N Engl J Med. 2023 Jan 12;388(2):142-153. doi: 10.1056/NEJMsa2206117.

ABSTRACT

BACKGROUND: Adverse events during hospitalization are a major cause of patient harm, as documented in the 1991 Harvard Medical Practice Study. Patient safety has changed substantially in the decades since that study was conducted, and a more current assessment of harm during hospitalization is warranted.

METHODS: We conducted a retrospective cohort study to assess the frequency, preventability, and severity of patient harm in a random sample of admissions from 11 Massachusetts hospitals during the 2018 calendar year. The occurrence of adverse events was assessed with the use of a trigger method (identification of information in a medical record that was previously shown to be associated with adverse events) and from review of medical records. Trained nurses reviewed records and identified admissions with possible adverse events that were then adjudicated by physicians, who confirmed the presence and characteristics of the adverse events.

RESULTS: In a random sample of 2809 admissions, we identified at least one adverse event in 23.6%. Among 978 adverse events, 222 (22.7%) were judged to be preventable and 316 (32.3%) had a severity level of serious (i.e., caused harm that resulted in substantial intervention or prolonged recovery) or higher. A preventable adverse event occurred in 191 (6.8%) of all admissions, and a preventable adverse event with a severity level of serious or higher occurred in 29 (1.0%). There were seven deaths, one of which was deemed to be preventable. Adverse drug events were the most common adverse events (accounting for 39.0% of all events), followed by surgical or other procedural events (30.4%), patient-care events (which were defined as events associated with nursing care, including falls and pressure ulcers) (15.0%), and health care-associated infections (11.9%).

CONCLUSIONS: Adverse events were identified in nearly one in four admissions, and approximately one fourth of the events were preventable. These findings underscore the importance of patient safety and the need for continuing improvement. (Funded by the Controlled Risk Insurance Company and the Risk Management Foundation of the Harvard Medical Institutions.).

PMID:36630622 | DOI:10.1056/NEJMsa2206117

Pediatrics. 2023 Jan 11:e2022059574. doi: 10.1542/peds.2022-059574. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: All US Food and Drug Administration-approved medications for Tourette syndrome are antipsychotics, and their use is limited by the risk of weight gain, metabolic changes, and drug-induced movement disorders. Several small trials suggest that ecopipam, a first-in-class, selective dopamine 1 receptor antagonist, reduces tics with a low risk for these adverse events. This trial sought to further evaluate the efficacy, safety, and tolerability of ecopipam in children and adolescents with moderate to severe Tourette syndrome.

METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, phase 2b trial. Subjects aged ≥6 to <18 years with a baseline Yale Global Tic Severity Score Total Tic Score of ≥20 were randomly assigned 1:1 to ecopipam (n = 76) or placebo (n = 77). The primary endpoint was mean change over 12 weeks in the Yale Global Tic Severity Score Total Tic Score. The Clinical Global Impression of Tourette Syndrome Severity was the secondary endpoint. Safety and tolerability were evaluated at each study visit.

RESULTS: Total tic scores were significantly reduced from baseline to 12 weeks in the ecopipam group compared with placebo (least squares mean differences -3.44, 95% confidence interval -6.09 to -0.79, P = .01). Improvement in Clinical Global Impression of Tourette Syndrome Severity was also greater in the ecopipam group (P = .03). More weight gain was seen in subjects assigned to placebo. No metabolic or electrocardiogram changes were identified. Headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%) were the most common adverse events.

CONCLUSIONS: Among children and adolescents with TS, ecopipam reduces tics to a greater extent than placebo, without observable evidence of common antipsychotic-associated side effects.

PMID:36628546 | DOI:10.1542/peds.2022-059574

BMC Complement Med Ther. 2023 Jan 10;23(1):9. doi: 10.1186/s12906-023-03836-w.

ABSTRACT

BACKGROUND: Tripterygium wilfordii Hook. F. (TwHF), a traditional Chinese medicine, is widely used in the treatment of rheumatoid arthritis. Due to multiorgan toxicity, particularly hepatotoxicity, the application of TwHF is restricted. To clarify the hepatotoxic substances, zebrafish, hepatocytes and macrophages were used for screening based on hepatotoxic injury patterns. This study provides a basis for further elucidation of the hepatotoxic mechanism of TwHF.

METHODS: First, 12 compounds were selected according to the chemical categories of TwHF. The fluorescence area and fluorescence intensity of zebrafish livers were observed and calculated. The viability of two hepatocyte lines was detected by CCK8 assay. TNF-α and IL-1β mRNA expression in bone marrow-derived macrophages was used to evaluate macrophage activation, a factor of potential indirect hepatotoxicity. Finally, the hepatotoxic characteristics of 4 representative components were verified in mice in vivo.

RESULTS: Parthenolide, triptolide, triptonide, triptobenzene H, celastrol, demethylzeylasteral, wilforlide A, triptotriterpenic acid A and regelidine significantly reduced the fluorescence area and fluorescence intensity of zebrafish livers. The viability of L-02 or AML-12 cells was significantly inhibited by parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral, and triptotriterpenic acid A. Parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral and triptobenzene H significantly increased TNF-α and IL-1β mRNA levels in macrophages, while triptophenolide, hypodiolide and wilforine significantly reduced TNF-α and IL-1β mRNA levels. Triptotriterpenic acid A, celastrol and triptobenzene H at a dose of 10 mg/kg significantly increased the levels of mouse serum alanine aminotransferase and aspartate aminotransferase and aggravated liver inflammation.

CONCLUSIONS: Parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral, triptotriterpenic acid A and triptobenzene H might be the main hepatotoxic components of TwFH. Among them, only triptotriterpenic acid A presents direct hepatotoxicity. Triptobenzene H exerts indirect liver damage by activating macrophages. Parthenolide, triptolide, triptonide, celastrol, and demethylzeylasteral can directly and indirectly cause liver injury.

PMID:36627617 | DOI:10.1186/s12906-023-03836-w

BMC Prim Care. 2023 Jan 10;24(1):7. doi: 10.1186/s12875-022-01960-z.

ABSTRACT

BACKGROUND: Team-based primary care reforms aim to improve care coordination by involving multiple interdisciplinary health professionals in patient care. Team-based primary care may support improved medication management for older adults with polypharmacy and multiple points of contact with the healthcare system. However, little is known about this association. This study compares sociodemographic and prescribing trends among older adults in team-based vs. traditional primary care models in Ontario and Quebec.

METHODS: We constructed two provincial cohorts using population-level health administrative data from 2006-2018. Our primary exposure was enrollment in a team-based model of care. Key endpoints included adverse drug events (ADEs), potentially inappropriate prescriptions (PIPs), and polypharmacy. We plotted prescribing trends across the observation period (stratified by model of care) in each province. We used standardized mean differences to compare characteristics of older adults and providers, as well as prescribing endpoints.

RESULTS: Formal patient/physician enrollment increased in both provinces since the time of policy implementation; team-based enrollment among older adults was higher in Quebec (47%) than Ontario (33%) by the end of our observation period. The distribution of sociodemographic characteristics was reasonably comparable between team-based and non-team-based patients in both provinces, aside from a persistently higher share of rural patients in team-based care. Most PIPs assessed either declined or remained relatively steady over time, regardless of model of care and province. Several PIPs were more common among team-based patients than non-team-based patients, particularly in Quebec. We did not detect notable trends in ADEs or polypharmacy in either province.

CONCLUSIONS: Our findings offer encouraging evidence that many PIPs are declining over time in this population, regardless of patients' enrollment in team-based care. Rates of decline appear similar across models of care, suggesting these models may not meaningfully influence prescribing endpoints. Additional efforts are needed to understand the impact of team-based care among older adults and improve primary care prescribing practices.

PMID:36627566 | PMC:PMC9832790 | DOI:10.1186/s12875-022-01960-z

Ther Drug Monit. 2023 Feb 1;45(1):102-109. doi: 10.1097/FTD.0000000000001035.

ABSTRACT

PURPOSE: Tacrolimus is an immunosuppressant widely used in transplantations requiring mandatory concentration-controlled dosing to prevent acute rejection or adverse effects, including new-onset diabetes mellitus (NODM). However, no relationship between NODM and tacrolimus exposure has been established. This study aimed to evaluate the relationship between cumulative tacrolimus exposure and NODM occurrence.

METHODS: A total of 452 kidney transplant patients were included in this study. Sixteen patients developed NODM during the first 3 months after transplant. We considered all tacrolimus concentration (C0) values collected until the diagnosis of NODM in these patients and until 3 months after transplant in the others. New tacrolimus cumulative exposure metrics were derived from the time profile of the tacrolimus morning predose concentration, C0: the percentage of C0 values > cutoff, the average of C0 values above the cutoff, and the percentage of the area under C0 versus time curve, AUCC0, above the cutoff. The cutoff chosen was 15 ng/mL, corresponding to the higher end of the therapeutic range for the early post-transplant period. The influence of these metrics on NODM and other clinical and biological characteristics was investigated using the Cox models.

RESULTS: The percentage of C0 > 15 mcg/L was statistically different between patients with and without NODM (P = 0.01). Only these tacrolimus C0-derived metrics were significantly associated with an increased risk of NODM [HR: 1.73 (1.43-2.10, P < 0.001)].

CONCLUSION: This study shows that tacrolimus concentrations >15 mcg/L affect the incidence of NODM.

PMID:36624577 | DOI:10.1097/FTD.0000000000001035

Drug Ther Bull. 2023 Jan 10:dtb-2022-000078. doi: 10.1136/dtb.2022.000078. Online ahead of print.

ABSTRACT

Overview of: European Medicines Agency. EMA recommends measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders November 2022.

PMID:36627180 | DOI:10.1136/dtb.2022.000078

Enferm Infecc Microbiol Clin (Engl Ed). 2023 Jan;41(1):65. doi: 10.1016/j.eimce.2022.05.011.

NO ABSTRACT

PMID:36621255 | PMC:PMC9817720 | DOI:10.1016/j.eimce.2022.05.011

Enferm Infecc Microbiol Clin (Engl Ed). 2023 Jan;41(1):65-66. doi: 10.1016/j.eimce.2022.05.012.

NO ABSTRACT

PMID:36621254 | PMC:PMC9817762 | DOI:10.1016/j.eimce.2022.05.012

Front Psychiatry. 2022 Dec 21;13:1096006. doi: 10.3389/fpsyt.2022.1096006. eCollection 2022.

ABSTRACT

BACKGROUND: Schizophrenia is considered one of the major risk factors for mortality from SARS-CoV-2 infection. Early antiviral treatment is important to decrease the risk of mortality. Currently, Paxlovid (nirmatrelvir-ritonavir) has been widely used in SARS-CoV-2 patients with risk factors. However, drug-drug interactions with anti-psychotics are prominent and complicated.

CASE PRESENTATION: We report a clozapine-treated patient with SARS-CoV-2 infection who developed neutropenia after coadministration with Paxlovid. In this case, clozapine was used for over 15 years, without neutropenia development. However, severe neutropenia (absolute neutrophil count = 523/μl) developed 3 days after the coadministration of Paxlovid 2 doses per day, valproic acid 1,000 mg per day and clozapine 100 mg per day. The development of neutropenia may be attributed to the complicated interaction among Paxlovid, SARS-CoV-2 infection, valproic acid, fluvoxamine and clozapine.

CONCLUSIONS: Neutropenia is a rare but life-threatening event if a concomitant infection occurs. The risk may increase during SARS-CoV-2 infection and the coadministration of clozapine and Paxlovid. Although the exact causes of neutropenia in this patient are not fully clear, the white blood cell count and absolute neutrophil count should be closely monitored during the administration of Paxlovid in clozapine-treated patients with SARS-CoV-2 infection.

PMID:36620672 | PMC:PMC9810620 | DOI:10.3389/fpsyt.2022.1096006

Middle East J Dig Dis. 2022 Apr;14(2):244-253. doi: 10.34172/mejdd.2022.279. Epub 2022 Apr 30.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have promising clinical activity and are essential medications for patients with several malignancies. However, by deranging the immune system, these novel agents could lead to immune-related adverse events (IRAEs). Hepatotoxicity with checkpoint inhibitors usually results in acute hepatitis or drug-induced liver injury. METHODS: This review article discusses the recent clinical evidence available regarding checkpoint inhibitor-induced hepatitis and reviews an approach to their diagnosis and management. CONCLUSION: ICIs have improved patients' outcomes with different forms of malignancy; however, ICIs-related liver damage is a clinically significant entity in these patients. All patients should be monitored carefully for IRAEs while undergoing treatment with ICIs.

PMID:36619143 | PMC:PMC9489307 | DOI:10.34172/mejdd.2022.279

Sensors (Basel). 2022 Dec 24;23(1):172. doi: 10.3390/s23010172.

ABSTRACT

Future deployment of 5G NR base stations in the 6425-7125 MHz band raises numerous concerns over the long-term impact on the satellite transponders located in geostationary orbit. To study this impact and understand whether 5G NR may cause adverse effect to the spaceborne receivers, the research which estimated the interference levels to the satellite bent pipe links was done. The study presents the evaluation of aggregate interference from 5G NR base stations located inside the victim satellites' footprints using Monte-Carlo analysis and calculation of signal-to-noise degradation and bit error rates of the fixed-satellite service (FSS) bent-pipe transponders for each scenario. The results of the study showed the feasibility of co-existence between 5G NR and satellite systems in the 6425-7125 MHz bands, and that no negative impact on the performance of the satellite links is expected.

PMID:36616767 | PMC:PMC9824803 | DOI:10.3390/s23010172

Nutrients. 2022 Dec 27;15(1):119. doi: 10.3390/nu15010119.

ABSTRACT

Honeybee products arouse interest in society due to their natural origin and range of important biological properties. Propolis (P) and royal jelly (RJ) attract scientists' attention because they exhibit antioxidant, anti-inflammatory, anti-bacterial, anti-tumor, and immunomodulatory abilities. In this study, we tested whether P and RJ could mitigate the adverse effects of cadmium (Cd) exposure, with particular emphasis on the reproductive function in female rats. In this line, one week of pretreatment was established. Six experimental groups were created, including (i) the control group (without any supplementation), (ii) the Cd group (receiving CdCl2 in a dose of 4.5 mg/kg/day), (iii) the P group (50 mg of P/kg/day), (iv) RJ group (200 mg of RJ/kg/day), (v) P + Cd group (rats pretreated with P and then treated with P and Cd simultaneously), (vi) RJ + Cd group (animals pretreated with RJ before receiving CdCl2 simultaneously with RJ). Cd treatment of rats adversely affected a number of measured parameters, including body weight, ovarian structure and ultrastructure, oxidative stress parameters, increased ovarian Cd content and prolonged the estrous cycle. Pretreatment and then cotreatment with P or RJ and Cd alleviated the adverse effects of Cd, transferring the clusters in the PCA analysis chart toward the control group. However, clusters for cotreated groups were still distinctly separated from the control and P, or RJ alone treated groups. Most likely, investigated honeybee products can alter Cd absorption in the gut and/or increase its excretion through the kidneys and/or mitigate oxidative stress by various components. Undoubtedly, pretreatment with P or RJ can effectively prepare the organism to overcome harmful insults. Although the chemical composition of RJ and P is relatively well known, focusing on proportion, duration, and scheme of treatment, as well as the effects of particular components, may provide interesting data in the future. In the era of returning to natural products, both P and RJ seem valuable materials for further consideration as anti-infertility agents.

PMID:36615776 | PMC:PMC9823550 | DOI:10.3390/nu15010119

Molecules. 2023 Jan 3;28(1):427. doi: 10.3390/molecules28010427.

ABSTRACT

Pain is a common clinical symptom among patients. Although various opioid analgesics have been developed, their side effects hinder their application. This study aimed to develop a novel opioid analgesic, HAGD (H-Tyr-D-AIa-GIy-Phe-NH2), with limited side effects. In vivo studies on mouse models as well as in vitro studies on Chinese hamster ovary (CHO) cells expressing human mu, delta, or kappa opioid receptors (CHOhMOP, CHOhDOP, and CHOhKOP, respectively) and human sperm were conducted. Compared with subcutaneous morphine (10 mg/kg), subcutaneous HAGD (10 mg/kg) produced equipotent or even greater antinociception with a prolonged duration by activating mu/delta opioid receptors in preclinical mouse pain models. The analgesic tolerance, rewarding effects (i.e., conditioned place preference and acute hyperlocomotion), and gastrointestinal transit inhibition of HAGD were significantly reduced compared with those of morphine. Both HAGD and morphine exhibited a withdrawal response and had no impacts on motor coordination. In CHOhMOP and CHOhDOP, HAGD showed specific and efficient intracellular Ca2+ stimulation. HAGD had minimal impact on human sperm motility in vitro, whereas 1 × 10-7 and 1 × 10-8 mol/L of morphine significantly declined sperm motility at 3.5 h. Overall, HAGD may serve as a promising antinociceptive compound.

PMID:36615612 | PMC:PMC9824695 | DOI:10.3390/molecules28010427

Molecules. 2023 Jan 1;28(1):346. doi: 10.3390/molecules28010346.

ABSTRACT

The κ-opioid receptor (KOR) has recently emerged as an alternative therapeutic target for the development of pain medications, without deleterious side effects associated with the μ-opioid receptor (MOR). However, modulation of KOR is currently under investigation for the treatment of depression, mood disorders, psychiatric comorbidity, and specific drug addictions. However, KOR agonists also trigger adverse effects including sedation, dysphoria, and hallucinations. In this respect, there is currently much debate on alternative paradigms. Recent effort has been devoted in search of biased ligands capable of selectively activating favorable signaling over signaling associated with unwanted side effects. On the other hand, the use of partial agonists is expected to allow the analgesia to be produced at dosages lower than those required to produce the adverse effects. More empirically, the unwanted central effects can be also avoided by using peripherally restricted agonists. In this review, we discuss the more recent trends in the design of KOR-selective, biased or partial, and finally, peripherally acting agonists. Special emphasis is given on the discussion of the most recent approaches for controlling functional selectivity of KOR-specific ligands.

PMID:36615540 | PMC:PMC9822356 | DOI:10.3390/molecules28010346

Int J Mol Sci. 2023 Jan 3;24(1):852. doi: 10.3390/ijms24010852.

ABSTRACT

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and the association with other autoimmune diseases is well-documented. There are many therapeutic options for the treatment of MS. Most of the available drugs cause drug-induced liver injury (DILI) to variable extents with heterogeneous clinical and biological manifestations, including liver injury with or without signs of hypersensitivity and autoimmunity. The diagnosis of DILI may be particularly difficult because MS is frequently associated with idiopathic autoimmune hepatitis. Recent advances suggest that MS and immune-mediated DILI could be promoted by genetic factors, including HLA genotype. In addition, some of these drugs may promote hepatitis B virus reactivation. This review explores the potential hepatotoxicity of drugs used to treat MS and the criteria to distinguish DILI from idiopathic autoimmune hepatitis associated with MS. The role of susceptible genes both promoting MS and causing the hepatotoxicity of the drug used for MS treatment is also discussed.

PMID:36614299 | PMC:PMC9821303 | DOI:10.3390/ijms24010852

Int J Environ Res Public Health. 2022 Dec 31;20(1):766. doi: 10.3390/ijerph20010766.

ABSTRACT

Inappropriate prescribing (IP) increases the risk of adverse medication reactions and hospitalizations in elderly patients. Therefore, it is crucial to evaluate prescribing patterns among this population. This study was designed to assess the prevalence of potentially inappropriate medication (PIMs) use and potential prescribing omissions (PPOs) among geriatrics with cardiovascular diseases (CVDs). In addition, it determined the predictors for IP in this population. A multi-center study was performed retrospectively on 605 patients' medical records collected randomly from seven governmental hospitals in Kuwait. Three of these hospitals have specialized cardiac centers (tertiary care). Inclusion criteria were age ≥ 65 years, diagnosed with at least one CVD, and attended the outpatient clinic during the last 6 months before data collection. A total of 383 patients (63.3%; 95% CI: 59.3-67.1%) were found using at least one PIM or having PPO or both, based on STOPP/START criteria. Three hundred and ninety-one patients (64.6%; 95% CI: 60.7-68.4%) were prescribed PIMs categorized as C and/or D medicines according to the Euro-FORTA list. Over one-quarter (28.8%; 95% CI: 25.2-32.6%) of the patients had drug-drug interactions class D that require therapy modification and/or X that should be avoided. Patients taking ≥ five medications had significantly higher PIMs based on STOPP and FORTA criteria, drug-drug interactions (p &lt; 0.001), and significantly higher PPOs based on START criteria (p = 0.041). Patients with three or more chronic diseases had significantly higher PIMs based on STOPP and FORTA criteria and PPOs based on START criteria (p-values: 0.028, 0.035, and 0.005, respectively). Significantly higher PIMs based on STOPP criteria and PPOs based on START criteria were found in general hospitals compared to specialized cardiac centers (p= 0.002, p= 0.01, respectively). These findings highlight the need to develop and implement multifaceted interventions to prevent or minimize inappropriate prescribing among the geriatric population with CVDs in Kuwait.

PMID:36613087 | PMC:PMC9819083 | DOI:10.3390/ijerph20010766

Cells. 2022 Dec 23;12(1):57. doi: 10.3390/cells12010057.

ABSTRACT

Despite potent anticancer activity, the clinical utilization of cisplatin is limited due to nephrotoxicity. As Organic Cation Transporter 2 (OCT2) has been shown to be one of the key transporters involved in the uptake of cisplatin into renal proximal tubules, OCT2 inhibitors such as cimetidine have been explored to suppress cisplatin-induced nephrotoxicity. Nonetheless, the impact of OCT2 inhibition or cimetidine on the anti-cancer effects of cisplatin has not been extensively examined. The main objective of the present study was to quantitatively characterize the anticancer effects of cisplatin and cimetidine and determine their nature of interactions in two cancer cell lines, OCT2-negative hepatocellular carcinoma (HCC) cell line, Huh7, and OCT2-positive breast cancer cell line, MDA-MB-468. First, we determined the static concentration-response curves of cisplatin and cimetidine as single agents. Next, with the help of three-dimensional (3D) response surface analyses and a competitive interaction model, we determined their nature of interactions at static concentrations to be modestly synergistic or additive in Huh7 and antagonistic in MDA-MB-468. These results were consistent with the cell-level pharmacodynamic (PD) modeling analysis which leveraged the time-course effects of drugs as single agents and drug combinations. Our developed PD model can be further used to design future preclinical studies to further investigate the cisplatin and cimetidine combinations in different in vitro and in vivo cancer models.

PMID:36611850 | PMC:PMC9818342 | DOI:10.3390/cells12010057

J Clin Med. 2022 Dec 22;12(1):83. doi: 10.3390/jcm12010083.

ABSTRACT

BACKGROUND: Restriction of oral potassium intake is a necessary dietary intervention for managing chronic hyperkalemia. These dietary changes may have negative impacts on nutrition status, particularly in geriatric cohorts with multiple comorbidities. Sodium zirconium cyclosilicate (SZC) is a newly introduced potassium binder intended for patients with hyperkalemia. We aimed to investigate whether the improvements in hyperkalemia with SZC therapy and the liberation of potassium intake restriction may improve nutrition status in a primarily geriatric patient cohort with chronic hyperkalemia.

METHODS: Patients who were maintained on SZC therapy for at least 3 months were retrospectively studied. Following the initiation of SZC and improvement in hyperkalemia, instructions on the restriction of potassium intake were loosened according to the institutional protocol. The change in nutrition status during the 3 month therapeutic period using SZC was investigated by referencing the prognostic nutritional index score (PNI), geriatric nutritional risk index score (GNRI), and controlling nutritional status (CONUT) scores.

RESULTS: A total of 24 patients (median age 78 years, 58% men, median estimated glomerular filtration rate 29.8 mL/min//1.73 m2) were included. Serum potassium level decreased significantly from 5.4 (5.1, 5.9) to 4.4 (4.2, 4.9) mEq/L without any drug-related adverse events, including hypokalemia. Nutrition-related scores, including the PNI score, the GNRI score, and the CONUT score, improved significantly following 3 months of SZC therapy (p &lt; 0.05 for all). Psoas muscle volume and average days for one movement also improved significantly during the therapeutic period (p &lt; 0.05 for both).

CONCLUSIONS: Mid-term SZC therapy and liberation of potassium intake restriction might improve nutrition status in geriatric patients with chronic hyperkalemia.

PMID:36614883 | DOI:10.3390/jcm12010083

J Clin Med. 2022 Dec 20;12(1):21. doi: 10.3390/jcm12010021.

ABSTRACT

BACKGROUND: pemafibrate is a newly-introduced selective peroxisome proliferator-activated receptor-α modulator, which decreases serum triglyceride levels with few drug-related adverse events and may reduce the risk of adverse cardiovascular events in carefully selected patients with hypertriglyceridemia. We aimed to understand which specific cohorts may benefit or not from pemafibrate therapy for adverse cardiovascular event risk reduction.

METHODS: patients with hypertriglyceridemia at baseline received pemafibrate therapy for two years or until October 2022. The factors that were associated with an increased risk of adverse cardiovascular events, defined as heart failure hospitalization, stroke, and acute coronary syndromes, were investigated.

RESULTS: a total of 121 patients (median 62 years, 88 men) remained on pemafibrate therapy for a median of 566 days without any drug-related adverse events. During a 3-month therapeutic period, triglyceride levels improved significantly from 302 (205, 581) mg/dL to 178 (117, 253) mg/dL (p &lt; 0.001). During the overall therapeutic period, there were nine cardiovascular events. Comorbid chronic heart failure, comorbid coronary disease, and a lower pemafibrate dosing were independently associated with the primary endpoint (p &lt; 0.05 for all). Those with multiple risk factors (N = 30) had a significantly higher cumulative incidence of the primary endpoint as compared with others (27% versus 3%, p &lt; 0.001).

CONCLUSION: pemafibrate significantly improves hypertriglyceridemia. A higher dose of pemafibrate should be considered to reduce the risk of adverse cardiovascular events, particularly in patients with chronic heart failure or coronary disease.

PMID:36614823 | DOI:10.3390/jcm12010021

Int J Mol Sci. 2022 Dec 21;24(1):141. doi: 10.3390/ijms24010141.

ABSTRACT

Cisplatin is associated with dose-limiting nephrotoxicity, and the timely detection of acute kidney injury (AKI) can affect morbimortality. Therefore, this study aimed to investigate the tools for monitoring renal function in AKI. This was a retrospective, cohort study. Cisplatin-treated patients with head and neck cancer were included. Nephrotoxicity was assessed using serum creatinine, estimated creatinine clearance, serum electrolytic alterations, and plasma kidney injury molecule-1 (KIM-1). The toxicity severity was classified according to Common Terminology Criteria for Adverse Events (CTCAE), and AKI was classified by Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN). A total of 81 participants were included, of whom only 32 did not have AKI. Almost 90% of participants had a decreased estimated glomerular filtration rate five (D5) days after chemotherapy. The AKI estimate differs between AKIN and RIFLE; more participants were diagnosed by the RIFLE at D5, 19.5% versus 2.4% by AKIN, and fifteen had a discordance between these classifications. All laboratory markers showed significant changes on D5. KIM-1 appeared a possible biomarker when considering CTCAE or AKIN classifications (p &lt; 0.05 on D5), but not when RIFLE classification was used (p = 0.0780). Further studies may seek to understand the profiles of different biomarkers together.

PMID:36613585 | DOI:10.3390/ijms24010141