug level abnormal, Acquired amegakaryocytic thrombocytopenia, Cutaneous T-cell dyscrasia, and Coronary No-reflow Phenomenon. For the first time, AEs related to the cardiovascular system and platelet function were unveiled. The severe AE reports that resulted in "hospitalization" and "death" accounted for 30.96% and 21.86%. This study highlights the risks of suicide and misuse of Alprazolam. Other potential severe or fatal AEs, such as those related to the cardiovascular system, platelet function, and others, require further research to determine their precise mechanisms and risk factors.

PMID:38553504 | PMC:PMC10980721 | DOI:10.1038/s41598-024-57909-y