Medicina (Kaunas). 2023 Dec 4;59(12):2119. doi: 10.3390/medicina59122119.

ABSTRACT

Background and objectives: Cyclophosphamide (CPA) is an alkylating agent that is used for the management of various types of malignancies and as an immunosuppressive agent for the treatment of immunological disorders. However, its use is limited by its potential to cause a wide range of pulmonary toxicities. Amentoflavone (AMV) is a flavonoid that had proven efficacy in the treatment of disease states in which oxidative stress, inflammation, and apoptosis may play a pathophysiologic role. This study investigated the potential ameliorative effects of the different doses of AMV on CPA-induced pulmonary toxicity, with special emphasis on its antioxidant, anti-inflammatory, and apoptosis-modulating effects. Materials and methods: In a rat model of CPA-induced pulmonary toxicity, the effect of AMV at two dose levels (50 mg/kg/day and 100 mg/kg/day) was investigated. The total and differential leucocytic counts, lactate dehydrogenase activity, and levels of pro-inflammatory cytokines in the bronchoalveolar lavage fluid were estimated. Also, the levels of oxidative stress parameters, sirtuin-1, Keap1, Nrf2, JAK2, STAT3, hydroxyproline, matrix metalloproteinases 3 and 9, autophagy markers, and the cleaved caspase 3 were assessed in the pulmonary tissues. In addition, the histopathological and electron microscopic changes in the pulmonary tissues were evaluated. Results: AMV dose-dependently ameliorated the pulmonary toxicities induced by CPA via modulation of the SIRT-1/Nrf2/Keap1 axis, mitigation of the inflammatory and fibrotic events, impaction of JAK-2/STAT-3 axis, and modulation of the autophagic and apoptotic signals. Conclusions: AMV may open new horizons towards the mitigation of the pulmonary toxicities induced by CPA.

PMID:38138222 | PMC:PMC10744450 | DOI:10.3390/medicina59122119

Medicina (Kaunas). 2023 Dec 1;59(12):2109. doi: 10.3390/medicina59122109.

ABSTRACT

Background and Objectives: In addition to a suboptimal and rapidly diminishing response to the coronavirus disease 2019 (COVID-19) vaccine, hemodialysis (HD) patients are at risk for developing a severe COVID-19 infection. In 2022, the combination of cilgavimab and tixagevimab (Evusheld, AstraZeneca) was approved for COVID-19 preexposure prophylaxis in high-risk groups. The purpose of this study was to evaluate the humoral response and short-term safety of this antibody combination in a group of HD patients. Materials and Methods: Seventy-three adult maintenance hemodialysis patients were recruited from a tertiary-care hospital for this double-blinded, non-randomized, placebo-controlled study. Patients were placed into two groups: the intervention group (n = 43) received a single 300 mg dosage of cilgavimab and tixagevimab, while the control group (n = 30) received a saline placebo. The titer of COVID-19-neutralizing antibodies was measured at baseline and after 1 and 6 months. The patients were evaluated for any drug-related adverse effects and monitored for six months for the emergence of any COVID-19-related events. Results: Patients in the intervention group were substantially older and had been on HD for longer (p = 0.002 and 0.006, respectively). The baseline antibody levels were higher in the Evusheld group. The antibody level in the intervention group increased significantly after 1 month and remained consistent for 6 months, whereas the antibody level in the control group fell significantly after 6 months during the study period (Wald χ2 = 30.620, p < 0.001). The drug-related adverse effects were modest and well-tolerated, and only seven patients experienced them. Six months after study enrollment, 10 patients in the intervention group and 6 patients in the control group had been infected with COVID-19, respectively. In the control group, ICU admission and mortality were observed, but in the intervention group, the infection was milder with no aggressive consequences. Conclusions: This study demonstrated the short-term safety and efficacy of tixagevimab-cilgavimab for COVID-19 preexposure prophylaxis in HD patients. These findings require more studies with more HD patients and longer follow-up periods.

PMID:38138212 | PMC:PMC10744812 | DOI:10.3390/medicina59122109

Medicina (Kaunas). 2023 Nov 21;59(12):2052. doi: 10.3390/medicina59122052.

ABSTRACT

Background and Objectives: Schizophrenia, a debilitating mental illness, is often associated with significant physical health risks. Many second-generation antipsychotics increase the risk of metabolic syndrome and cardiovascular disease. Community pharmacists are highly accessible and could play a role in monitoring cardiometabolic adverse drug events in people with schizophrenia. However, it remains uncertain whether mental health professionals perceive this as valuable. This study aimed to explore the opinions of mental healthcare professionals regarding the role of community pharmacists in reducing the incidence of cardiometabolic adverse events in people with schizophrenia and their integration into a multidisciplinary mental health team. Materials and Methods: Qualitative semi-structured interviews were conducted with Australian psychiatrists, mental health nurses and mental health pharmacists. Transcription of the interviews underwent thematic analysis using an inductive approach. Results: Eleven mental healthcare professionals from metropolitan and regional areas across Australia were interviewed, leading to the identification of five overarching themes. These themes encompassed the following aspects: the benefits of community pharmacists' involvement in managing cardiometabolic adverse drug events in people with schizophrenia, improving communication pathways with community pharmacists, defining roles and responsibilities for monitoring cardiometabolic parameters and managing adverse cardiometabolic drug events, fostering collaboration between community pharmacists and mental health care professionals, and recognising the acceptance of community pharmacists' integration within a multidisciplinary team. Mental health professionals believed that community pharmacists could play a role in reducing the incidence of cardiometabolic adverse events in schizophrenia. However, they underscored the need for enhanced communication and collaboration pathways with other healthcare professionals, emphasised the importance of more comprehensive mental health first aid training, and identified potential barriers for community pharmacists such as remuneration, workload, and staff resources. Conclusions: Mental health professionals acknowledged the benefits of incorporating community pharmacists into multidisciplinary teams as a strategy to reduce the incidence of adverse events among individuals with schizophrenia. They recognise the competence of community pharmacists in monitoring cardiometabolic adverse events. However, these professionals have also highlighted specific perceived barriers to the complete integration of community pharmacists within these teams. Notably, there are concerns related to remuneration, staff resources, time constraints, acceptance by other healthcare professionals and patients, and the need for improved communication pathways. Addressing these barriers and providing targeted training could facilitate the valuable inclusion of community pharmacists in the comprehensive care of people with schizophrenia.

PMID:38138155 | PMC:PMC10744378 | DOI:10.3390/medicina59122052

Lancet HIV. 2023 Dec 20:S2352-3018(23)00258-8. doi: 10.1016/S2352-3018(23)00258-8. Online ahead of print.

ABSTRACT

BACKGROUND: In two phase 3 trials for first-line therapy in adults with HIV-1, doravirine showed non-inferior efficacy, a favourable safety profile, and a superior lipid profile to darunavir and efavirenz through to 48 and 96 weeks. Here we report 192-week results from both studies.

METHODS: DRIVE-FORWARD and DRIVE-AHEAD are multicentre, double-blind, randomised, active comparator-controlled, phase 3 trials of first-line antiretroviral treatment in adults with HIV-1. Eligible participants (aged ≥18 years) were naive to antiretroviral therapy, had plasma HIV-1 RNA 1000 copies per mL or more at screening, had no known resistance to any of the trial drugs, and had creatinine clearance 50 mL per min or more. DRIVE-FORWARD was conducted at 125 sites in 15 countries and compared doravirine (100 mg) with ritonavir-boosted darunavir (ritonavir [100 mg] and darunavir [800 mg]), each administered orally once daily with two nucleoside or nucleotide reverse transcriptase inhibitors (tenofovir disoproxil fumarate [300 mg] and emtricitabine [200 mg] or abacavir sulfate [600 mg] and lamivudine [300 mg]). DRIVE-AHEAD was conducted at 126 sites in 23 countries and compared doravirine (100 mg), lamivudine (300 mg), and tenofovir disoproxil fumarate (300 mg) with that of efavirenz (600 mg), emtricitabine (200 mg), and tenofovir disoproxil fumarate (300 mg), all administered orally once daily. DRIVE-FORWARD enrolment was between Dec 1, 2014, and June 1, 2020, and DRIVE-AHEAD enrolment was between June 10, 2015, and Aug 10, 2020. After the 96-week double-blind phase, eligible participants could enter an open-label extension and either continue doravirine or switch from comparator to doravirine for an additional 96 weeks. Efficacy (HIV-1 RNA <50 copies per mL) and safety assessments (adverse events and changes in laboratory parameters) were pooled. The DRIVE-FORWARD and DRIVE-AHEAD trials were registered with ClinicalTrials.gov, NCT02275780 and NCT02403674.

FINDINGS: Of 1494 participants treated in the double-blind phase (1261 [84%] male and 233 [16%] female), 550 continued doravirine and 502 switched to doravirine in the extension. Using the FDA snapshot approach, HIV-1 RNA less than 50 copies per mL was maintained in 457 (83%) of 550 participants who continued doravirine and 404 (80%) of 502 participants who switched to doravirine. Protocol-defined virological failure and development of resistance were low, occurring mainly before week 96. Two (<1%) of 550 participants who continued doravirine reported serious drug-related adverse events, and three (1%) who continued doravirine and one (<1%) of 502 who switched to doravirine discontinued due to drug-related adverse events. Participants continuing or switching to doravirine showed generally favourable lipid profiles, little weight gain, and small decreases in estimated glomerular filtration rates, with no discontinuations due to increased creatinine or renal adverse events.

INTERPRETATION: Favourable efficacy and safety profiles for doravirine at week 96 were maintained through to week 192 in participants who continued or switched to doravirine, supporting use of doravirine for long-term first-line HIV-1 treatment and for virologically suppressed adults switching therapy.

FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

PMID:38141637 | DOI:10.1016/S2352-3018(23)00258-8

J Pers Med. 2023 Dec 14;13(12):1706. doi: 10.3390/jpm13121706.

ABSTRACT

Introduction: Kidney transplantation stands out as the optimal treatment for patients with end-stage kidney disease, provided they meet specific criteria for a secure outcome. With the exception of identical twin donor-recipient pairs, lifelong immunosuppression becomes imperative. Unfortunately, immunosuppressant drugs, particularly calcineurin inhibitors like tacrolimus, bring about adverse effects, including nephrotoxicity, diabetes mellitus, hypertension, infections, malignancy, leukopenia, anemia, thrombocytopenia, mouth ulcers, dyslipidemia, and wound complications. Since achieving tolerance is not feasible, patients are compelled to adhere to lifelong immunosuppressive therapies, often involving calcineurin inhibitors, alongside mycophenolic acid or mTOR inhibitors, with or without steroids. Area covered: Notably, these drugs, especially calcineurin inhibitors, possess narrow therapeutic windows, resulting in numerous drug-related side effects. This review focuses on the prevalent immunosuppressive drug-related side effects encountered in kidney transplant recipients, namely nephrotoxicity, post-transplant diabetes mellitus, leukopenia, anemia, dyslipidemia, mouth ulcers, hypertension, and viral reactivations (cytomegalovirus and BK virus). Additionally, other post-kidney-transplantation drugs such as valganciclovir may also contribute to adverse events such as leukopenia. For each side effect, we propose preventive measures and outline appropriate treatment strategies.

PMID:38138933 | DOI:10.3390/jpm13121706

Prim Care Companion CNS Disord. 2023 Dec 14;25(6):23cr03605. doi: 10.4088/PCC.23cr03605.

NO ABSTRACT

PMID:38134407 | DOI:10.4088/PCC.23cr03605

Mult Scler. 2023 Dec 22:13524585231215268. doi: 10.1177/13524585231215268. Online ahead of print.

ABSTRACT

BACKGROUND: Despite increasing evidence that Epstein-Barr virus (EBV) plays a causal role in MS, no treatments have been shown to reduce EBV turnover. We studied the effect of famciclovir on salivary EBV shedding in people with MS (NCT05283551) in a pilot, proof-of-concept study.

METHODS: People with MS receiving natalizumab provided weekly saliva samples for 12 weeks before starting famciclovir 500 mg twice daily for 12 weeks. Twelve saliva samples were provided on treatment and 12 following treatment. A real-time qPCR Taqman assay was used to detect EBV DNA in saliva. The proportion of saliva samples containing EBV DNA was compared using the Friedman test.

RESULTS: Of 30 participants (19 F; mean age 41 years; median EDSS 3.5), 29 received famciclovir, and 24 completed the 12-week course. Twenty-one participants provided at least one usable saliva sample in all epochs. Ten of the 21 had shedding in at least one sample pre-drug; 7/21 when taking famciclovir (not significant). No difference in EBV DNA copy number was seen. There were no drug-related serious adverse events.

CONCLUSION: No significant effect of famciclovir on EBV shedding was seen in this small pilot study. Given the low numbers, a small effect of famciclovir cannot be excluded. Salivary EBV shedding in this natalizumab-treated cohort was lower than in previous studies, which requires replication.

PMID:38131621 | DOI:10.1177/13524585231215268

World J Clin Cases. 2023 Dec 16;11(35):8425-8430. doi: 10.12998/wjcc.v11.i35.8425.

ABSTRACT

BACKGROUND: This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer. It presents a unique case of a woman with estrogen receptor-positive, HER2-negative breast cancer who developed brain metastasis. The report highlights her initial favorable response to abemaciclib and letrozole therapy prior to the discontinuation due to drug-induced lung damage (DILD).

CASE SUMMARY: In this comprehensive case summary, we present the clinical course of a woman in her 60s, who 11 years following primary breast cancer surgery, was diagnosed with multiple brain metastases. As a third-line systemic therapy, she underwent treatment with abemaciclib and letrozole. This treatment approach yielded a near-partial response in her metastatic brain lesions. However, abemaciclib administration ceased due to the emergence of DILD, as confirmed by a computed tomography scan. The DILD improved after 1 mo of cessation. Despite ongoing therapeutic efforts, the patient's condition progressively deteriorated, ultimately resulting in death due to progression of the brain metastases.

CONCLUSION: This case underscores the challenge of managing adverse events in responsive brain metastasis patients, given the scarcity of therapeutic options.

PMID:38130622 | PMC:PMC10731188 | DOI:10.12998/wjcc.v11.i35.8425

Korean J Pain. 2023 Dec 22. doi: 10.3344/kjp.23246. Online ahead of print.

ABSTRACT

BACKGROUND: : Failed back surgery syndrome (FBSS) is a chronic condition that is characterized by persistent back pain following one or more spinal surgeries. Pharmacological interventions, such as the use of opioids and gabapentinoids, are frequently used in the treatment of FBSS. However, prolonged and excessive use of these medications can lead to dependence and adverse effects. This study investigates trends in opioid and gabapentinoid prescriptions among patients with FBSS in Korea from 2016 to 2020.

METHODS: : Data from the Health Insurance and Review Agency were analyzed, and claims listing FBSS were selected for the study. Prescription patterns of opioids and gabapentinoids were classified based on the number of days prescribed per year.

RESULTS: : Of the 390,095 patients diagnosed with FBSS, 41.6% of the patients were prescribed gabapentinoids, and 42.0% of them were prescribed opioids, while 10.6% of the patients were classified as long-term gabapentinoid users, 11.4% as long-term opioid users, and 7.4% of the patients were found to have long-term prescriptions for both drugs. The proportion of patients who received both gabapentinoid and opioid prescriptions increased annually. The doses of opioids prescribed have also increased along with the increase in the number of patients receiving opioid prescriptions.

CONCLUSIONS: : The prescription rates of opioids and gabapentinoids among patients with FBSS in Korea continue to increase steadily, posing potential risks of addiction and adverse effects. Further research is needed to better understand the actual status of addiction in patients with FBSS.

PMID:38130090 | DOI:10.3344/kjp.23246

Am J Med Qual. 2024 Jan-Feb 01;39(1):21-32. doi: 10.1097/JMQ.0000000000000161. Epub 2023 Dec 28.

ABSTRACT

Context and implementation approaches can impede the spread of patient safety interventions. The objective of this article is to characterize factors associated with improved outcomes among 9 hospitals implementing a medication safety intervention. Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a pharmacist-driven intervention that led to a sustained reduction in nephrotoxic medication-associated acute kidney injury (NTMx-AKI) at 1 hospital. Using qualitative comparative analysis, the team prospectively assessed the association between context and implementation factors and NTMx-AKI reduction during NINJA spread to 9 hospitals. Five hospitals reduced NTMx-AKI. These 5 had either (1) a pharmacist champion and >2 pharmacists working on NINJA (Scon 1.0, Scov 0.8) or (2) a nephrologist-implementing NINJA with minimal competing organizational priorities (Scon 1.0, Scov 0.2). Interviews identified ways NINJA team leaders obtained pharmacist support or successfully implemented without that support. In conclusion, these findings have implications for future spread of NINJA and suggest an approach to study spread of safety interventions more broadly.

PMID:38127682 | DOI:10.1097/JMQ.0000000000000161

J Med Syst. 2023 Dec 21;48(1):5. doi: 10.1007/s10916-023-02022-2.

ABSTRACT

Physician reviews influence how patients seek care, but dishonest reviews can be detrimental to a physician practice. It is unclear if reviews can be challenged, and processes differ and are not readily apparent. The objective of this observational study was to determine the ability to challenge dishonest negative reviews online. Commonly used websites for physician reviews as of August 2021 were utilized: Healthgrades, Vitals, RateMDs, Zocdoc, Yelp, and Google Business. Each review platform's website was tested for leaving a physician review and process of appeal and possible removal of a negative review. The process for appeal and the steps involved in posting and appealing a review were determined, whether individuals are verified patients and criteria for verification, how physicians can respond, and the process of appealing false or defamatory reviews.Any individual can leave reviews by searching for a physician's name or practice and visiting their profile page and can then provide a rating and written review of their experience with the physician. Many require verification to prevent suspicious activity but not proof of a medical visit, allowing significant potential for inaccurate review postings. Posting a review can be done by anyone without verification of a visit. It is challenging for physicians to remove negative online reviews, as most review platforms have strict policies against. This review concludes that physicians should be aware of their online presence and the steps that can be taken to address issues to mitigate adverse effects on their practices.

PMID:38127210 | DOI:10.1007/s10916-023-02022-2

Cad Saude Publica. 2023 Dec 22;39(12):e00077923. doi: 10.1590/0102-311XPT077923. eCollection 2023.

ABSTRACT

The use of triggers for the active search and detection of adverse drug events (ADEs) has been gaining ground within pharmacovigilance services. Thus, the main objective of the study was to propose a new list of triggers to be used in a center specialized in hematology in Rio de Janeiro, Brazil. The update of the list of triggers consisted of revising the current list, with the exclusion and inclusion of new triggers. To verify the performance of the new list of triggers, a cross-sectional study was conducted in which the new triggers were used to investigate the occurrence of ADEs in patients attended in the emergency unit or hospitalized from January to March 2022. For each suspected ADEs, the patient's profile and adverse drug reactions (ADRs) were characterized regarding causality and severity. The performance of the triggers and their ability to capture ADEs were estimated using the following indicators: frequency of the trigger per 100 medical records, frequency of ADEs per 100 records, and positive predictive value (PPV). To evaluate the overall performance of the proposed new list, the PPV was estimated. A total of 374 prescriptions for triggers were identified in 186 medical records. The most efficient in the detection of possible ADEs were: lidocaine, loperamide, bisacodyl, filgrastim and glycerin clyster. The overall PPV of the new suggested list was 48% versus 10% of the previous list. This study demonstrated the importance of an updated list of triggers for the monitoring of ADEs and improvement of the care provided.

PMID:38126560 | DOI:10.1590/0102-311XPT077923

Int J Surg Case Rep. 2023 Dec 15;114:109157. doi: 10.1016/j.ijscr.2023.109157. Online ahead of print.

ABSTRACT

INTRODUCTION: The management of patients with complex oncological histories poses unique challenges, particularly when they are on targeted chemotherapy agents known for specific side effects. This case report illuminates the multifaceted complexities encountered in such scenarios, with a focus on the rare complications associated with targeted therapies.

CASE PRESENTATION: We present a 50-year-old male with an extensive oncological background, including childhood retinoblastoma and radiation-induced leiomyosarcoma. Recently diagnosed with skull base osteosarcoma, he was undergoing treatment with Regorafenib. Admitted with sepsis due to Pseudomonas aeruginosa-induced community-acquired pneumonia, his clinical course was complicated by lung cavitation leading to a spontaneous pneumothorax. This report highlights the absence of empyema, a crucial differential in the diagnosis.

DISCUSSION: This case unravels the intricate interplay between targeted chemotherapy, concurrent medications like prednisone, and their potential to cause severe complications such as pneumonia and pneumothorax. It delves into the mechanisms by which Regorafenib can lead to lung cavitation and abscess formation, a rare but significant risk. The importance of a multidisciplinary approach for prompt diagnosis and treatment, including surgical intervention, is highlighted. The pathology of the surgically resected lobe revealed metastatic high-grade leiomyosarcoma, adding another layer of complexity to the case.

CONCLUSION: This case serves as a cautionary tale highlighting the need for vigilant monitoring of patients on targeted chemotherapy agents, especially those with complex medical histories. It highlights the importance of considering potential drug-related complications and the rationale behind therapeutic choices, including antibiotic selection and surgical decision-making, in the management of acute medical conditions in these patients.

PMID:38128294 | DOI:10.1016/j.ijscr.2023.109157

J Clin Pharmacol. 2023 Dec 21. doi: 10.1002/jcph.2399. Online ahead of print.

ABSTRACT

The human body is subservient to the age-related changes that affect not only the outer appearance, but also organs and tissues. They also concern the processes of pharmacokinetics and dynamics. This means that the absorption, distribution and metabolism of drugs used by an elderly patient will be slowed down. Therefore, it becomes necessary to prescribe a special dosing regimen for older people. An actual problem is also that with age, many patients require more drugs than young people. This increases the risk of side effects, because many drugs are difficult to combine with each other. Pharmacy of our time is a science that is constantly developing and modernizing, which allows changing therapy for the better: prescribing drugs in smaller quantities, with a smaller range of adverse reactions and a better effect. The aim of the work is to analyze the impact and relationship of older age on the pharmacotherapy of patients, as well as the risks of drug-induced diseases. To carry out this work, such research methods as analysis, synthesis, comparative analysis, classification, analogy, abstraction, induction and generalization were used. The features of the stages of pharmacokinetics and pharmacodynamics in the elderly were considered; studied the data of clinical studies, literature in geriatrics; the effects of a combination or increase in the dosage of drugs have been noted. After the collection of research data and the analysis, it turned out that it is real and necessary to avoid the negative consequences of pharmacotherapy in elderly and senile patients. Considering the natural age-related changes in the condition and functioning of organs and systems, constantly monitoring the effectiveness of drugs and undesirable reactions of the body to them, adjusting treatment protocols will have a favorable result and help optimize pharmacotherapy for the elderly, reduce the risk of side effects and diseases caused by medications. This article is protected by copyright. All rights reserved.

PMID:38129179 | DOI:10.1002/jcph.2399

Pharmacoepidemiol Drug Saf. 2023 Dec 21. doi: 10.1002/pds.5747. Online ahead of print.

ABSTRACT

PURPOSE: Antipsychotic agents, which may increase the risk of infection through dopaminergic dysregulation, are prescribed to a fraction of patients following critical illness. We compared the rate of recurrent sepsis among patients who filled a prescription for antipsychotics with high- or low-D2 affinity.

METHODS: Population-based cohort with active comparator design. We included sepsis survivors older than 65 years with intensive care unit admission and new prescription of antipsychotics in Ontario 2008-2019. The primary outcome were recurrent sepsis episodes within 1 year of follow-up. Patients who filled a prescription within 30 days of hospital discharge for high-D2 affinity antipsychotics (e.g., haloperidol) were compared with patients who filled a prescription within 30 days of hospital discharge for low-D2 affinity antipsychotics (e.g., quetiapine). Multivariable zero-inflated Poisson regression models with robust standard errors adjusting for confounding at baseline were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI).

RESULTS: Overall, 1879 patients filled a prescription for a high-D2, and 1446 patients filled a prescription for a low-D2 affinity antipsychotic. Patients who filled a prescription for a high-D2 affinity antipsychotic did not present a higher rate of recurrent sepsis during 1 year of follow-up, compared with patients who filled a prescription for a low-D2 affinity antipsychotic (IRR: 1.12; 95% CI: 0.94, 1.35).

CONCLUSIONS: We did not find conclusive evidence of a higher rate of recurrent sepsis associated with the prescription of high-D2 affinity antipsychotics (compared with low-D2 affinity antipsychotics) by 1 year of follow-up in adult sepsis survivors with intensive care unit admission.

PMID:38126218 | DOI:10.1002/pds.5747

Medicine (Baltimore). 2023 Dec 15;102(50):e36557. doi: 10.1097/MD.0000000000036557.

ABSTRACT

BACKGROUND: Retinopathy of prematurity (ROP) increases with the survival of late preterm infants, but its relationship with neurodevelopmental outcomes in preterm infants remains controversial. To investigate the relationship between ROP and its severity and adverse neurodevelopmental outcomes in preterm infants.

METHODS: We conducted a meta-analysis. All relevant literature before November 2022 were retrieved from PubMed, Embase, Cochrane Library Web of Science, CNKI, CBM, Wan fang Data, and VIP Database. According to the inclusion criteria and exclusion criteria, eligible literature were included to conduct clinical trial quality assessment, and the Newcastle-Ottawa scale was used to evaluate the quality of evidence. Meta-analysis was performed using RevMan5.3. Data extraction, quality assessment, and meta-analysis were performed independently by 2 people. Mean difference or standardized mean difference of motor, language and cognitive scores (Bayley III or Bayley II) were used as effect sizes for continuous data analysis, all of which were represented by 95% CI. For heterogeneity (I2 ≥ 50% or P < .10), a random effects model was used, otherwise a fixed effects model was used.

RESULTS: A total of 6 literature were included. The results of the ROP group for motor (comprehensive motor, proportional motor, and fine motor), language and cognitive scores were -5.57 (95%CI, -1.43 to 0.04), -0.95 (95%CI, 1.4-0.50), -1.34 (95% CI, 1.77-0.92), -1.75 (95% CI, 2.26-1.24) and -5.56 (95% CI, 9.56-1.57). Additionally, the results of severe ROP group for motor (comprehensive motor, proportional motor, fine motor), language and cognitive scores were -8.32 (95%CI, -8.91 to 7.74), -1.10 (95%CI, -1.83 to -0.36), -1.08 (95%CI, -1.75 to -0.41), -7.03 (95%CI, -7.71 to 6.35), and -7.96 (95%CI, -8.5 to -7.42).

CONCLUSIONS: The Bayley Scale scores of the ROP group were lower than those of the not ROP group, and the scores of the severe ROP were significantly lower than those of the not severe ROP group. These findings suggest that ROP can indeed delay motor, language and cognitive, especially in severe cases.

PMID:38115287 | DOI:10.1097/MD.0000000000036557

BMC Nephrol. 2023 Dec 19;24(1):375. doi: 10.1186/s12882-023-03437-2.

ABSTRACT

BACKGROUND: Kidney dysfunction is a common, progressive condition that is increasingly becoming a global public health issue. Because the kidneys are the major route for drug excretion, impaired renal function can change the pharmacokinetics and pharmacodynamics of drugs that are renally excreted. Additionally, patients with kidney dysfunction often have co-morbidities and the associated use of multiple medications which increases the risk of drug-related problem (DRP) occurrence. This study aimed to determine the prevalence, types, and factors associated with DRPs in patients with kidney dysfunction.

METHOD: We conducted a prospective observational study over 3 months among hospitalized patients diagnosed with acute kidney injury or chronic kidney disease who were hospitalized in the medical ward, and patients attending the renal outpatient clinic at Mbarara Regional Referral Hospital. A total of 183 participants were enrolled through the use of a consecutive sampling technique. DRPs were classified according to the PCNE classification version 9.1. Data analysis was carried out using SPSS version 25.

RESULTS: A total of 174 patients with kidney dysfunction were included in the study with a mean ± SD age of 50.34 ± 18.13 years. A total of 219 DRPs were incurred by 138 (79.3%) study participants. The most common DRPs were 'Untreated symptoms or indication' (35.6%) followed by 'adverse event (possibly) occurring' (28.3%), and 'effect of drug treatment not optimal' (23.3%). Antimicrobials were the most involved drugs in suboptimal drug treatment (31.3%) and unnecessary drug treatment (32.1%). The study showed that length of hospital stay ≥ 5 days (AOR = 6.39, 95% CI: 1.75-23.27; p-value = 0.005) significantly increased the risk of DRP occurrence.

CONCLUSION: The current results, in agreement with previous literature, showed a high burden of DRPs among patients with kidney dysfunction. Antimicrobials were the most involved drugs in suboptimal as well as in unnecessary drug treatment. Longer hospital stay significantly increased the risk of DRPs. The high prevalence of DRPs in patients with kidney dysfunction and the potential impact on antimicrobial resistance underscores the importance of regular medication reviews and close monitoring of patients with renal dysfunction.

PMID:38114948 | PMC:PMC10731752 | DOI:10.1186/s12882-023-03437-2

Drug Ther Bull. 2023 Dec 11:dtb-2023-000069. doi: 10.1136/dtb.2023.000069. Online ahead of print.

NO ABSTRACT

PMID:38123946 | DOI:10.1136/dtb.2023.000069

J Allergy Clin Immunol Pract. 2023 Dec 18:S2213-2198(23)01368-5. doi: 10.1016/j.jaip.2023.12.019. Online ahead of print.

ABSTRACT

BACKGROUND: Berotralstat is a first-line, once-daily oral plasma kallikrein inhibitor approved for prophylaxis of hereditary angioedema (HAE) attacks in patients ≥12 years.

OBJECTIVE: This analysis examined the safety and effectiveness of long-term prophylaxis with berotralstat.

METHODS: APeX-2 was a Phase 3, parallel-group, multicenter trial in patients with HAE caused by C1 inhibitor deficiency (NCT03485911). Part 1 was a randomized, double-blind, placebo-controlled evaluation of 150 and 110 mg berotralstat over 24 weeks. In Part 2, berotralstat-treated patients continued the same treatment and placebo-treated patients were re-randomized to 150 or 110 mg berotralstat for 24 weeks. In Part 3, all patients were treated with open-label berotralstat at 150 mg, which could be continued for up to an additional 4 years. In Part 3, the primary endpoint was long-term safety and tolerability. Secondary endpoints included HAE attack rates and quality of life (QoL).

RESULTS: Eighty-one patients entered Part 3. Treatment-emergent adverse events (TEAEs) occurred in 82.7% of patients, with most being mild or moderate in severity. The most common TEAEs were nasopharyngitis, urinary tract infection, abdominal pain, arthralgia, coronavirus infection, and diarrhea. Drug-related TEAEs occurred in 14.8% of patients, but none were serious. For patients who completed 96 weeks of berotralstat treatment (n=70), mean (standard error) change in attack rate from baseline was -2.21 (0.20) attacks/month. Clinically meaningful improvements in QoL were also observed, with the largest improvements in the functioning domain.

CONCLUSION: Berotralstat was generally well tolerated, provided rapid and sustained reductions in HAE attacks, and improved QoL over 96 weeks.

PMID:38122865 | DOI:10.1016/j.jaip.2023.12.019

Urol Pract. 2024 Jan;11(1):172-178. doi: 10.1097/UPJ.0000000000000470. Epub 2023 Dec 20.

ABSTRACT

INTRODUCTION: Clinical guidelines recommend monitoring for metabolic derangements while on preventive pharmacologic therapy for kidney stone disease. The study objective was to compare the frequency of side effects among patients receiving alkali citrate, thiazides, and allopurinol.

METHODS: Using claims data from working-age adults with kidney stone disease (2008-2019), we identified those with a new prescription for alkali citrate, thiazide, or allopurinol within 12 months after their index stone-related diagnosis or procedure. We fit multivariable logistic regression models, adjusting for cohort characteristics like comorbid illness and medication adherence, to estimate 2-year measured frequencies of claims-based outcomes of acute kidney injury, falls/hip fracture, gastritis, abnormal liver function tests/hepatitis, hypercalcemia, hyperglycemia/diabetes, hyperkalemia, hypokalemia, hyponatremia, and hypotension.

RESULTS: Our cohort consisted of 1776 (34%), 2767 (53%), and 677 (13%) patients prescribed alkali citrate, thiazides, or allopurinol, respectively. Comparing unadjusted rates of incident diagnoses, thiazides compared to alkali citrate and allopurinol were associated with the highest rates of hypercalcemia (2.3% vs 1.5% and 1.0%, respectively, P = .04), hypokalemia (6% vs 3% and 2%, respectively, P < .01), and hyperglycemia/diabetes (17% vs 11% and 16%, respectively, P < .01). No other differences with the other outcomes were significant. In adjusted analyses, compared to alkali citrate, thiazides were associated with a higher odds of hypokalemia (OR=2.01, 95% CI 1.44-2.81) and hyperglycemia/diabetes (OR=1.52, 95% CI 1.26-1.83), while allopurinol was associated with a higher odds of hyperglycemia/diabetes (OR=1.34, 95% CI 1.02-1.75).

CONCLUSIONS: These data provide evidence to support clinical guidelines that recommend periodic serum testing to assess for adverse effects from preventive pharmacologic therapy.

PMID:38117963 | DOI:10.1097/UPJ.0000000000000470