Tag: statistics

Probl Endokrinol (Mosk). 2022 Oct 12;68(6):43-48. doi: 10.14341/probl13151.

ABSTRACT

BACKGROUND: Pregnancy is a condition with important structural and physiological changes in the thyroid gland. In this regard, experts of thyroid associations have recommended developing specific reference intervals taking into account the natural and socio-geographical characteristics of the region under study.

AIM: To conduct an epidemiological analysis and evaluate TSH reference intervals in pregnant women living in the central regions of the Russian Federation with mild iodine deficiency.

MATERIALS AND METHODS: We have conducted the observational multicenter cross-sectional study included 2008 healthy pregnant women at different trimesters of pregnancy, from three regions of the Russian Federation (Moscow, Ivanovo and Smolensk). We assessed the level of thyroid-stimulating hormone, antibodies to thyroid peroxidase, antibodies to serum thyroglobulin, the level of iodine concentration in the morning portion of urine (cerium arsenic method) and we have conducted a questionnaire (date birth and gestational age). Women with elevated titers of anti-TPO and/or anti-TG antibodies were excluded from the study (245 women). As a result, we assessed high and medium levels of TSH and its overestimation with iodine sufficiency in pregnant women. The results are presented using the calculation of 2.5 and 97.5 percentiles.

RESULTS: We confirmed the presence of iodine deficiency in the study areas. The median concentration of iodine in the urine was: in Moscow 106 μg/l, in Ivanovo 119 μg/l, in Smolensk 134 μg/l. Pregnant women were divided into 2 groups according to iodine adequacy. In the group with optimal iodine supply, the level of TSH was 0,006-3,36 in the 1st trimester, 0,20-3,74 in the 2nd trimester, and 0,33-3,68 mIU/L in the 3rd trimester. In the group with mild iodine deficiency – in the 1st trimester it was 0,11-3,00, in the 2nd trimester 0,22-3,78, in the 3rd trimester 0,07-3,04 mIU/l. Statistical analysis of the data revealed that when comparing the level of TSH by trimester, depending on the place of residence, no statistical difference was found (p = 0,239).

CONCLUSION: We obtained that the level of TSH in healthy pregnant women living in the central regions of the Russian Federation does not exceed 3.8 mIU/l in all trimesters.

PMID:36689710 | DOI:10.14341/probl13151

Probl Endokrinol (Mosk). 2022 Aug 15;68(6):30-42. doi: 10.14341/probl13144.

ABSTRACT

AIM: To determine significant factors affecting the survival of patients with ectopic ACTH syndrome (EAS).

MATERIALS AND METHODS: A multi-center, observational study with a retrospective analysis of patients with EAS. The end point of the study was the fatal outcome of patients from various causes. In order to identify predictors of survival or mortality, univariate and multifactorial Cox regression analyses were carried out. ROC-analysis was used to determine the prognostic threshold values of individual predictors. The survival analysis was carried out using the Kaplan-Mayer method. Statistical data processing was carried out by using IBM SPSS Statistics 23.

RESULTS: The age of patients at the time of diagnosis ranged from 12 to 76 years (Me 40 years [28;54]). The age of the studied population was 55 years [38; 64] for women and 42 years [32; 54] for men. The median period of observation was 50 months [13;91], with a maximum follow-up of 382 months. 92 patients (60,9%) had bronchopulmonary NET, 17 (11,3%) – thymic carcinoid, 8 – pancreatic NET, 5 -pheochromocytoma, 1- cecum NET, 1- appendix carcinoid tumor, 1 – medullary thyroid cancer and 26 (17,2%) patients had an occult NET. The primary tumor was removed in 101 patients (66,9%). Bilateral adrenalectomy was performed in 42 (27,8%) cases. Metastases were revealed in 23,2% (n=35) of patients. Relapse of the disease was observed in 24,4%, long-term remission was preserved in 64 patients (74,4%). Death occurred in 42 patients (28%). The average age of survivors was 47,0±15,2 versus 53,5±15,6 years for the deceased (p=0,022). The average survival time from diagnosis for the deceased was 32 months, Me 16,5 months [7;54]. Multivariate analysis revealed that the following factors have a direct impact on survival: age of diagnosis ≥51 years (OR 4,493; 95% CI 2,056-9,818, p<0,001), bronchopulmonary neuroendocrine tumor (NET) (OR 0,281; 95% CI 0,119-0,665, p=0,004), the presence of distant metastases (OR 2,489; 95% CI 1,141-5,427, p=0,022), late-night salivary cortisol (LNSC) ≥122,2 nmol/L (OR 2,493; 95% CI 1,014-6,128, p=0,047).

CONCLUSION: The prognosis of patients with EAS is influenced by the age of diagnosis, NET localization, distant metastases and level of LNSC. The most common cause of ectopic ACTH syndrome was bronchopulmonary NET which was associated with the best survival rate.

PMID:36689709 | DOI:10.14341/probl13144

Probl Endokrinol (Mosk). 2022 Jul 31;68(6):12-21. doi: 10.14341/probl12892.

ABSTRACT

BACKGROUND: The issues of monitoring the effectiveness of iodine deficiency prevention programs are an important component in the process of iodine elimination. Neonatal thyrotropin (TSH) has been used as a criterion for the severity of iodine deficiency since 1994, however, the question of the “cut-off point” of the neonatal TSH level has been widely discussed in the recent literature.

AIM: Evaluate the criterion for neonatal hyperthyroidism above 5 mIU/l from the perspective of monitoring iodine deficiency and establish a «cut-off point» on the model of healthy pregnant women with adequate iodine status.

MATERIALS AND METHODS: A prospective study was conducted in a population of pregnant women in the city of Tyumen, with the formation of observation groups according to the level of iodine excretion in the urine – the main group (with adequate iodine status throughout the entire gestation period) and the comparison group (women with iodine levels less than 150 μg/l). The results of neonatal screening for congenital hypothyroidism in children of women participating in the study were evaluated. The frequency of neonatal TSH above 5mIU/l was assessed in the observation groups. ROC-analysis was performed and a «cut-off point» of the level of neonatal TSH was established as an indicator of iodine deficiency.

RESULTS: The median urinary iodine concentration in the population of pregnant women in Tyumen was 159.05 μg/l, the incidence of goiter was 0.38%, the incidence of neonatal hyperthyroidism above 5 mIU/l was 2.88%, which characterizes adequate iodine intake in the pregnant population women. The frequency of neonatal TSH above 5 mIU/l in newborns from women from the main group was 1.47%, and in the comparison group – 9.3% (p = 0.076). ROC analysis revealed a threshold value of neonatal TSH of 2.77 mIU/l at the cut-off point, which corresponded to the highest value of the Youden index. Urinary iodine concentrations greater than 150 μg/l were predicted for nTSH values below this value.

CONCLUSION: Analysis of databases of neonatal screening for congenital hypothyroidism makes it possible to effectively, quickly and at minimal cost annually assess the iodine status in the population. The established «cut-off point» of neonatal TSH in the model of healthy pregnant women with adequate iodine intake in our work is 2.77 mIU/l, the absence of statistically significant differences in the incidence of neonatal hyperthyroidism above 5 mIU/l from women with different iodine status during pregnancy indicate the need to revise the existing threshold of 5 mIU/l and may be an incentive to conduct large-scale studies in regions with different iodine supply.

PMID:36689707 | DOI:10.14341/probl12892

Prosthet Orthot Int. 2022 Dec 28. doi: 10.1097/PXR.0000000000000201. Online ahead of print.

ABSTRACT

BACKGROUND: Prostheses are a primary rehabilitative intervention for people after lower limb amputation. To appropriately measure the effectiveness of prosthetic interventions, valid and reliable measures of prosthetic mobility are required. The Prosthetic Limb Users Survey of Mobility (PLUS-M) is a promising instrument for measuring prosthesis users’ mobility. However, German translations of the PLUS-M short forms have not yet been validated.

OBJECTIVES: Rasch validation of the German translation of the PLUS-M short forms in people with lower limb amputation.

STUDY DESIGN: This study is based on a cross-sectional survey of prosthesis-using lower limb amputees from a nation-wide cohort.

METHODS: PLUS-M data (the 7-item and the 12-item shortforms; PLUS-M-7 and PLUS-M-12, respectively) from 194 lower limb prosthesis users were subjected to Rasch analysis, an advanced statistical method for assessing if the measurement properties of a questionnaire comply with a wide spectrum of psychometric requirements.

RESULTS: Analysis showed appropriate rating scale functioning, good internal construct validity (item fit), unidimensionality, and good targeting of the PLUS-M-7 and PLUS-M-12 short forms. Moreover, the greater conditional measurement precision of PLUS-M-12 (regarding higher test information and lower standard error of mobility estimates) was quantified.

CONCLUSIONS: Rasch analysis of the German translation of both PLUS-M short forms showed good psychometric qualities. In addition, our study showed that test scores from the PLUS-M-12 are more accurate. Therefore, the PLUS-M-12 is recommended for individual-level clinical applications (e.g., classification or change assessment).

PMID:36689667 | DOI:10.1097/PXR.0000000000000201

Proc Natl Acad Sci U S A. 2023 Jan 31;120(5):e2218663120. doi: 10.1073/pnas.2218663120. Epub 2023 Jan 23.

ABSTRACT

Complex systems can exhibit sudden transitions or regime shifts from one stable state to another, typically referred to as critical transitions. It becomes a great challenge to identify a robust warning sufficiently early that action can be taken to avert a regime shift. We employ landscape-flux theory from nonequilibrium statistical mechanics as a general framework to quantify the global stability of ecological systems and provide warning signals for critical transitions. We quantify the average flux as the nonequilibrium driving force and the dynamical origin of the nonequilibrium transition while the entropy production rate as the nonequilibrium thermodynamic cost and thermodynamic origin of the nonequilibrium transition. Average flux, entropy production, nonequilibrium free energy, and time irreversibility quantified by the difference in cross-correlation functions forward and backward in time can serve as early warning signals for critical transitions much earlier than other conventional predictors. We utilize a classical shallow lake model as an exemplar for our early warning prediction. Our proposed method is general and can be readily applied to assess the resilience of many other ecological systems. The early warning signals proposed here can potentially predict critical transitions earlier than established methods and perhaps even sufficiently early to avert catastrophic shifts.

PMID:36689655 | DOI:10.1073/pnas.2218663120

J Chem Theory Comput. 2023 Jan 23. doi: 10.1021/acs.jctc.2c00976. Online ahead of print.

ABSTRACT

The dynamics of molecules are governed by rare event transitions between long-lived (metastable) states. To explore these transitions efficiently, many enhanced sampling protocols have been introduced that involve using simulations with biases or changed temperatures. Two established statistically optimal estimators for obtaining unbiased equilibrium properties from such simulations are the multistate Bennett acceptance ratio (MBAR) and the transition-based reweighting analysis method (TRAM). Both MBAR and TRAM are solved iteratively and can suffer from long convergence times. Here, we introduce stochastic approximators (SA) for both estimators, resulting in SAMBAR and SATRAM, which are shown to converge faster than their deterministic counterparts, without significant accuracy loss. Both methods are demonstrated on different molecular systems.

PMID:36689637 | DOI:10.1021/acs.jctc.2c00976

Medwave. 2023 Jan 23;23(1):e2592. doi: 10.5867/medwave.2023.01.2592.

ABSTRACT

Introduction: The SARS-CoV-2 pandemic has affected the entire population, especially vulnerable people with risk factors, such as people over 65 years. Globally and nationally, health protection measures were established to reduce transmission and the impact of the disease on the healthcare system, such as using face masks, hand washing, and social distancing, among others. This led to restrictions on activities outside the home, which affected the cognitive sphere of the population, especially people over 65 years of age. Objective: To demonstrate that social isolation causes changes in the cognitive status of people over 65 years of age. Methods: A longitudinal study was conducted from 2019 to 2020, with the participation of 37 older adults in a parish club of support activities who voluntarily agreed to participate by signing the informed consent form. The Folstein Mini-Mental State Examination was administered to all of them at two points in the study: before the pandemic and after six months of strict social isolation established as a control measure for the SARS-CoV-2 pandemic. We looked for cognitive status differences during this period and studied qualitative-quantitative sociodemographic variables. Results: The club members were older people, predominantly women. Mean age of the participants was 75.4 years; 89.2% had little schooling (less than ten years of formal education). Identified prevalent diseases were arterial hypertension and type-2 diabetes mellitus. In the first evaluation, six out of thirty-seven participants had slight cognitive deficits (16.2%), all females; there were no cases of cognitive impairment; the rest had normal cognitive status (31 out of 37, or 83.8%). After the second evaluation (at the end of strict isolation due to the pandemic), we observed that 11 (29.7%) participants had slight cognitive deficits (ten female and one male), which represents an increase of 13.5%. In addition, four participants (10.8%) showed mild cognitive impairment, all females. Such changes were statistically significant (p-value < 0.05). We conclude that social isolation due to the SARS-CoV-2 pandemic was related to changes in the cognitive status of the elderly.

PMID:36689629 | DOI:10.5867/medwave.2023.01.2592

Diabetes Care. 2023 Jan 23:dc221145. doi: 10.2337/dc22-1145. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine effect of mini-dose, ready-to-use glucagon on incidence of exercise-associated hypoglycemia (EAH) in adults with type 1 diabetes.

RESEARCH DESIGN AND METHODS: Individuals initially participated in the in-clinic training phase for which they were randomly assigned to a crossover design: 150 µg glucagon (treatment arm A) or placebo (arm B) subcutaneously, immediately before exercise, plus 50% reduction in continuous subcutaneous insulin infusion (CSII) basal delivery rate. Completers were then rerandomly assigned in the 12-week outpatient investigational phase: arm A, B, or open-label C, 150 µg glucagon alone. Participants were to undertake their usual aerobic exercise at moderate to high intensity for 30 to 75 min in real-world settings. Data were analyzed for incidence of level 1 hypoglycemia based on self-monitoring blood glucose and for various secondary and exploratory end points.

RESULTS: Of 48 participants who completed the training phase, 45 continued to the outpatient phase. For all exercise sessions in the outpatient phase (n = 795), incidence of level 1 hypoglycemia was lower in both glucagon arms (A, 12% [P < 0.0001]; C, 16% [P = 0.0032]) than in the placebo arm (B, 39%). Times below range, in range, and above range from 0 to 300 min did not significantly differ among treatment arms. Consumed grams of exercise carbohydrates were lower with glucagon use than with placebo use but did not reach statistical significance (P = 0.12). Adverse events were similar among treatment arms.

CONCLUSIONS: Mini-dose glucagon with or without 50% reduction in CSII basal delivery rate may help to decrease EAH incidence in adults with type 1 diabetes.

PMID:36689626 | DOI:10.2337/dc22-1145

Stroke. 2023 Feb;54(2):476-487. doi: 10.1161/STROKEAHA.122.040065. Epub 2023 Jan 23.

ABSTRACT

BACKGROUND: Symptomatic intracranial hemorrhage (sICH) is a severe complication of reperfusion therapy for ischemic stroke. Multiple models have been developed to predict sICH or intracranial hemorrhage (ICH) after reperfusion therapy. We provide an overview of published models and validate their ability to predict sICH in patients treated with endovascular treatment in daily clinical practice.

METHODS: We conducted a systematic search to identify models either developed or validated to predict sICH or ICH after reperfusion therapy (intravenous thrombolysis and/or endovascular treatment) for ischemic stroke. Models were externally validated in the MR CLEAN Registry (n=3180; Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). The primary outcome was sICH according to the Heidelberg Bleeding Classification. Model performance was evaluated with discrimination (c-statistic, ideally 1; a c-statistic below 0.7 is considered poor in discrimination) and calibration (slope, ideally 1, and intercept, ideally 0).

RESULTS: We included 39 studies describing 40 models. The most frequently used predictors were baseline National Institutes of Health Stroke Scale (NIHSS; n=35), age (n=22), and glucose level (n=22). In the MR CLEAN Registry, sICH occurred in 188/3180 (5.9%) patients. Discrimination ranged from 0.51 (SPAN-100 [Stroke Prognostication Using Age and National Institutes of Health Stroke Scale]) to 0.61 (SITS-SICH [Safe Implementation of Treatments in Stroke Symptomatic Intracerebral Hemorrhage] and STARTING-SICH [STARTING Symptomatic Intracerebral Hemorrhage]). Best calibrated models were IST-3 (intercept, -0.15 [95% CI, -0.01 to -0.31]; slope, 0.80 [95% CI, 0.50-1.09]), SITS-SICH (intercept, 0.15 [95% CI, -0.01 to 0.30]; slope, 0.62 [95% CI, 0.38-0.87]), and STARTING-SICH (intercept, -0.03 [95% CI, -0.19 to 0.12]; slope, 0.56 [95% CI, 0.35-0.76]).

CONCLUSIONS: The investigated models to predict sICH or ICH discriminate poorly between patients with a low and high risk of sICH after endovascular treatment in daily clinical practice and are, therefore, not clinically useful for this patient population.

PMID:36689584 | DOI:10.1161/STROKEAHA.122.040065

Stroke. 2023 Feb;54(2):448-456. doi: 10.1161/STROKEAHA.122.040542. Epub 2023 Jan 23.

ABSTRACT

BACKGROUND: Distal embolization (DE) is a common complication of endovascular treatment (EVT). We investigated the association of radiological thrombus characteristics and treatment details with DE.

METHODS: Patients with thin-slice (≤2.5 mm) baseline noncontrast computed tomography and computed tomography angiography from the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) were included. Thrombus annotation was performed manually on coregistered scans by experienced readers. We assessed thrombus location, distance from internal carotid artery terminus, length, perviousness, absolute attenuation, and hyperdense artery sign. In addition, we evaluated balloon guide catheter use during EVT, first-line EVT approach, the number of thrombectomy passes, and prior intravenous thrombolysis administration. DE was defined as the occurrence of emboli distal to the target artery or in new territories during EVT. The association between thrombus characteristics, treatment details, and DE was evaluated using descriptive statistics and multivariable mixed-effects logistic regression, resulting in adjusted odds ratios (aOR) with 95% CI. Interaction between IVT and radiological thrombus characteristics was assessed by adding interaction terms in separate models.

RESULTS: In total, 496 out of 1105 (44.9%) ESCAPE-NA1 patients were included. DE was detected in 251 out of 496 patients (50.6%). Patients with DE had longer thrombi (median, 28.5 [interquartile range, 20.8-42.3] mm versus 24.4 [interquartile range, 17.1-32.4] mm; P<0.01). There were no statistically significant differences in the other thrombus characteristics. Factors associated with DE were thrombus length (aOR, 1.02 [95% CI, 1.01-1.04]), balloon guide catheter use (aOR, 0.49 [95% CI, 0.29-0.85]), and number of passes (aOR, 1.24 [95% CI, 1.04-1.47]). In patients with hyperdense artery sign, IVT was associated with reduced odds of DE (aOR, 0.55 [95% CI, 0.31-0.97]), P for interaction=0.04.

CONCLUSIONS: DE was associated with longer thrombi, no balloon guide catheter use, and more EVT passes. IVT was associated with a reduced risk of DE in patients with hyperdense artery sign. These findings may support treatment decisions on IVT and EVT approaches.

PMID:36689583 | DOI:10.1161/STROKEAHA.122.040542