Category: Statistics

Graefes Arch Clin Exp Ophthalmol. 2023 Jan 12. doi: 10.1007/s00417-022-05952-8. Online ahead of print.

ABSTRACT

PURPOSE: Bevacizumab, ranibizumab, and aflibercept are commonly used to treat neovascular age-related macular degeneration (nAMD). The results of various interventional, mostly randomized head-to-head studies, indicate statistical non-inferiority of these three drugs. The results of these studies are often interpreted as the three drugs being freely interchangeable, resulting in some health systems to pressure ophthalmologists to preferentially use the less expensive bevacizumab. This study analyzes switching from aflibercept or ranibizumab to bevacizumab and back under real-world conditions in order to investigate the assumption of interchangeability of the drugs.

METHODS: Treatment data of IVT patients with diagnosed nAMD were extracted from the clinical Berlin Macular Registry database. Patients who underwent a drug switch from aflibercept or ranibizumab to bevacizumab were subject of this study. Statistical comparisons were pre-planned for best corrected visual acuity, central retinal thickness, macular volume, and length of injection interval. Additional endpoints were analyzed descriptively.

RESULTS: Mean visual acuity decreased from 0.57 ± 0.05 under aflibercept/ranibizumab to 0.68 ± 0.06 logMAR after the switch (P = 0.001; N = 63). CRT increased from 308 ± 11 µm to 336 ± 16 µm (P = 0.011; N = 63). About half of the subjects were switched back: visual acuity increased from 0.69 ± 0.08 logMAR to 0.58 ± 0.09 logMAR (N = 26). CRT decreased from 396 ± 28 to 337 ± 20 µm (N = 28).

CONCLUSION: The data provides real-world evidence that there is loss of visual acuity and an increase in retinal edema after switching to bevacizumab. Thus, the assumption of free interchangeability cannot be confirmed in this cohort.

PMID:36633668 | DOI:10.1007/s00417-022-05952-8

Eur J Pediatr. 2023 Jan 12. doi: 10.1007/s00431-022-04761-9. Online ahead of print.

ABSTRACT

Early assessment of refractory Mycoplasma pneumoniae pneumonia (RMPP) with plastic bronchitis (PB) allows timely removal of casts using fiberoptic bronchoscopic manipulation, which relieves airway obstruction and limit sequelae development. This study aimed to analyze clinical data for risk factors and develop a nomogram for early predictive evaluation of RMPP with PB. The clinical data of 1-14 year-old patients with RMPP were retrospectively analyzed. Patients were classified into a PB or non-PB group. The general characteristics, clinical symptoms, laboratory test results, imaging findings, and microscopic changes of the two groups were compared. A statistical analysis of the risk factors for developing PB was performed, and a nomogram model of risk factors was constructed. Of 120 patients with RMPP included, 68 and 52 were in the non-PB and PB groups, respectively. Using multivariate logistic regression analysis, fever before bronchoscopy, extrapulmonary complications, pleural effusion, cough duration, and lactate dehydrogenase (LDH) levels were identified as risk factors. A nomogram was constructed based on the results of the multivariate analysis. The area under the receiver operating characteristic curve value of the nomogram was 0.944 (95% confidence interval: 0.779-0.962). The Hosmer-Lemeshow test displayed good calibration of the nomogram (p = 0.376, R2 = 0.723).

CONCLUSION: The nomogram model constructed in this study based on five risk factors (persistent fever before bronchoscopy, extrapulmonary complications, pleural effusion, cough duration, and LDH levels) prior to bronchoscopy can be used for the early identification of RMPP-induced PB.

WHAT IS KNOWN: • Refractory Mycoplasma pneumoniae pneumonia (RMPP) in children has been increasingly reported and recognized, which often leads to serious complications. • Plastic bronchitis (PB) is considered to be one of the causes of RMPP, and bronchoscopic treatment should be improved as soon as possible to remove plastic sputum thrombus in bronchus.

WHAT IS NEW: • This study determined the risk factors for RMPP-induced PB. • The nomogram model constructed in this study prior to bronchoscopy can be used for the early identification of RMPP-induced PB, which facilitate the early bronchoscopic removal of casts, thereby promoting recovery and reducing cases with poor RMPP prognosis.

PMID:36633659 | DOI:10.1007/s00431-022-04761-9

Se Pu. 2023 Jan;41(1):47-57. doi: 10.3724/SP.J.1123.2022.04017.

ABSTRACT

Premature ovarian failure (POF) is a prevalent gynecological disease. In traditional Chinese medicine, it is believed that POF is directly related to abnormal function of the liver and kidneys. As such, regulation of the liver metabolism through the use of medicinal and edible substances is important for the treatment of POF. Pine pollen, a traditional Chinese medicinal and edible pollen variety, contains various active substances, such as sex hormones and phytohormones, which have been used to inhibit inflammation, regulate the immune system, and protect reproductive tissues. Using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS), this study examined the influence of pine pollen on the liver metabolome of cyclophosphamide-induced POF model Sprague Dawley (SD) rats. The variations in the metabolites present in the liver tissue of control SD rats, model SD rats, and SD rats treated with various doses of pine pollen or estrogen were analyzed using principal component analysis (PCA) in combination with orthogonal partial least squares discriminant analysis (OPLS-DA) and other multivariate statistical methods to reveal the mechanism of pine pollen intervention in the livers of POF SD rats. An animal model experiment was conducted using six groups of ten-week-old rats. Cyclophosphamide was administered intraperitoneally to the model group and four intervention groups at a dosage of 60 mg/kg for 1 d followed by a dosage of 10 mg/kg for 14 d. Within the following four weeks, each of the four intervention groups received the intragastric administration of 0.1, 0.5, or 1.5 g/kg bodyweight (BW) of pine pollen, or 0.075 g/kg BW of conjugated estrogens (positive control). Equal quantities of normal saline were administered to the control and cyclophosphamide-treated model groups. Subsequently, the rat livers were subject to pseudotargeted metabolomics, and a total of 687 liver metabolites were discovered using both positive and negative ions. The metabolites differing in content were screened using the t-test (p<0.05) and the fold change (FC>2 or <0.5) in univariate analysis, and the variable importance in projection (VIP>1) in multivariate analysis. It was found that in comparison with the control group, the contents of 32 metabolites significantly increased, while those of 28 metabolites significantly decreased in the model group. The majority of these metabolites were involved α-linolenic acid metabolism, vitamin B6 metabolism, and purine metabolism, along with the lysine degradation and glycolysis/gluconeogenesis metabolic pathways. Compared with the cyclophosphamide-induced model group, the estrogen group exhibited increased levels of 47 metabolites and decreased levels of 29 metabolites, wherein 34 metabolites were restored to the levels found in the control group. These metabolites mainly involved the vitamin B6, lysine, glycolysis/gluconeogenesis, arginine and proline, and cysteine and methionine metabolic pathways. In the low/medium/high-dose pine pollen groups, the contents of 34/32/34 metabolites increased, the contents of 30/37/24 metabolites decreased, and the contents of 47/38/34 metabolites were restored to the levels found in the control group, respectively. These metabolites were mainly involved in vitamin B6 metabolism, purine metabolism, and the glycolysis/gluconeogenesis metabolic pathway. These results therefore indicate that the restoring effect of pine pollen is equivalent or superior to that of conjugated estrogen. Additionally, based on the known metabolic pathways, it appears that when estrogen interferes with the liver metabolism, the key metabolic pathways that become affected are the arginine and proline metabolism and cysteine and methionine metabolism pathways. In contrast, pine pollen intervention affected existing metabolic pathways that were known to be disordered by cyclophosphamide. The use of pine pollen may therefore restore the levels of many metabolites. It should be noted that 23 overlaps exist between the estrogen-restored metabolites and the pine pollen-restored metabolites, including a variety of acylcarnitines, such as ACar 10∶0. As a result, pine pollen extract may be able to normalize the liver metabolic abnormalities induced by POF. This study therefore establishes a theoretical reference for the development of functional applications for pine pollen and for the treatment of POF.

PMID:36633076 | DOI:10.3724/SP.J.1123.2022.04017

Hepatology. 2023 Jan 13. doi: 10.1097/HEP.0000000000000030. Online ahead of print.

ABSTRACT

BACKGROUND AIMS: Immunotherapy-based regimes have changed the management of hepatocellular carcinoma (HCC). However, evidence of efficacy in patients with impaired liver function is unknown. This systematic review and meta-analysis assesses survival of HCC patients and liver dysfunction treated with immunotherapy-based regimens.

METHODS: Systematic review and meta-analysis of original articles or abstracts reporting survival (OS) of HCC patients treated with immunotherapy according to liver function between 2017-2022. OS according to Restricted Mean Survival Time (RMST) and median OS, and hazard ratio (HR) of Child-Pugh B or B/C versus Child-Pugh A were assessed while considering the line of treatment.

RESULTS: Of 2.218 articles considered, 15 articles recruiting 2.311 patients were included. Of these, 639 (27.7%) were Child-Pugh B and 34 (1.5%) C. RMST was 8.36 (95%CI, 6.15-10.57; I2=93%) months, estimated from 8 studies. The HR was reported in 8 studies for survival between Child-Pugh B versus Child-Pugh A and metanalysis disclosed a 1.65 HR (95% CI 1.45-1.84, I2=0% heterogeneity P=0.45). Treatment line data were available for 47% of the patients and three studies included patients treated with atezolizumab-bevacizumab in first line.

CONCLUSIONS: The high heterogeneity across studies reflects the incapacity of the current evidence to support the indication of immunotherapy in HCC patients with relevant liver dysfunction. It is mandatory to report complementary information to Child-Pugh classification such as prior liver decompensation, use of concomitant medication to control ascites, or signs of clinically significant portal hypertension to allow better patient stratification in future studies.

PMID:36632997 | DOI:10.1097/HEP.0000000000000030

Hepatology. 2023 Jan 13. doi: 10.1097/HEP.0000000000000265. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Telehealth (TH) interventions may improve access to care, disease-specific and quality outcomes in chronic liver diseases (CLD). We aimed to systematically evaluate outcomes of TH interventions in CLD.

METHODS: We used key terms and searched PubMed/EMBASE from inception to 01/10/2022. Two authors independently screened abstracts. Disagreements were resolved by a third reviewer. We included any type of CLD, including post-transplant patients, and extracted outcomes as defined by authors for each etiology of CLD (sustained virological response (SVR) in Hepatitis C (HCV) or weight loss in nonalcoholic fatty liver disease, NAFLD). Meta-analysis was not performed due to the heterogeneity of data. Quality assessment was performed using the Newcastle Ottawa scale for observational studies and the Cochrane Risk of Bias tool for clinical trials.

RESULTS: Of 4,250 studies screened, forty-three met the inclusion criteria. Of these, twenty-eight reported HCV treatment outcomes. All studies showed no statistically significant differences between SVR rates in TH groups compared to control groups or historic cohorts. Eight studies evaluating liver transplant-related processes and outcomes demonstrated improved rates of transplant evaluation and referrals and decreased short-term readmission rates. Three randomized controlled trials and one observational study on NAFLD showed improved weight loss outcomes. One retrospective study showed reduced mortality risk in CLD patients with at least one TH encounter.

CONCLUSION: TH interventions in patients with CLD consistently show equivalent or improved clinical outcomes compared to traditional encounters. TH in CLD can bridge the gap in access while maintaining the quality of care for underserved populations.

PMID:36632994 | DOI:10.1097/HEP.0000000000000265

Nutr Cancer. 2023 Jan 12:1-11. doi: 10.1080/01635581.2023.2165693. Online ahead of print.

ABSTRACT

Low phase angle (PhA) is related with poor clinical status of cancer patients. The objective of this study was to establish sex- and age-specific cutoff points and examine the association between PhA and overall survival (OS) in Chinese cancer patients. This cohort study included data on 1,814 patients with cancer from December 2013 to October 2020. The association between low PhA and overall survival was analyzed using the Kaplan-Meier method and Cox regression model. Among 1,814 participants, there were 993 (54.70%) male and 821 (45.30%) female patients. The optimal cutoff points of low PhA were 4.8°, 4.2°, 4.4°, and 3.8° for the young male, elderly male, young female, and elderly female, respectively. Low PhA was independently associated with poorer OS in young female, elderly female and male (HR: 1.59, 95% CI: 1.08-2.34; HR: 1.65, 95% CI: 1.03-2.67; HR: 2.00, 95% CI: 1.45-2.75). In addition, low PhA was demonstrated to be an adverse prognostic factor in patients with lung cancer, colorectal cancer, and esophagus cancer (HR: 1.85, 95% CI: 1.39-2.47; HR: 2.05, 95% CI: 1.13-3.70; HR: 2.92, 95% CI: 1.49-5.71). Based on cutoff points, low PhA was associated with worse prognosis in patients with cancer.

PMID:36632984 | DOI:10.1080/01635581.2023.2165693

Ann Hepatol. 2023 Jan 9:100897. doi: 10.1016/j.aohep.2023.100897. Online ahead of print.

ABSTRACT

INTRODUCTION AND OBJECTIVES: Novel predictors of prognosis in cirrhotic patients have been emerging in recent years and studies show that the lactate/albumin ratio can serve as an early prognostic marker in different patient groups. We aimed to uncover the clinical significance of the lactate/albumin ratio in hospitalized patients with acutely decompensated cirrhosis.

MATERIALS AND METHODS: A retrospective single-center cohort study was conducted in a tertiary medical center. Subjects included had an established diagnosis of liver cirrhosis and were admitted to the ICU or the Internal Medicine department with a clinical picture of acute-on-chronic liver failure between the years 2010 and 2021. The primary outcome was to assess the utility of the lactate/albumin ratio as a prognostic marker to predict mortality in hospitalized cirrhotic patients with acute-on-chronic hepatic failure.

RESULTS: Two hundred seventy-nine patients were included in this study. Univariate analysis revealed that mean WBC count, Platelet/Creatinine ratio, Aspartate Transaminase (AST), Lactate, and MELD Score were all significantly associated with the primary outcome. Multivariate analysis showed that the lactate/albumin ratio was the strongest statistically significant (p<0.001) predictor of death during hospitalization – OR 13.196 (95% CI 3.6- 48.3), followed by mean WBC count, MELD score, and serum lactate levels. A ROC curve was constructed, which resulted in an area under the curve (AUC) equal to 0.77. Crosstabs from the ROC showed a sensitivity of 66.7% and a specificity of 76.2% when the lactate/albumin ratio chosen as a cutoff was 0.9061 CONCLUSIONS: Elevated lactate/albumin ratio predicts in-hospital mortality in hospitalized cirrhotics with acute-on-chronic hepatic failure.

PMID:36632976 | DOI:10.1016/j.aohep.2023.100897

Chemosphere. 2023 Jan 9:137796. doi: 10.1016/j.chemosphere.2023.137796. Online ahead of print.

ABSTRACT

Glyphosate-based herbicides (GBHs) are one of the most commonly used herbicides worldwide. Numerous in vitro and in vivo model system studies have demonstrated endocrine-disrupting chemical (EDC) properties associated with glyphosate/GBH exposure. The present hypothesis-testing study evaluated the potential inverse dose-dependent relationship between increasing urinary glyphosate and decreasing concentrations of blood sex hormones. Demographic and newly available lab test data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed with survey regression modeling (adjusted for age, gender, race, and country of birth) in Statistical Analysis System (SAS) software. A total of 225, 615, 858 weighted-persons (sample n = 2130 persons) were examined for concentrations of urinary glyphosate and the serum sex hormones (including: total testosterone, total estradiol, and sex hormone binding globulin (SHBG)) among males and females, 6 years-old or older. This study revealed about 82% of the population of the United States examined had detectable urinary concentrations of glyphosate. A significant inverse correlation between concentrations of glyphosate and total estradiol and a trend towards an inverse correlation between concentrations of glyphosate and total testosterone were observed. Concentrations of SHBG and glyphosate did not correlate. Ratios of total testosterone:SHBG and total estradiol:SHBG (estimating the fraction of active sex hormones in the blood) were significantly inversely correlated with urinary concentrations of glyphosate. This epidemiological study associates widespread and ongoing glyphosate/GBH exposures with human endocrine-disruptions. Future studies should examine these phenomena in other databases and other endocrine-related disorders.

PMID:36632954 | DOI:10.1016/j.chemosphere.2023.137796

J Infect. 2023 Jan 9:S0163-4453(23)00009-9. doi: 10.1016/j.jinf.2023.01.008. Online ahead of print.

NO ABSTRACT

PMID:36632942 | DOI:10.1016/j.jinf.2023.01.008

Diabetes Res Clin Pract. 2023 Jan 8:110244. doi: 10.1016/j.diabres.2023.110244. Online ahead of print.

ABSTRACT

AIMS: To determine the burden and leading reasons for mental health hospitalisation among Australians with diabetes.

METHODS: We determined incidence of hospitalisation for all mental health disorders in people with type 1 or type 2 diabetes of all ages by linking the National Diabetes Services Scheme to hospital admission datasets from 2010-2017. We compared those with type 2 diabetes aged 15 and above to the general population using excess hospitalisations per 100,000 person-years associated with diabetes.

RESULTS: Depressive disorders were the leading reason for mental health admission in Australians with diabetes, responsible for 6.09 (95% CI 5.78 – 6.42) and 7.05 (6.95 – 7.14) admissions per 1,000 person-years in those with type 1 and type 2 diabetes, respectively. When considering only one admission per person, mental health admission rates were up to 90% lower. Among males with type 2 diabetes, stress and adjustment disorders were the leading cause of excess admissions compared to the general population, while depressive disorders were the leading cause in females.

CONCLUSIONS: We found a substantial burden of psychiatric hospitalisations among Australians with diabetes, reinforcing the importance of mental health awareness among diabetes clinicians, and support by psychiatric teams for those with diabetes to prevent readmission.

PMID:36632938 | DOI:10.1016/j.diabres.2023.110244