Int J Mol Sci. 2023 Aug 30;24(17):13424. doi: 10.3390/ijms241713424.

ABSTRACT

Cyclophosphamide causes side effects in cancer patients, including hepatotoxicity. Probiotics have recently emerged as potential approaches for the administration of many diseases. This study aimed to evaluate the protective effects of Lactiplantibacillus plantarum P101 against cyclophosphamide-induced liver injury and elucidate the underlying mechanism. In this study, Lactiplantibacillus plantarum P101 or Lactobacillus rhamnosus GG were pre-administered to mice with varying duration (1 week, 2 weeks, and 3 weeks) before being intraperitoneally injected with cyclophosphamide at a dose of 30 mg/kg/day for 7 days to induce liver injury. Results demonstrated that cyclophosphamide-induced liver injury was characterized by histopathological disorders, including irregular central venous shape and hepatic vascular rupture, as well as a severe inflammation response and oxidative stress. The administration of probiotics for 3 weeks exerted the most significant improvements in alleviating liver injury, oxidative stress, and inflammation when compared to the shorter intervention duration. Notably, Lactiplantibacillus plantarum P101 exhibited more pronounced effects than Lactobacillus rhamnosus GG. Furthermore, Lactiplantibacillus plantarum P101 enhanced the antioxidant defense system by activating the Nrf2/ARE signaling pathway, ultimately alleviating hepatotoxicity and hepatocyte apoptosis. In conclusion, this study highlighted the potential of Lactiplantibacillus plantarum P101 to alleviate cyclophosphamide-induced hepatotoxicity.

PMID:37686229 | PMC:PMC10488115 | DOI:10.3390/ijms241713424

Sci Rep. 2023 Sep 8;13(1):14865. doi: 10.1038/s41598-023-41899-4.

ABSTRACT

In-vivo toxicity assessment is an important step prior to clinical development and is still the main source of data for overall risk assessment of a new molecular entity (NCE). All in-vivo studies are performed according to regulatory requirements and many efforts have been exerted to minimize these studies in accordance with the (Replacement, Reduction and Refinement) 3Rs principle. Many aspects of in-vivo toxicology packages can be optimized to reduce animal use, including the number of studies performed as well as study durations, which is the main focus of this analysis. We performed a statistical comparison of adverse findings observed in 116 short-term versus 78 long-term in-house or in-house sponsored Contract Research Organizations (CRO) studies, in order to explore the possibility of using only short-term studies as a prediction tool for the longer-term effects. All the data analyzed in this study was manually extracted from the toxicology reports (in PDF formats) to construct the dataset. Annotation of treatment related findings was one of the challenges faced during this work. A specific focus was therefore put on the summary and conclusion sections of the reports since they contain expert assessments on whether the findings were considered adverse or were attributed to other reasons. Our analysis showed a general good concordance between short-term and long-term toxicity findings for large molecules and the majority of small molecules. Less concordance was seen for certain body organs, which can be named as "target organ systems' findings". While this work supports the minimization of long-term studies, a larger-scale effort would be needed to provide more evidence. We therefore present the steps performed in this study as an open-source R workflow for the Comparison of Short-term and Long-term Toxicity studies (CSL-Tox). The dataset used in the work is provided to allow researchers to reproduce such analysis, re-evaluate the statistical tools used and promote large-scale application of this study. Important aspects of animal research reproducibility are highlighted in this work, specifically, the necessity of a reproducible adverse effects reporting system and utilization of the controlled terminologies in-vivo toxicology reports and finally the importance of open-source analytical workflows that can be assessed by other scientists in the field of preclinical toxicology.

PMID:37684321 | PMC:PMC10491674 | DOI:10.1038/s41598-023-41899-4

Nat Commun. 2023 Sep 8;14(1):5529. doi: 10.1038/s41467-023-41066-3.

ABSTRACT

Immune checkpoint inhibitors cause side effects ranging from autoimmune endocrine disorders to severe cardiotoxicity. Periodic Fasting mimicking diet (FMD) cycles are emerging as promising enhancers of a wide range of cancer therapies including immunotherapy. Here, either FMD cycles alone or in combination with anti-OX40/anti-PD-L1 are much more effective than immune checkpoint inhibitors alone in delaying melanoma growth in mice. FMD cycles in combination with anti-OX40/anti-PD-L1 also show a trend for increased effects against a lung cancer model. As importantly, the cardiac fibrosis, necrosis and hypertrophy caused by immune checkpoint inhibitors are prevented/reversed by FMD treatment in both cancer models whereas immune infiltration of CD3+ and CD8+ cells in myocardial tissues and systemic and myocardial markers of oxidative stress and inflammation are reduced. These results indicate that FMD cycles in combination with immunotherapy can delay cancer growth while reducing side effects including cardiotoxicity.

PMID:37684243 | PMC:PMC10491752 | DOI:10.1038/s41467-023-41066-3

Prim Care Companion CNS Disord. 2023 Sep 5;25(5):22cr03448. doi: 10.4088/PCC.22cr03448.

NO ABSTRACT

PMID:37683621 | DOI:10.4088/PCC.22cr03448

Medicine (Baltimore). 2023 Sep 8;102(36):e34965. doi: 10.1097/MD.0000000000034965.

ABSTRACT

RATIONALE: Acute lymphoblastic leukemia (ALL) represents approximately 1-quarter of all new cases of childhood cancer. Although overall survival following diagnosis has improved in recent years, the toxicity of chemotherapy remains a concern.

PATIENT CONCERNS: We describe an 11-year-old male patient diagnosed with T-cell precursor ALL who developed compounded complications during the induction phase of chemotherapy. Patient was hospitalized in the Department of Pediatric Hematology, Oncology, and Transplantology of the Medical University of Lublin, Poland. The patient's induction therapy was started according to the AIEOP-BFM ALL 2017 protocol IAp (International Collaborative Treatment Protocol for Children and Adolescents with Acute Lymphoblastic Leukemia).

DIAGNOSES: Patient developed compounded complications such as cholecystitis, hepatotoxicity, pancreatitis and myelosuppression.

INTERVENTIONS: The patient was treated with leukapheresis, received a broad-spectrum antibiotic, potassium supplementation and hepatoprotective treatment and laparotomy cholecystectomy.

OUTCOMES: In the available literature, there is a limited amount of similar clinical cases with multiple complications in pediatric patients with ALL. Toxicities cause delays in the treatment of the underlying disease.

LESSONS: In children with acute lymphoblastic leukemia, there are side effects during the treatment such as cholecystitis and pancreatitis. Complications during treatment require a quick response and modification of disease management. Abdominal ultrasound performed before treatment makes it possible to observe the dynamics of lesions. Genetic mutation analysis could allow us to more precisely respond to the possible susceptibility to and appearance of complications after the use of a given chemotherapeutic agent.

PMID:37682188 | PMC:PMC10489477 | DOI:10.1097/MD.0000000000034965

Medicine (Baltimore). 2023 Sep 8;102(36):e35138. doi: 10.1097/MD.0000000000035138.

ABSTRACT

BACKGROUND: This study compared the effectiveness of nalmefene and fentanyl in reducing the incidence and severity of etomidate-induced myoclonus.

METHODS: One hundred fifty patients were randomized to receive 0.25ug/kg of nalmefene, 1ug/kg of fentanyl, or the same volume of normal saline 3 minutes prior to etomidate-induced anesthesia. The primary observational indexes were the severity level and incidence of etomidate-induced myoclonus, and the secondary observational index included blood pressure, heart rate, and the incidence of adverse effects from anesthesia induction to resuscitation, such as cough, chest wall rigidity, dizziness, nausea, pain after awakening, and intraoperative awareness.

RESULTS: The incidence of myoclonus was significantly lower in the nalmefene group (8.0%) than in the fentanyl group (32.0%) (P = .003) and in the normal saline group (72.0%) (P = .000). The severity level of myoclonus in the nalmefene group was significantly lower than the fentanyl group (P = .001) and normal saline group (P = .000). Meanwhile, the incidences of cough and chest wall rigidity during anesthesia induction were significantly lower in the nalmefene group compared with the fentanyl group (P = .003, P = .027). There were no statistically significant differences in heart rate and mean arterial pressure among the 3 gruops (P > .05). There was no difference in the incidence of adverse effects among the 3 groups during recovery from anesthesia (P > .05).

CONCLUSION: Intravenous injection of 0.25ug/kg of nalmefene 3 minutes prior to etomidate is more effective in preventing etomidate-induced myoclonus during general anesthesia than 1ug/kg of fentanyl.

PMID:37682124 | PMC:PMC10489433 | DOI:10.1097/MD.0000000000035138

Cells. 2023 Aug 25;12(17):2147. doi: 10.3390/cells12172147.

ABSTRACT

In the emerging era of cancer immunotherapy, immune checkpoint blockades (ICBs) and adoptive cell transfer therapies (ACTs) have gained significant attention. However, their therapeutic efficacies are limited due to the presence of cold type tumors, immunosuppressive tumor microenvironment, and immune-related side effects. On the other hand, dendritic cell (DC)-based vaccines have been suggested as a new cancer immunotherapy regimen that can address the limitations encountered by ICBs and ACTs. Despite the success of the first generation of DC-based vaccines, represented by the first FDA-approved DC-based therapeutic cancer vaccine Provenge, several challenges remain unsolved. Therefore, new DC vaccine strategies have been actively investigated. This review addresses the limitations of the currently most adopted classical DC vaccine and evaluates new generations of DC vaccines in detail, including biomaterial-based, immunogenic cell death-inducing, mRNA-pulsed, DC small extracellular vesicle (sEV)-based, and tumor sEV-based DC vaccines. These innovative DC vaccines are envisioned to provide a significant breakthrough in cancer immunotherapy landscape and are expected to be supported by further preclinical and clinical studies.

PMID:37681880 | PMC:PMC10486560 | DOI:10.3390/cells12172147

Int J Environ Res Public Health. 2023 Aug 23;20(17):6628. doi: 10.3390/ijerph20176628.

ABSTRACT

BACKGROUND: There have been multiple reported pharmacy initiatives to reduce opioid misuse and accidental overdose to address our nation's public health crisis. To date, there has not been a description in the literature of a community pharmacy follow-up initiative for dispensed opioids.

METHODS: A follow-up program was designed and implemented in community pharmacies as part of a previously developed opioid overdose and misuse prevention program (ONE Program). Five to twelve days after the dispensing of an opioid, pharmacy technicians called the patient to follow up on opioid safety topics. Pharmacy technicians used a questionnaire to inquire about medication disposal plans, if the patient was taking the medication more than prescribed, medication side effects, and if the patient needed a pharmacist consultation. The results from that questionnaire were documented.

RESULTS: During the first 18 months of the follow-up program, 1789 phone calls were completed. Of those contacted, 40% were still using their opioid medication, and over 10% were experiencing side effects which triggered a pharmacist consult. Patients were reminded of proper medication disposal methods, and most patients (78%) desired to dispose of unused medication at the pharmacy medication disposal box.

CONCLUSIONS: Follow-up phone calls post-opioid medication dispensing were shown to add value to a previously established opioid misuse and accidental overdose prevention program and allowed for the fulfillment of the Pharmacist Patient Care Process.

PMID:37681768 | PMC:PMC10487139 | DOI:10.3390/ijerph20176628

Medicine (Baltimore). 2023 Sep 8;102(36):e34983. doi: 10.1097/MD.0000000000034983.

ABSTRACT

BACKGROUND: To assess the safety and efficacy of sorafenib and sunitinib as first-line treatments for metastatic renal cell carcinoma (mRCC), to provide evidence-based support for clinical decision-making regarding rational drug use.

METHODS: Until May 10, 2023, a comprehensive search was conducted across PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, and Wanfang databases to identify clinical studies comparing sorafenib with sunitinib as first-line treatment for mRCC. The literature was screened, data extracted, and quality evaluated independently by 2 researchers. Meta-analysis was conducted using Revman5.4 software.

RESULTS: A total of 3741 patients were enrolled in 20 studies. The meta-analysis results indicated that there were no significant differences in the 2- and 5-year progression-free survival (PFS) and overall survival (OS) rates between the sorafenib and sunitinib groups (P > .05). The disease control rate (DCR) was comparable between the 2 groups (P > .05), while the objective response rate (ORR) was higher in the sunitinib group (P = .03). However, subgroup analysis revealed no significant differences in ORR, DCR, 2- and 5-year PFS, and OS rates between sorafenib and sunitinib among both Asian populations as well as European and American populations (P > .05). In terms of drug-related adverse events, the incidence of grade ≥ 3 hypertension, leukopenia, neutropenia, thrombocytopenia, anemia, nausea and vomiting were significantly lower in the sorafenib group compared to the sunitinib group (P < .05).

CONCLUSION: In the first-line treatment of mRCC, sorafenib exhibits comparable efficacy to sunitinib but with lower toxicity.

PMID:37682147 | DOI:10.1097/MD.0000000000034983

Heliyon. 2023 Aug 27;9(9):e19441. doi: 10.1016/j.heliyon.2023.e19441. eCollection 2023 Sep.

ABSTRACT

Adverse drug events constitute a major challenge for the success of clinical trials. Several computational strategies have been suggested to estimate the risk of adverse drug events in preclinical drug development. While these approaches have demonstrated high utility in practice, they are at the same time limited to specific information sources. Thus, many current computational approaches neglect a wealth of information which results from the integration of different data sources, such as biological protein function, gene expression, chemical compound structure, cell-based imaging and others. In this work we propose an integrative and explainable multi-modal Graph Machine Learning approach (MultiGML), which fuses knowledge graphs with multiple further data modalities to predict drug related adverse events and general drug target-phenotype associations. MultiGML demonstrates excellent prediction performance compared to alternative algorithms, including various traditional knowledge graph embedding techniques. MultiGML distinguishes itself from alternative techniques by providing in-depth explanations of model predictions, which point towards biological mechanisms associated with predictions of an adverse drug event. Hence, MultiGML could be a versatile tool to support decision making in preclinical drug development.

PMID:37681175 | PMC:PMC10481305 | DOI:10.1016/j.heliyon.2023.e19441

Sci Rep. 2023 Sep 7;13(1):14722. doi: 10.1038/s41598-023-41996-4.

ABSTRACT

Animals tend to alternate between different choices, which requires the ability to remember recent choices. The Y-maze spontaneous alternation test is widely used in various animal models for assessing short-term memory, and its precise evaluation depends upon the accurate determination of the arm visit sequence. However, an objective method for defining arm visits is lacking owing to uncertainty regarding the extent to which an animal must go into the arm to be considered visited. Here, we conducted quantitative analyses on mice behavior in the Y-maze while systematically varying the arm visit threshold and assessed the effect of acute social isolation on spatial working memory. Our results revealed that 24-h social isolation significantly reduced spontaneous alternation rate when the arm threshold was set at the distal part of the arm. Furthermore, the memory of the recently visited arms faded away faster in the socially isolated mice. However, other behavioral factors were comparable to those of the group-housed mice, indicating a specific impairment of short-term memory. Our findings suggest that the location of arm visit threshold is critical for the precise evaluation of short-term memory, and our study provides a method for comprehensively and systematically assessing spontaneous alternation behavior in the Y-maze.

PMID:37679447 | PMC:PMC10485067 | DOI:10.1038/s41598-023-41996-4

Signal Transduct Target Ther. 2023 Sep 8;8(1):338. doi: 10.1038/s41392-023-01548-8.

ABSTRACT

Genome instability has been identified as one of the enabling hallmarks in cancer. DNA damage response (DDR) network is responsible for maintenance of genome integrity in cells. As cancer cells frequently carry DDR gene deficiencies or suffer from replicative stress, targeting DDR processes could induce excessive DNA damages (or unrepaired DNA) that eventually lead to cell death. Poly (ADP-ribose) polymerase (PARP) inhibitors have brought impressive benefit to patients with breast cancer gene (BRCA) mutation or homologous recombination deficiency (HRD), which proves the concept of synthetic lethality in cancer treatment. Moreover, the other two scenarios of DDR inhibitor application, replication stress and combination with chemo- or radio- therapy, are under active clinical exploration. In this review, we revisited the progress of DDR targeting therapy beyond the launched first-generation PARP inhibitors. Next generation PARP1 selective inhibitors, which could maintain the efficacy while mitigating side effects, may diversify the application scenarios of PARP inhibitor in clinic. Albeit with unavoidable on-mechanism toxicities, several small molecules targeting DNA damage checkpoints (gatekeepers) have shown great promise in preliminary clinical results, which may warrant further evaluations. In addition, inhibitors for other DNA repair pathways (caretakers) are also under active preclinical or clinical development. With these progresses and efforts, we envision that a new wave of innovations within DDR has come of age.

PMID:37679326 | PMC:PMC10485079 | DOI:10.1038/s41392-023-01548-8

Curr Opin Neurol. 2023 Oct 1;36(5):410-415. doi: 10.1097/WCO.0000000000001196. Epub 2023 Aug 30.

ABSTRACT

PURPOSE OF REVIEW: Myasthenia Gravis (MG) is a rare neurological disorder affecting the neuromuscular junction. Clinical hallmarks are fatigability and weakness affecting the extraocular, axial, limb and/or respiratory muscles. Despite immunosuppressive treatment, mainly based on corticosteroids and nonsteroidal immunosuppressants, the burden of MG is still significant, both in terms of inadequate disease control and burdensome side effects. Driven by such limits, the past years have been characterized by an escalation of MG drug development, with novel molecules which now focuses on having a more targeted effect, with a higher safety and efficacy profile.

RECENT FINDINGS: As the pathogenic mechanism of MG are slowly being unravelled, new potential targets for treatments are being considered. This has led since 2017 to the Food and Drug Administration (FDA)-approval of three new drugs that either act by blocking the complement system (i.e., eculizumab and ravulizumab) or by blocking the neonatal Fc receptor thus preventing immunoglobulin recycling and reducing imunoglobulin G (IgG) antibodies (i.e., efgartigimod). Other drugs, with similar mechanism of action, are currently under review for approval.

SUMMARY: The repertoire of available and developmental therapies for MG is rapidly expanding, finally responding to the unmet need of a more targeted and effective therapeutic approach in MG.

PMID:37678337 | DOI:10.1097/WCO.0000000000001196

Clin J Oncol Nurs. 2023 Mar 16;27(2):181-189. doi: 10.1188/23.CJON.181-189.

ABSTRACT

BACKGROUND: Germline and somatic biomarker testing for BRCA1/2 pathogenic variants can provide important susceptibility, prognostic, and predictive information, guiding recommendations for care.

OBJECTIVES: This article reviews BRCA1/2, DNA damage and repair mechanisms, prevention and screening guidelines for patients with germline pathogenic BRCA1/2 variants, indications for poly (ADP-ribose) polymerase (PARP) inhibitor therapy, associated side effects, tumor resistance, and implications for nurses.

METHODS: A comprehensive review of the CINAHL®, MEDLINE®, and PubMed® databases was performed using the following search terms: BRCA1/2, PARP inhibitors, and genomic testing.

FINDINGS: PARP inhibitors are indicated for select patients with malignancies associated with BRCA1/2 pathogenic variants. Awareness of PARP inhibitors, their mechanism of action, indications for use, and associated side effects helps oncology nurses guide patients and families in care recommendations, provide detailed patient education, effectively monitor for side effects, and promote adherence to therapy.

PMID:37677830 | DOI:10.1188/23.CJON.181-189

Oncol Nurs Forum. 2022 Dec 16;50(1):25-34. doi: 10.1188/23.ONF.25-34.

ABSTRACT

PURPOSE: To explore cancer survivors' access to and use and disposal of opioids in the context of the opioid epidemic.

PARTICIPANTS & SETTING: Community-based recruitment strategies were employed for individuals aged 18 years or older who were previously diagnosed with cancer, completed cancer treatment within the past five years, or were cancer free, and who were prescribed opioids for cancer-related pain.

METHODOLOGIC APPROACH: This qualitative study used semistructured interviews. Data were analyzed using applied thematic analysis techniques.

FINDINGS: Themes included the following: (a) restrictive policies affecting opioid access and supply, (b) decreased opioid use because of concerns of addiction and other opioid-related side effects, and (c) lack of clarity on safeguarding and disposal of opioids.

IMPLICATIONS FOR NURSING: Cancer survivors may encounter barriers to opioid access, alter medication-taking behavior over fear of addiction and side effects, and face inadequate education regarding proper disposal of opioids. Nurses can advocate for appropriate access to prescribed opioids, assess opioid-taking behavior, provide education regarding storage and disposal, and implement educational interventions accordingly.

PMID:37677788 | DOI:10.1188/23.ONF.25-34

PLoS One. 2023 Sep 7;18(9):e0289222. doi: 10.1371/journal.pone.0289222. eCollection 2023.

ABSTRACT

BACKGROUND: Loss to follow-up (LTFU) is an unsuccessful treatment outcome for tuberculosis (TB) patients. In Malaysia, LTFU affects around 1 in 20 TB patients. Integration of qualitative research methods and evidence will provide a better understanding of LTFU and its underlying issues. In this study, we qualitatively explored TB patients' experiences in receiving treatment and their reasons for leaving TB care.

METHOD: In-depth interviews of 15 patients with a history of LTFU were conducted from January to September 2020. Interview guides were developed to explore TB patients' experiences while receiving treatment, including challenges faced and reasons for treatment interruption. Data were thematically analysed using the framework method.

RESULTS: We identified 11 emerging themes that occurred at four levels of interaction with TB patients. First, at the patient personal level, TB beliefs referring to patients' perception of illness and wellness, patients' perceived role of traditional and complementary medicine, and substance abuse were important. Second, the healthcare system and treatment factors that were highlighted included the organisation of care and treatment, interaction with healthcare professionals, particularly in communication and counselling, and TB medications' side effects. Third, structural factors including financial burden, logistical and transportation issues and work-related factors were identified to be barriers to treatment continuation. Fourth, the interpersonal level interaction of patients should not be neglected; this includes family relationships and support as well as peer influence.

CONCLUSION: Study findings put forth issues and challenges faced by TB patients while receiving treatment and underscore areas where actions can be taken. This will contribute to informing the development and implementation of future TB control strategies that are responsive to TB patients' needs and concerns, to effectively address LTFU and ensure better treatment completion rates among TB patients in Malaysia.

PMID:37676902 | PMC:PMC10484432 | DOI:10.1371/journal.pone.0289222

Scand J Immunol. 2023 Jul;98(1):e13274. doi: 10.1111/sji.13274. Epub 2023 May 4.

ABSTRACT

Increased levels of neutrophil extracellular traps (NETs) have been detected in individuals with vaccine complications after the ChAdOx1 nCov vaccine with a correlation between the severity of vaccine side effects and the level of NETosis. DNases may disrupt NETs by degrading their content of DNA, and a balance has been reported between NETs and DNases. Because of this and since the inflammatory marker NETs may be used as a confirmatory test in diagnosing VITT, it is of interest to monitor levels of DNase in patients with increased NETs levels. The current novel rapid DNase ELISA was tested in blood samples of patients with known increased levels of NETs with or without VITT after ChAdOx1 nCoV-19 vaccination. DNase levels in VITT patients were significantly increased compared with normal unvaccinated blood donors and compared with patients with post-vaccination symptoms but not VITT. However, since EDTA was found to inhibit DNase, serum and not EDTA-plasma samples should be applied for DNase testing. The novel DNase assay may serve as a supplementary test to the NETs test when analysing samples from patients with suspected increased NETs levels.

PMID:37676118 | DOI:10.1111/sji.13274

Cochrane Database Syst Rev. 2023 Sep 7;9:CD013472. doi: 10.1002/14651858.CD013472.pub2.

ABSTRACT

BACKGROUND: Preterm birth interferes with brain maturation, and subsequent clinical events and interventions may have additional deleterious effects. Music as therapy is offered increasingly in neonatal intensive care units aiming to improve health outcomes and quality of life for both preterm infants and the well-being of their parents. Systematic reviews of mixed methodological quality have demonstrated ambiguous results for the efficacy of various types of auditory stimulation of preterm infants. A more comprehensive and rigorous systematic review is needed to address controversies arising from apparently conflicting studies and reviews.

OBJECTIVES: We assessed the overall efficacy of music and vocal interventions for physiological and neurodevelopmental outcomes in preterm infants (< 37 weeks' gestation) compared to standard care. In addition, we aimed to determine specific effects of various interventions for physiological, anthropometric, social-emotional, neurodevelopmental short- and long-term outcomes in the infants, parental well-being, and bonding.

SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, RILM Abstracts, and ERIC in November 2021; and Proquest Dissertations in February 2019. We searched the reference lists of related systematic reviews, and of studies selected for inclusion and clinical trial registries.

SELECTION CRITERIA: We included parallel, and cluster-randomised controlled trials with preterm infants < 37 weeks` gestation during hospitalisation, and parents when they were involved in the intervention. Interventions were any music or vocal stimulation provided live or via a recording by a music therapist, a parent, or a healthcare professional compared to standard care. The intervention duration was greater than five minutes and needed to occur more than three times.

DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data. We analysed the treatment effects of the individual trials using RevMan Web using a fixed-effects model to combine the data. Where possible, we presented results in meta-analyses using mean differences with 95% CI. We performed heterogeneity tests. When the I2 statistic was higher than 50%, we assessed the source of the heterogeneity by sensitivity and subgroup analyses. We used GRADE to assess the certainty of the evidence.

MAIN RESULTS: We included 25 trials recruiting 1532 infants and 691 parents (21 parallel-group RCTs, four cross-over RCTs). The infants gestational age at birth varied from 23 to 36 weeks, taking place in NICUs (level 1 to 3) around the world. Within the trials, the intervention varied widely in type, delivery, frequency, and duration. Music and voice were mainly characterised by calm, soft, musical parameters in lullaby style, often integrating the sung mother's voice live or recorded, defined as music therapy or music medicine. The general risk of bias in the included studies varied from low to high risk of bias. Music and vocal interventions compared to standard care Music/vocal interventions do not increase oxygen saturation in the infants during the intervention (mean difference (MD) 0.13, 95% CI -0.33 to 0.59; P = 0.59; 958 infants, 10 studies; high-certainty evidence). Music and voice probably do not increase oxygen saturation post-intervention either (MD 0.63, 95% CI -0.01 to 1.26; P = 0.05; 800 infants, 7 studies; moderate-certainty evidence). The intervention may not increase infant development (Bayley Scales of Infant and Toddler Development (BSID)) with the cognitive composition score (MD 0.35, 95% CI -4.85 to 5.55; P = 0.90; 69 infants, 2 studies; low-certainty evidence); the motor composition score (MD -0.17, 95% CI -5.45 to 5.11; P = 0.95; 69 infants, 2 studies; low-certainty evidence); and the language composition score (MD 0.38, 95% CI -5.45 to 6.21; P = 0.90; 69 infants, 2 studies; low-certainty evidence). Music therapy may not reduce parental state-trait anxiety (MD -1.12, 95% CI -3.20 to 0.96; P = 0.29; 97 parents, 4 studies; low-certainty evidence). The intervention probably does not reduce respiratory rate during the intervention (MD 0.42, 95% CI -1.05 to 1.90; P = 0.57; 750 infants; 7 studies; moderate-certainty evidence) and post-intervention (MD 0.51, 95% CI -1.57 to 2.58; P = 0.63; 636 infants, 5 studies; moderate-certainty evidence). However, music/vocal interventions probably reduce heart rates in preterm infants during the intervention (MD -1.38, 95% CI -2.63 to -0.12; P = 0.03; 1014 infants; 11 studies; moderate-certainty evidence). This beneficial effect was even stronger after the intervention. Music/vocal interventions reduce heart rate post-intervention (MD -3.80, 95% CI -5.05 to -2.55; P < 0.00001; 903 infants, 9 studies; high-certainty evidence) with wide CIs ranging from medium to large beneficial effects. Music therapy may not reduce postnatal depression (MD 0.50, 95% CI -1.80 to 2.81; P = 0.67; 67 participants; 2 studies; low-certainty evidence). The evidence is very uncertain about the effect of music therapy on parental state anxiety (MD -0.15, 95% CI -2.72 to 2.41; P = 0.91; 87 parents, 3 studies; very low-certainty evidence). We are uncertain about any further effects regarding all other secondary short- and long-term outcomes on the infants, parental well-being, and bonding/attachment. Two studies evaluated adverse effects as an explicit outcome of interest and reported no adverse effects from music and voice.

AUTHORS' CONCLUSIONS: Music/vocal interventions do not increase oxygen saturation during and probably not after the intervention compared to standard care. The evidence suggests that music and voice do not increase infant development (BSID) or reduce parental state-trait anxiety. The intervention probably does not reduce respiratory rate in preterm infants. However, music/vocal interventions probably reduce heart rates in preterm infants during the intervention, and this beneficial effect is even stronger after the intervention, demonstrating that music/vocal interventions reduce heart rates in preterm infants post-intervention. We found no reports of adverse effects from music and voice. Due to low-certainty evidence for all other outcomes, we could not draw any further conclusions regarding overall efficacy nor the possible impact of different intervention types, frequencies, or durations. Further research with more power, fewer risks of bias, and more sensitive and clinically relevant outcomes are needed.

PMID:37675934 | DOI:10.1002/14651858.CD013472.pub2

Pulm Pharmacol Ther. 2023 Sep 5:102252. doi: 10.1016/j.pupt.2023.102252. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Chronic refractory cough is a challenging condition that requires a thorough evaluation and management approach. P2X3 receptors that are ATP-dependent play an important part in nerve fiber sensitization and pathological pain pathways. We conducted this systematic review and meta-analysis to determine the long-term safety and efficacy of P2X3 receptor antagonist drugs in chronic cough.

METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase to identify all relevant published studies through January 15, 2023 that assessed P2X3 antagonists in chronic cough. The protocol was registered in the PROSPERO database with ID: CRD42023422408. Efficacy outcomes were awake (daytime) cough frequency, night cough frequency, 24-h cough frequency, Cough Severity Diary, and total Leicester Cough Questionnaire score. We used the random-effect model to pool the data using RStudio and CMA software.

RESULTS: A total of 11 randomized controlled trials comprising 1350 patients receiving a p2x3 antagonist compared to the placebo group were included in this meta-analysis. A significant decrease in 24-h cough frequency (MD = -4.99, 95% CI [-7.15 to 2.82], P < 0.01), awake (daytime) cough frequency (MD = -7.18, 95% CI [-9.98 to 4.37], P > 0.01), and total Leicester Cough Questionnaire score (MD = 1.74, 95% CI [1.02 to 2.46], P < 0.01) exhibited between the P2X3 antagonist and placebo groups. The frequency of the night cough showed an insignificant difference between the two groups. According to the safety, drug-related adverse events, dysgeusia, hypogeusia, and ageusia significantly increased between the P2X3 antagonist and placebo groups.

CONCLUSION: P2X3 receptor antagonists are promising drugs for treating chronic cough by significantly reducing the frequency, severity, and quality. Some potential side effects may include drug-related adverse events such as hypogeusia, ageusia, and dysgeusia.

PMID:37678663 | DOI:10.1016/j.pupt.2023.102252

J Ocul Pharmacol Ther. 2023 Sep 7. doi: 10.1089/jop.2023.0056. Online ahead of print.

ABSTRACT

Purpose: The melanocortin receptor pan-agonist PL9643, a potential therapy for ocular diseases, was investigated in a phase 2, 12-week study in patients with dry eye disease (DED). Methods: This was a placebo-controlled study evaluating efficacy and safety of thrice-daily PL9643. Placebo (vehicle) was similar to tears. Primary endpoints were intra-patient changes in inferior corneal fluorescein staining and ocular discomfort after 12 weeks. Secondary endpoints were changes in additional DED signs or symptoms. Multiple secondary endpoints were not adjusted for multiplicity. Patients with moderate or severe DED were analyzed in addition to the overall intent-to-treat (ITT) population. Results: In the ITT population (n = 160) the PL9643 group did not demonstrate significant treatment difference versus placebo at week 12/day 85 for the primary endpoints (P > 0.05). In patients with moderate or severe DED (n = 53), PL9643 treatment demonstrated either nominally significant (P < 0.05) or trending (P < 0.1) improvement over placebo in mean change from baseline at week 12/day 85 in several sign endpoints, including fluorescein staining in inferior, superior, corneal sum, and total sum regions; lissamine green staining in temporal, nasal, conjunctival sum, and total sum regions; and tear film breakup time. Conjunctival redness also showed (nonsignificant) improvement at week 12/day 85. There were no drug-related adverse events (AEs) and no drug-related discontinuations. Conclusions: PL9643 showed no significant efficacy for the ITT population; however, efficacy results across several signs and symptoms in the subpopulation of moderate to severe DED patients, the low number of ocular AEs, and no tolerability issues suggest that PL9643 shows promise as a therapeutic for DED. Clinical Trial Registration number: NCT04268069.

PMID:37677000 | DOI:10.1089/jop.2023.0056