Tag: statistics

Nephrol Dial Transplant. 2022 Sep 15:gfac271. doi: 10.1093/ndt/gfac271. Online ahead of print.

ABSTRACT

BACKGROUND: Calciprotein particles (CPP), colloidal mineral-protein nanoparticles, have emerged as potential mediators of phosphate toxicity in dialysis patients, with putative links to vascular calcification, endothelial dysfunction, and inflammation. We hypothesized that phosphate binder therapy with sucroferric oxyhydroxide (SO) would reduce endogenous CPP levels, and attenuate pro-calcific and pro-inflammatory effects of patient serum towards human vascular cells in vitro.

METHODS: This secondary analysis of a randomized, controlled cross-over study compared the effect of two-week phosphate binder washout with high-dose (2000 mg/d) and low-dose (250 mg/d) SO therapy in 28 hemodialysis patients on serum CPP levels, inflammatory cytokine/chemokine arrays, and human aortic smooth muscle cell (HASMC) and coronary artery endothelial cell (HCAEC) bioassays.

RESULTS: In our cohort (75% male, 62 ± 12 years) high-dose SO reduced primary (amorphous) and secondary (crystalline) CPP levels [-62 (-76 to -44)%, P < 0.0001 and -38 (-62 to -0.14)%, P < 0.001, respectively] compared with washout. Nine of 14 plasma cytokines/chemokines significantly decreased with high-dose SO, with consistent reductions in Interleukin-6 (IL-6) and IL-8. Exposure of HASMC and HCAEC cultures to serum of SO-treated patients reduced calcification and markers of activation (IL-6, IL-8, and vascular cell adhesion protein 1) compared with washout. Serum-induced HASMC calcification and HCAEC activation was ameliorated by removal of the CPP-containing fraction from patient sera. Effects of CPP removal were confirmed in an independent cohort of chronic kidney disease patients.

CONCLUSIONS: High-dose SO reduced endogenous CPP formation in dialysis patients and yielded serum with attenuated pro-calcific and inflammatory effects in vitro.

PMID:36107466 | DOI:10.1093/ndt/gfac271

Prague Med Rep. 2022;123(3):140-165. doi: 10.14712/23362936.2022.14.

ABSTRACT

Before coronavirus disease 2019 (COVID-19) emerged, proning had been demonstrated to improve oxygenation in those with acute hypoxic respiratory failure and be performed in non-intensive care settings. This benefit was further exemplified by the COVID-19 pandemic, leading to awake prone positioning (APP). We assessed the efficacy of routine APP versus standard care in preventing death and invasive mechanical ventilation (IMV) in non-intubated hypoxic COVID-19 patients. PubMed, Cochrane Library, Scopus, and medRxiv databases were used from January 1st, 2020, to January 15th, 2022, to identify randomized controlled trials (RCTs). Routine APP group were encouraged to be self-prone, whereas the standard care group received care according to local clinical practice and allowed APP crossover as rescue therapy. We included eight COVID-19 RCTs assessing 809 APP vs. 822 standard care patients. APP group had less IMV requirement (26.5% vs. 30.9%; OR – odds ratio 0.77; P=0.03) than the standard care group, with subgroup analysis showing greater benefit (32.5% vs. 39.1%; OR 0.75; P=0.02) for those mainly requiring oxygen support of non-invasive mechanical ventilation (NIMV) and high-flow nasal cannula (HFNC). The time to IMV initiation was similar (mean 8.3 vs. 10.0 days; P=0.66) for patients requiring NIMV and HFNC. Patients mainly receiving supplemental oxygen and non-rebreather masks had improved oxygenation parameters, although not statistically significant. Other outcomes involving all-cause hospital mortality, hospital and ICU (intensive care unit) length of stay, and adverse events were comparable. APP appeared to be an important modality for reducing IMV requirements, especially in those requiring NIMV and HFNC.

PMID:36107444 | DOI:10.14712/23362936.2022.14

JAMA Netw Open. 2022 Sep 1;5(9):e2231790. doi: 10.1001/jamanetworkopen.2022.31790.

ABSTRACT

IMPORTANCE: Relatively little is known about the persistence of symptoms in patients with COVID-19 for more than 1 year after their acute illness.

OBJECTIVE: To assess the health outcomes among hospitalized COVID-19 survivors over 2 years and to identify factors associated with increased risk of persistent symptoms.

DESIGN, SETTING, AND PARTICIPANTS: This was a longitudinal cohort study of patients who survived COVID-19 at 2 COVID-19-designated hospitals in Wuhan, China, from February 12 to April 10, 2020. All patients were interviewed via telephone at 1 year and 2 years after discharge. The 2-year follow-up study was conducted from March 1 to April 6, 2022. Statistical analysis was conducted from April 20 to May 5, 2022. The severity of disease was defined by World Health Organization guideline for COVID-19.

EXPOSURES: COVID-19.

MAIN OUTCOMES AND MEASURES: The main outcome was symptom changes over 2 years after hospital discharge. All patients completed a symptom questionnaire for evaluation of symptoms, along with a chronic obstructive pulmonary disease assessment test (CAT) at 1-year and 2-year follow-up visits.

RESULTS: Of 3988 COVID-19 survivors, a total of 1864 patients (median [IQR] age, 58.5 [49.0-68.0] years; 926 male patients [49.7%]) were available for both 1-year and 2-year follow-up visits. The median (IQR) time from discharge to follow-up at 2 years was 730 (719-743) days. At 2 years after hospital discharge, 370 patients (19.8%) still had symptoms, including 224 (12.0%) with persisting symptoms and 146 (7.8%) with new-onset or worsening of symptoms. The most common symptoms were fatigue, chest tightness, anxiety, dyspnea, and myalgia. Most symptoms resolved over time, but the incidence of dyspnea showed no significant change (1-year vs 2-year, 2.6% [49 patients] vs 2.0% [37 patients]). A total of 116 patients (6.2%) had CAT total scores of at least 10 at 2 years after discharge. Patients who had been admitted to the intensive care unit had higher risks of persistent symptoms (odds ratio, 2.69; 95% CI, 1.02-7.06; P = .04) and CAT scores of 10 or higher (odds ratio, 2.83; 95% CI, 1.21-6.66; P = .02).

CONCLUSIONS AND RELEVANCE: In this cohort study, 2 years after hospital discharge, COVID-19 survivors had a progressive decrease in their symptom burden, but those with severe disease during hospitalization, especially those who required intensive care unit admission, had higher risks of persistent symptoms. These results are related to the original strain of the virus, and their relevance to infections with the Omicron variant is not known.

PMID:36107425 | DOI:10.1001/jamanetworkopen.2022.31790

Eur J Dent Educ. 2022 Sep 15. doi: 10.1111/eje.12854. Online ahead of print.

ABSTRACT

INTRODUCTION: Traditional manikin training has limitations that virtual reality can address. This study investigated the effectiveness of two part-task training simulation methods, a virtual reality (VR Sim) versus a plastic manikin (PM Sim), on learning outcomes for local anesthesia skills for second year pre-clinical dental students.

METHODS: In an experimental study, fifty-eight second year students were randomly assigned to one of two groups, VR Sim or PM Sim. Both groups completed the same pre-post survey. The VR Sim group practiced with a VR simulation, completed a built-in treatment test and a transfer test with a live person and evaluated by an expert teaching assistant (TA) with a rubric. The PM Sim group practiced with a plastic manikin, completed a treatment test on the same manikin evaluated by a TA, followed by the same transfer test with a live person and evaluated by a TA with a rubric.

RESULTS: Covering knowledge and skills in the delivery of local anesthesia, mean final transfer test scores were statistically significantly higher for the PM Sim compared to VR Sim, F(1, 57) = 9.719, p = 0.003 with an effect size, η²_p = .148. Scores on respective treatments tests were similar to final transfer test scores for each group suggesting differences were localized to the practice methods. Pre-survey results indicated participants had low prior experience with VR technology.

CONCLUSION: While outcomes showed higher results for plastic manikin tutor training over the VR training method, they are complementary. As students practice more with the technology and the VR simulation they may improve further. Likewise, as the technology for haptics with VR improves beyond hand controllers so may the experience and learning of this skill for students.

PMID:36107420 | DOI:10.1111/eje.12854

Cancer Med. 2022 Sep 15. doi: 10.1002/cam4.4992. Online ahead of print.

ABSTRACT

BACKGROUND: While several studies have reported the association between 9/11 exposure and cancer risk, cancer survival has not been well studied in the World Trade Center (WTC) exposed population. We examined associations of 9/11-related exposures with mortality in WTC Health Registry enrollees diagnosed with cancer before and after 9/11/2001.

PATIENTS AND METHODS: This is a longitudinal cohort study of 5061 enrollees with a first-ever primary invasive cancer diagnosis between 1995 and 2015 and followed through 2016. Based on the timing of first cancer diagnosis, pre-9/11 (n = 634) and post-9/11 (n = 4427) cancer groups were examined separately. 9/11-related exposures included witnessing traumatic events, injury on 9/11, and 9/11-related post-traumatic stress disorder (PTSD). Associations of exposures with all-cause mortality were examined using Cox proportional hazards regression. In the post-9/11 group, cancer-specific mortality was evaluated by enrollee group (WTC rescue/recovery workers vs. non-workers) using Fine and Gray’s proportional sub-distribution hazard models, adjusting for baseline covariates, tumor characteristics, and treatment.

RESULTS: In the pre-9/11 group, 9/11-related exposures were not associated with all-cause mortality. In the post-9/11 group, increased risk of all-cause mortality was associated with PTSD (adjusted HR = 1.35; 95% CI = 1.11-1.65), but not with injury or witnessing traumatic events. Cancer-specific mortality was not statistically significantly associated with 9/11-related exposures. In rescue/recovery workers, increased non-cancer mortality risk was associated with PTSD (aHR = 2.13, 95% CI = 1.13-4.00) and witnessing ≥3 traumatic events (aHR = 2.00, 95% CI = 1.13-3.55).

CONCLUSIONS: We did not observe associations between 9/11-related exposures and cancer-specific mortality. Similar to findings in the non-cancer WTC exposed population, PTSD was associated with increased risk of all-cause mortality in cancer patients.

PMID:36107389 | DOI:10.1002/cam4.4992

Cancer Med. 2022 Sep 15. doi: 10.1002/cam4.5166. Online ahead of print.

ABSTRACT

INTRODUCTION: Immediate postmastectomy reconstruction for breast cancer has been widely used due to its unique esthetic and psychological effects. However, no other population-based study has investigated the effects of different reconstruction types on the survival in patients with triple negative breast cancer (TNBC).

METHODS: We selected patients who met the eligibility criteria from the Surveillance, Epidemiology, and End Results cancer registry (N = 9760). We then assessed the effect of different reconstructive surgical approaches (implant, autologous, implant and autologous combined reconstruction) on the overall survival (OS) and breast cancer-specific survival (BCSS) by using the Kaplan-Meier survival curve and Cox proportional hazard regression analyses. The nomograms were used to predict OS and BCSS. And the competitive risk model was used to assess breast cancer-specific death (BCSD) and non-breast cancer-specific death (NBCSD).

RESULTS: Statistical analysis suggested that the three reconstruction methods had better OS and BCSS with lower hazard than mastectomy alone (log-rank test, p < 0.05). Multivariate stratified analysis showed that patients aged 40-60 years had the greatest improvement in OS (Adjusted hazard ratio [AHR], 0.646; 95% Confidence Interval [CI], 0.439-0.950; p = 0.026) with combined reconstruction. BCSS could be improved only by implant reconstruction (AHR, 0.672; 95% CI, 0.514-0.878; p = 0.004). In addition, autologous reconstruction (AHR, 0.570; 95% CI, 0.350-0.929; p = 0.024) and implant reconstruction (AHR, 0.538; 95% CI, 0.339-0.853; p = 0.008) improved OS in patients >60 years of age. The survival prediction model quantified the survival benefits of TNBC patients undergoing different surgeries. Moreover, the C-indexes showed the good predictive ability of the nomograms.

CONCLUSIONS: Our results suggest that for TNBC patients, there is a survival benefit of immediate postmastectomy reconstruction compared with mastectomy alone. Among them, implant reconstruction has the most obvious advantage.

PMID:36106621 | DOI:10.1002/cam4.5166

J Endourol. 2022 Sep 15. doi: 10.1089/end.2022.0233. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effects of CO2 pneumoperitoneum on venous hemodynamics and cardiopulmonary function during transperitoneal or retroperitoneal laparoscopic surgery.

METHODS: A single institution prospective study. 43 patients with renal cell carcinoma undergoing retroperitoneal (22) or transperitoneal (21) laparoscopic partial nephrectomy were enrolled. Hemodynamic functions were monitored by Swan-Ganz and radial artery catheters. Transesophageal echocardiography was used to measure the diameter and blood flow of the inferior vena cava (IVC). Measured parameters were recorded at baseline, 10 min, 30 min, 60 min following insufflation to 14 mmHg and 10 min following desufflation.

RESULTS: For hemodynamic changes in transperitoneal laparoscopic group (TPL) and retroperitoneal laparoscopic group (RPL), transperitoneal CO2 insufflation resulted in a rapid parallel increase in central intravenous pressure (CVP), peak airway pressure (AWP) and IVC blood flow velocity after the first 30 minutes of pneumoperitoneum (p＜0.05). In contrast, CVP, AWP and IVC blood flow velocity increased progressively in RPL. The variation of those parameters was significantly lower than that of TRL (p＜0.001；p=0.002；p=0.004). The mean maximum CVP in the two groups was 20 and 16 mmHg, respectively. The IVC diameter at the cavoatrial junction was significantly reduced in TPL after 10 minutes of insufflation, but it remained unchanged in RPL throughout the surgery. For cardiopulmonary function changes, heart output decreased after a short period of pneumoperitoneum, but no statistical differences were observed between the two groups. The increments of partial pressure of arterial carbon dioxide and end-tidal carbon dioxide tension were significantly higher in RPL than TPL (p＜0.001; p＜0.001).

CONCLUSIONS: Compared with retroperitoneal pneumoperitoneum, transperitoneal pneumoperitoneum has significantly effects on IVC hemodynamics. Elevated intraabdominal pressure (IAP) causes higher AWP and venous return resistance, which lead to the significantly increase of CVP during transperitoneal approach. Adjusting the balance between IAP and CVP might be an effect way to control intravenous bleeding.

PMID:36106602 | DOI:10.1089/end.2022.0233

Health Serv Res. 2022 Sep 15. doi: 10.1111/1475-6773.14065. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the effects of Medicare eligibility and enrollment on the use of high-value and low-value care services.

DATA SOURCES/STUDY SETTING: The 2002-2019 Medical Expenditure Panel Survey.

STUDY DESIGN: We employed a regression discontinuity design, which exploits the discontinuity in eligibility for Medicare at age 65 years and compares individuals just before and after age 65. Our primary outcomes included use of high-value care services (eight services) and low-value care services (seven services). To examine the effects of Medicare eligibility, we conducted a regression discontinuity analysis. To examine the effects of Medicare enrollment, we used the discontinuity in the probability of having Medicare coverage around the age eligibility cutoff and conducted an instrumental variable analysis.

DATA COLLECTION/EXTRACTION METHODS: N/A.

PRINCIPAL FINDINGS: Medicare eligibility and enrollment led to statistically significant increases in the use of only two high-value services: cholesterol measurement [2.1 percentage points (95%: 0.4-3.7) (2.2% relative change) and 2.4 percentage points (95%: 0.4-4.4)] and receipt of the influenza vaccine [3.0 percentage points (95%: 0.3-5.6) (6.0% relative change) and 3.6 percentage points (95%: 0.4-6.8)]. Medicare eligibility and enrollment led to statistically significant increases in the use of two low-value services: antibiotics for acute upper respiratory infection [6.9 percentage points (95% CI: 0.8-13.0) (24.0% relative change) and 8.2 percentage points (95% CI: 0.8-15.5)] and radiographs for back pain [4.6 percentage points (95% CI: 0.1-9.2) (36.8% relative change) and 6.2 percentage points (95% CI: 0.1-12.3)]. However, there was no significant change in the use of other high-value and low-value care services.

CONCLUSION: Medicare eligibility and enrollment at age 65 years led to increases in the use of some high-value and low-value care services, but there were no changes in the use of the majority of other services. Policymakers should consider refining the Medicare program to enhance the value of care delivered.

PMID:36106508 | DOI:10.1111/1475-6773.14065

J Pediatr Endocrinol Metab. 2022 Sep 16. doi: 10.1515/jpem-2022-0232. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to determine the prevalence and predictors of euthyroid sick syndrome (ESS) in pediatric intensive care, and to establish a link between thyroid function tests and mortality.

METHODS: Between January 2015 and March 2020, children admitted to our pediatric intensive care unit (PICU) and tested for free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) levels were included. Patients with decreased fT3, with normal or decreased fT4, and normal or decreased TSH levels were assigned to the ESS group. The association between biochemical indicators and ESS, as well as the relationship between fT3 and mortality, were examined.

RESULTS: A total of 141 (36%) of 386 children included to study were classified in the ESS group. The ESS group had a higher rate of 28-day mortality (12 [8.5%] vs. 9 [3.7%]). Blood urea nitrogen (BUN), albumin, platelet, lactate, and pediatric index of mortality 3 [PIM3 (%)] were significantly associated with ESS (odds ratios in order: 1.024, 0.422, 0.729, 1.208, 1.013). Multivariate regression analysis showed that BUN, albumin, platelet, and lactate were independently associated with ESS progression. The area under curve (AUC [95%CI]) for fT3 was 0.644 (0.555-0.789) to detect mortality. Children with a fT3 level lower than 2.31 pg/mL had significantly higher 28-day mortality (log rank test, p=0.001).

CONCLUSIONS: Our study identified BUN, albumin, lactate, and platelet count as independent risk factors for ESS progression in children. Furthermore, our findings indicated a correlation between fT3 and mortality, which makes fT3 an ideal candidate to be included in mortality indices.

PMID:36106490 | DOI:10.1515/jpem-2022-0232

J Phys Chem B. 2022 Sep 15. doi: 10.1021/acs.jpcb.2c04899. Online ahead of print.

ABSTRACT

Classical molecular dynamics simulations are a versatile tool in the study of biomolecular systems, but they usually rely on a fixed bonding topology, precluding the explicit simulation of chemical reactivity. Certain modifications can permit the modeling of reactions. One such method, multiscale reactive molecular dynamics, makes use of a linear combination approach to describe condensed-phase free energy surfaces of reactive processes of biological interest. Before these simulations can be performed, models of the reactive moieties must first be parametrized using electronic structure data. A recent study demonstrated that gas-phase electronic structure data can be used to derive parameters for glutamate and lysine which reproduce experimental pK_a values in both bulk water and the staphylococcal nuclease protein with remarkable accuracy and transferability between the water and protein environments. In this work, we first present a new model for aspartate derived in similar fashion and demonstrate that it too produces accurate pK_a values in both bulk and protein contexts. We also describe a modification to the prior methodology, involving refitting some of the classical force field parameters to density functional theory calculations, which improves the transferability of the existing glutamate model. Finally and most importantly, this reactive molecular dynamics approach, based on rigorous statistical mechanics, allows one to specifically analyze the fundamental physical causes for the marked pK_a shift of both aspartate and glutamate between bulk water and protein and also to demonstrate that local steric and electrostatic effects largely explain the observed differences.

PMID:36106487 | DOI:10.1021/acs.jpcb.2c04899