Nevin Manimala

World Neurosurg. 2022 May 4:S1878-8750(22)00574-5. doi: 10.1016/j.wneu.2022.04.121. Online ahead of print.

ABSTRACT

OBJECTIVE: Randomized controlled trials (RCTs) have come under scrutiny due to a frequent lack of reproducibility, due in part to shortcomings of the common p<0.05 threshold for significance. Here, we utilize fragility indices to assess the statistical robustness of RCTs evaluating low-dose ketamine during scoliosis surgery to reduce opioid tolerance and postoperative pain.

METHODS: RCTs evaluating outcomes after intraoperative ketamine infusion in adolescent idiopathic scoliosis (AIS) patients were included. Relevant outcomes included pain, opioid consumption, quality of life, anesthesia, sedation, adverse effects, and length of stay. The dichotomous or continuous fragility index (FI or CFI) was determined by manipulating each outcome event until reversal of significance (a=0.05) was achieved. The corresponding fragility quotients (FQ) were calculated by dividing the FI or CFI by the sample size.

RESULTS: Of 27 studies screened, 6 studies (61 outcome events) were included. The median FI for dichotomous events was 2.0 (FQ=0.045), suggesting that altering the outcome of only 2 patients (or 4.5 out of 100) would reverse trial significance. For continuous events, altering the treatment of only 6 patients (or 14.1 out of 100) would reverse significance. Outcome events that were originally reported as significant (p<0.05) were considerably more fragile (FI=1.5; CFI=3.5) than events that were reported as nonsignificant (FI=2.0; CFI=7.0).

CONCLUSIONS: While evidence for ketamine use is promising, our fragility analysis suggests that RCT findings may be underpowered in some cases. Given the importance of RCTs in clinical decision-making, fragility indices should be reported alongside p-values to indicate the strength of statistical findings.

PMID:35525439 | DOI:10.1016/j.wneu.2022.04.121

Int J Surg. 2022 May 4:106640. doi: 10.1016/j.ijsu.2022.106640. Online ahead of print.

ABSTRACT

BACKGROUND: How the extent of confounding adjustment impact (hospital) volume-outcome relationships in published studies on pancreatic cancer surgery is unknown.

METHODS: A systematic literature search was conducted for studies that investigated the relationship between volume and outcome using a risk adjustment procedure by querying the following databases: PubMed, Cochrane Central Register of Controlled Trials, Livivo, Medline and the International Clinical Trials Registry Platform (last query: 2020/09/16). Importance of risk-adjusting covariates were assessed by effect size (odds ratio, OR) and statistical significance. The impact of covariate adjustment on hospital (or surgeon) volume effects was analyzed by regression and meta-regression models.

RESULTS: We identified 87 studies (75 based on administrative data) with nearly 1 million patients undergoing pancreatic surgery that included in total 71 covariates for risk adjustment. Of these, 33 (47%) had statistically significant effects on short-term mortality and 23 (32%) did not, while for 15 (21%) factors neither effect size nor statistical significance were reported. The most important covariates for short term mortality were patient-specific factors. Concerning the covariates, single comorbidities (OR: 4.6, 95% CI: 3.3 to 6.3) had the strongest impact on mortality followed by hospital volume (OR: 2.9, 95% CI: 2.5 to 3.3) and the procedure (OR: 2.2, 95% CI: 1.9 to 2.5). Among the single comorbidities, coagulopathy (OR: 4.5, 95% CI: 2.8 to 7.2) and dementia (OR: 4.2, 95% CI: 2.2 to 8.0) had the strongest influence on mortality. The regression analysis showed a significant decrease hospital volume effect with an increasing number of covariates considered (OR: 0.06, 95% CI: 0.10 to -0.03, P < 0.001), while such a relationship was not observed for surgeon volume (P = 0.35).

CONCLUSIONS: This analysis demonstrated a significant inverse relationship between the extent of risk adjustment and the volume effect, suggesting the presence of unmeasured confounding and overestimation of volume effects. However, the conclusions are limited in that only the number of included covariates was considered, but not the effect size of the non-included covariates.

PMID:35525416 | DOI:10.1016/j.ijsu.2022.106640

Exp Gerontol. 2022 May 4:111831. doi: 10.1016/j.exger.2022.111831. Online ahead of print.

ABSTRACT

AIMS: This study aimed to evaluate the impact of a 12-week calorie-restricted diet and recreational sports training on gene expressions IL15, ATROGIN1 and MURF-1 in skeletal muscle of T2D patients.

METHODS: Older adults with T2D (n = 39, 60 ± 6.0 years, BMI 33.5 ± 0.6 kg/m²) were randomly allocated to Diet+Soccer (DS), Diet+Running (DR) or Diet (D). The training sessions were moderate-to-high-intensity and performed 3 × 40 min/week for 12-weeks. Gene expression from vastus lateralis muscle obtained by qRT-PCR, dual-energy X-ray and fasting blood testing measurements were performed before and after 12-weeks. Statistical analysis adopted were two-way ANOVA and Paired t-test for gene expression, and RM-ANOVA test for the remainder variables.

RESULTS: Total body weight was reduced in ~4 kg representing body fat mass in all groups after 12-weeks (P < 0.05). HbA1c values decreased in all groups post-intervention. Lipids profile improved in the training groups (P < 0.05) after 12-weeks. ATROGIN1 and MURF-1 mRNA reduced in the DS (1.084 ± 0.14 vs. 0.754 ± 1.14 and (1.175 ± 0.34 vs. 0.693 ± 0.12, respectively; P < 0.05), while IL15 mRNA increased in the DR (1056 ± 0,12 vs. 1308 ± 0,13; P < 0.05) after 12-weeks intervention.

CONCLUSION: Recreational training with a moderate calorie-restricted diet can downregulates the expression of atrophy-associated myokines and increases the expression of anti-inflammatory gene IL15.

PMID:35525396 | DOI:10.1016/j.exger.2022.111831

Exp Gerontol. 2022 May 4:111830. doi: 10.1016/j.exger.2022.111830. Online ahead of print.

ABSTRACT

BACKGROUND: We hypothesized that cumulative anesthesia exposure over the course of routine treatment of colorectal cancer in older adults can increase long-term risk of Alzheimer’s disease (AD), Alzheimer’s disease-related dementias (ADRD) and other chronic neurocognitive disorders (CND).

METHODS: We conducted a SEER-Medicare-based retrospective cohort study of 84,770 individuals age 65 years and older diagnosed with colorectal cancer between 1998 and 2007 using a proportional hazards model with inverse probability weighted estimators. The primary exploratory variable was a time-variant measure of cumulative anesthesia exposure for abdominal and pelvic procedures, updated continuously.

RESULTS: Our primary outcomes, AD and ADRD, occurred in 6005/84,770 (7.1%) and 14,414/83,444 (17.3%) individuals respectively. No statistically significant association was found between cumulative anesthesia exposure and AD (hazard ratio [HR]:0.99; 95% CI, 0.97-1.01). However, it was moderately associated with the risk of ADRD (HR, 1.02; 95% CI, 1.004-1.03) and some secondary outcomes including most notably: cerebral degeneration (HR, 1.05; 95% CI, 1.03-1.06), hepatic encephalopathy (HR, 1.13; 95% CI, 1.10-1.17), encephalopathy-not elsewhere classified (HR,1.10; 95% CI: 1.08-1.12), and incident/perioperative delirium (HR, 1.02; 95% CI, 1.01-1.03). Furthermore, we observed an association between cumulative anesthesia exposure and incident/perioperative delirium (HR, 1.06; 95% CI, 1.04-1.08), with perioperative delirium being associated with increased AD risk (HR, 2.05; 95% CI, 1.92-2.09).

CONCLUSION: Cumulative anesthesia exposure for abdominal and pelvic procedures was not associated with increased risk of AD directly and had a small but statistically significant association with ADRD, and a number of other CNDs. Cumulative anesthesia exposure was also associated with perioperative delirium, which had an independent adverse association with AD risk.

PMID:35525395 | DOI:10.1016/j.exger.2022.111830

J AAPOS. 2022 May 4:S1091-8531(22)00089-1. doi: 10.1016/j.jaapos.2021.12.011. Online ahead of print.

ABSTRACT

PURPOSE: To determine whether subfoveal choroidal thickness and central foveal thickness differ according to the presence of fixation preference in patients with intermittent exotropia without anisometropia or amblyopia.

METHODS: Children ≥4 years of age with either monocular (fixation preference) or alternating intermittent exotropia on three consecutive visits who had no anisometropia, no amblyopia, and spherical equivalent of ± 1.25 D or less in both eyes were recruited for this study. Subfoveal choroidal thickness and central foveal thickness, measured using spectral domain optical coherence tomography, in the monocular group and the alternating group were compared.

RESULTS: A total of 81 patients were enrolled: 46 in the monocular exotropia group and 35 in the alternating exotropia group. The interocular difference in subfoveal choroidal thickness was -11.0 ± 18.0 μm in the monocular group (dominant eye – nondominant eye) and 1.9 ± 22.2 μm in the alternating group (right eye – left eye). The difference between groups was statistically significant (P = 0.005). The interocular difference in central foveal thickness was 1.1 ± 5.7 μm in the monocular group (dominant eye – nondominant eye) and 0.9 ± 5.0 μm in the alternating group (right eye – left eye). The difference between groups was not significant.

CONCLUSIONS: In patients with intermittent exotropia without amblyopia, the difference in subfoveal choroidal thickness between the eyes in the monocular group was significantly greater than that between eyes in the alternating group. These findings suggest the presence or absence of fixation preference may affect subfoveal choroidal thickness.

PMID:35525387 | DOI:10.1016/j.jaapos.2021.12.011

Spine J. 2022 May 4:S1529-9430(22)00172-3. doi: 10.1016/j.spinee.2022.04.012. Online ahead of print.

ABSTRACT

BACKGROUND CONTEXT: Awake spine surgery is growing in popularity, and may facilitate earlier postoperative recovery, reduced cost, and fewer complications than spine surgery conducted under general anesthesia (GA). However, trends in adoption of awake (ie, non-GA) spine surgery have not been previously studied.

PURPOSE: To investigate temporal trends in non-GA spine surgery utilization and outcomes in the United States.

STUDY DESIGN/SETTING: A retrospective observational study.

PATIENT SAMPLE: PATIENTS: undergoing cervical or lumbar decompression or/and fusion from the American College of Surgeons National Surgical Quality Improvement Program database records dated 2005-2019.

OUTCOME MEASURES: The primary outcome was adoption trends of awake cervical and lumbar spine operations from 2005 to 2019. The secondary outcomes included the outcomes trends of 30-day complications, readmission rates, and length of stay in cervical and lumbar spine operations from 2005 to 2019.

METHODS: Patients were stratified into 2 groups: GA and non-GA (regional, epidural, spinal, monitored anesthesia care/intravenous sedation). Pearson chi-squared or Fisher exact test and independent sample t test were used to compare demographics between groups. Jonckheere-Terpstra test was used to determine whether trends and outcomes of non-GA operations from 2005-2019 were statistically significant. No non-GA spine operations were reported in the database during 2005-2006.

RESULTS: We included 301,521 patients who underwent cervical or lumbar spine operations from 2005-2019. GA was used in 294,903 (97.8%) operations; 6,618 (2.2%) operations were non-GA. Patients in the non-GA cohort were more likely to be younger (50.1 vs. 57.2 years; P<0.001), less likely to have American Society of Anesthesiologists classification ≥3 (39.7% vs. 48.3%; P<0.001), and to have lower BMI (27.8 vs. 31.5 kg/m²; P<0.001), outpatient admission status (10.8% vs. 4.0%; P<0.001), and fewer bleeding disorders (0.0% vs. 1.2%; P<0.001). The proportion of non-GA spine operations increased from nearly 0% in 2005 to 2.1% in 2019. The increase in non-GA operations was statistically significant in cervical (0.0% to 1.1%) and lumbar (0.0% to 2.9%) operations. For non-GA lumbar operations performed 2007-2019, 30-day complication rates, readmission rates, and mean length of stay all decreased (19.1% to 5.4%, P<0.05; 5.9% to 2.8%, P<0.05; 30.9 hours to 24.9 hours, P<0.05, respectively). Similarly, for non-GA cervical operations performed 2007-2019, 30-day complication rates, readmission rates, and mean length of stay all decreased (20.1% to 6.1%, P<0.05; 6.7% to 3.7%, P <0.05; 27.0 to 20.0 hours P<0.05, respectively).

CONCLUSIONS: Our trends analysis revealed increasing utilization and improved outcomes of non-GA spine surgery from 2005-2019; however, the proportion of non-GA spine operations remains small. Future research should investigate the barriers to adoption of non-GA spine surgery.

PMID:35525378 | DOI:10.1016/j.spinee.2022.04.012

Sci Total Environ. 2022 May 4:155688. doi: 10.1016/j.scitotenv.2022.155688. Online ahead of print.

ABSTRACT

In the last decades, several studies have shown that pesticides frequently occur above water quality thresholds in small streams draining arable land and are associated with changes in invertebrate communities. However, we know little about the potential propagation of pesticide effects from agricultural stream sections to least impacted stream sections that can serve as refuge areas. We sampled invertebrates and pesticides along six small streams in south-west Germany. In each stream, the sampling was conducted at an agricultural site, at an upstream forest site (later considered as “refuge”), and at a transition zone between forest and agriculture (later considered as “edge”). Pesticide exposure was higher and the proportion of pesticide-sensitive species (SPEAR_pesticides) was lower in agricultural sites compared to edge and refuge sites. Notwithstanding, at some edge and refuge sites, which were considered as being least impacted, we estimated unexpected pesticide toxicity (sum toxic units) exceeding thresholds where field studies suggested adverse effects on freshwater invertebrates. We conclude that organisms in forest sections within a few kilometres upstream of agricultural areas can be exposed to ecologically relevant pesticide levels. In addition, although not statistically significant, the abundance of pesticide-sensitive taxa was slightly lower in edge compared to refuge sites, indicating a potential influence of adjacent agriculture. Future studies should further investigate the influence of spatial relationships, such as the distance between refuge and agriculture, for the propagation of pesticide effects and focus on the underlying mechanisms.

PMID:35525352 | DOI:10.1016/j.scitotenv.2022.155688

Sci Total Environ. 2022 May 4:155604. doi: 10.1016/j.scitotenv.2022.155604. Online ahead of print.

ABSTRACT

The concentrations of uranium and nine elements (As, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Zn) in snow and rainwater samples were determined. Samples were collected in Thessaloniki-northern Greece in three sites, one in the industrial area close to an oil production power plant and two in the centre of the city. Snow samples were collected during January-February 2019 and 2021 whereas in the case of rainwater, a two-year survey has been performed during 2019 and 2020. The activity concentrations of the uranium radioisotopes were measured by alpha spectrometry whereas the metal(loid)s concentrations were determined by inductively coupled plasma mass spectroscopy (ICP-MS). The elevated concentrations of uranium (U) and the deviation of the isotopic ratio of U-234/U-238 from the equilibrium value indicated intensive dissolution of uranium. The results were analyzed using statistical analysis (Shapiro-Wilk, Friedman and Kruskal-Wallis tests). The obtained data and the calculated enrichment factors (Efs) denote variation of the concentration values between industrial and urban area and different elemental distribution influenced from anthropogenic contributions, meteorological conditions and the COVID-19 pandemic.

PMID:35525341 | DOI:10.1016/j.scitotenv.2022.155604

Comput Methods Programs Biomed. 2022 Apr 22;221:106807. doi: 10.1016/j.cmpb.2022.106807. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: The automatic diagnosis of heart diseases from the electrocardiogram (ECG) signal is crucial in clinical decision-making. However, the use of computer-based decision rules in clinical practice is still deficient, mainly due to their complexity and a lack of medical interpretation. The objetive of this research is to address these issues by providing valuable diagnostic rules that can be easily implemented in clinical practice. In this research, efficient diagnostic rules friendly in clinical practice are provided.

METHODS: In this paper, interesting parameters obtained from the ECG signals analysis are presented and two simple rules for automatic diagnosis of Bundle Branch Blocks are defined using new markers derived from the so-called FMM_ecg delineator. The main advantages of these markers are the good statistical properties and their clear interpretation in clinically meaningful terms.

RESULTS: High sensitivity and specificity values have been obtained using the proposed rules with data from more than 35,000 patients from well known benchmarking databases. In particular, to identify Complete Left Bundle Branch Blocks and differentiate this condition from subjects without heart diseases, sensitivity and specificity values ranging from 93% to 99% and from 96% to 99%, respectively. The new markers and the automatic diagnosis are easily available at https://fmmmodel.shinyapps.io/fmmEcg/, an app specifically developed for any given ECG signal.

CONCLUSIONS: The proposal is different from others in the literature and it is compelling for three main reasons. On the one hand, the markers have a concise electrocardiographic interpretation. On the other hand, the diagnosis rules have a very high accuracy. Finally, the markers can be provided by any device that registers the ECG signal and the automatic diagnosis is made straightforwardly, in contrast to the black-box and deep learning algorithms.

PMID:35525215 | DOI:10.1016/j.cmpb.2022.106807

Spectrochim Acta A Mol Biomol Spectrosc. 2022 Apr 28;278:121303. doi: 10.1016/j.saa.2022.121303. Online ahead of print.

ABSTRACT

Environmental sustainable analytical methods were developed by mathematical modification of UV absorption spectra for quality control study of multicomponent formulations consisting of remogliflozin (REM) and teneligliptin (TEN), with good sensitivity and selectivity. Then analytes were quantified by measuring the peak amplitude of the first derivative spectra at zero crossing points at 230.2 nm and 213.8 nm for REG and TEN in the first derivative method. The second method involves the formation of ratio spectra and taking the absorption difference at two selected wavelengths of peak and trough of a spectrum. In the ratio first derivative method peak amplitudes were measured at 235.2 nm and 259.1 nm for simultaneous quantification of REM and TEN respectively. The fourth method was based on the measurement of the peak amplitude of zero-order spectra of analytes generated from the mixture spectrum by subtraction of a constant from the ratio spectrum followed by multiplication with divisor spectrum, Further, the proposed methods were validated systematically to confirm the linearity, precession, accuracy, sensitivity, and selectivity. Finally, validated UV spectroscopic methods were applied for simultaneous quantification of REM and TEN from formulation, and laboratory mixed solutions and statistically compared with the reported HPLC method. Further, recently developed AGREE, Hexagonal greenness and white analytical chemistry, a whiteness evaluation tools were applied to the proposed UV spectroscopic methods and found to be safer analytical methods, compared to the reported expensive, time-consuming and toxic HPLC method. Hence, proposed UV spectroscopic methods could be used for routine quality control of formulations containing REM and TEN.

PMID:35525182 | DOI:10.1016/j.saa.2022.121303