Medicine (Baltimore). 2024 Mar 22;103(12):e37562. doi: 10.1097/MD.0000000000037562.

ABSTRACT

RATIONALE: Immune-related adverse events following treatment with immune checkpoint inhibitors can affect almost every organ. Tislelizumab, a novel humanized Ig G4 programmed death receptor 1 inhibitor, was started for bladder cancer in 2019, but the adverse effects of this drug may not yet be known due to its short time on the market, and there are still some clinical safety concerns. There are few reports of adrenal insufficiency after tislelizumab treatment, which is easily missed, misdiagnosed and life-threatening.

PATIENT CONCERNS: A 67-year-old male with bladder cancer who developed rash, water-sodium retention, electrolyte disturbances, hypoalbuminemia, low-grade fever, nausea and vomiting, and fatigue after 2 cycles of tislelizumab.

DIAGNOSIS: Immune checkpoint inhibitor-related adrenal hypofunction and Psoriasisby.

INTERVENTIONS: Suspended tislelizumab treatment and continued glucocorticoid therapy.

OUTCOMES: The patient showed significant improvement in the above symptoms. But bladder cancer reemerged at the same site.

CONCLUSIONS: The advent of immune-related adverse events has increased the complexity of the application of tislelizumab in the treatment of bladder cancer and further research is needed to develop the best treatment guidelines. Early diagnosis and treatment are crucial since the adverse events could endanger lives.

PMID:38518047 | PMC:PMC10956970 | DOI:10.1097/MD.0000000000037562

Clin Transl Sci. 2024 Mar;17(3):e13769. doi: 10.1111/cts.13769.

ABSTRACT

Tislelizumab, an anti-programmed cell death protein 1 monoclonal antibody, has demonstrated improved survival benefits over standard of care for multiple cancer indications. We present the clinical rationale and data supporting tislelizumab dose recommendation in patients with advanced tumors. The phase I, first-in-human, dose-finding BGB-A317-001 study (data cutoff [DCO]: August 2017) examined the following tislelizumab dosing regimens: 0.5-10 mg/kg every 2 weeks (q2w), 2-5 mg/kg q2w or q3w, and 200 mg q3w. Similar objective response rates (ORRs) were reported in the 2 and 5 mg/kg q2w or q3w cohorts. Safety outcomes (grade ≥3 adverse events [AEs], AEs leading to dose modification/discontinuation, immune-mediated AEs, and infusion-related reactions) were generally comparable across the dosing range examined. These results, alongside the convenience of a fixed q3w dose, formed the basis of choosing 200 mg q3w as the recommended dosing regimen for further clinical use. Pooled exposure-response (E-R) analyses by logistic regression using data from study BGB-A317-001 (DCO: August 2020) and three additional phase I/II studies (DCOs: 2018-2020) showed no statistically significant correlation between tislelizumab pharmacokinetic exposure and ORR across multiple solid tumor types or classical Hodgkin's lymphoma, nor was exposure associated with any of the safety end points evaluated over the dose range tested. Hence, tislelizumab showed a relatively flat E-R relationship. Overall, the totality of data, including efficacy, safety, and E-R analyses, together with the relative convenience of a fixed q3w dose, provided clinical rationale for the recommended dosing regimen of tislelizumab 200 mg q3w for multiple cancer indications.

PMID:38515348 | PMC:PMC10958174 | DOI:10.1111/cts.13769

MMW Fortschr Med. 2024 Mar;166(5):12-14. doi: 10.1007/s15006-024-3731-8.

NO ABSTRACT

PMID:38514537 | DOI:10.1007/s15006-024-3731-8

Drug Ther Bull. 2024 Mar 22:dtb-2024-000018. doi: 10.1136/dtb.2024.000018. Online ahead of print.

ABSTRACT

The BNF is jointly published by the Royal Pharmaceutical Society and BMJ. BNF is published in print twice a year and interim updates are issued and published monthly in the digital versions. The following summary provides a brief description of some recent key changes that have been made to BNF content.

PMID:38519120 | DOI:10.1136/dtb.2024.000018

Front Pharmacol. 2024 Mar 7;15:1346169. doi: 10.3389/fphar.2024.1346169. eCollection 2024.

ABSTRACT

Background: Recommended standard treatment for leprosy is multidrugtherapy (MDT/WHO), consisting Rifampicin+Dapsone+Clofazimine. Other medications are recommended in cases of resistance, adverse reactions and intolerances, including ROM regimen, Rifampicin+Ofloxacin+Minocycline. Therefore, pharmacovigilance is an important tool in understanding these adverse drug reactions (ADRs), supporting pharmacotherapy management and medication safety. This study seeks to evaluate ADRs comparing two therapeutic regimens, MDT and ROM, used in treatment of patients with leprosy, analyzing prognostic factors regarding risk and safety. Methods:A retrospective cohort study was performed by assessing medical records of 433 patients diagnosed with leprosy from 2010 to 2021 at a National Reference Center in Brazil. They were subject to 24 months or more of treatment with MDT or ROM regimens. ADR assessments were analyzed by two experienced researchers, who included clinical and laboratory variables, correlating them with temporality, severity and the causality criteria of Naranjo and WHO. Results: The findings observed an average of 1.3 reactions/patient. Out of individuals experiencing reactions, 67.0% (69/103) were utilizing MDT/MB, while 33.0% (34/103) were using ROM. The median time for ADR of 79 days for MDT and 179 days for ROM. In first reaction, Dapsone was the most frequently involved medication; the most affected system was hematopoietic. As compared to Clofazimine, results indicated that use of Dapsone was associated with 7% increased risk of ADR occurrence (HR: 1.07; p = 0.866). Additionally, Rifampicin was linked to 31% increased risk of ADRs (HR: 1.31; p = 0.602); and Ofloxacin showed 35% elevated risk (HR: 1.35; p = 0.653). Conversely, results for Minocycline indicated 44% reduction in the risk of ADRs (HR: 0.56; p = 0.527), although statistical significance was not reached. The use of MDT conferred 2.51 times higher risk of developing ADRs in comparison to ROM. Conclusion: The comparison between MDT and ROM revealed that MDT caused more ADRs, and these reactions were more severe, indicating less safety for patients. Dapsone was the most common medication causing ADRs, followed by Rifampicin. The combination with Clofazimine was associated with an additional risk of ADRs, warranting further studies to confirm this hypothesis. Given the high magnitude of ADRs, healthcare teams need to monitor patients undergoing leprosy treatment with focus on pharmacovigilance.

PMID:38515839 | PMC:PMC10955366 | DOI:10.3389/fphar.2024.1346169

AIDS Res Ther. 2024 Mar 21;21(1):17. doi: 10.1186/s12981-024-00604-9.

ABSTRACT

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years).

METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis.

RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years.

CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities.

TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

PMID:38515183 | DOI:10.1186/s12981-024-00604-9

Neurology. 2024 Apr 23;102(8):e209316. doi: 10.1212/WNL.0000000000209316. Epub 2024 Mar 21.

NO ABSTRACT

PMID:38513190 | DOI:10.1212/WNL.0000000000209316

Prim Care Companion CNS Disord. 2024 Mar 14;26(2):23cr03631. doi: 10.4088/PCC.23cr03631.

NO ABSTRACT

PMID:38512205 | DOI:10.4088/PCC.23cr03631

Am J Nurs. 2024 Apr 1;124(4):23. doi: 10.1097/01.NAJ.0001010564.78302.59. Epub 2024 Mar 21.

NO ABSTRACT

PMID:38511705 | DOI:10.1097/01.NAJ.0001010564.78302.59

Pharmazie. 2024 Feb 29;79(1):35-40. doi: 10.1691/ph.2024.3660.

ABSTRACT

Background and aim: Drug-related problems (DRPs), e.g.drug-drug interactions (DDI), can lead to adversedrug reactions (ADRs) and thus complications during hospitalization. For this reason, such DRP, DDI and ADR should be identified and characterized as early as possible during hospital admission. We aimed to perform a clinical-pharmaceutical medication reconciliation in which patient-related information was collected and compared to drug-related information in a medication review. Investigations: During a 24-week-period, we consecutively invited patients electively admitted to Urology, Otolaryngology, Oral and Maxillofacial Surgery, General and Visceral Surgery, and Oncology Departments of a 300-bed hospital. A clinical pharmacist performed a patient interview asking for medication, ADR, and adherence. The medication reconciliation considered packages for a brown-bag analysis, medication lists, and data from the clinical information-system (CIS). In a medication review, we matched patient-related information to drug-related information from the drug label, guidelines, drug-databases and websites to identify DRPs. Results: In the study, 356 patients (median age: 58 years) taking 1,712 drugs participated. Of all patients, 7.3% reported ADR and 10.7% missing adherence. 5.3% brought packages that enabled a brown-bag analysis and 21.1% a medication list. In 76.7% of patients, information from CIS was incomplete or not up-to-date. Among the most frequently identified DRPs were "Medication without diagnosis" (31.2%) and "Inappropriate timing of administration" (11.5%). The proportion of patients affected by severe DDI ranged from 0.8%-16.6%, depending on the drug information source. Conclusions: Incomplete patient data, frequently identified DRPs and inconsistent drug-based information make pharmaceutical involvement in medication reconciliation on admission a necessity.

PMID:38509626 | DOI:10.1691/ph.2024.3660

Pharmazie. 2024 Feb 29;79(1):29-34. doi: 10.1691/ph.2024.3630.

ABSTRACT

Zinc is an essential microelement, and its deficit causes various diseases and symptoms. In adults, especially in elderly individuals, zinc shortage can cause symptoms such as taste disorder, dermatitis, and susceptibility to infection. In children, zinc deficiency can lead to growth retardation. In 2017, the indication for zinc acetate dihydrate (NOBELZIN®) was expanded from Wilson's disease to include hypozincemia, leading to wider use of zinc acetate dihydrate. At five years after this broadening of use, we conducted a post-marketing study (PMS) to investigate the utilization, safety, and effectiveness of zinc acetate dihydrate. Over 52 weeks, the overall incidence of adverse drug reactions (ADRs) was 9.4% (87/928). The most common ADR was copper deficiency (2.4%), followed by nausea (1.4%). Among 928 patients, 19 (2%) developed serious ADRs. Of the patients with copper deficiency, 92% were >65 years of age, and all had comorbidities at baseline. Physicians evaluated the effectiveness of zinc acetate dihydrate using three categories: "effective", "not effective", and "indeterminate". The overall efficacy rate was 83.0%. The average serum zinc levels were elevated from 50-60 μg/dL to >90 μg/dL within 12 weeks, and were maintained up to 52 weeks after administration. Among the symptomatic sub-categories, the efficacy rate was highest in pressure ulcer (96.2%; 25/26), followed by in stomatitis (87.5%; 42/48), and taste disorder (87.4%; 181/207). Among pediatric patients with developmental symptoms, an efficacy rate of 66% was achieved. In conclusion, zinc acetate dihydrate has been safely used, and has produced beneficial effects on various diseases and symptoms.

PMID:38509625 | DOI:10.1691/ph.2024.3630

Cureus. 2024 Feb 18;16(2):e54416. doi: 10.7759/cureus.54416. eCollection 2024 Feb.

ABSTRACT

We present a rare case of irinotecan-induced transient dysarthria in a 60-year-old female undergoing FOLFIRI (folinic acid (leucovorin), fluorouracil (5-FU), and irinotecan) chemotherapy for metastatic colorectal cancer. In eight out of the 12 cycles, an isolated, self-limiting "lingual dysarthria" with tongue stiffness consistently occurred during infusion and resolved promptly upon completion. Cranial imaging done during the initial episode and after the completion of the chemotherapy regimen were unremarkable. This temporal correlation suggests a drug-induced effect, proposed to be related to cholinergic hyperactivity associated with the drug's reversible inhibition of acetylcholinesterase. The hypoglossal nucleus, responsible for the motor function of the tongue, is selectively affected due to dense innervation by muscarinic cholinergic receptors (in comparison to other brainstem nuclei). This aligned with acute cholinergic syndrome common to irinotecan, and dysarthria might just be a rare manifestation of this common phenomenon. Its reversibility and atropine responsiveness support the cholinergic hypothesis. Clinicians should be mindful of this rare adverse event to avoid premature cessation of effective chemotherapy. Patient education on potential side effects and a comprehensive dysarthria work-up are crucial.

PMID:38510900 | PMC:PMC10951681 | DOI:10.7759/cureus.54416

Inflamm Bowel Dis. 2024 Mar 20:izae040. doi: 10.1093/ibd/izae040. Online ahead of print.

ABSTRACT

BACKGROUND: Antitumor necrosis factor (anti-TNF) antibody treatment has led to marked improvements in the management of patients with inflammatory bowel diseases (IBDs). Nevertheless, anti-TNF therapy is associated with potential adverse drug reactions (ADRs). Our prospective, randomized trial investigated the effect of intensified clinical pharmacist counselling in a multidisciplinary team on medication safety in anti-TNF-treated IBD patients.

METHODS: Patients with IBD with ongoing anti-TNF treatment were enrolled in our tertiary center AdPhaNCED trial and randomized to either receive conventional standard of care (control group) or additional clinical pharmacist counselling (intervention group) over 12 months. The primary end point consisted of the number and severity of ADRs associated with anti-TNF therapy. Secondary end points included patient satisfaction with medication information and medication safety.

RESULTS: One hundred twenty-seven IBD patients were included in this study. Anti-TNF-related ADRs were significantly lower in the intervention compared with the control group (0.20 vs 0.32 [mean] ADR/patient/month, P = .006) after 12 months. The risk of more severe ADRs (Common Terminology Criteria for Adverse Events [CTCAE] grade ≥2) was significantly higher in the control compared with the intervention group (hazard ratio, 0.34; P = .001). The probability of ADR resolution (hazard ratio, 2.02; P < .001) and patient satisfaction with medication information (14.82 vs 11.60; P < .001) were significantly higher in the intervention group compared with the control group.

CONCLUSIONS: Our study results demonstrate that intensified pharmacist counselling significantly reduces the occurrence and severity of therapy-related ADRs and improves patient satisfaction. Clinical pharmacists should therefore be part of a holistic approach to IBD care delivered by a multidisciplinary team.

PMID:38507608 | DOI:10.1093/ibd/izae040

Sci Rep. 2024 Mar 18;14(1):6486. doi: 10.1038/s41598-024-57302-9.

ABSTRACT

Brominated flame retardants (BFRs) are a group of chemicals widely used in various applications to prevent or slow down the spread of fire. However, they have adverse effects on human health. There is a relative scarcity of population-based studies regarding BFRs, particularly their impact on the respiratory system. This study aimed to investigate the influence of BFRs on pulmonary function using data from the National Health and Nutrition Examination Survey. The study found that elevated serum concentrations of certain BFRs were associated with pulmonary ventilatory dysfunction. Adjusted analyses revealed positive correlations between PBDE47, PBDE183, and PBDE209 concentrations and ventilatory dysfunction. The analysis of mixed BFRs showed a positive relationship with pulmonary ventilation dysfunction, with PBDE47 making the most significant contribution. Our study demonstrates that both individual and combined BFRs exposure can lead to impaired pulmonary ventilation function. These findings provide evidence of the adverse effects of BFRs on lung function, emphasizing the importance of further investigating the potential health consequences of these compounds. Further large-scale longitudinal studies are needed to investigate this relationship in the future.

PMID:38499858 | DOI:10.1038/s41598-024-57302-9

Schizophr Bull. 2024 Mar 19:sbae028. doi: 10.1093/schbul/sbae028. Online ahead of print.

ABSTRACT

INTRODUCTION: Clozapine, a second-generation antipsychotic (SGA), is considered the gold standard medication to treat patients with treatment-resistant schizophrenia (TRS). Despite its efficacy, clozapine is associated with adverse effects, notably neutropenia and agranulocytosis. Other hematological adverse effects are less common. Severe anemia is a rare adverse effect seldom reported in the literature and is typically associated with pure red cell aplasia (PRCA). Nevertheless, the benefits of clozapine in managing TRS make rechallenge a reasonable option.

CASE REPORT: We present the case of a 35-year-old man with TRS, resistant to previous antipsychotics, who experienced severe anemia during clozapine treatment. An investigation for clozapine-induced anemia revealed PRCA on myelogram. After discontinuing clozapine, the patient's hemoglobin levels recovered. Subsequent treatments with olanzapine, zuclopenthixol, and aripiprazole proved ineffective, leading us to consider a clozapine rechallenge. The rechallenge, monitored for 58 days, resulted in improved psychiatric symptoms and stable hemoglobin levels. The patient remained stable during 6 months of follow-up, with no hematological changes.

DISCUSSION: PRCA is a very rare adverse effect of clozapine. The cause of drug-induced PRCA is still unknown; for clozapine, there are no studies. Rechallenge after a severe and rare adverse effect is a complex decision. This case is the first to report a successful clozapine rechallenge following severe anemia without other blood dyscrasias, emphasizing the imperative need for close monitoring during the rechallenge process. Further study is warranted to understand the predictive factors for a successful outcome in clozapine rechallenges.

PMID:38502910 | DOI:10.1093/schbul/sbae028

J Neurol. 2024 Mar 19. doi: 10.1007/s00415-024-12301-8. Online ahead of print.

ABSTRACT

BACKGROUND: The approval of selumetinib in patients with neurofibromatosis type 1(NF1) and inoperable plexiform neurofibromas (PN) has reshaped the landscape of clinical management of the disease, and further comprehensive evaluation of the drug's efficacy and safety is needed.

METHODS: Original articles reporting on the efficacy and safety of elumetinib in patients with NF1 were comprehensively searched in the Pubmed database, Embase database, Cochrane Library, and Web of Science database and screened for inclusion of studies that met the criteria. We pooled the objective response rate (ORR), disease control rate (DCR), disease progression rate (DPR), and the rate of improvement in PN-related complications using meta-analysis. The incidence of drug-related adverse events was also statistically analyzed.

RESULTS: This study included 10 clinical trials involving 268 patients. The pooled ORR was 68.0% (95% CI 58.0-77.3%), the DCR was 96.8% (95% CI 90.8-99.7%) and the DPR was only 1.4% (95% CI 0-4.3%). The pooled improvement rate was 75.3% (95% CI 56.2-90.9%) for pain and 77.8% (95% CI 63.1-92.5%) for motor disorders. Most adverse events were mild, with the most common being gastrointestinal reactions (diarrhea: 62.5%; vomiting: 54.5%).

CONCLUSION: Our study demonstrates that selumetinib is effective in patients with NF1 and PN, significantly improving the serious complications associated with PN as well as having tolerable toxicities. Our findings help to increase clinicians' confidence in applying selumetinib and promote the clinical adoption and benefit of the new drug.

PMID:38502338 | DOI:10.1007/s00415-024-12301-8

CNS Drugs. 2024 Mar 19. doi: 10.1007/s40263-024-01078-z. Online ahead of print.

ABSTRACT

Drug-induced movement disorders (DIMDs) are associated with use of dopamine receptor blocking agents (DRBAs), including antipsychotics. The most common forms are drug-induced parkinsonism (DIP), dystonia, akathisia, and tardive dyskinesia (TD). Although rare, neuroleptic malignant syndrome (NMS) is a potentially life-threatening consequence of DRBA exposure. Recommendations for anticholinergic use in patients with DIMDs were developed on the basis of a roundtable discussion with healthcare professionals with extensive expertise in DIMD management, along with a comprehensive literature review. The roundtable agreed that "extrapyramidal symptoms" is a non-specific term that encompasses a range of abnormal movements. As such, it contributes to a misconception that all DIMDs can be treated in the same way, potentially leading to the misuse and overprescribing of anticholinergics. DIMDs are neurobiologically and clinically distinct, with different treatment paradigms and varying levels of evidence for anticholinergic use. Whereas evidence indicates anticholinergics can be effective for DIP and dystonia, they are not recommended for TD, akathisia, or NMS; nor are they supported for preventing DIMDs except in individuals at high risk for acute dystonia. Anticholinergics may induce serious peripheral adverse effects (e.g., urinary retention) and central effects (e.g., impaired cognition), all of which can be highly concerning especially in older adults. Appropriate use of anticholinergics therefore requires careful consideration of the evidence for efficacy (e.g., supportive for DIP but not TD) and the risks for serious adverse events. If used, anticholinergic medications should be prescribed at the lowest effective dose and for limited periods of time. When discontinued, they should be tapered gradually.

PMID:38502289 | DOI:10.1007/s40263-024-01078-z

Pain. 2024 Mar 15. doi: 10.1097/j.pain.0000000000003211. Online ahead of print.

ABSTRACT

Moderate-to-severe acute postsurgical pain (APSP) can prolong the recovery and worsen the prognosis of patients who undergo spinal surgery. Esketamine and pregabalin may resolve APSP without causing hyperpathia or respiratory depression after surgery. However, there are other risks, such as dissociative symptoms. We designed a randomized controlled trial to investigate the effect of the combination of these 2 drugs on the incidence of APSP in patients who underwent resection of spinal neoplasms. Patients aged 18 to 65 years were randomized to receive esketamine (a bolus dose of 0.5 mg·kg-1 and an infusion dose of 0.12 mg·kg-1·h-1 for 48 hours after surgery) combined with oral pregabalin (75-150 mg/day, starting 2 hours before surgery and ending at 2 weeks after surgery) or an identical volume of normal saline and placebo capsules. The primary outcome was the proportion of patients with moderate-to-severe APSP (visual analog scale score ≥ 40) during the first 48 hours after surgery. Secondary outcomes included the incidence of drug-related adverse events. A total of 90 patients were randomized. The incidence of moderate-to-severe APSP in the combined group (27.3%) was lower than that in the control group (60.5%) during the first 48 hours after surgery (odds ratio = 0.25, 95% CI = 0.10-0.61; P = 0.002). The occurrence of mild dissociative symptoms was higher in the combined group than in the control group (18.2% vs 0%). In conclusion, esketamine combined with pregabalin could effectively alleviate APSP after spinal surgery, but an analgesic strategy might increase the risk of mild dissociative symptoms.

PMID:38501980 | DOI:10.1097/j.pain.0000000000003211

J Korean Med Sci. 2024 Mar 18;39(10):e84. doi: 10.3346/jkms.2024.39.e84.

ABSTRACT

BACKGROUND: As the prevalence of hypertension increases with age and the proportion of the older population is also on the rise, research on the characteristics of older hypertensive patients and the importance of frailty is necessary. This study aimed to identify clinical characteristics of older hypertension in Korea and to investigate these characteristics based on frailty status.

METHODS: The HOW to Optimize eLDerly systolic BP (HOWOLD-BP) is a prospective, multicenter, open-label, randomized clinical trial that aims to compare intensive (target systolic blood pressure [SBP] ≤ 130 mmHg) with standard (target SBP ≤ 140 mmHg) treatment to reduce cardiovascular events in older hypertensive Korean patients aged ≥ 65 years. Data were analyzed through a screening assessment of 2,085 patients recruited from 11 university hospitals. Demographic, functional (physical and cognitive), medical history, laboratory data, quality of life, and medication history of antihypertensive drugs were assessed.

RESULTS: The mean age was 73.2 years (standard deviation ± 5.60), and 48.0% (n = 1,001) were male. Prevalent conditions included dyslipidemia (66.5%), obesity (body mass index ≥ 25 kg/m², 53.6%), and diabetes (28.9%). Dizziness and orthostatic hypotension were self-reported by 1.6% (n = 33) and 1.2% (n = 24), respectively. The majority of patients were on two antihypertensive drugs (48.4%), while 27.5% (n = 574) and 20.8% (n = 433) were on 1 and 3 antihypertensive medications, respectively. Frail to pre-frail patients were older and also tended to have dependent instrumental activities of daily living, slower gait speed, weaker grip strength, lower quality of life, and lower cognitive function. The frail to pre-frail group reported more dizziness (2.6% vs. 1.2%, P < 0.001) and had concerning clinical factors, including lower glomerular filtration rate, more comorbidities such as diabetes, stroke, and a history of admission. Frail to pre-frail older hypertensive patients used slightly more antihypertensive medications than robust older hypertensive patients (1.95 vs. 2.06, P = 0.003). Pre-frail to frail patients often chose beta-blockers as a third medication over diuretics.

CONCLUSION: This study described the general clinical characteristics of older hypertensive patients in Korea. Frail hypertensive patients face challenges in achieving positive clinical outcomes because of multifactorial causes: they are older, have more morbidities, decreased function, lower quality of life and cognitive function, and take more antihypertensive medications. Therefore, it is essential to comprehensively evaluate and monitor disease-related or drug-related adverse events more frequently during regular check-ups, which is necessary for pre-frail to frail older patients with hypertension.

TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003787.

PMID:38501181 | DOI:10.3346/jkms.2024.39.e84

Eur Rev Med Pharmacol Sci. 2024 Mar;28(5):2084-2094. doi: 10.26355/eurrev_202403_35621.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the efficacy and tolerability of perampanel, which was used in a cohort of patients with refractory epilepsy for up to 3.5 years in a real-world setting in Saudi Arabia.

PATIENTS AND METHODS: Data from the medical records of patients treated with perampanel between March 13th, 2017, and September 6th, 2020, at neurology clinics at King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh and Jeddah, Saudi Arabia, was collected. The Liverpool Adverse Events Profile (LAEP) scale was also used to measure the adverse effects of perampanel.

RESULTS: Of the 75 included patients, 66.7% responded to perampanel at the last follow-up, including 22.7% seizure-free for at least the last six months, and 44% of patients responded with a ≥ 50% reduction in seizure frequency from baseline. The overall incidence of adverse effects that led to perampanel discontinuation was 13.3%; the most common adverse effect was aggressive behavior followed by sedation. Pre-existing psychiatric comorbidity was significantly associated with the incidence of psychiatric and behavioral adverse effects on perampanel (p = 0.0206). The mean score of LEAP was 40. The most frequently rated adverse effects in LEAP were "feelings of anger and aggression to others", "nervousness and/or agitation" and "sleepiness". The efficacy and tolerability of perampanel were dose-dependent. Dose 6 mg/day was the most frequently used dose that was taken by about one-third of patients at their last visit.

CONCLUSIONS: Perampanel was effective as an adjunctive treatment for intractable seizures, with a responder rate of 66.7%. The long-term tolerability of perampanel was generally good. Aggressive behavior was the most common reason for perampanel discontinuation. Patients should be counseled and monitored for these adverse effects, particularly those with a history of previous psychiatric and behavioral problems.

PMID:38497889 | DOI:10.26355/eurrev_202403_35621