Category: Statistics

BMC Geriatr. 2022 May 7;22(1):402. doi: 10.1186/s12877-022-03096-2.

ABSTRACT

INTRODUCTION: With rising age, the incidence of physical and mental problems increases. Physiological and social changes occur across the lifespan that can affect an individual’s health and ability. The present study was aimed to determine older adult’s ability to recognize cognitive changes and its relation with mental health status.

MATERIALS AND METHODS: A descriptive correlational design was used to recruit 423 older adults who were referred to health centers in Tabriz, Iran in 2019 to receive primary health care. A systematic random sampling method was used for selecting participants. Data collection tools included a demographic-social questionnaire, General Health Questionnaire for assessing mental health (with 4 subscales) and a questionnaire of ability to recognize cognitive changes (with 8 sub-scales). Data were analyzed using descriptive statistics and inferential statistics.

RESULTS: The mean score of mental health of the older adults was 56.35 (8.40) which shows moderately impaired mental health. The most impaired aspect of mental health detected was the social function dimension 13.20 (2.67). The average of the total ability score was 41.19 (4.78) and the physical strength dimension had the highest average of 9.08 (1.80) and the empowerment obligation dimension had the lowest average of 3.06 (1.08). There was significant relationship between dimensions of depression (r = 0.21, p < 0.001), anxiety (r = 0.1, p = 0.04) and social functioning (r = 0.17), p < 0.001) with the ability to recognize cognitive changes of the older adults.

CONCLUSION: Negative mood states and social functioning were associated with the ability to recognize cognitive changes in this population of older adults. This sample exhibited moderately impaired mental health status and relatively large burdens of untreated affective symptoms. Although causality cannot be determined with this cross-sectional design, use of social programs to keep older adults mentally active, as well as cognitive rehabilitation programs could be tested with longitudinal designs for their impact on cognitive change recognition.

PMID:35525932 | DOI:10.1186/s12877-022-03096-2

Contemp Clin Trials. 2022 May 4:106782. doi: 10.1016/j.cct.2022.106782. Online ahead of print.

ABSTRACT

It is not uncommon that clinical studies of the same intervention contradicted with each other, e.g., one study produced positive results, while the other produced negative results. Ioanndis (2005a) found that among 49 highly-cited original clinical research studies, published in New England Journal of Medicine, Journal of the American Medical Association, Lancet or in a high-impact medical specialty journal, 32% of them were contradicted in subsequent large-scale studies, or were shown to have potentially overestimated the efficacy of the experimental intervention. This finding is disturbing and of serious concern given the widespread impact of these highly-cited studies and the rigorous standards used to design and conduct the studies. We perform Bayesian analysis of these highly-cited clinical studies based on Bayesian factor. We identified one cause of the issue: p values strongly overstated the experimental evidence. For the highly-cited studies, when the p value was 0.05, there was a 74.4% percentage chance that the null hypothesis was true. The use of a p value of 0.05 as the criterion for significance caused many researchers to mistakenly draw conclusions of positive findings, which were then contradicted by subsequent large-scale studies.

PMID:35525531 | DOI:10.1016/j.cct.2022.106782

Anal Chim Acta. 2022 May 22;1208:339814. doi: 10.1016/j.aca.2022.339814. Epub 2022 Apr 8.

ABSTRACT

Metabolism studies are one of the important steps in pharmaceutical research. LC-MS combined with metabolomics data-processing approaches have been developed for rapid screening of drug metabolites. Mass defect filter (MDF) is one of the LC/MS-based metabolomics data processing approaches and has been applied to screen drug metabolites. Although MDF can remove most interference ions from an incubation sample, the true positive rate of the retaining ions is relatively low (approximately 10%). To improve the efficacy of MDF, we developed a two-stage data-processing approach by combining MDF and stable isotope tracing (SIT) for metabolite identification. Pioglitazone (PIO), which is an antidiabetic drug used to treat type 2 diabetes mellitus, was taken as an example drug. Our results demonstrated that this new approach could substantially increase the validated rate from about 10% to 74%. Most of these validated metabolite signals (13/14) could be verified as PIO structure-related metabolites. In addition, we applied this approach to identify uncommon metabolite signals (a mass change beyond the window of 50 Da around its parent drug, MDF1). SIT could remove most interference ions (approximately 98%) identified by MDF1, and four out of five validated metabolite signals could be verified as PIO structure-related metabolites. Interestingly, a lot of the verified metabolites (10/17) were novel PIO metabolites. Among these novel metabolites, nine were thiazolidinedione ring-opening signals that might be related to the toxicity of PIO. Our developed approach could significantly improve the efficacy in drug metabolite identification compared with that of MDF.

PMID:35525585 | DOI:10.1016/j.aca.2022.339814

Environ Pollut. 2022 May 4:119401. doi: 10.1016/j.envpol.2022.119401. Online ahead of print.

ABSTRACT

Due to the high radiotoxicity in high concentrations, plutonium isotopes have drawn high attentions in the consideration of radiation risk, especially their sources, level, environmental behaviors, including deposition, retention and migration behaviors. However, such research in the Qinghai-Tibet Plateau is still missing, where is deemed as an environmental sensitive area. ^239,240Pu in surface soil collected from the Qinghai-Tibet Plateau were determined for the first time in this work. The concentrations of ^239,240Pu are in the range of 0.0176-1.95 Bq/kg, falling into the reported ranges in the background areas from the similar latitude belt. The ²⁴⁰Pu/²³⁹Pu atomic ratio range was measured to be 0.146-0.225, which is similar with the global fallout values. Both indicate that the global fallout is the major source of plutonium in this region, and the low plutonium level will not cause any radiation risk so far. Based on the statistical analysis of the possible parameters (organic content, moisture content, average annual precipitation, altitudes, topography and human activity), the large variations of ^239,240Pu concentrations were mainly attributed to the retention process related factors including soil organic content and human activity disturbances. While, the deposition related factors including the average annual precipitation, altitudes, topography made insignificant influence on the spatial distribution of ^239,240Pu concentrations due to the low ^239,240Pu concentrations in atmosphere, less wet deposition amount and insignificant re-suspended amount. The highest ^239,240Pu concentrations of 0.805-1.95 Bq/kg were mainly due to the good retention condition in the sampling sites with higher soil organic content and less human activity disturbances.

PMID:35525518 | DOI:10.1016/j.envpol.2022.119401

J Affect Disord. 2022 May 4:S0165-0327(22)00504-3. doi: 10.1016/j.jad.2022.05.002. Online ahead of print.

ABSTRACT

BACKGROUND: The risk factors of Posttraumatic Stress Symptoms (PTSS) and depressive symptoms have been well-established, but whether the network structure of their symptoms changes over time remains unclear. This study aims to examine the six-year changes of network structure of PTSS and depressive symptoms among Wenchuan earthquake adult survivors in China.

METHODS: In this pooled cross-sectional study, respondents were sampled from the same population at each of the five waves (N = 1343, 1205, 1177, 1376, and 1339). The network structure of them was investigated using network analyses.

RESULTS: The study shows network connections stable across waves were the positive connections between hyperarousal and intrusions, hyperarousal and somatic symptoms, and two dimensions of positive effects. Stable negative connections were those between depressed affects and positive effects, avoidance and depressed affects, avoidance with interpersonal symptoms and avoidance with somatic symptoms. Across waves, fearful emotion consistently was the strongest bridge symptom connecting with PTSS symptoms. However, for PTSS the strongest bridge symptom varied across time as it was avoidance in wave 1 but were hyperarousal in other four waves.

LIMITATIONS: This study was based on a pooled cross-sectional survey, which inhibits conclusions regarding causal influences between symptoms at the individual patient level.

CONCLUSIONS: The network structure of PTSS and depressive symptoms was partly stable, yet also varied across survey waves. Core symptom clusters for PTSS and depressive symptoms were avoidance and depressed affect, respectively. The central role of these clusters in PTSS and depressive symptoms has important implications to future psychiatric programs.

PMID:35525508 | DOI:10.1016/j.jad.2022.05.002

Theor Popul Biol. 2022 May 4:S0040-5809(22)00029-6. doi: 10.1016/j.tpb.2022.04.001. Online ahead of print.

ABSTRACT

When we examine the life history of humans against our closest primate relatives, the other great apes, there is notably a greater longevity in humans which includes a distinctive postmenopausal life stage, leading to the question, “How did human females evolve to have old-age infertility?” In their paper “Mate choice and the origin of menopause” (Morton et al., 2013), Morton et al. developed an agent-based model (ABM) to investigate the novel hypothesis that ancestral male mating choices, particularly forgoing mating with older females, was the driving force behind the evolution of menopause. From their model, they concluded that indeed male preference for young female mates could have driven females to lose fertility at older ages through deleterious mutations, leading to menopause. In this work, we revisit their male-mate-choice hypothesis by formulating an analogous mathematical model using a system of ordinary differential equations (ODEs). We first show that our ODE model recreates the qualitative behaviour and hence conclusions of key scenarios in Morton et al. (2013). However, since our ODE system is less computationally demanding than their ABM, we also conduct a broader sensitivity analysis over a range of parameters and differing initial conditions to analyse the dependence on their conclusions to underlying assumptions. Our results challenge those of Morton et al. as we find that even the slightest deviation from an exclusive mating preference for younger females would counteract the evolution of menopause. Consequently, we propose that their male-mate-choice hypothesis is incomplete and needs further explanation of how a male strategy to exclusively mate with young females could have arisen in our common ancestors and remained evolutionary stable for long enough to drive the evolution of old-age female infertility.

PMID:35525440 | DOI:10.1016/j.tpb.2022.04.001

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

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

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 4:111830. 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