Epilepsy Behav. 2021 Mar 26;118:107897. doi: 10.1016/j.yebeh.2021.107897. Online ahead of print.

ABSTRACT

OBJECTIVES: The primary objective of this long-term follow-up (LTFU) trial was to evaluate the long-term safety and tolerability of brivaracetam (BRV). The secondary objective was to evaluate the maintenance of efficacy of BRV (including quality of life) over time.

METHODS: This open-label, multicenter, flexible-dose trial (N01379 [NCT01339559]) was conducted in adults (≥16 years) with focal or generalized-onset seizures, who had participated in a placebo (PBO)-controlled trial of adjunctive BRV (N01258: NCT01405508 or N01358: NCT01261325).

RESULTS: Seven hundred and sixty-six patients received BRV in this LTFU trial (753 had focal seizures and 13 had generalized-onset seizures). Kaplan-Meier-estimated retention was 71.9% at 12 months, and 53.7% at 36 months. Treatment-emergent adverse events (TEAEs) were reported by 643 (83.9%) patients, most commonly headache (104 [13.6%] patients) and dizziness (100 [13.1%] patients). Two hundred and fifty-seven (33.6%) patients had drug-related TEAEs, most commonly somnolence (49 [6.4%] patients) and dizziness (41 [5.4%] patients). Permanent discontinuation of BRV due to TEAEs occurred in 91 (11.9%) patients. Patients with focal seizures had a median percentage reduction in focal seizure frequency of 52.0% and 51.7% were 50% responders (sustained over time); 26.0% were seizurefree for 6 months, and 17.9% were seizurefree for 12 months. 42.4% of patients at 12 months and 46.8% at 24 months had clinically meaningful improvements in Patient Weighted Quality of Life in Epilepsy Questionnaire 31 total score.

CONCLUSIONS: In this select group of patients who entered the LTFU trial, BRV was generally safe and well tolerated. Results indicate the long-term efficacy of BRV in patients with focal seizures.

PMID:33780735 | DOI:10.1016/j.yebeh.2021.107897

Eur J Prev Cardiol. 2021 Mar 29:zwab045. doi: 10.1093/eurjpc/zwab045. Online ahead of print.

ABSTRACT

AIMS: The key role of inflammation in the pathogenesis of coronary artery disease (CAD) is an urgent call for innovative treatments. Several trials have proposed colchicine as a therapeutic option for secondary prevention in CAD patients but its utilization is hampered by fears about drug-related adverse events (DAEs) and conflicting evidences. The aim of this meta-analysis was to consolidate evidence on the efficacy and safety of colchicine for secondary prevention in patients with CAD.

METHODS AND RESULTS: A systematic search in electronic bibliographic databases of Medline, Scopus, Embase, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) assessing the cardiovascular effects of colchicine in CAD patients, compared with placebo. Outcomes of interest were the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and DAEs. Estimates were pooled using inverse-variance random-effects model. A total of 11 RCTs, including 12 869 patients, were identified as eligible. A total of 6501 patients received colchicine, while 6368 received placebo. After a median follow-up of 6 months (interquartile range, 1-16), patients receiving colchicine had a lower risk of MACCE [6% vs. 8.8%, relative risk (RR) = 0.67, 95% confidence interval (CI) 0.56-0.80, I2 = 19%], myocardial infarction (3.3% vs. 4.3%, RR = 0.76, 95% CI 0.61-0.96, I2 = 17%), coronary revascularization (2.9% vs. 4.2%, RR = 0.61, 95% CI 0.42-0.89, I2 = 40%), stroke (0.4% vs. 0.9%, RR = 0.48, 95% CI 0.30-0.77, I2 = 0%), hospitalization for cardiovascular cause (0.9% vs. 2.9%, RR = 0.32, 95% CI 0.12-0.87, I2 = 0%). Colchicine was associated with an increased risk of gastrointestinal DAEs (11% vs. 9.2%, RR = 1.67, 95% CI 1.20-2.34, I2 = 76%), myalgia (18% vs. 16%, RR = 1.16, 95% CI 1.02-1.32, I2 = 0%) and DAEs-related discontinuation (4.1% vs. 3%, RR = 1.54, 95% CI 1.02-2.32, I2 = 65%). However, gastrointestinal DAEs and discontinuation may be prevented with a lower daily dose. Colchicine did not increase the risk of cardiovascular death (0.7% vs. 1%, RR = 0.73, 95% CI 0.45-1.21, I2 = 14%), all-cause death (2% vs. 1.9%, RR = 1.01, 95% CI 0.71-1.43, I2 = 16%), or other DAEs.

CONCLUSIONS: The use of colchicine in patients with CAD is safe and efficacious for MACCE prevention.

PMID:33779702 | DOI:10.1093/eurjpc/zwab045

J Oncol Pharm Pract. 2021 Mar 27:10781552211005072. doi: 10.1177/10781552211005072. Online ahead of print.

ABSTRACT

This study aimed to implement pharmaceutical care using the therapeutic outcome monitoring (TOM) method for pharmacotherapeutic follow-up of oncological patients. This was a prospective longitudinal study involving patients undergoing oral chemotherapy. The study environment was an outpatient pharmacy at a tertiary-level oncology hospital. Ninety patients who received oral chemotherapy were evaluated, and 27 patients were followed up in accordance with the exclusion criteria and acceptability of participation in the study. The patients were predominantly diagnosed with gynecological tumors, with a mean age of 57.56 ± 13.06. The average consumption of drugs per patient was 4.63 ± 4.85, and more than 55% of patients had undergone oral antineoplastic therapy for more than a year. The main therapeutic groups used were drugs that acted on the gastrointestinal tract and metabolism (34%). All patients had at least one drug-related problem (DRP). In total, 133 DRP were identified. Approximately 33% of patients had DRPs related to antineoplastic therapy; non-adherence, incorrect administration, and the probability of adverse events were among the frequently reported DRPs. We identified 43 negative outcomes associated with medication (NOM), with untreated health problems (47%) and non-quantitative insecurity (30%) being the most frequently reported. 81 pharmaceutical interventions were performed, and 96% were accepted. The main errors avoided with the interventions were untreated health problems, misuse, and interruptions associated with medication administration. The TOM method effectively achieved the desired results of therapy, improving the use of medicines, and thus increasing patient safety.

PMID:33779371 | DOI:10.1177/10781552211005072

Alzheimers Dement (N Y). 2021 Mar 24;7(1):e12158. doi: 10.1002/trc2.12158. eCollection 2021.

ABSTRACT

INTRODUCTION: Inflammatory markers have long been observed in the brain, cerebrospinal fluid (CSF), and plasma of Alzheimer's disease (AD) patients, suggesting that inflammation contributes to AD and might be a therapeutic target. However, non-steroidal anti-inflammatory drug trials in AD and mild cognitive impairment (MCI) failed to show benefit. Our previous work seeking to understand why people with the inflammatory disease rheumatoid arthritis are protected from AD found that short-term treatment of transgenic AD mice with the pro-inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) led to an increase in activated microglia, a 50% reduction in amyloid load, an increase in synaptic area, and improvement in spatial memory to normal. These results called into question the consensus view that inflammation is solely detrimental in AD. Here, we tested our hypothesis that modulation of the innate immune system might similarly be used to treat AD in humans by investigating the ability of GM-CSF/sargramostim to safely ameliorate AD symptoms/pathology.

METHODS: A randomized, double-blind, placebo-controlled trial was conducted in mild-to-moderate AD participants (NCT01409915). Treatments (20 participants/group) occurred 5 days/week for 3 weeks plus two follow-up (FU) visits (FU1 at 45 days and FU2 at 90 days) with neurological, neuropsychological, blood biomarker, and imaging assessments.

RESULTS: Sargramostim treatment expectedly changed innate immune system markers, with no drug-related serious adverse events or amyloid-related imaging abnormalities. At end of treatment (EOT), the Mini-Mental State Examination score of the sargramostim group increased compared to baseline (P = .0074) and compared to placebo (P = .0370); the treatment effect persisted at FU1 (P = .0272). Plasma markers of amyloid beta (Aβ40 [decreased in AD]) increased 10% (P = .0105); plasma markers of neurodegeneration (total tau and UCH-L1) decreased 24% (P = .0174) and 42% (P = .0019), respectively, after sargramostim treatment compared to placebo.

DISCUSSION: The innate immune system is a viable target for therapeutic intervention in AD. An extended treatment trial testing the long-term safety and efficacy of GM-CSF/sargramostim in AD is warranted.

PMID:33778150 | PMC:PMC7988877 | DOI:10.1002/trc2.12158

Clin Kidney J. 2020 May 4;14(3):884-890. doi: 10.1093/ckj/sfaa027. eCollection 2021 Mar.

ABSTRACT

BACKGROUND: The incidence of acute tubulointerstitial nephritis (ATIN) related to drugs has dramatically increased over recent years. A new subtype of ATIN, apparently different from classical drug-related ATIN, has emerged that has been related to the administration of immune checkpoint inhibitors (ICIs). We investigated these differences between ICI-related ATIN (ICI ATIN) and non-ICI-related ATIN in terms of clinical features, response to treatment with steroids and the evolution of kidney function.

METHODS: A total of 47 patients diagnosed with ATIN from two centres were recruited. Of these, 13 patients presented with ATIN during ICI treatment and 34 were diagnosed with ATIN attributed to other drugs. The main demographic, clinical and analytical variables such as gender, age and current medication were recorded. The type of malignancy, oncological treatment, ICI dose and presence of extrarenal immune-related adverse events were also reviewed. Renal biopsy diagnosis, time to drug withdrawal and ATIN-specific treatment, as well as laboratory data during follow-up, were also studied.

RESULTS: Patients diagnosed with ICI ATIN presented with lower creatinine (ICI ATIN 3.8 ± 1.03 versus classical ATIN 5.98 ± 4.15 mg/dL, P = 0.007) at diagnosis and higher urinary leucocyte counts (ICI ATIN 263.2 ± 418.04 versus classical ATIN 133.55 ± 284.62, P = 0.048) compared with patients with non-ICI-related ATIN. Time from initiation of the culprit drug to ATIN diagnosis was longer in patients with ICI ATIN than in those with classical ATIN (197.07 ± 184.99 versus 114.4 ± 352.16 days, P = 0.006). In addition, during follow-up, the slope of decreasing creatinine over time was lower for ICI ATIN compared with non-ICI-related ATIN.

CONCLUSIONS: In this study, we analysed differences between ICI ATIN and classical ATIN. We found that patients with ICI ATIN presented with a larger latency period after culprit drug initiation, milder acute kidney injury and slower creatinine amelioration compared with those with classical ATIN. These results may, in part, be ascribed to potential differences in the pathological mechanisms involved in ATIN development, suggesting that ICI and classical ATIN may be different diseases with similar renal histologies.

PMID:33777371 | PMC:PMC7986364 | DOI:10.1093/ckj/sfaa027

Transpl Infect Dis. 2021 Mar 27:e13607. doi: 10.1111/tid.13607. Online ahead of print.

ABSTRACT

Recommended preventive strategies before kidney transplantation include screening and treatment of latent tuberculosis infection (LTBI), and updating of the recommended vaccines. We prospectively evaluated in dedicated infectious diseases consultations, from 2014 to 2018, the clinical and vaccination data of new adult kidney allograft candidates. Patients were offered an updated vaccination schedule, if appropriate, and were screened for LTBI using chest imaging and interferon gamma release assay (IGRA). Overall, 467 patients with median age of 58 [46-66] years were evaluated, of whom 302 patients (65%) were men (sex ratio 1.83), and 333 (71%) were on dialysis. Main causes of renal insufficiency were diabetes (25%) and autoimmune nephropathies (18%). The vaccination coverage was low and varied according to the different types of vaccines and patients. Vaccination or immunization rates were 24%, 6%, 54%, and 51% for tetanus-diphtheria-polio-acellular pertussis, Pneumococcus, hepatitis B, and seasonal influenza, respectively. ID consultation successfully rose patients' vaccinations coverage, in fulfillment with recommendations, in 465 (99%) patients. LTBI treatment was administered in 78 (16.7%) patients and caused drug-related adverse events in 9 (11%). A dedicated infectious disease consultation should become a critical tool for coordinating infection prevention strategies.

PMID:33773002 | DOI:10.1111/tid.13607

Diabet Med. 2021 Mar 27:e14561. doi: 10.1111/dme.14561. Online ahead of print.

ABSTRACT

Chronic kidney disease (CKD) is an increasingly identified complication of diabetes (1). The occurrence of CKD in a person with type 1 diabetes mellitus (T1DM or type 2 diabetes mellitus (T2DM) creates an added challenge for the diabetes care provider. Increased risk of drug-related adverse events, including hypoglycemia, possibility of drug-drug interactions, and the need to minimize associated complications, all contribute to the complexity of managing diabetes and CKD (2). This clinical situation also increases the responsibility of the treating physician, as it becomes imperative to preserve renal function while ensuring glycemic control.

PMID:33772854 | DOI:10.1111/dme.14561

Sr Care Pharm. 2021 Apr 1;36(4):217-222. doi: 10.4140/TCP.n.2021.217.

ABSTRACT

OBJECTIVE: To evaluate the impact of pharmacy interventions on recurrence of falls in older people.

DESIGN: Prospective case-crossover study.

SETTING: LECOM Health Nursing and Rehabilitation (LNR) and Senior Living Center (SLC) and Millcreek Community Hospital older adult behavioral health and inpatient rehabilitation units (IRU).

PARTICIPANTS: Twenty and 15 residents of the SLC and LNR, respectively, and 5 and 2 patients of the older adult behavioral health unit and IRU, respectively, experienced a fall during the 8-week study period.

INTERVENTIONS: Medication reviews were conducted by a pharmacist assessing for fall risk-increasing drugs (FRIDs). Adverse effects, drug interactions, and nonpharmacologic causes were evaluated, and recommendations were made to reduce future fall risk.

MAIN OUTCOME MEASURES: Recommendation acceptance rate, FRID use, and incidence of recurrent falls.

RESULTS: Eighty percent of fall risk-reduction recommendations were accepted and implemented by the medical team. The mean number of potential FRIDs prescribed per participant was reduced from 3.71 to 3.38. There was a 12.4% reduction in recurrent falls after pharmacy intervention (P = 0.0336; odds ratio [95% confidence interval] = 1.783 [1.045-3.112]).

CONCLUSION: Pharmacist interventions for older people who experience a fall were associated with a high acceptance rate by health care providers, a reduction in FRID use, and decreased rate of recurrent falls.

PMID:33766194 | DOI:10.4140/TCP.n.2021.217

Sr Care Pharm. 2021 Apr 1;36(4):208-216. doi: 10.4140/TCP.n.2021.208.

ABSTRACT

OBJECTIVE: To evaluate deprescribing of select high-risk medications (HRMs) in an Acute Care for the Elderly (ACE) unit with pharmacist involvement compared with usual care in older people.

DESIGN: Retrospective, single-center case-control study.

SETTING: Medical-surgical units at an urban academic medical center.

PARTICIPANTS: Patients 65 years of age and older admitted April-June 2019, with 1 or more of the following target HRMs prior to admission were included in the study: acid suppressants, antipsychotics, or insulin. Patients admitted to the ACE unit were included in the case group; all other patients were randomly matched by HRMs in a 2:1 ratio into the control group.

INTERVENTIONS: The Acute Care for the Elderly pharmacist reviewed patients' medications to identify and deprescribe select HRMs. Deprescribing was defined as discontinuation, dose or frequency reduction.

RESULTS: A total of 47 patients with 56 HRMs and 89 patients with 126 HRMs were included in the case and control groups, respectively. The primary outcome of HRMs deprescribed were similar between the case and control groups (21.4% and 25.4%; P = 0.56). Among the HRMs deprescribed (discontinued, dose or frequency reduced), 83.2% were complete discontinuations in case patients and 34.4% were complete discontinuations in control patients.

PMID:33766193 | DOI:10.4140/TCP.n.2021.208

Curr Opin Ophthalmol. 2021 May 1;32(3):191-197. doi: 10.1097/ICU.0000000000000757.

ABSTRACT

PURPOSE OF REVIEW: Antivascular endothelial growth factor (VEGF) agents have provided historic therapeutic breakthroughs in the treatment of retinal disease. New anti-VEGF agents are emerging for the treatment of retinal vascular diseases. Both systemic and ocular adverse effect need to be understood in managing patients. This review aims to highlight the adverse effects seen with routine use of bevacizumab, ranibizumab and aflibercept, as well as with new medications such as brolucizumab and abicipar.

RECENT FINDINGS: We review the recent findings of intraocular inflammation (IOI) of brolucizumab and abicipar in the context of the efficacy and safety reported with the routine anti-VEGF agents. Specifically, brolucizumab has been reported to cause occlusive retinal vasculitis in the setting of IOI, which has not been seen in other anti-VEGF medications. In addition, abicipar appears to cause IOI at a higher rate of patients than other anti-VEGF agents have previously.

SUMMARY: Newer anti-VEGF agents pose a significant risk of adverse events not seen with routine anti-VEGF agents.

PMID:33770015 | DOI:10.1097/ICU.0000000000000757

Curr Opin Ophthalmol. 2021 Mar 23. doi: 10.1097/ICU.0000000000000757. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Antivascular endothelial growth factor (VEGF) agents have provided historic therapeutic breakthroughs in the treatment of retinal disease. New anti-VEGF agents are emerging for the treatment of retinal vascular diseases. Both systemic and ocular adverse effect need to be understood in managing patients. This review aims to highlight the adverse effects seen with routine use of bevacizumab, ranibizumab and aflibercept, as well as with new medications such as brolucizumab and abicipar.

RECENT FINDINGS: We review the recent findings of intraocular inflammation (IOI) of brolucizumab and abicipar in the context of the efficacy and safety reported with the routine anti-VEGF agents. Specifically, brolucizumab has been reported to cause occlusive retinal vasculitis in the setting of IOI, which has not been seen in other anti-VEGF medications. In addition, abicipar appears to cause IOI at a higher rate of patients than other anti-VEGF agents have previously.

SUMMARY: Newer anti-VEGF agents pose a significant risk of adverse events not seen with routine anti-VEGF agents.

PMID:33769327 | DOI:10.1097/ICU.0000000000000757

Taiwan J Ophthalmol. 2020 Jul 27;11(1):64-70. doi: 10.4103/tjo.tjo_32_20. eCollection 2021 Jan-Mar.

ABSTRACT

PURPOSE: This prospective study evaluates whether rituximab is a safe and potentially effective treatment for nonparaneoplastic autoimmune retinopathy (npAIR).

MATERIALS AND METHODS: Five npAIR patients were enrolled in a Phase I/II, prospective, nonrandomized, open-label, single-center study. All patients received a cycle of 1000 mg intravenous rituximab at weeks 0 and 2, with a second cycle of rituximab 6 to 9 months later. Clinical evaluation was performed at baseline, 6 and 12 weeks after each rituximab cycle, and then every 3 months for a total duration of 18 months. The primary outcome for this study was treatment success based on visual field and full-field electroretinography at 6 months. The secondary outcomes included treatment success at months 12 and 18, drug-related adverse events, changes in visual symptoms, and changes in quality of life.

RESULTS: Two patients met criteria for treatment success: one based solely on electroretinography and the other based solely on visual field area, but treatment success was not sustained. Clinical response over the course of the 18-month study showed disease stabilization in three patients and treatment failure in two patients. There were no severe drug-related adverse events.

CONCLUSION: This is the first clinical trial prospectively evaluating the effect of rituximab in npAIR and, although rituximab was well tolerated, there was no clear-cut clinical improvement conferred by B cell depletion with rituximab.

PMID:33767957 | PMC:PMC7971443 | DOI:10.4103/tjo.tjo_32_20

Drug Ther Bull. 2021 Apr;59(4):54-55. doi: 10.1136/dtb.2020.000078.

ABSTRACT

Commentary on: Mehta SR, Wood DA, Storey RF, et al Complete Revascularization with Multivessel PCI for Myocardial Infarction. N Engl J Med 2019; 381:1411-21. Commentary by: Dr Emma Magavern and Dr Teck Khong Clinical Pharmacology, St George's, University of London, UK. Series Editor: Dr Teck Khong, DTB Associate Editor Clinical Pharmacology, St George's, University of London, UK.

PMID:33766922 | DOI:10.1136/dtb.2020.000078

Lancet Haematol. 2021 Mar 22:S2352-3026(21)00028-4. doi: 10.1016/S2352-3026(21)00028-4. Online ahead of print.

ABSTRACT

BACKGROUND: The haematological benefit of standard-of-care anti-C5 treatment for haemolytic paroxysmal nocturnal haemoglobinuria is limited by residual intravascular haemolysis or emerging C3-mediated extravascular haemolysis. Therefore, the aim of this phase 2 study was to assess the safety, tolerability, pharmacokinetics and pharmacodynamics, and activity of the new complement factor B inhibitor, iptacopan, in patients with paroxysmal nocturnal haemoglobinuria who have active haemolysis despite anti-C5 therapy.

METHODS: In this multicentre, open-label, single-arm, phase 2 trial, we enrolled adult patients (aged 18-80 years) with paroxysmal nocturnal haemoglobinuria who showed signs of active haemolysis despite receiving eculizumab treatment. Patients were enrolled at Federico II University Hospital (Naples, Italy), Hôpital Saint-Louis (Paris, France), and University Hospital Essen (Essen, Germany). For enrolment, patients were required to show lactate dehydrogenase more than 1·5-times the upper limit of normal and a paroxysmal nocturnal haemoglobinuria type 3 erythrocyte or granulocyte clone size of 10% or greater. Patients with bone marrow failure, on systemic steroid or immunosuppressive drugs, or with severe comorbidities were excluded from the study. Iptacopan was given orally as an add-on therapy at a dose of 200 mg twice daily. The primary endpoint was the effect of iptacopan on the reduction of chronic residual intravascular haemolysis measured as change in lactate dehydrogenase from baseline value to week 13. At 13 weeks, patients could opt into a long-term study extension (ongoing), allowing for modifications of standard treatment. This trial is registered at ClinicialTrials.gov, NCT03439839.

FINDINGS: Between May 31, 2018, and April 9, 2019, ten patients had twice daily 200 mg iptacopan. Iptacopan resulted in marked reduction of lactate dehydrogenase from baseline versus at week 13 (mean 539 IU/L [SD 263] vs 235 IU/L [44], change from baseline -309·2 IU/L [SD 265·5], 90% CI -473·77 to -144·68, p=0·0081), associated with significant improvement of haemoglobin concentrations (mean 97·7 g/L [SD 10·5] vs 129·5 g/L [18·3] change from baseline 31·9 g/L [14·5], 90% CI 23·42-40·28, p<0·0001). All biomarkers of haemolysis improved on iptacopan treatment. Observed haematological benefits were maintained longer than the 13-week study period, throughout the study extension, including seven patients who stopped concomitant standard-of-care treatment and continued iptacopan as monotherapy. There were no deaths or treatment-related serious adverse events during the study period. Of three non-related serious adverse events, two occurred in the same patient (one during run-in and before exposure to iptacopan).

INTERPRETATION: Iptacopan at a chronic dose of 200 mg twice daily was well tolerated without any major drug-related safety findings and shows lactate dehydrogenase reduction and haemoglobin normalisation in most patients with paroxysmal nocturnal haemoglobinuria at week 13 and beyond, even in monotherapy. On the basis of these data, iptacopan will be tested as monotherapy in pivotal trials investigating its haematological benefit in a broader paroxysmal nocturnal haemoglobinuria population.

FUNDING: Novartis Institutes for Biomedical Research.

PMID:33765419 | DOI:10.1016/S2352-3026(21)00028-4

Int J Clin Pharm. 2021 Mar 24. doi: 10.1007/s11096-021-01237-y. Online ahead of print.

ABSTRACT

Background Geriatric patients represent a vulnerable population in terms of adverse drug events (ADEs). Objective The aims of this study were to determine the prevalence and preventability of hospital admissions to a geriatric ward related to ADEs, to identify medications involved in these ADEs and to describe potential preventability aspects of ADE-related admissions. Setting University Hospital Hradec Králové, Czech Republic. Methods This cross-sectional study evaluated acute hospital admissions to the geriatric ward of University Hospital Hradec Králové over a period of nine months (April-December 2017). Medication reviews were performed in order to identify ADE-related hospital admissions. Causality was assessed using the World Health Organization-Uppsala Monitoring Centre criteria. Modified Schumock-Thornton algorithm was used to assess the preventability of ADEs. Main outcome measure 9-month-prevalence of ADE-related hospital admissions. Results A total of 366 hospital admissions were included. The 9-month-prevalence of ADE-related hospital admissions was 11.75% [95% confidence interval 8.45-15.05]. Antithrombotic agents and diuretics represented the most common medication classes associated with ADEs (30.2% each). Electrolyte disturbances and gastrointestinal haemorrhages and ulcerations were the most frequently observed ADEs associated with hospital admission. Out of 43 ADE-related hospitalisations, 23 (53.5%) were considered potentially preventable. Conclusion The contribution of ADEs to hospital admission to the geriatric ward was not negligible. Our results also suggest that 53.5% of identified ADE-related admissions could be potentially prevented. This finding demonstrates just how important the research on the preventability of medication-related hospitalisations is. Further studies and implementations are still needed aiming to minimize the risk of medication-related harm.

PMID:33763812 | DOI:10.1007/s11096-021-01237-y

Vnitr Lek. 2021 Winter;67(1):51-56.

ABSTRACT

The COVID-19 pandemic represents a wide-ranging form of involvement from asymptomatic through mild respiratory form to bilateral bronchopneumonia with acute respiratory and multiorgan fatal failure. Patients with comorbidities (obesity, cardiovascular diseases, diabetes mellitus) are particularly at risk of a more severe course of infection. We present a 33-year old lean patient with a medical history of ulcerative colitis on immunosuppressive treatment with Azathioprine, after unsuccessful in vitro fertilization one week before the onset of symptoms, admitted to hospital for two-week-long cough with sore throat with fever ap to 40°C. CT confirmed bilateral bronchopneumonia without etiological detection of the infectious agent. Three PCR tests (two of nasopharyngeal swabs and one of bronchoalveolar lavage (BAL)) were negative for COVID-19, including antigen and antibody tests. Complex parenteral ATB treatment with high-flow nasal oxygen therapy was ineffective, and artificial lung ventilation was indicated for acute respiratory failure. After 4 days antifungal treatment of Fluconazole, condition of patient progressed to hepatic and multiorgan failure and the patient died on day 14 of hospitalization. Post-mortem histological examination revealed the presence of coronavirus in the cells of lung parenchyma. The case recalls that even young patients with immunosuppressive treatment are at risk for the critical course of COVID-19 disease. The negativity of the tests was due to the capture of the patient only after the second week of infection, at the time of the diagnostic window between the positive PCR test and the formation of antibodies. The persistent effect of immunosuppression was most likely the reason for the lack of antibody response.

PMID:33752392

Int J Clin Pract. 2021 Mar 23:e14164. doi: 10.1111/ijcp.14164. Online ahead of print.

ABSTRACT

AIM: This study evaluated the effect of intracavitary levobupivacaine infusion diluted with locally applied isotonic solution for pain control in cystoscopy.

METHODS: Included in this study are 100 patients who had previously undergone transurethral tumor resection for bladder tumor and were followed up by cystoscopy. The patients were randomized into five groups (n = 20). In the first, second, third, and fourth groups, 4, 6, 8, and 10 mL of levobupivacaine HCl (5.0 mg/mL) were mixed with 26, 24, 22, and 20 mL of isotonic solution, respectively. Hence, the total mixture was 30 mL for each group. The fifth group was the control group. In this group, the standard method commonly used in most clinics was utilized. That is, a gel containing Cathejell-2% lidocaine (25 mg lidocaine) was applied for local analgesia. Cystoscopic interventions were performed with a 17.5 Fr rigid cystoscope and 0°, 30°, and 70° lens. During cystoscopy and 30 min later, the pain status of patients was assessed using the Visual Analogue Scale (VAS), and patient satisfaction was questioned.

RESULTS: The mean VAS score during and after the cystoscopy procedure was significantly lower in the levobupivacaine groups compared to the lidocaine group. In addition, patient satisfaction in the levobupivacaine groups was significantly higher than in the lidocaine group. No drug-related side-effects were observed in all groups.

CONCLUSION: Thus, levobupivacaine is a more effective drug than lidocaine alone to control pain during cystoscopy. The use of levobupivacaine is recommended to prevent possible complications of general anesthesia by eliminating the need for the aforementioned as well as its cost-saving advantage.

PMID:33754424 | DOI:10.1111/ijcp.14164

Drug Ther Bull. 2021 Mar 22:dtb-2021-000016. doi: 10.1136/dtb.2021.000016. Online ahead of print.

ABSTRACT

Every month, DTB scans sources of information on treatments, disease management and other healthcare topics for key items to bring to our readers' attention and help them keep up to date. To do this, we produce succinct, contextualised summaries of the information concerned.

PMID:33753352 | DOI:10.1136/dtb.2021.000016

Exp Neurol. 2021 Mar 19:113705. doi: 10.1016/j.expneurol.2021.113705. Online ahead of print.

ABSTRACT

Anticancer therapeutics can provoke severe side effects that impair the patient's quality of life. A frequent dose-limiting side effect of platinum-based anticancer therapy is neurotoxicity. Its pathophysiology is poorly understood, and effective preventive or therapeutic measures are missing. Therefore, elucidation of the molecular mechanism of platinating drug-induced neurotoxicity and the development of preventive strategies is urgently needed. To this end, we aim to use C. elegans as a 3R-compliant in vivo model. The 3R principles were conceived for animal welfare in science concerning animal experiments, which should be replaced, reduced or refined. We can analytically demonstrate dose-dependent uptake of cisplatin (CisPt) in C. elegans, as well as genotoxic and cytotoxic effects based on DNA adduct formation (i.e., 1,2-GpG intrastrand crosslinks), induction of apoptosis, and developmental toxicity. Measuring the impairment of pharyngeal pumping as a marker of neurotoxicity, we found that especially CisPt reduces the pumping frequency at concentrations where basal and touch-provoked movement were not yet affected. CisPt causes glutathione (GSH) depletion and RNAi-mediated knockdown of the glutamate-cysteine ligase GCS-1 aggravates the CisPt-induced inhibition of pharyngeal pumping. Moreover, N-acetylcysteine (NAC) mitigated CisPt-triggered toxicity, indicating that GSH depletion contributes to the CisPt-induced pharyngeal damage. In addition to NAC, amifostine (WR1065) also protected the pharynx of C. elegans from the toxic effects of CisPt. Measuring pharyngeal activity by the electrophysiological recording of neurotransmission in the pharynx, we confirmed that CisPt is neurotoxic in C. elegans and that NAC is neuroprotective in the nematode. The data support the hypothesis that monitoring the pharyngeal activity of C. elegans is a useful surrogate marker of CisPt-induced neurotoxicity. In addition, a low GSH pool reduces the resistance of neurons to CisPt treatment, and both NAC and WR1065 are capable of attenuating platinum-induced neurotoxicity during post-incubation in C. elegans. Overall, we propose C. elegans as a 3R-compliant in vivo model to study the molecular mechanisms of platinum-induced neurotoxicity and to explore novel neuroprotective therapeutic strategies to alleviate respective side effects of platinum-based cancer therapy.

PMID:33753139 | DOI:10.1016/j.expneurol.2021.113705

Dtsch Arztebl Int. 2021 Jan 11;118(1-2):12-13. doi: 10.3238/arztebl.m2021.0048.

NO ABSTRACT

PMID:33750532 | DOI:10.3238/arztebl.m2021.0048