Category: Nevin Manimala

J Pharm Pharmacol. 2023 Jul 19:rgad067. doi: 10.1093/jpp/rgad067. Online ahead of print.

ABSTRACT

OBJECTIVES: To illustrate the metabolic regulatory mechanisms of Jiangzhi decoction (JZD) against non-alcoholic fatty liver disease (NAFLD).

METHODS: High-fat diet (HFD)-induced NAFLD rats were treated with JZD. The pathological morphology, lipid indexes and liver function were detected. Metabolic profiles were examined by liquid chromatography-mass spectrometry (LC-MS). Multivariate and univariate statistical analysis were used to search the differential metabolites. Pathway enrichment analysis was carried out using Kyoto Encyclopedia of Genes and Genomes database. Compound-gene networks were built by Cytoscape software.

RESULTS: JZD significantly alleviated the pathological conditions and improved lipid index levels. Multivariate analysis showed a good separation among different groups. Three hundred and twenty-seven metabolites in HFD versus control and 301 metabolites in JZD versus HFD were identified to be significantly different. Pathway enrichment analysis showed that lipid metabolism pathways were prominent altered pathways. Importantly, the relationships were more distant between JZD and HFD groups in all five lipid metabolism pathways, including arachidonic acid metabolism, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism and sphingolipid metabolism, while those were obviously closer between JZD and control groups. Simultaneously, JZD treatment restored the levels of disturbed differential metabolites in HFD group.

CONCLUSION: JZD had an effect on alleviating NAFLD via regulating relevant lipid metabolism.

PMID:37467485 | DOI:10.1093/jpp/rgad067

J Low Genit Tract Dis. 2023 Jul 19. doi: 10.1097/LGT.0000000000000759. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to determine the screening history and associated outcomes of women diagnosed with cervical cancer after age 65.

METHODS: All patients from 2012 to 2021 diagnosed with squamous, adenocarcinoma, neuroendocrine, or adenosquamous cervical cancer after age 65 in a single managed care organization (MCO) were included in this retrospective cohort study. Demographic, medical, screening, pathologic, follow-up, and treatment data were extracted. Statistical analysis was done using chi-square test and logistic regression. Cancer-specific survival was estimated using the Kaplan-Meier method.

RESULTS: Of 2,175 patients screened, 209 met inclusion criteria. Only 26.3% of patients had appropriate cervical cancer screening and 41% of patients died of their disease. Managed care organization membership duration of more than 5 years positively correlated with proper cervical cancer screening (p < .001); however, 64% of the long-term members still did not meet criteria to end screening at age 65, with 42.6% of these patients having more than 25 physician visit opportunities to address screening. Increased physician visits correlated with earlier stage at diagnosis of cervical cancer (p = .012). Median cancer-specific survival was significantly better in properly screened patients at 68 vs 30 months, respectively (p = .03).

CONCLUSIONS: Most patients diagnosed with cervical cancer after age 65 did not have adequate previous screening, including those who were MCO members for more than 5 years. There were many missed opportunities for screening, despite multiple provider touchpoints. Our data suggest that adequate screening confers a survival benefit secondary to earlier stage at diagnosis. Further study in this age group is needed to redefine the criteria to end cervix cancer screening.

PMID:37467471 | DOI:10.1097/LGT.0000000000000759

Health Aff (Millwood). 2023 Jul 19:101377hlthaff202300146. doi: 10.1377/hlthaff.2023.00146. Online ahead of print.

ABSTRACT

The initial marketing of the opioid analgesic OxyContin in 1996 increased fatal drug overdoses over the course of the opioid epidemic in the US. However, the long-term impacts of this marketing on complications of injection drug use, a key feature of the ongoing crisis, are undetermined. This study evaluated the effects of exposure to initial OxyContin marketing on the long-term trajectories of injection drug use-related outcomes in the US. We used a difference-in-differences analysis to compare outcomes in states with high versus low exposure to initial marketing before and after the 2010 reformulation of OxyContin, which facilitated the use of illicit drugs and the spread of infectious disease. Exposure to initial OxyContin marketing statistically significantly increased rates of fatal synthetic opioid-related overdoses; acute hepatitis A, B, and C viral infections; and infective endocarditis-related deaths. The greatest burden of adverse long-term outcomes has been in states that experienced the highest exposure to early OxyContin marketing. Our findings indicate that OxyContin marketing decisions from the mid-1990s increased viral and bacterial complications of injection drug use and illicit opioid-related overdose deaths twenty-five years later.

PMID:37467441 | DOI:10.1377/hlthaff.2023.00146

Diabetes. 2023 Jul 19:db230247. doi: 10.2337/db23-0247. Online ahead of print.

ABSTRACT

Previous studies have suggested that cardiovascular autonomic neuropathy (CAN) may predict rapid kidney function decline among persons with diabetes. We analyzed the association between baseline CAN and subsequent glomerular filtration rate (GFR) decline among individuals with type 1 diabetes (T1D) from the Preventing Early Renal Loss in Diabetes (PERL) study (N=469) and with type 2 diabetes (T2D) from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (N=7,973). Baseline CAN was ascertained using ECG-derived heart rate variability indices. Its association with GFR slopes, rapid kidney function decline (GFR loss ≥-5 ml/min/1.73 m2/year), and ≥40% GFR loss was evaluated by linear mixed effect, logistic, and Cox regression, respectively. Participants with CAN experienced more rapid GFR decline, by an excess 1.15 (95%CI [-1.93, -0.37], P= 4.0×10-3) ml/min/1.73m2/year in PERL and 0.34 (95%CI [-0.49, -0.19], P= 6.3×10-6) ml/min/1.73m2/year in ACCORD. This translated in 2.11 (95% CI [1.23-3.63], P=6.9×10-3) and 1.39 (95% CI [1.20-1.61], P=1.1×10-5) odds ratios of rapid kidney function decline in PERL and ACCORD, respectively. Baseline CAN was also associated with a greater risk of ≥40% GFR loss events during follow-up (HR=2.60, 95%CI [1.15-5.45], p=0.02 in PERL and HR=1.54, 95%CI [1.28-1.84], P=3.8×10-6 in ACCORD). These associations remained significant after adjustment for potential confounders, including baseline GFR and albuminuria. Our findings indicate that CAN is a strong, independent predictor of rapid kidney function decline in both T1D and T2D. Further studies of the link between these two complications may help develop new therapies to prevent kidney function decline in patients with diabetes.

PMID:37467433 | DOI:10.2337/db23-0247

J Clin Oncol. 2023 Jul 12:JCO2202279. doi: 10.1200/JCO.22.02279. Online ahead of print.

ABSTRACT

PURPOSE: The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups.

PATIENTS AND METHODS: All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158).

RESULTS: IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P < .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors (P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women (P = .003, .012, respectively).

CONCLUSION: Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.

PMID:37467395 | DOI:10.1200/JCO.22.02279

Plast Reconstr Surg. 2023 Jul 18. doi: 10.1097/PRS.0000000000010931. Online ahead of print.

ABSTRACT

BACKGROUND: Publication bias (PB) is the preferential publishing of studies with statistically significant results. PB can skew findings of systematic reviews (SR) and meta-analyses (MA), with potential consequences for patient care and health policy. This study aims to determine the extent by which SRs and MAs in the plastic surgery literature evaluate and report PB.

METHODS: This cross-sectional study assessed PB reporting and analysis from plastic surgery studies published between January 1, 2015 and June 19, 2020. Full-texts of SRs and MAs were assessed by two reviewers for PB assessment methodology and analysis. Post-hoc assessment of studies that did not originally analyze PB was performed using Egger’s regression, Duval and Tweedie’s trim-and-fill, and Copas selection models.

RESULTS: There were 549 studies evaluated, of which 531 full-texts were included. PB was discussed by 183 (34.5%) studies, and formally assessed by 97 (18.3%) studies. Among SR and MAs that formally assessed PB, PB was present in 24 (10.7%), not present in 52 (23.1%), and inconclusive in 8 (3.6%) studies; 141 (62.7%) studies did not report the results of their PB assessment. Funnel plots were the most common assessment method (n=88, 39.1%), and 60 (68.2%) studies published funnel plots. The post-hoc assessment revealed PB in 17/20 (85.0%) studies.

CONCLUSION: PB is inadequately reported and analyzed amongst studies in the plastic surgery literature. Most studies that assessed PB found PB, as did post-hoc analysis of non-reporting studies. Increased assessment and reporting of PB amongst SRs and MAs would improve quality of evidence in plastic surgery.

PMID:37467390 | DOI:10.1097/PRS.0000000000010931

J Proteome Res. 2023 Jul 19. doi: 10.1021/acs.jproteome.3c00155. Online ahead of print.

ABSTRACT

Repeated measures experimental designs, which quantify proteins in biological subjects repeatedly over multiple experimental conditions or times, are commonly used in mass spectrometry-based proteomics. Such designs distinguish the biological variation within and between the subjects and increase the statistical power of detecting within-subject changes in protein abundance. Meanwhile, proteomics experiments increasingly incorporate tandem mass tag (TMT) labeling, a multiplexing strategy that gains both relative protein quantification accuracy and sample throughput. However, combining repeated measures and TMT multiplexing in a large-scale investigation presents statistical challenges due to unique interplays of between-mixture, within-mixture, between-subject, and within-subject variation. This manuscript proposes a family of linear mixed-effects models for differential analysis of proteomics experiments with repeated measures and TMT multiplexing. These models decompose the variation in the data into the contributions from its sources as appropriate for the specifics of each experiment, enable statistical inference of differential protein abundance, and recognize a difference in the uncertainty of between-subject versus within-subject comparisons. The proposed family of models is implemented in the R/Bioconductor package MSstatsTMT v2.2.0. Evaluations of four simulated datasets and four investigations answering diverse biological questions demonstrated the value of this approach as compared to the existing general-purpose approaches and implementations.

PMID:37467362 | DOI:10.1021/acs.jproteome.3c00155

Environ Sci Technol. 2023 Jul 19. doi: 10.1021/acs.est.2c07056. Online ahead of print.

ABSTRACT

Satellite remote sensing is a promising method of monitoring emissions that may be missing in inventories, but the accuracy of these estimates is often not clear. We demonstrate here a comprehensive evaluation of errors in anthropogenic sulfur dioxide (SO₂) emission estimates from NASA’s OMI point source catalog for the contiguous US by comparing emissions from the catalog with high-quality emission inventory data over different dimensions including size of individual sources, aggregate vs individual source errors, and potential bias in individual source estimates over time. For sources that are included in the catalog, we find that errors in aggregate (sum of error for all included sources) are relatively low. Errors for individual sources in any given year can be substantial, however, with over- or underestimates in terms of total error ranging from -80 to 110 kt (roughly 10-90th percentile). We find that these errors are not necessarily random over time and that there can be consistently positive or negative biases for individual sources. We did not find any overall statistical relationship between the degree of isolation of a source and bias, either at a 40 or 70 km scales. For a sub-set of sources where inventory emissions over a radius of 70 km around an OMI detection are larger than twice the emissions within 40 km, the OMI value is consistently overestimated. We find, as expected, that emission sources not included in the catalog are the largest aggregate source of difference between the satellite estimates and inventories, especially in more recent years where source emission magnitudes have been decreasing and note that trends in satellite detections do not necessarily track trends in total emissions. We find that the OMI-based SO₂ emissions are accurate in aggregate, when summed over a number of sources, but must be interpreted more cautiously at the individual source level. Similar analyses would be valuable for other satellite emission estimates; however, in many cases, the appropriate high-quality reference data may need to be generated.

PMID:37467360 | DOI:10.1021/acs.est.2c07056

J Pediatric Infect Dis Soc. 2023 Jul 19:piad051. doi: 10.1093/jpids/piad051. Online ahead of print.

ABSTRACT

BACKGROUND: Tick-borne diseases have grown in incidence over recent decades. As a result, diagnostic testing has become more common, often performed as broad antibody-based panels for multiple tick-transmitted pathogens. Rocky Mountain spotted fever (RMSF) is rare in our region yet may cause severe morbidity, leading to diagnostic screening in low-risk patients. We sought to describe trends in RMSF diagnostic testing, rate of IgG seropositivity, and clinical features of those tested.

METHODS: We performed a retrospective chart review of patients ≤ 21 years old undergoing testing for RMSF and/or with an ICD-9/10 code for RMSF. Patients were categorized by infection likelihood based on clinical and laboratory criteria adapted from CDC’s case definition of spotted fever rickettsioses. Clinical data were collected and analyzed with descriptive statistics.

RESULTS: 170 patients were included. 5.8% met CDC criteria for rickettsial infection, 6.5% had an elevated IgG titer but lacked suggestive symptoms, and 87.6% had a negative IgG titer. Many patients tested were unlikely to have RMSF, including 50% lacking fever, 20% lacking any RMSF ‘classic triad’ symptoms, 13% without acute illness, and 22% tested during months with low tick activity. Convalescent serology was performed in 7.6% of patients and none underwent R. rickettsii PCR testing.

CONCLUSIONS: Diagnostic testing was frequently performed in patients unlikely to have RMSF. We identified many opportunities for improving test utilization. Reserving testing for those with higher pre-test probability, performing convalescent serology, and utilizing PCR may improve accuracy of RMSF diagnosis and reduce clinical challenges stemming from inappropriate testing.

PMID:37467350 | DOI:10.1093/jpids/piad051

Eur J Orthod. 2023 Jul 19:cjad029. doi: 10.1093/ejo/cjad029. Online ahead of print.

ABSTRACT

BACKGROUND: During orthodontic therapy, bond failure of molar tubes may delay treatment. With the high failure rate of molar tubes, alternative bonding techniques were tested to improve bond strength.

OBJECTIVES: To compare the failure rates of molar tubes bonded with conventional and alternative bonding techniques by adding a layer of compomer adhesive at the molar/tube interface.

TRIAL DESIGN: Single-centre, single-blinded, split-mouth, randomized clinical trial.

METHODS: Patients aged 12 years or older, who required fixed appliance orthodontic treatment without extraction and with no occlusal interference were eligible to participate. They were allocated randomly using a simple non-stratified split-mouth design with a 1:1 allocation ratio. Blinding was only possible for the patients and data analysts. Molar tubes bonded with the modified bonding technique had an additional layer of compomer at the occlusal molar/tube interface. The patients were followed-up for nine months. Outcome measures included the survival time of molar tubes and the number of molar tubes debonded. The bond failure of molar tubes was analyzed using Kaplan-Meier and Cox regression analysis (P < 0.05).

RESULTS: Thirty patients were recruited, randomized, and analyzed (mean age 20.33 years). The failure rate of molar tubes bonded with the modified bonding technique was 4.2 per cent and that of molar tubes bonded with the conventional bonding technique was 6.7 per cent. This difference was not statistically significant (P > 0.05). The dental arch and molar type were found to be as significant predictors for molar tube failure rate. No harm was detected during treatment.

LIMITATIONS: The effect of compomer to reduce enamel demineralization was not tested.

CONCLUSIONS AND IMPLICATIONS: The modified bonding technique did not significantly reduce the failure rate of molar tubes. The molar tubes bonded on the upper arch and second molars are more susceptible to debond.

REGISTRATION: The trial was registered with ClinicalTrials.gov on 21 May 2022 (Registration number: NCT05391386).

FUNDING: This research did not receive any funding.

PMID:37467348 | DOI:10.1093/ejo/cjad029