BMC Vet Res. 2023 Jul 24;19(1):91. doi: 10.1186/s12917-023-03644-x.

ABSTRACT

BACKGROUND: Corticosteroids are widely used with low rates of reported side effects and a broad level of comfort in the hands of most veterinarians. With a low side effect reporting level of < 5% and high level of comfort there may be complacency and underestimation of the impact side effects of corticosteroids may have on a pet and pet owner.

OBJECTIVE: The objective of this clinical study was to describe the experience and perception of an owner who administered anti-inflammatory doses of oral prednisolone and prednisone to their dog for up to 14 days. We hypothesized dogs receiving anti-inflammatory doses of prednisone and prednisolone would experience much greater rates of side effects by day 14 then reported in current literature.

ANIMALS: There were 45 dogs initially enrolled in the study.

RESULTS: At each study point, 31 owners provided results. On day 5, 74% (23/31) reported at least 1 change in their dog's behavior including polyuria, polydipsia, polyphagia, polypnea and/or increased vocalization, with 11 individuals (35%) reporting these changes greatly increased. On day 14, 90% of owners (28/31) reported at least 1 change in their dog's behavior including polyuria, polydipsia, polyphagia, and/or polypnea as the most common changes noted. Overall, 61% (19/31) of owners reported an increase in filling of the water bowl over baseline and one-third (11/31) of pet owners reported cleaning up urinary accidents for pets who had been continent prior to the start of the study. Pet owner steroid satisfaction remained high through day 14 at 4.5/5 (1 = very unsatisfied, 5 = very satisfied).

CONCLUSION: This study highlights the impact short term anti-inflammatory doses of prednisone or prednisolone have on dog behaviour and confirms our hypothesis that by day 14, 90% of dogs experienced one or more behaviour changes, with polyuria and polydipsia most commonly reported. Adverse events were noted regardless of starting dosage or regimen. Although most pet owners expressed satisfaction with steroid treatment due to its high efficacy, 70% would select a more costly treatment if that treatment had fewer side effects.

PMID:37488543 | PMC:PMC10364361 | DOI:10.1186/s12917-023-03644-x

Sci Rep. 2023 Jul 24;13(1):11901. doi: 10.1038/s41598-023-39161-y.

ABSTRACT

Transcranial direct current stimulation (tDCS) has been tested to modulate cognitive control or response inhibition using various electrode montages. However, electrode montages and current polarities have not been systematically compared when examining tDCS effects on cognitive control and response inhibition. In this randomized, sham-controlled study, 38 healthy volunteers were randomly grouped into receiving one session of sham, anodal, and cathodal each in an electrode montage that targeted either the dorsolateral prefrontal cortex (DLPFC) or the fronto-medial (FM) region. Participants performed a combined flanker Go/No-Go task during stimulation. No effect of tDCS was found in the DLPFC and FM groups neither using anodal nor cathodal stimulation. No major adverse effects of tDCS were identified using either montage or stimulation type and the two groups did not differ in terms of the reported sensations. The present study suggests that single-session tDCS delivered in two two-electrode montages might not affect cognitive control or response inhibition, despite using widely popular stimulation parameters. This is in line with the heterogeneous findings in the field and calls for further systematic research to exclude less reliable methods from those with more pronounced effects, identify the determinants of responsiveness, and develop optimal ways to utilize this technique.

PMID:37488206 | PMC:PMC10366169 | DOI:10.1038/s41598-023-39161-y

BMC Gastroenterol. 2023 Jul 24;23(1):249. doi: 10.1186/s12876-023-02890-5.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the efficacy, adverse events, patient compliance, and cost of dual therapy with Ilaprazole-amoxicillin (IA) at high dose versus Ilaprazole-amoxicillin-furazolidone-bismuth (IAFB) quadruple therapy for the Helicobacter pylori (H.pylori) infection among Chinese patients.

METHODS: 200 patients who had tested positive for H. pylori and undergoing upper gastrointestinal endoscopy after being diagnosed with chronic gastritis participated in this open-label randomized controlled clinical trial. Patients were randomized to Group A and Group B: the 14-day IA dual treatment group (101) and IAFB quadruple treatment group (99). The 13 C urea breath test was conducted to determine whether H. pylori had been eliminated 4-6 weeks after the treatment. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the two treatment groups.

RESULTS: Eradication rates in group A were 92.1% and 94.9%, depending on the intention-to-treat (ITT), per-protocol (PP), respectively, which was similar to group B (91.9% and 93.6%). There was no significant difference observed in adverse events between the two groups (P = 0.518). Interestingly, compliance was significantly higher in group A compared to the group B (P = 0.031). In addition, drug costs were significantly lower for group A in comparison to the group B.

CONCLUSIONS: IA dual therapy was found to be equally effective, safer and less costly than IAFB quadruple therapy. Therefore, these therapies can be potentially considered as first-line regimens for empirical treatment.

PMID:37488516 | DOI:10.1186/s12876-023-02890-5

Cureus. 2023 Jun 22;15(6):e40812. doi: 10.7759/cureus.40812. eCollection 2023 Jun.

ABSTRACT

Anti-tumor necrosis factor inhibitors are increasingly being recommended to treat and control a wide range of diseases, including Crohn's disease, ulcerative colitis, rheumatoid, and psoriatic arthritis. Serious pulmonary consequences, ranging from infectious disease to pulmonary edema, airway involvement, and even interstitial lung disease, are well-known multisystemic side effects. Interstitial lung disease is a well-known but uncommon condition. This report presents a case of a 49-year-old man with ulcerative colitis who developed interstitial pneumonitis following three infusions of infliximab therapy based on clinical, radiologic, and pathology data that are consistent with drug-induced interstitial pneumonitis. After stopping infliximab and starting steroid therapy, we noticed complete symptom resolution and improvement in respiratory symptoms and imaging.

PMID:37485130 | PMC:PMC10362944 | DOI:10.7759/cureus.40812

EClinicalMedicine. 2023 Jul 5;61:102076. doi: 10.1016/j.eclinm.2023.102076. eCollection 2023 Jul.

ABSTRACT

BACKGROUND: Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP.

METHODS: A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398.

FINDINGS: Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were -2.1 (95% CI -2.9, -1.4; p < 0.0001) and -0.9 (95% CI -1.4, -0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] -7.6, [-9.4, -5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] -37%, [-47%, -28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (-2.6 [95% CI -3.5, -1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (-19.1 [95% CI -29.8, -8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related.

INTERPRETATION: These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP.

FUNDING: KeyMed Biosciences (Chengdu) Limited.

PMID:37483544 | PMC:PMC10359732 | DOI:10.1016/j.eclinm.2023.102076

Immunol Rev. 2023 Jul 21. doi: 10.1111/imr.13243. Online ahead of print.

ABSTRACT

Immune checkpoint inhibitors (ICIs) have become a mainstay of cancer therapy, with over 80 FDA-approved indications. Used in a variety of settings and in combination with each other and with traditional chemotherapies, the hyperactive immune response induced by ICIs can often lead to immune-related adverse events in bystander normal tissues such as the kidneys, lungs, and the heart. In the kidneys, this immune-related adverse event manifests as acute interstitial nephritis (ICI-AIN). In the era of widespread ICI use, it becomes vital to understand the clinical manifestations of ICI-AIN and the importance of prompt diagnosis and management of these complications. In this review, we delve into the clinical phenotypes of ICI-AIN and how they differ from traditional drug-induced AIN. We also detail what is known about the mechanistic underpinnings of ICI-AIN and the important diagnostic and therapeutic implications behind harnessing those mechanisms to further our understanding of these events and to formulate effective treatment plans to manage ICI-AIN.

PMID:37482912 | DOI:10.1111/imr.13243

Cochrane Database Syst Rev. 2023 Jul 18;7(7):CD013660. doi: 10.1002/14651858.CD013660.pub2.

ABSTRACT

BACKGROUND: Apnoea of prematurity (AoP) is defined as a pause in breathing for 20 seconds or longer, or for less than 20 seconds when accompanied by bradycardia and hypoxaemia, in a preterm infant. An association between the severity of apnoea and neurodevelopmental delay has been reported. Continuous positive airway pressure (CPAP) is a form of non-invasive ventilatory assistance that has been shown to be relatively safe and effective in preventing and treating respiratory distress among preterm infants. It is less clear whether CPAP treatment is safe and effective in the prevention and treatment of AoP.

OBJECTIVES: 1. To assess the effects of CPAP on AoP in preterm infants (this may be compared to supportive care or mechanical ventilation). 2. To assess the effects of different CPAP delivery systems on AoP in preterm infants.

SEARCH METHODS: Searches were conducted in September 2022 in the following databases: Cochrane Library, MEDLINE, Embase, and CINAHL. We also searched clinical trial registries and the reference lists of studies selected for inclusion.

SELECTION CRITERIA: We included all randomised and quasi-randomised controlled trials (RCTs) in which researchers determined that CPAP was necessary for AoP in preterm infants (born before 37 weeks). Cross-over studies were also included, provided sufficient data were available for analysis.

DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane and Cochrane Neonatal, including independent assessment of risk of bias and extraction of data by at least two review authors. Discrepancies were resolved by involvement of a third author. We used the GRADE approach to assess the certainty of evidence for the following outcomes: 1) failed CPAP; 2) apnoea; 3) adverse effects of CPAP.

MAIN RESULTS: We included four single-centre trials conducted in Malaysia, Spain, Germany, and North America, involving 138 infants with a mean/median gestation of 26 to 28 weeks. Two studies were parallel-group RCTs and two were cross-over trials. None of the studies compared CPAP with supportive care. All trials compared one form of CPAP with another. Two compared a variable flow device with ventilator CPAP, one compared two different variable flow devices, and one compared a variable flow device with bubble CPAP. Interventions were administered for periods ranging between six and 48 hours, with pressures between 4 and 6 cm H2O. We assessed all trials as having a high risk of bias for blinding of participants and personnel, and two studies for blinding of outcome assessors. We found a high risk of a carry-over effect in two studies where the washout period was not adequately described, and a high risk of bias in a study that appeared to use an analysis method not generally accepted for cross-over studies. Comparison 1. CPAP and supportive care compared to supportive care alone We did not identify any study for inclusion in this comparison. Comparison 2. CPAP delivered by different types of devices 2a. Variable flow compared to ventilator CPAP Two studies were included in this comparison. We are very uncertain whether there is any difference in the incidence of failed CPAP, defined as the need for mechanical ventilation (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.01 to 2.90; 1 study, 26 participants; very low-certainty). We are very uncertain whether there is any difference in the frequency of apnoea events (mean difference (MD) per four-hour interval -0.10, 95% CI -1.30 to 1.10; 1 study, 26 participants; very low-certainty). We are uncertain whether there is any difference in adverse events. Neurodevelopmental outcomes were not reported. 2b. Variable flow compared to bubble CPAP We included one study in this comparison, but it did not report our pre-specified outcomes. 2c. Infant Flow variable flow CPAP compared to Medijet variable flow CPAP We are very uncertain whether there is any difference in the incidence of failed CPAP (RR 2.62, 95% CI 0.91 to 7.53; 1 study, 80 participants; very low-certainty). The frequency of apnoea was not reported, and we do not know whether there is any difference in adverse events. Neurodevelopmental outcomes were not reported. Comparison 3. CPAP compared to mechanical ventilation We did not identify any studies for inclusion in this comparison.

AUTHORS' CONCLUSIONS: Due to the limited available evidence, we are very uncertain whether any CPAP device is more effective than other forms of supportive care, other CPAP devices, or mechanical ventilation for the prevention and treatment of AoP. The devices used in these studies included two types of variable flow CPAP device: bubble CPAP and ventilator CPAP. For each comparison, data were only available from a single study. There are theoretical reasons why these devices might have different effects on AoP, therefore further trials are indicated.

PMID:37481707 | PMC:PMC10363278 | DOI:10.1002/14651858.CD013660.pub2

Res Social Adm Pharm. 2023 Jul 19:S1551-7411(23)00324-8. doi: 10.1016/j.sapharm.2023.07.006. Online ahead of print.

ABSTRACT

BACKGROUND: For years, there has been controversy about the meaning of medication-related problems (MRPs). This has led several authors to attempt to redefine and classify this term with the aim of using it correctly in the healthcare setting. So far without achieving the desired objective, resulting in erroneous results in the sources of information and thus in malpractice in the sector.

OBJECTIVE: To describe and analyze the appropriateness of the existing indexing of scientific publications in the MEDLINE bibliographical database with respect to drug-related problems (DRPs) and to determine whether the descriptors used fulfilled the function of suitably representing this concept.

METHODS: A descriptive study was conducted, using the following search terms: Medication Errors; Drug Interactions; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Contraindications, Drug. The sample size was calculated by estimating population parameters in an infinite population (expected value = 0.05; precision of interval = 0.05; level of confidence = 0.95) and the selection method was simple random sampling without replacement, taking the total number of bibliographical references in the database as the basis. The agreement of the indexing with DRPs was evaluated with the coefficient of determination (R2), and the Cohen kappa coefficient was used for the association between the definition of the descriptors and the objective of the article.

RESULTS: The 1930 records analyzed showed a total of 2888 different major topics. These major topics were present, with at least one of the five descriptors studied, in 482 (25.0%; 95% CI 23.0-27.0) documentary files, with statistically significant differences between the two phases analyzed (χ2 = 183.8; degrees of freedom (df) = 1; p < 0.001): 1st phase, 295 (13.3%; 95% CI 13.7-16.9) and 2nd phase, 187 (9.7%; 95% CI 8.4-11.0). Overall scientific output with the five descriptors showed a coefficient of determination (R2) of 0.9 (p < 0.001) and the relationship between the objective of the study and the definitions of the five descriptors was 0.9 (p < 0.001).

CONCLUSIONS: There was a very good direct exponential trend of the overall scientific output retrieved with the terms associated with DRPs, although the progression of the five descriptors separately did not show a growth model conforming to expectations. There was a moderate agreement between the objective of the study and the definition of each of the five descriptors used and a low relationship between the objective of the study and the concept of DRPs used for this investigation. It is essential to have a descriptor that unifies the terminological diffusion that has existed up till now, since process (causes) and effects (outcomes) have been mixed together under the various definitions and classifications of DRPs found in the studies.

PMID:37481351 | DOI:10.1016/j.sapharm.2023.07.006

Int Immunopharmacol. 2023 Jul 20;122:110553. doi: 10.1016/j.intimp.2023.110553. Online ahead of print.

ABSTRACT

BACKGROUND: Palmoplantar pustulosis (PPP), a chronic, recurrent pustular dermatosis associated with erythema, scales, and sterile pustules on the palms and soles, is commonly encountered in dermatology clinics. Whether PPP is a variant of psoriasis or a distinct condition is still debated. Although biological agents have been successfully used to treat moderate-to-severe psoriasis, existing literature on PPP is limited to case reports or small case series. The lack of well-documented clinical studies makes it difficult to select the ideal treatment for this condition. This review aims to discuss the efficacy and safety of biological agents in PPP treatment based on randomized controlled trials with the hope of inspiring dermatologist clinicians to propose new therapeutic approaches.

OBJECTIVES: This review aims to obtain high-level evidence to assess the efficacy and safety of biological agents in the treatment of patients with PPP.

METHODS: We searched the PubMed, Embase, and Cochrane databases up to May 18, 2023, for high-quality randomized controlled trials that reported at least one adverse event after PPP treatment with biological agents in patients > 18 years of age. RevMan 5.3 software was used for the meta-analysis.

RESULTS: Nine trials involving 799 participants were included in the analysis. We used ppPASI 75 as the primary efficacy measure. Anti-IL-23 and anti-IL-17A agents afforded 4.14-fold and 1.95-fold better outcomes than placebo treatment at weeks 16 and 12, respectively (P-value = 0.009, RR = 4.14, 95% confidence interval [CI; 1.43-11.98]; P-value = 0.02, RR = 1.95, 95% CI [1.11-3.42]). Moreover, anti-IL-23 agents at a dose of 100 mg were more effective than at 200 mg, indicating that 100 mg may be the best dose for anti-IL-23 agents. Next, we investigated the safety of biological agents for PPP treatment. The incidence of total adverse events (AEs) was 1.25 times higher for biological agents than for controls, indicating a good safety profile (RR = 1.25, P-value ＜ 0.00001, 95% CI [1.13, 1.37]). Additionally, we divided the common AEs into 16 categories and found that anti-IL-23 agents were more likely to induce infections. In conclusion, we evaluated safety and efficacy in a comprehensive comparison and found that anti-IL-23 agents conferred good clinical efficacy with a low incidence of AEs and could be recommended with caution.

LIMITATIONS: Only a few relevant, high-quality, randomized controlled trials were included in the study.

CONCLUSION: This study showed that biological agents can be used to treat patients with PPP with good efficacy; however, AEs cannot be ignored. Multi-center, high-quality clinical studies with large sample sizes are needed to further evaluate the effects and safety of biological agents in PPP treatment.

PMID:37480749 | DOI:10.1016/j.intimp.2023.110553

Am J Otolaryngol. 2023 Jul 10;44(6):103992. doi: 10.1016/j.amjoto.2023.103992. Online ahead of print.

ABSTRACT

OBJECTIVE: A systematic review of the evidence on the success of Drug-Induced Sleep Endoscopy (DISE) directed surgery in children with obstructive sleep apnea (OSA) defined as cure rate.

DATA SOURCES: The PRISMA guidelines were followed and three databases (PubMed, Embase and Cochrane Library) were searched for studies on DISE directed surgery in children.

ENDPOINTS: Pre- and post-surgical change in polysomnography (PSG); change in surgical target; side effects.

REVIEW METHODS: Study quality was assessed using the modified Delphi technique quality appraisal tool for case series. Risk of bias was assessed using the Cochrane Collaboration's tool for assessing risk of bias.

RESULTS: A total of 1805 studies were found. The most important reasons for exclusion were as follows: none-DISE studies, reports on adults, conflation of results on syndromic and healthy patients, no relevant outcome measurements. Five studies with a total of 376 patients (range: 26-126) were included. The surgeons changed the planned strategy in 50.4 % of patients according to the DISE findings. Comparison of pre- and post-surgical sleep monitoring revealed an average decrease in apnea-hypopnea index (AHI) of 11.1 and a treatment success (AHI < 5) and cure (AHI < 2) of 78 % and 53 %, respectively. The quality of the included studies was moderate especially due to small populations, designs without randomization or control groups, lack of analysis of drop outs, short follow-up, and considerable level of bias.

CONCLUSION: DISE directed surgery has been shown to change the surgical approach when treating children with OSA. If this can be transferred into a better outcome compared to standard surgical treatment is unknown, due to the current poor level of evidence. To decide whether or not DISE should be included in the treatment of children with OSA, we suggest further data, preferably an RCT, to increase the level of evidence.

PMID:37480683 | DOI:10.1016/j.amjoto.2023.103992

Orphanet J Rare Dis. 2023 Jul 21;18(1):207. doi: 10.1186/s13023-023-02800-8.

ABSTRACT

BACKGROUND: Treatment recommendations for urea cycle disorders (UCDs) include supplementation with amino acids involved in the urea cycle (arginine and/or citrulline, depending on the enzyme deficiency), to maximize ammonia excretion through the urea cycle, but limited data are available regarding the use of citrulline. This study retrospectively reviewed clinical and biological data from patients with UCDs treated with citrulline and/or arginine at a reference center since 1990. The aim was to describe the prescription, impact, and safety of these therapies. Data collection included patient background, treatment details, changes in biochemical parameters (plasma ammonia and amino acids concentrations), decompensations, and patient outcomes.

RESULTS: Overall, 79 patients (median age at diagnosis, 0.9 months) received citrulline and/or arginine in combination with a restricted protein diet, most with ornithine transcarbamylase (n = 57, 73%) or carbamoyl phosphate synthetase 1 (n = 15, 19%) deficiencies. Most patients also received ammonium scavengers. Median follow-up was 9.5 years and median exposure to first treatment with arginine + citrulline, citrulline monotherapy, or arginine monotherapy was 5.5, 2.5, or 0.3 years, respectively. During follow-up, arginine or citrulline was administered at least once (as monotherapy or in combination) in the same proportion of patients (86.1%); the overall median duration of exposure was 5.9 years for arginine + citrulline, 3.1 years for citrulline monotherapy, and 0.6 years for arginine monotherapy. The most common switch was from monotherapy to combination therapy (41 of 75 switches, 54.7%). During treatment, mean ammonia concentrations were 35.9 µmol/L with citrulline, 49.8 µmol/L with arginine, and 53.0 µmol/L with arginine + citrulline. Mean plasma arginine concentrations increased significantly from the beginning to the end of citrulline treatment periods (from 67.6 µmol/L to 84.9 µmol/L, P < 0.05). At last evaluation, mean height and weight for age were normal and most patients showed normal or adapted behavior (98.7%) and normal social life (79.0%). Two patients (2.5%) experienced three treatment-related gastrointestinal adverse reactions.

CONCLUSIONS: This study underlines the importance of citrulline supplementation, either alone or together with arginine, in the management of patients with UCDs. When a monotherapy is considered, citrulline would be the preferred option in terms of increasing plasma arginine concentrations.

PMID:37480106 | PMC:PMC10362745 | DOI:10.1186/s13023-023-02800-8

BMC Womens Health. 2023 Jul 21;23(1):385. doi: 10.1186/s12905-023-02474-1.

ABSTRACT

OBJECTIVE: It has been reported that recombinant bovine basic fibroblast growth factor (rbFGF) may possess possible biological functions in promoting the process of wound healing. Consequently, our study aimed to investigate the hemostatic effect of topically applied rbFGF in patients who underwent a loop electrosurgical excision procedure (LEEP).

METHODS: In this retrospective analysis, we meticulously examined clinicopathologic data from a cohort of 90 patients who underwent LEEP at our institution between 2020 and 2021. Subsequently, we conducted inquiries with the patients to ascertain the degree of vaginal bleeding experienced during the postoperative periods of 3 and 6 weeks, comparing it to their preoperative menstrual flow. The magnitude of the menstrual volume alteration was then quantified using a menstrual volume multiplier(MVM). The primary endpoints of our investigation were to assess the hemostatic effect of rbFGF by means of evaluating the MVM. Additionally, the secondary endpoints encompassed the assessment of treatment-related side effects of such as infection and dysmenorrhea.

RESULTS: Our findings demonstrated a significant reduction in hemorrhage following cervical LEEP. Specifically, in the per-protocol analysis, the study group exhibited a statistically significantly decrease in MVM after 3 weeks (0 [0-0] vs. 1 [0-1], respectively; p < 0.001) and after 6 weeks (1 [1] vs. 2 [1-3], respectively; p < 0.001) of the procedure. No notable disparities were observed in the remaining outcomes between the two groups. Moreover, a logistic regression analysis was employed to explore the relationship between significant bleeding and rbFGF treatment (p < 0.001, OR = -2.47, 95% CI -4.07 ~-1.21), while controlling for confounding factors such as age, BMI, and surgical specimen.

CONCLUSIONS: In conclusion, our study findings highlight that the application of recombinant bovine basic fibroblast growth factorcan effectively mitigate hemorrhage subsequent to cervical loop electrosurgical excision procedure.

PMID:37479994 | PMC:PMC10362730 | DOI:10.1186/s12905-023-02474-1

BMC Anesthesiol. 2023 Jul 21;23(1):245. doi: 10.1186/s12871-023-02135-8.

ABSTRACT

BACKGROUND: The number of non-intubated general anesthesia outside the operating room is growing as the increasing demand for comfort treatment. Non-intubated general anesthesia outside the operating room requires rapid onset of anesthesia, smoothness, quick recovery, and few postoperative complications. Traditional anesthetic regimens (propofol alone or propofol and opioids/dezocine/midazolam, etc.) have severe respiratory and circulatory depression and many systemic adverse effects. In this paper, we compare the effectiveness and safety of propofol and subclinical doses of esketamine with other traditional regimens applied to non-intubated general anesthesia through a systematic review and meta-analysis.

METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and Sinomed databases for the period from January 2000 to October 2022. We rigorously screened the literature according to predefined inclusion and exclusion criteria, while risk assessment of the studies was performed using The Cochrane Collaboration's tool, and statistical analysis of the data was performed using RevMan 5.4 software. The main outcome indicators we evaluated were the various hemodynamic parameters and incidence of various adverse effects between the experimental and control groups after induction of anesthesia.

RESULTS: After a rigorous screening process, a total of 14 papers were included in the final meta-analysis. After risk bias assessment, three of the papers were judged as low risk and the others were judged as having moderate to high risk. Forest plots were drawn for a total of 16 indicators. Meta-analysis showed statistically significant differences in HR' WMD 3.27 (0.66, 5.87), MAP' WMD 9.68 (6.13, 13.24), SBP' WMD 5.42 (2.11, 8.73), DBP' WMD 4.02 (1.15, 6.88), propofol dose' SMD -1.39 (-2.45, -0.33), hypotension' RR 0.30 (0.20, 0.45), bradycardia' RR 0.33 (0.14, 0.77), hypoxemia or apnea' RR 0.45 (0.23, 0.89), injection pain' RR 0.28 (0.13, 0.60), intraoperative choking' RR 0.62 (0.50, 0.77), intraoperative body movements' RR 0.48 (0.29, 0.81) and overall incidence of adverse reactions' RR 0.52 (0.39, 0.70).The indicators that were not statistically different were time to wake up' WMD - 0.55 (-1.29, 0.19), nausea and vomiting 0.84' RR (0.43, 1.67), headache and dizziness' RR 1.57 (0.98, 2.50) and neuropsychiatric reaction' RR 1.05 (0.28, 3.93). The funnel plot showed that the vast majority of studies fell within the funnel interval, but the symmetry was relatively poor.

CONCLUSION: In non-intubated general anesthesia, the combination of subclinical doses of esketamine and propofol did reduce circulatory and respiratory depression, injection pain, and other adverse effects, while the incidence of esketamine's own side effects such as neuropsychiatric reactions did not increase, and the combination of the two did not cause the occurrence of new and more serious adverse reactions, and the combination of the two was safe and effective.

TRIAL REGISTRATION: PROSPREO registration number: CRD 42022368966.

PMID:37479982 | PMC:PMC10360232 | DOI:10.1186/s12871-023-02135-8

Hum Vaccin Immunother. 2023 Aug 1;19(2):2234788. doi: 10.1080/21645515.2023.2234788.

ABSTRACT

Billions of coronavirus disease 19 (COVID-19) vaccines have been administered worldwide. However, limited data on side effects have been reported in athletes. This study aimed to describe the incidence of side effects following COVID-19 vaccination in athletes and to identify the factors associated with the main side effects in this population. Information on COVID-19 vaccination, side effects, and overall symptom duration was retrospectively collected from recreational and competitive athletes. A total of 460 participants were included in this study. Fever and arm pain were more frequently reported after the first-dose vaccination, 9.6% vs 4.6%, p = .007 and 81.3% vs 24.9%, p ≤ .001. Myalgia was more common after the second-dose vaccination, 0.65% vs. 7.1% p ≤ .001. Males were more likely to present with arm pain after the first and second vaccinations. Those with SARS-CoV-2 infection before vaccination were less likely to present with arm pain after the first dose of vaccination (OR: 0.162, p ≤ .001) and more likely to present with fever after the second dose of vaccination (OR: 3.442, p = .046). First-dose vaccination with the BNT162b2 vaccine compared to other brands was characterized by lower odds of fever (OR: 0.394, p = .017). Our results indicated mild adverse effects and a short duration of symptoms in athletes following COVID-19 vaccination.

PMID:37470390 | DOI:10.1080/21645515.2023.2234788

Surg Endosc. 2023 Jul 20. doi: 10.1007/s00464-023-10193-9. Online ahead of print.

ABSTRACT

BACKGROUND: Intraoperative ureteral injury, a serious complication of abdominopelvic surgeries, can be avoided through ureter visualization. Near-infrared fluorescence imaging offers real-time anatomical visualization of ureters during surgery. Pudexacianinium (ASP5354) chloride is an indocyanine green derivative under investigation for intraoperative ureter visualization during colorectal or gynecologic surgery in adult and pediatric patients.

METHODS: In this phase 2 study (NCT04238481), adults undergoing laparoscopic colorectal surgery were randomized to receive one intravenous dose of pudexacianinium 0.3 mg, 1.0 mg, or 3.0 mg. The primary endpoint was successful intraoperative ureter visualization, defined as observation of ureter fluorescence 30 min after pudexacianinium administration and at end of surgery. Safety and pharmacokinetics were also assessed.

RESULTS: Participants received pudexacianinium 0.3 mg (n = 3), 1.0 mg (n = 6), or 3.0 mg (n = 3). Most participants were female (n = 10; 83.3%); median age was 54 years (range 24-69) and median BMI was 29.3 kg/m2 (range 18.7-38.1). Successful intraoperative ureter visualization occurred in 2/3, 5/6, and 3/3 participants who received pudexacianinium 0.3 mg, 1.0 mg, or 3.0 mg, respectively. Median intensity values per surgeon assessment were 1 (mild) with the 0.3-mg dose, 2 (moderate) with the 1.0-mg dose, and 3 (strong) with the 3.0-mg dose. A correlation was observed between qualitative (surgeon's recognition/identification of the ureter during surgery) and quantitative (video recordings of the surgeries after study completion) assessment of fluorescence intensity. Two participants experienced serious adverse events, none of which were drug-related toxicities. One adverse event (grade 1 proteinuria) was related to pudexacianinium. Plasma pudexacianinium concentrations were dose-dependent and the mean (± SD) percent excreted into urine during surgery was 22.3% ± 8.0% (0.3-mg dose), 15.6% ± 10.0% (1.0-mg dose), and 39.5% ± 12.4% (3.0-mg dose).

CONCLUSIONS: In this study, 1.0 and 3.0 mg pudexacianinium provided ureteral visualization for the duration of minimally invasive, laparoscopic colorectal procedures and was safe and well tolerated.

PMID:37474823 | DOI:10.1007/s00464-023-10193-9

Am J Hematol. 2023 Jul 20. doi: 10.1002/ajh.27033. Online ahead of print.

ABSTRACT

Although ruxolitinib improves splenomegaly and constitutional symptoms in patients with myelofibrosis (MF), a substantial proportion of patients discontinue ruxolitinib because of intolerance. This phase 2 trial investigated the safety and efficacy of jaktinib, a novel JAK inhibitor in patients with ruxolitinib-intolerant MF. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profiles. Between December 18, 2019, and November 24, 2021, 51 patients were enrolled, 45 treated with jaktinib 100 mg bid (100 mg bid group) and six received non-100 mg bid doses (non-100 mg bid group). The SVR35 at week 24 in the 100 mg bid group was 43.2% (19/44, 95% CI 29.7%-57.8%). There were 41.9% (13/31) of transfusion-independent patients with hemoglobin (HGB) ≤100 g/L who had HGB elevation ≥20 g/L within 24 weeks. The proportion of patients with a ≥50% decrease in the total symptom score (TSS 50) at week 24 was 61.8% (21/34). The most commonly reported grade ≥3 treatment-emergent adverse events (TEAEs) in the 100 mg bid group were anemia 31.1%, thrombocytopenia 22.2%, and infectious pneumonia 17.8%. A total of 16 (35.6%) in the 100 mg bid group had serious adverse events, and 4 (8.9%) were considered possibly drug related. These results indicate jaktinib can provide a treatment option for patients with MF who are intolerant to ruxolitinib.

PMID:37470365 | DOI:10.1002/ajh.27033

J Med Virol. 2023 Jul;95(7):e28947. doi: 10.1002/jmv.28947.

ABSTRACT

Azvudine is recommended by Chinese health authorities for COVID-19 treatment but has not been tested in real-world clinical studies. This study aimed to evaluate the real-world effectiveness of Azvudine among COVID-19 nonhospitalized patients. This was a retrospective cohort study, looking at nonhospitalized patients who tested positive for SARS-CoV-2. Patients admitted between December 19, 2022 and January 5, 2023 were included. Those who received Azvudine treatment were in the Azvudine group, while those who received supportive treatment were the control group. The primary outcome was the disease progression rate by Day 28. Secondary outcomes were individual disease progression outcomes (death or COVID-19-related hospitalization) and duration of fever. The safety outcomes were assessed based on adverse events (AEs) overall, as well as AEs that were considered to be related to the drug. A total of 804 patients with high risk for progression were enrolled in our study. Among them, 317 (39.43%) received treatment with Azvudine. Our study found that Azvudine could reduce the rate of disease progression, as well as rate of COVID-19-related hospitalization in patients comparing the control group. Furthermore, if taken within 3 days of the onset of symptoms, it could also shorten the duration of fever. Despite a higher incidence of drug-related AEs compared to supportive treatment, the majority of these were mild. Azvudine has been found to be effective in reducing the rate of disease progression of COVID-19, albeit with a slight increase in AEs.

PMID:37470209 | DOI:10.1002/jmv.28947

DEN Open. 2023 Jul 17;4(1):e271. doi: 10.1002/deo2.271. eCollection 2024 Apr.

ABSTRACT

Dabigatran is a useful and widely used drug for stroke prevention in patients with atrial fibrillation. However, it has been reported to cause esophagitis. Herein, we report the case of a 77-year-old man with dabigatran-induced esophagitis with blue pigmentation, which is known to be a rare adverse effect. The patient presented to our hospital with a tightness of the chest and anorexia. Computed tomography revealed a thickening of the entire esophageal wall, with an upper esophageal predominance. Esophagogastroduodenoscopy was performed, which showed that the cervical and upper thoracic esophagus had blue pigmentation with edematous changes, partial narrowing, and longitudinal sloping. We replaced dabigatran with edoxaban, a similar anticoagulation medication. The patient was closely monitored for 1 month after switching to edoxaban. The follow-up esophagogastroduodenoscopy showed marked improvements, revealing resolution of the bluish discoloration and edematous changes, and the patient's complaints regarding the tightness of the chest and anorexia were also resolved. It is important to recognize that such side effects can occur with dabigatran, a drug that is frequently used in daily practice. Considering the fact that strong edematous changes can cause indigo carmine pigmentation associated with dabigatran stagnation, we recommend switching to another anticoagulant if esophagitis occurs during dabigatran administration.

PMID:37469668 | PMC:PMC10352591 | DOI:10.1002/deo2.271

Belitung Nurs J. 2021 Jun 28;7(3):195-202. doi: 10.33546/bnj.1337. eCollection 2021.

ABSTRACT

BACKGROUND: Patients with newly diagnosed pulmonary tuberculosis often suffer from adverse drug reaction symptoms, which leads to the automatic discontinuation of anti-tuberculosis drugs. Thus, understanding symptom experience of adverse drug reactions is necessary.

OBJECTIVE: This study aimed to examine differences in symptoms experienced in four dimensions: presence, frequency, severity, and distress of adverse drug reactions, between male and female patients.

METHODS: This was a quantitative survey with a cross-sectional design, with data collected between January and April 2020. A total of 394 patients with newly diagnosed pulmonary tuberculosis was selected through a purposive sampling technique. The symptom experiences of adverse drug reactions were measured using a validated instrument. Data were analyzed using mean, standard deviation, and independent t-test.

RESULTS: The most commonly reported symptom was itchiness (24.1% in males and 34.9% in females). Vomiting occurred as the most frequent symptom among males (x̄ ± SD = 2.73 ± .88), and fatigue was found to be the most severe and distressing symptom across male patients (x̄ ± SD = 2.50 ± 1.61 and 2.06 ± 1.30, respectively). In contrast, yellowing of the eyes and skin was most frequent and severe among females (x̄ ± SD = 3.17 ± .75 and 3.83 ± 1.47, respectively). In addition, flu-like symptoms were evaluated as the most distressing symptom for female patients (x̄ ± SD = 2.80 ± 1.09). The symptom burdens of the females ranged significantly and reached higher than those of the male patients at a p-value of .05 (t = 3.33).

CONCLUSION: Females taking anti-tuberculosis drugs should be carefully monitored to deal with adverse drug reaction symptoms. This finding would help to decrease the severity of disease and improve their quality of life.

PMID:37469342 | PMC:PMC10353636 | DOI:10.33546/bnj.1337

Nat Commun. 2023 Jul 19;14(1):4323. doi: 10.1038/s41467-023-40064-9.

ABSTRACT

In vitro secondary pharmacology assays are an important tool for predicting clinical adverse drug reactions (ADRs) of investigational drugs. We created the Secondary Pharmacology Database (SPD) by testing 1958 drugs using 200 assays to validate target-ADR associations. Compared to public and subscription resources, 95% of all and 36% of active (AC50 < 1 µM) results are unique to SPD, with bias towards higher activity in public resources. Annotating drugs with free maximal plasma concentrations, we find 684 physiologically relevant unpublished off-target activities. Furthermore, 64% of putative ADRs linked to target activity in key literature reviews are not statistically significant in SPD. Systematic analysis of all target-ADR pairs identifies several putative associations supported by publications. Finally, candidate mechanisms for known ADRs are proposed based on SPD off-target activities. Here we present a freely-available resource for benchmarking ADR predictions, explaining phenotypic activity and investigating clinical properties of marketed drugs.

PMID:37468498 | PMC:PMC10356841 | DOI:10.1038/s41467-023-40064-9