Nevin Manimala

JAMA Netw Open. 2022 Sep 1;5(9):e2234200. doi: 10.1001/jamanetworkopen.2022.34200.

ABSTRACT

IMPORTANCE: Observational comparative effectiveness studies can inform the positioning of biologic therapies for older patients with inflammatory bowel disease (IBD) who are underrepresented in clinical trials.

OBJECTIVE: To compare the effectiveness and safety of vedolizumab vs tumor necrosis factor (TNF) for older patients with IBD.

DESIGN, SETTING, AND PARTICIPANTS: This active comparator, new-user design, comparative effectiveness study was conducted between January 1, 2005, and December 31, 2018, among 754 older patients (aged ≥50 years) with IBD from the Danish National Patient Register. The mean follow-up after treatment initiation took place at 32 to 40 weeks. Statistical analysis was performed from February 1 to April 27, 2022.

INTERVENTIONS: Treatment with vedolizumab or TNF antagonists.

MAIN OUTCOMES AND MEASURES: The primary effectiveness outcome was treatment failure, defined as the composite risk of IBD-related hospitalization, IBD-related surgery, or a new corticosteroid prescription more than 6 weeks after initiation of treatment with biologic therapy. Secondary effectiveness outcomes were time to each individual component of the composite effectiveness outcome. The primary safety outcome was the risk of serious infections, defined as infections requiring hospitalization. A 1:1 propensity score-matched analysis was conducted, accounting for patient-, disease-, and treatment-associated factors.

RESULTS: The study compared 377 older patients with IBD with incident use of vedolizumab (202 women [53.6%]; mean [SD] age, 61.2 [8.3] years; 177 [46.9%] with Crohn disease) vs 377 patients with incident use of TNF antagonists (206 women [54.6%]; mean [SD] age, 61.3 [8.1] years; 182 [48.3%] with Crohn disease). Overall, vedolizumab was associated with an increased risk of treatment failure compared with TNF antagonists (1-year risk, 45.4% vs 34.7%; adjusted hazard ratio [HR], 1.31; 95% CI, 1.02-1.69), including higher risk of IBD-related hospitalization (1-year risk, 27.8% vs 16.3%; adjusted HR, 1.48; 95% CI, 1.03-2.15) and IBD-related major abdominal surgery (1-year risk, 21.3% vs 8.0%; adjusted HR, 2.39; 95% CI, 1.45-3.94). In subgroup analysis by IBD phenotype, among patients with Crohn disease, vedolizumab was associated with a 77% higher risk of treatment failure (adjusted HR, 1.77; 95% CI, 1.21-2.58), while no difference in risk of treatment failure was seen among patients with ulcerative colitis (adjusted HR, 1.04; 95% CI, 0.75-1.43; P = .03 for interaction). There was no significant difference in the risk of serious infections, overall (1-year risk, 8.2% vs 8.7%; adjusted HR, 1.04; 95% CI, 0.58-1.85) and by IBD phenotype.

CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of older patients with IBD, vedolizumab was associated with a higher risk of treatment failure compared with TNF antagonists, particularly among patients with Crohn disease, without offering a significant safety advantage.

PMID:36178685 | DOI:10.1001/jamanetworkopen.2022.34200

Transfusion. 2022 Sep 30. doi: 10.1111/trf.17128. Online ahead of print.

ABSTRACT

BACKGROUND: Transfusion of cold-stored platelet concentrates (CS-PCs) appears effective in massively bleeding patients. However, few studies have evaluated their in vivo hemostatic function in severe thrombocytopenia.

STUDY DESIGN AND METHODS: The in vivo function of plasma-depleted human PCs was evaluated in rabbits with a blocked reticuloendothelial system and busulfan-induced thrombocytopenia. On day 1, a human apheresis PC was processed in a platelet additive solution (PAS-PC) and split evenly for cold or room temperature storage (RTS). On days 3, 6, or 9, RTS- or CS-PAS-PCs were transfused (4.0 × 10⁹ platelets/kg) after plasma depletion into two to four rabbits that developed adequate thrombocytopenia (<25 × 10⁹ /L). Ear bleeding time was measured by two incisions in small veins. The hemostatic rate was defined as the percentage of rabbits achieving bleeding cessation within 600 s at either incision. The experiment was repeated using five different PCs on each storage day.

RESULTS: The mean pre-transfusion rabbit platelet count was 8.6 ± 5.2 × 10⁹ /L. The hemostatic rates with RTS- and CS-PAS-PCs were both 100% on day 3, 93 ± 15% and 73 ± 15% on day 6 (p = .07), and 65 ± 36% and 73 ± 37% on day 9 (p = .27), respectively, with no statistical differences. Total platelet counts were significantly lower after CS-PAS-PC than RTS-PAS-PC transfusion on all days (e.g., 58.7 ± 5.7 vs. 42.4 ± 14.7 × 10⁹ /L, p = .0007, day 9), and did not reach 50 × 10⁹ /L in several experiments. Platelet count increments correlated significantly with hemostatic efficacy for CS-PAS-PC transfusion only.

DISCUSSION: CS-PAS-PCs might achieve similar hemostasis as RTS-PAS-PCs in thrombocytopenic patients with mild bleeding. Hemostatic efficacy could be improved by transfusing more CS-PAS-PCs.

PMID:36178666 | DOI:10.1111/trf.17128

Environ Sci Pollut Res Int. 2022 Sep 30. doi: 10.1007/s11356-022-23211-5. Online ahead of print.

ABSTRACT

Rapid changes in land use and land cover (LULC) have ecological and environmental effects in metropolitan areas. Since the 1990s, Saudi Arabia’s cities have undergone tremendous urban growth, causing urban heat islands, groundwater depletion, air pollution, loss of ecosystem services, etc. This study evaluates the variance and heterogeneity in land surface temperature (LST) because of LULC changes in Abha-Khamis Mushyet, Saudi Arabia, from 1990 to 2020. The research aims to determine the impact of urban biophysical parameters on the High-High (H-H) LST cluster using geospatial, statistical, and machine learning techniques. The support vector machine (SVM) was used to map LULC. The land surface temperature (LST) has been derived using the mono-window algorithm (MWA). The local indicator of spatial associations (LISA) model was implemented on the spatiotemporal LST maps to identify LST clusters. Also, the parallel coordinate plot (PCP) approach was employed to examine the relationship between LST clusters and urban biophysical variables as a proxy of LULC. LULC maps show that urban areas rose by > 330% between 1990 and 2020. Built-up areas had an 83.6% transitional probability between 1990 and 2020. In addition, vegetation and agricultural land have been transformed into built-up areas by 17.9% and 21.8% respectively between 1990 and 2020. Uneven LULC changes in terms of built-up areas lead to increased LST hotspots. High normalized difference built-up index (NDBI) was linked to LST hotspots but not normalized difference water index (NDWI) or normalized difference vegetation index (NDVI). This research could help policymakers develop mitigation strategies for urban heat islands.

PMID:36178650 | DOI:10.1007/s11356-022-23211-5

Methods Mol Biol. 2023;2554:91-106. doi: 10.1007/978-1-0716-2624-5_7.

ABSTRACT

Proteome Integral Solubility Alteration (PISA) is a recently developed mass spectrometry-based, deep proteomics method for unbiased, proteome-wide target deconvolution of ligands, requiring no chemical ligand modification. PISA can be applied to living cells for studying target engagement in vivo or alternatively to protein extracts to identify in vitro ligand-interacting proteins. Here we describe the PISA workflow optimized in our lab. PISA improves the target discovery throughput 10-100 folds compared to the previously used proteomics methods and provides higher statistical significance for target candidates by enabling several biological replicates. Sample multiplexing makes all-in-one analysis of multiple ligands simultaneously possible. PISA dramatically reduces analysis costs, allowing many research questions in need of target deconvolution to be addressed, and unlocks the potential of miniaturizing biological models, including primary cells.

PMID:36178622 | DOI:10.1007/978-1-0716-2624-5_7

Egypt Heart J. 2022 Sep 30;74(1):69. doi: 10.1186/s43044-022-00308-3.

ABSTRACT

BACKGROUND: Cardiac resynchronization therapy (CRT) is a standard treatment in patients with heart failure; however, approximately 20-40% of recipients of (CRT) do not respond to it based on the current patients’ selection criteria. The purpose of this study was to identify the baseline parameters that predict the CRT response and how the ECG morphology can affect the outcome. The study aimed to evaluate the Strauss ECG criteria as a predictor of response in patients undergoing cardiac resynchronization therapy.

RESULTS: Out of 70 patients, 3 patients missed the 6-month follow-up after CRT implantation, so the study enrolled 67 patients that have been classified according to ECG morphology of LBBB to 37 patients with non-Strauss ECG criteria-one of whom died after 4 months-and 30 patients with Strauss ECG criteria. The number of responders in the study was 50 patients with percentage 75.8%; 52% of CRT responder (26 patients) had non-Strauss ECG criteria, while 48% of CRT responders (24 patients) had Strauss ECG criteria with P value = 0.463. While there was no statistical significance of overall CRT response nor 6-month hospitalization and mortality between patients of Strauss and non-Strauss ECG criteria, there was a significant improvement in NYHA class, EF assessed by biplane Simpson’s, end-systolic volume, global longitudinal strain and global circumferential strain by speckle tracking echocardiography in patients with Strauss ECG criteria of LBBB.

CONCLUSIONS: There is no statistical significance in overall CRT response nor the 6-month hospitalization and mortality after 6 months of follow-up between patients with Strauss and non-Strauss ECG criteria of LBBB; however, patients with Strauss ECG criteria have better improvement in NYHA class, echocardiographic parameters such as EF and ESV and speckle tracking parameters (GLS and GCS).

PMID:36178602 | DOI:10.1186/s43044-022-00308-3

Geroscience. 2022 Sep 30. doi: 10.1007/s11357-022-00667-4. Online ahead of print.

ABSTRACT

Beta-guanidinopropionic acid (GPA) is a creatine analog suggested as a treatment for hypertension, diabetes, and obesity, which manifest primarily in older adults. A notable side effect of GPA is the induction of mitochondrial DNA deletion mutations. We hypothesized that mtDNA deletions contribute to muscle aging and used the mutation promoting effect of GPA to examine the impact of mtDNA deletions on muscles with differential vulnerability to aging. Rats were treated with GPA for up to 4 months starting at 14 or 30 months of age. We examined quadriceps and adductor longus muscles as the quadriceps exhibits profound age-induced deterioration, while adductor longus is maintained. GPA decreased body and muscle mass and mtDNA copy number while increasing mtDNA deletion frequency. The interactions between age and GPA treatment observed in the quadriceps were not observed in the adductor longus. GPA had negative mitochondrial effects in as little as 4 weeks. GPA treatment exacerbated mtDNA deletions and muscle aging phenotypes in the quadriceps, an age-sensitive muscle, while the adductor longus was spared. GPA has been proposed for use in age-associated diseases, yet the pharmacodynamics of GPA differ with age and include the detrimental induction of mtDNA deletions, a mitochondrial genotoxic stress that is pronounced in muscles that are most vulnerable to aging. Further research is needed to determine if the proposed benefits of GPA on hypertension, diabetes, and obesity outweigh the detrimental mitochondrial and myopathic side effects.

PMID:36178599 | DOI:10.1007/s11357-022-00667-4

J Patient Rep Outcomes. 2022 Sep 30;6(1):105. doi: 10.1186/s41687-022-00510-6.

ABSTRACT

BACKGROUND: While a substantial body of work postulates that adaptation (response-shift effects) may serve to hide intervention benefits, much of the research was conducted in observational studies, not randomized-controlled trials. This scoping review identified all clinical trials that addressed response shift phenomena, and characterized how response-shift effects impacted trial findings.

METHODS: A scoping review was done of the medical literature from 1968 to 2021 using as keywords “response shift” and “clinical trial.” Articles were included if they were a clinical trial that explicitly examined response-shift effects; and excluded if they were not a clinical trial, a full report, or if response shift was mentioned only in the discussion. Clinical-trials papers were then reviewed and retained in the scoping review if they focused on randomized participants, showed clear examples of response shift, and used reliable and valid response-shift detection methods. A synthesis of review results further characterized the articles’ design characteristics, samples, interventions, statistical power, and impact of response-shift adjustment on treatment effect.

RESULTS: The search yielded 2148 unique references, 25 of which were randomized-controlled clinical trials that addressed response-shift effects; 17 of which were retained after applying exclusion criteria; 10 of which were adequately powered; and 7 of which revealed clinically-important response-shift effects that made the intervention look significantly better.

CONCLUSIONS: These findings supported the presumption that response shift phenomena obfuscate treatment benefits, and revealed a greater intervention effect after integrating response-shift related changes. The formal consideration of response-shift effects in clinical trials research will thus not only improve estimation of treatment effects, but will also integrate the inherent healing process of treatments.

KEY POINTS: This scoping review supported the presumption that response shift phenomena obfuscate treatment benefits and revealed a greater intervention effect after integrating response-shift related changes. The formal consideration of response-shift effects in clinical trials research will not only improve estimation of treatment effects but will also integrate the inherent healing process of treatments.

PMID:36178598 | DOI:10.1186/s41687-022-00510-6

Arch Osteoporos. 2022 Sep 30;17(1):130. doi: 10.1007/s11657-022-01165-y.

ABSTRACT

The study analyzes whether the COVID-19 pandemic affects annual hip fractures (HF) rates and weekly emergency department (ED) consultations and hospitalizations due to trauma in older people. During the COVID-19 pandemic, HF rates and ED consultation and hospitalization rates due to trauma decreased.

PURPOSE: To describe the effect of the COVID-19 pandemic on annual HF rates and weekly ED consultation and hospitalization rates due to trauma in Chile in 2020, compared to 2016-2019.

METHODS: A retrospective study was conducted based on data from Chile’s Department of Statistics and Health Information. Annual HF admissions, weekly ED consultations and hospitalizations due to trauma were described for the years 2016-2020, grouping the years 2016-2019 to compare them with 2020. Rates were calculated per 100.000 inhabitants.

RESULTS: From 2016 to 2020, a total of 35.050 patients aged ≥ 65 years were hospitalized in Chile with a diagnosis of HF, with the lowest number of admissions in 2020 (6.423). During 2020, annual HF rate was 273.6/100.000, representing a decrease of 18.5% compared to the average annual HF rate of 2016-2019 (335.7/100.000). In 2020, the weekly consultation rate due to trauma in older adults decreased by 20.8% and the weekly hospitalization rate due to trauma in older adults decreased by 18.5%.

CONCLUSION: During the COVID-19 pandemic, osteoporotic HF rates decreased, along with ED consultation and hospitalization rates due to trauma in older adults. This could be a result of mobility restrictions and a significant increase in the proportion of self-reliant older adults in the Chilean population.

PMID:36178593 | DOI:10.1007/s11657-022-01165-y

Neurosurg Rev. 2022 Sep 30. doi: 10.1007/s10143-022-01877-2. Online ahead of print.

ABSTRACT

Antiplatelet treatment (APT) has been reported to be used in some patients with aneurysmal subarachnoid hemorrhage (aSAH) after endovascular treatment, but there is controversy among different studies regarding its clinical effects. This study intends to conduct a meta-analysis to evaluate the impact of APT on aSAH patients after endovascular treatment. The PubMed, EMBASE, and Cochrane Library databases were systematically searched up to January 2022 for eligible English publications. Quality assessment was conducted for the included studies. Publication bias and heterogeneity were assessed by Egger’s test and the I² statistic, respectively. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by meta-analysis. Robustness was checked by subgroup and sensitivity analyses. In total, 597 and 522 patients with and without APT, respectively, in 5 retrospective studies were retained for the meta-analysis. Pooled analyses showed that the APT group had a lower mortality (41/499 [8%] versus 56/402 [14%]; OR = 0.533; 95% CI, 0.347-0.820; P = 0.004) and a higher proportion of favorable clinical outcomes (400/532 [75%] versus 266/421 [63%]; OR = 1.801; 95% CI, 1.359-2.414; P = 0.000) than the control group. There was no significant difference in the incidence of hemorrhagic complications (39/564 [7%] versus 26/503 [5%]; OR = 1.386; 95% CI, 0.825-2.329; P = 0.218) between groups. Although the incidence of delayed cerebral ischemia (DCI) was significantly lower in the APT group (65/512 [13%] versus 105/447 [23%]; OR = 0.325; 95% CI, 0.107-0.988; P = 0.048), it showed substantial heterogeneity (I² = 64.7%). Subsequent sensitivity analysis suggested that the meta-analysis was robust. Subgroup analyses revealed that long-term (> 2 weeks) APT (60/479 [13%] versus 103/428 [24%]; OR = 0.212; 95% CI, 0.056-0.806; P = 0.023) significantly reduced the DCI rate and that different grouping methods in the included studies may be a source of heterogeneity. In the absence of randomized controlled trials, a meta-analysis of retrospective studies suggested that APT was associated with reduced mortality and better functional outcomes in aSAH patients after endovascular treatment without an increased incidence of hemorrhagic complications. Long-term APT was also associated with a decrease in the incidence of DCI. Well-designed randomized controlled trials are warranted and updated meta-analyses are needed to verify our findings.

PMID:36178562 | DOI:10.1007/s10143-022-01877-2

Egypt Heart J. 2022 Sep 30;74(1):70. doi: 10.1186/s43044-022-00309-2.

ABSTRACT

BACKGROUND: Endothelial dysfunction and no-reflow share microcirculatory obstruction as a common pathophysiological mechanism. This study evaluated the relationship between systemic peripheral endothelial dysfunction assessed by flow-mediated dilatation (FMD) of the brachial artery and no-reflow in patients with ST-segment elevation myocardial infarction (STEMI) who received successful fibrinolysis.

RESULTS: This study included 150 patients managed by the percutaneous coronary intervention (PCI) after successful fibrinolysis. Patients were divided according to coronary angiographic success into normal flow versus no-reflow groups. According to FMD measured through brachial artery ultrasound, patients were divided based on their endothelial function into endothelial dysfunction versus normal endothelial function. No-reflow occurred in 44 patients (29.3%). No-reflow patients had longer pain to door time (6.52 ± 1.82 vs 5.19 ± 1.85 h), more Killip class II (36.4% vs 16%, p = 0.006), and lower FMD (7.26 ± 1.92 vs 8.23 ± 2.76%, p = 0.036). Also, they showed more endothelial dysfunction; however, this difference was statistically nonsignificant (97.7% vs 87.7%, p = 0.055). One hundred and thirty-six patients (90.7%) had endothelial dysfunction. They were older (57.51 ± 5.92 vs 50.86 ± 4.55 years, p value ≤ 0.001), more smokers (41.2% vs 14.3%, p = 0.04). Patients with normal endothelial function had a more myocardial blush grade (MBG) 3 (78.6% vs 26.5%, p value = 0.001) in comparison with more MBG 2 in those with endothelial dysfunction (41.9% vs 14.3%, p value = 0.001). Endothelial dysfunction patients had nonsignificant more no-reflow (31.6% vs 7.1%, p-value: 0.06). There was a significant weak positive correlation between thrombolysis in myocardial infarction (TIMI) flow and FMD (r = 0.174, p = 0.033) and a significant moderate positive correlation between MBG and FMD (r = 0.366, p < 0.001). Patients with TIMI I flow had significantly lower FMD compared with patients with TIMI II and TIMI III flow post-PCI. FMD ≤ 6% could predict post-procedural TIMI I flow.

CONCLUSIONS: In STEMI patients who underwent PCI within 24 h after successful fibrinolysis, those who had no-reflow showed worse peripheral systemic endothelial function as they had lower brachial artery FMD. Also, FMD showed a significant positive correlation with the post-procedural angiographic flow (TIMI flow and MBG). FMD ≤ 6% could predict TIMI I flow.

PMID:36178560 | DOI:10.1186/s43044-022-00309-2