Category: Nevin Manimala

Drug Saf. 2022 Dec 23. doi: 10.1007/s40264-022-01266-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Little is known about the role played by anticoagulants in COVID-19.

OBJECTIVE: The aim of this study was to assess the impact of previous anticoagulant treatment on risk of hospitalization due to COVID-19, progression to severe COVID-19 and susceptibility to COVID-19 infection.

METHODS: We conducted a multiple population-based case-control study in northwest Spain, in 2020, to assess (1) risk of hospitalization: cases were all patients admitted due to COVID-19 with PCR confirmation, and controls were a random matched sample of subjects without a positive PCR; (2) progression: cases were hospitalized COVID-19 subjects, and controls were all non-hospitalized COVID-19 patients; and (3) susceptibility: cases were patients with a positive PCR (hospitalized and non-hospitalized), and the controls were the same as for the hospitalization model. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a generalized linear mixed model.

RESULTS: The consumption of antivitamin K and direct-acting anticoagulants apparently was not associated with the risk of progression to severe COVID-19 (OR 0.93 [95% CI 0.74-1.17] and OR 1.04 [95% CI 0.79-1.36], respectively). Antivitamin K anticoagulants were associated with a significantly lower risk of hospitalization (OR 0.77 [95% CI 0.64-0.93]), which, in part, can be explained by a decreased risk of susceptibility to infection (OR 0.83 [95% CI 0.74-0.92]). The use of direct-acting anticoagulants was not associated with the risk of hospitalization, although it also seems to decrease susceptibility (OR 0.85 [95% CI 0.74-0.98]). It has also been observed that low-molecular-weight heparins were associated with an increased risk of progression to severe COVID-19 (OR 1.25 [95% CI 1.01-1.55]).

CONCLUSION: The results of this study have shown that antivitamin K anticoagulants and direct-acting anticoagulants do not increase the risk of progression to more severe stages. Antivitamin K consumption was associated with a lower risk of hospitalization and susceptibility to infection.

PMID:36562942 | DOI:10.1007/s40264-022-01266-0

Mol Cell Biochem. 2022 Dec 23. doi: 10.1007/s11010-022-04624-9. Online ahead of print.

ABSTRACT

Although 2,4-DNP is claimed to promote fast weight reduction, it is also related with an intolerable high risk of serious side effects to various tissues. On the other hand, it is known to have neuroprotective effects. These different effects of 2,4-DNP may be due to the administration conditions. For this reason, in this study, it was aimed for the first time to clarify the oxidative changes that occur in the brain during the use of 2,4-DNP, depending on the dose, time and gender. For this purpose, 60 Wistar rats (30 male, 30 female) were divided into ten groups: control groups, short-term/long-term groups and low dose/high dose groups. Except for the control groups, 2,4-DNP was administered to the other groups by oral gavage. End of the experiment, thiobarbituric acid-reactive substances (TBARs), glutathione (GSH), nitric oxide (NOx) and ascorbic acid (AA) levels were measured in the brain tissues of sacrificed animals. 2,4-DNP administration showed attenuation impact on oxidative stress depending on both dose, time and gender. It can be said that it is more beneficial in terms of neuroprotection, especially in the short-term and male groups. In conclusion, our findings suggest that, depending on the dose, time, and gender, 2,4-DNP may be beneficial in the treatment of neurodegenerative disorders.

PMID:36562917 | DOI:10.1007/s11010-022-04624-9

Can J Public Health. 2022 Dec 23. doi: 10.17269/s41997-022-00728-3. Online ahead of print.

ABSTRACT

OBJECTIVES: Female marriage before age 18 is a global health issue related to gender inequality, but it is understudied in Canada. This study examined marriage trends among mothers aged < 18 versus older mothers and the sociodemographic correlates of marriage among adolescent mothers aged < 18 and older adolescent mothers.

METHODS: Using the Canadian Vital Statistics – Birth Database, marriage prevalence was estimated by maternal age groups (< 18-year, 18-19-year, 20-24-year, and 25-49-year) between 1989-1990 and 2017-2018 (n = 10,399,250). Multivariable logistic regression was then used to examine the sociodemographic characteristics associated with marriage within adolescent maternal age group (< 18-year, 18-19-year, and 20-24-year) among births registered between 2000 and 2018.

RESULTS: From 1989-1990 to 2017-2018, marriage prevalence declined 80.5%, 60.2%, 47.3%, and 16.0% in the < 18-year, 18-19-year, 20-24-year, and 25-49-year groups, respectively. Within the < 18-year, 18-19-year, and 20-24-year adolescent maternal age groups, older maternal age, larger parental age gap, foreign-born parents, rurality, and earlier birth period were associated with higher adjusted odds of marriage. Higher maternal neighbourhood income was associated with marriage among births to mothers aged 18-19 and 20-24 years but not among those to mothers aged < 18 years.

CONCLUSION: Marriage prevalence declined among mothers of all ages, but the shifts away from marriage appear stronger among younger mothers. The sociodemographic correlates of marriage are generally similar among mothers below age 18 and slightly older adolescent mothers.

PMID:36562916 | DOI:10.17269/s41997-022-00728-3

Breast Cancer Res Treat. 2022 Dec 23. doi: 10.1007/s10549-022-06844-5. Online ahead of print.

ABSTRACT

PURPOSE: A 4-weekly schedule of pegylated liposomal doxorubicin (PLD) has been approved for the treatment of metastatic breast cancer (MBC). Phase II trials have suggested interest in a 2-weekly regimen. This study aimed to compare the efficacy and safety of these two schedules.

METHODS: Data from MBC patients treated with PLD between 2011 and 2021 were retrospectively collected. The objective was to demonstrate the noninferiority of the 2-weekly versus the 4-weekly schedule in terms of 6-month progression-free survival (PFS). The prespecified noninferiority margin was calculated as 1.20. A propensity score to receive either schedule was estimated using a gradient boosting algorithm. Survival analyses using Cox regression models weighted by the propensity score were performed to compare the schedules.

RESULTS: Among the 192 patients included, 96 (50%) underwent each schedule. The median number of previous systemic therapies was 4 (IQR, 3 to 6). Anthracyclines were previously given in early breast cancer in 63.9% of patients. The median follow-up was 10.0 months (IQR, 5.0 to 20.1). A comparable distribution of adverse events was observed. The median PFS was 3.2 months (95% CI, 2.9 to 3.9), and the median overall survival was 12.1 months (95% CI, 10.8 to 14.9). The weighted hazard ratio for PFS was 1.12 (90% CI, 0.82 to 1.54), including the noninferiority boundaries.

CONCLUSION: PLD appeared to be a well-tolerated drug in this heavily pretreated MBC population. The efficacy and safety of the 2-weekly schedule did not provide any advantage, suggesting no interest in changing the registered regimen.

PMID:36562910 | DOI:10.1007/s10549-022-06844-5

Radiol Med. 2022 Dec 23. doi: 10.1007/s11547-022-01577-3. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this multicentric study was to assess which imaging method has the best inter-reader agreement for glenoid bone loss quantification in anterior shoulder instability. A further aim was to calculate the inter-method agreement comparing bilateral CT with unilateral CT and MR arthrography (MRA) with CT measurements. Finally, calculations were carried out to find the least time-consuming method.

METHOD: A retrospective evaluation was performed by 9 readers (or pairs of readers) on a consecutive series of 110 patients with MRA and bilateral shoulder CT. Each reader was asked to calculate the glenoid bone loss of all patients using the following methods: best fit circle area on both MRA and CT images, maximum transverse glenoid width on MRA and CT, CT PICO technique, ratio of the maximum glenoid width to height on MRA and CT, and length of flattening of the anterior glenoid curvature on MRA and CT. Using Pearson’s correlation coefficient (PCC), the following agreement values were calculated: the inter-reader for each method, the inter-method for MRA with CT quantifications and the inter-method for CT best-fit circle area and CT PICO. Statistical analysis was carried out to compare the time employed by the readers for each method.

RESULTS: Inter-reader agreement PCC mean values were the following: 0.70 for MRA and 0.77 for CT using best fit circle diameter, 0.68 for MRA and 0.72 for CT using best fit circle area, 0.75 for CT PICO, 0.64 for MRA and 0.62 for CT anterior straight line and 0.49 for MRA and 0.43 for CT using length-to-width ratio. CT-MRA inter-modality PCC mean values were 0.9 for best fit circle diameter, 0.9 for best fit circle area, 0.62 for anterior straight line and 0.94 for length-to-width methods. PCC mean value comparing unilateral CT with PICO CT methods was 0.8. MRA best fit circle area method was significantly faster than the same method performed on CT (p = 0.031), while no significant difference was seen between CT and MRA for remaining measurements.

CONCLUSIONS: CT PICO is the most reliable imaging method, but both CT and MRA can be reliably used to assess glenoid bone loss. Best fit circle area CT and MRA methods are valuable alternative measurement techniques.

PMID:36562906 | DOI:10.1007/s11547-022-01577-3

Lifetime Data Anal. 2022 Dec 23. doi: 10.1007/s10985-022-09585-1. Online ahead of print.

ABSTRACT

For discrete-time survival data, conditional likelihood inference in Cox’s hazard odds model is theoretically desirable but exact calculation is numerical intractable with a moderate to large number of tied events. Unconditional maximum likelihood estimation over both regression coefficients and baseline hazard probabilities can be problematic with a large number of time intervals. We develop new methods and theory using numerically simple estimating functions, along with model-based and model-robust variance estimation, in hazard probability and odds models. For the probability hazard model, we derive as a consistent estimator the Breslow-Peto estimator, previously known as an approximation to the conditional likelihood estimator in the hazard odds model. For the hazard odds model, we propose a weighted Mantel-Haenszel estimator, which satisfies conditional unbiasedness given the numbers of events in addition to the risk sets and covariates, similarly to the conditional likelihood estimator. Our methods are expected to perform satisfactorily in a broad range of settings, with small or large numbers of tied events corresponding to a large or small number of time intervals. The methods are implemented in the R package dSurvival.

PMID:36562895 | DOI:10.1007/s10985-022-09585-1

Dig Dis Sci. 2022 Dec 23. doi: 10.1007/s10620-022-07793-1. Online ahead of print.

ABSTRACT

BACKGROUND: Acute pancreatitis (AP) is a common gastrointestinal disease in which infection is a serious complication. Understanding its bacterial spectrum and antibiotic resistance is of great significance for treatment.

OBJECTIVE: This retrospective study analyzed the Medical Information Mart for Intensive Care database with the aim of identifying the distribution characteristics of pathogenic bacteria in AP patients.

METHODS: First, 2089 AP patients were classified and analyzed statistically according to culture results. Second, the bacterial profile, antibiotic resistance, and antibiotic-use data of positive culture group were analyzed. Third, logistic regression analysis was used to identify the rick factors of culture results, and culture results correlations with mortality.

RESULTS: This study included 1486 patients in negative culture group, 603 patients in positive cultures. Enterococcus spp. (71%), Enterococcus faecium (61%), and Staphylococcus aureus coagulase-positive (54%) exhibited the highest proportions of drug resistance. Logistic regression revealed five factors related to positive culture (the number of antibiotics, length of stay in hospital, length of stay in intensive care unit, mechanical ventilation, and parenteral nutrition) and four factors related to distribution of multidrug-resistant bacterial infection (age, hemoglobin, length of stay in hospital, and duration on antibiotics).

CONCLUSIONS: This study found that enteric bacteria were the most common source of infection (26.7%). Carbapenems, penicillins containing enzyme inhibitors, fifth-generation cephalosporins, oxazolidinones, and some of the aminoglycoside antibiotics had high sensitivity, which can guide the use of clinical empiric antibiotics. Positive culture was an independent risk factor for in-hospital all-cause mortality of AP patients.

PMID:36562889 | DOI:10.1007/s10620-022-07793-1

J Patient Rep Outcomes. 2022 Dec 23;6(1):129. doi: 10.1186/s41687-022-00534-y.

ABSTRACT

BACKGROUND: The Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) is a 10-item patient-reported outcome (PRO) measure designed to assess the severity of mitochondrial disease symptoms. Analyses of data from a clinical trial with PMM patients were conducted to evaluate the psychometric properties of the PMMSA and to provide score interpretation guidelines for the measure.

METHODS: The PMMSA was completed as a daily diary for approximately 14 weeks by individuals in a Phase 2 randomized, placebo-controlled crossover trial evaluating the safety, tolerability, and efficacy of subcutaneous injections of elamipretide in patents with mitochondrial disease. In addition to the PMMSA, performance-based assessments, clinician ratings, and other PRO measures were also completed. Descriptive statistics, psychometric analyses, and score interpretation guidelines were evaluated for the PMMSA.

RESULTS: Participants (N = 30) had a mean age of 45.3 years, with the majority of the sample being female (n = 25, 83.3%) and non-Hispanic white (n = 29, 96.6%). The 10 PMMSA items assessing a diverse symptomology were not found to form a single underlying construct. However, four items assessing tiredness and muscle weakness were grouped into a “general fatigue” domain score. The PMMSA Fatigue 4 summary score (4FS) demonstrated stable test-retest scores, internal consistency, correlations with the scores produced by reference measures, and the ability to differentiate between different global health levels. Changes on the PMMSA 4FS were also related to change scores produced by the reference measures. PMMSA severity scores were higher for the symptom rated as “most bothersome” by each subject relative to the remaining nine PMMSA items (most bothersome symptom mean = 2.88 vs. 2.18 for other items). Distribution- and anchor-based evaluations suggested that reduction in weekly scores between 0.79 and 2.14 (scale range: 4-16) may represent a meaningful change on the PMMSA 4FS and reduction in weekly scores between 0.03 and 0.61 may represent a responder for each of the remaining six non-fatigue items, scored independently.

CONCLUSIONS: Upon evaluation of its psychometric properties, the PMMSA, specifically the 4FS domain, demonstrated strong reliability and construct-related validity. The PMMSA can be used to evaluate treatment benefit in clinical trials with individuals with PMM. Trial registration ClinicalTrials.gov identifier, NCT02805790; registered June 20, 2016; https://clinicaltrials.gov/ct2/show/NCT02805790 .

PMID:36562873 | DOI:10.1186/s41687-022-00534-y

Cell Tissue Res. 2022 Dec 23. doi: 10.1007/s00441-022-03732-8. Online ahead of print.

ABSTRACT

In this study, a biological conduit, consisting of an adipocyte-derived mesenchymal stem cell (AdMSCs) sheet and amniotic membrane (AM), was designed for the reconstruction of peripheral nerve defects. To evaluate the effect of the produced conduit on neural regeneration, a 10-mm sciatic nerve defect was created in rats, and experiments were carried out on six groups, i.e., sham control group (SC), negative control group (NC), nerve autograft group (NG), the biological conduit (AdMSCs + AM) group, the commercial PGA tube conduit (PGA) group, and the conduit only consisting of AM (AM) group. The effects of different nerve repair methods on the peripheral nerve and gastrocnemius muscle were evaluated by functional, histological, and immunohistochemical tests. When the number of myelinated axons was compared between the groups of AdMSCs + AM and PGA, it was higher in the AdMSCs + AM group (p < 0.05). The percentage of gastrocnemius collagen bundle area of AdMSCs + AM group was found to be statistically lower than the PGA group (p < 0.05). The muscle fiber diameter of AdMSCs + AM group was lower than that of the NG group, but significantly higher than that of the PGA group and the AM group (p < 0.001). Muscle weight index was significantly higher in the AdMSCs + AM group compared to the PGA group (p < 0.05). It was observed that nerve regeneration was faster in the AdMSCs + AM group, and there was an earlier improvement in pin-prick score and sciatic functional index compared to the PGA group and the AM group. In conclusion, the biological conduit prepared from the AdMSCs sheet and AM is regarded as a new biological conduit that can be used as an alternative treatment method to nerve autograft in clinical applications.

PMID:36562866 | DOI:10.1007/s00441-022-03732-8

Pediatr Surg Int. 2022 Dec 23;39(1):60. doi: 10.1007/s00383-022-05344-3.

ABSTRACT

BACKGROUND: Our study aimed to compare the clinical outcomes and cost-efficiency of antibiotic management versus laparoscopic appendectomy for acute uncomplicated appendicitis (AUA) in children during the COVID-19 pandemic when resources were limited and transmission risks uncertain.

METHOD: In this prospective comparative cohort study, we analyzed the data of 139 children diagnosed with AUA meeting the following inclusion criteria: 5-18 years of age, symptoms duration of ≤ 48 h, appendix diameter ≤ 11 mm and no appendicolith. Treatment outcomes between non-operative management group (78/139) and upfront laparoscopic appendectomy group (61/139) were compared. Antibiotic regimes were intravenous ceftriaxone/metronidazole or amoxicillin/clavulanic acid for 48 h, followed by oral antibiotics to complete total 10-days course.

RESULTS: 8/78 (10.3%) children had early failure (within 48 h) requiring appendectomy. 17/70 (24.3%) patients experienced late recurrence within mean follow-up time of 16.2 ± 4.7 months. There were no statistical differences in peri-operative complications, negative appendicectomy rate, and incidence of perforation and hospitalization duration between antibiotic and surgical treatment groups. Cost per patient in upfront surgical group was significantly higher ($6208.5 ± 5284.0) than antibiotic group ($3588.6 ± 3829.8; p = 0.001).

CONCLUSION: Despite 24.3% risk of recurrence of appendicitis in 16.2 ± 4.7 months, antibiotic therapy for AUA appears to be a safe and cost-effective alternative to upfront appendectomy.

PMID:36562855 | DOI:10.1007/s00383-022-05344-3