Classification of maternal thyroid function in early pregnancy using repeated blood samples

Objective: The assessment of maternal thyroid function in early pregnancy is debated. It is well-established that pregnancy-specific reference ranges preferably should be used. We speculated if the use of repeated blood samples drawn in early pregnancy would influence the classification of maternal thyroid function. Design: Cohort study Methods: Pregnant women with repeated early pregnancy blood samples were identified in the North Denmark Region Pregnancy Cohort. Each sample was used for the measurement of TSH, free T4 (fT4), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers). Method- and pregnancy week-specific reference ranges were used for classification of maternal thyroid function. Results: Among 1,466 pregnancies included, 89 women had TSH above the upper reference limit in the first sample (median pregnancy week 8), and 44 (49.4%) of these similarly had high TSH in the second sample (median week 10). A total of 47 women had TSH below the lower reference limit in the first sample, and 19 (40.4 %) of these similarly had low TSH in the second sample. Regarding women classified with isolated changes in fT4 in the first sample, less than 20% were similarly classified as such in the second sample. The percentage agreement between the samples was dependent on the level of TSH in the first sample and the presence of TPO- and Tg-Ab. Conclusion: In a large cohort of pregnant women, the classification of maternal thyroid function varied considerably with the use of repeated blood samples. Results emphasize a focus on the severity of thyroid function abnormalities in pregnant women.

Comparing performance on the Months of the Year Backwards test in hospitalised patients with delirium, dementia, and no cognitive impairment: an exploratory study

Purpose To investigate performance of the Months of the Year Backwards (MOTYB) test in older hospitalised patients with delirium, dementia, and no cognitive impairment. Methods Secondary analysis of data from a case–control study of 149 hospitalised patients aged ≥ 65 years with delirium [with or without dementia (N = 50)], dementia [without delirium (N = 46)], and no cognitive impairment (N = 53). Verbatim transcripts of MOTYB audio recordings were analysed to determine group differences in response patterns. Results In the total sample [median age 85y (IQR 80–88), 82% female], patients with delirium were more often unable to recite months backward to November (36/50 = 72%) than patients with dementia (21/46 = 46%; p < 0.01) and both differed significantly from patients without cognitive impairment (2/53 = 4%; p’s < 0.001). 121/149 (81%) of patients were able to engage with the test. Patients with delirium were more often unable to engage with MOTYB (23/50 = 46%; e.g., due to reduced arousal) than patients with dementia (5/46 = 11%; p < 0.001); both groups differed significantly (p’s < 0.001) from patients without cognitive impairment (0/53 = 0%). There was no statistically significant difference between patients with delirium (2/27 = 7%) and patients with dementia (8/41 = 20%) in completing MOTYB to January, but performance in both groups differed (p < 0.001 and p < 0.02, respectively) from patients without cognitive impairment (35/53 = 66%). Conclusion Delirium was associated with inability to engage with MOTYB and low rates of completion. In patients able to engage with the test, error-free completion rates were low in delirium and dementia. Recording of engagement and patterns of errors may add useful information to MOTYB scoring.

Potential Role of Natriuretic Response to Furosemide Stress Test During Acute Heart Failure

Background: Poor natriuresis has been associated with a poorer response to diuretic treatment and worse prognosis in acute heart failure. Recommendations on how and when to measure urinary sodium (UNa) are lacking. We aim to evaluate UNa quantification after a furosemide stress test (FST) capacity to predict appropriate decongestion during acute heart failure hospitalization. Methods: Patients underwent an FST on day-1 of admission, and UNa was measured 2 hours after, dividing patients into low or high UNa based on the sample median value. A semiquantitative composite congestive score (CCS; 0–9) and NT pro-BNP (N-terminal pro-B-type natriuretic peptide) quantification were assessed before the FST and at day 5 after the FST. Results: Median UNa after FST in the 65 patients included was 113 (97–122) mmol/L. At day 5, a lower proportion of patients with a low UNa reached a 30% decrease in NT-proBNP levels (21 [66%] for low UNa versus 31 [94%] for high UNa; P =0.005) and an appropriate grade of decongestion (CCS<3) (20 [62%] for low UNa versus 32 [97%] for high UNa; P <0.001). A UNa>83 mmol/L 2 hours after FST had a 96% sensitivity to predict an NT-proBNP reduction ≥30% and 95% to predict a CCS<3 at day 5. Low UNa patients presented a lower cumulative diuresis and weight loss and presented more often with prolonged hospitalization, worsening heart failure, and readmission because of acute heart failure or death at 6 months. Conclusions: Low natriuresis after an FST identified patients at a higher risk of an inadequate diuretic response and an inappropriate decongestion. FST-guided diuretic treatment might help to improve decongestion, shorten hospitalizations, and to reduce adverse outcomes.

Food Preferences in a Greenlandic Population

Objectives The overall aim was to describe food reward in an Inuit population in Greenland. More specifically, the objective was to first test the differences in food reward for sweet relative to savory food (taste bias) after four weeks on a traditionally Inuit diet (TID) vs a Westernized diet (WD). If no differences in taste bias were found between diet groups, we aimed to describe food reward in a pooled sample (median [IQR]). We hypothesized that participants would have higher preferences for sweet compared to savory foods. Methods After a dietary intervention in Greenland (20% of foods provided), we measured behavioral components of food reward using the Leeds Food Preference Questionnaire. The reward components, explicit liking and implicit wanting, were measured in response to images of Western foods varying in fat content and taste after four weeks on either TID or WD. A positive bias score reflected preference for sweet over savory, and oppositely a negative bias score reflected preference for savory over sweet foods. Results Participant characteristics were similar in the two diet groups (age (mean (SD): TID = 58.1 (11.5) vs. WD = 55.4 (9.5) years); sex: TID = 50% vs. WD = 54% women; body mass index (mean (SD): TID = 26.6 (5.5) vs. WD = 27.9 (4.7) kg/m2). In these preliminary, unadjusted analyses, we found no differences in explicit liking (P = 0.77) or implicit wanting (P = 0.70) bias score for sweet over savory foods after four weeks following either TID (n = 26) or WID (n = 24). Altogether, participants in the two diet groups had a greater explicit liking (−11.5 [−19.9; −2.8]) and implicit wanting (−21.6 [−44.2; −5.2]) for savory compared to sweet foods. Conclusions This is the first study to examine explicit and implicit aspects of food reward in an Inuit population. Contrary to our hypothesis, this population did not prefer sweet over savory Western foods. Funding Sources The study was supported by unrestricted grants from The Novo Nordisk Foundation. Royal Greenland and the supermarket chains Kalaallit Nunaanni Brugseni & Pilersuisoq supported the study with foods and food logistics.

Faster lumbar spine bone loss in midlife predicts subsequent fracture independent of starting bone mineral density

Context Bone mineral density (BMD) decreases rapidly during the menopause transition (MT), and continues to decline in postmenopause. Objective To examine whether faster BMD loss during the combined MT and early postmenopause is associated with incident fracture, independent of starting BMD, before the MT. Design and Setting The Study of Women’s Health Across the Nation (SWAN), a longitudinal cohort study. Patients or Participants 451 women, initially pre- or early perimenopausal, and transitioned to postmenopause. Main outcome measures Time to first fracture after early postmenopause. Results In Cox proportional hazards regression, adjusted for age, body mass index, race/ethnicity, study site, use of vitamin D and calcium supplements, and use of bone--detrimental or beneficial medications, each SD decrement in lumbar spine (LS) BMD before the MT was associated with a 78% increment in fracture hazard (p=0.007). Each 1% per year faster decline in LS BMD was related to a 56% greater fracture hazard (p=0.04). Rate of LS BMD decline predicted future fracture, independent of starting BMD. Women with a starting LS BMD below the sample median, and a LS BMD decline rate faster than the sample median had a 2.7-fold greater fracture hazard (p=0.03). At the FN, neither starting BMD nor rate of BMD decline was associated with fracture. Conclusions At the LS, starting BMD before the MT and rate of decline during the combined MT and early postmenopause are independent risk factors for fracture. Women with below-median starting LS BMD and faster-than-median LS BMD decline have the greatest fracture risk.

Approximating the Normal Sample Median Distribution in Process Control

The present work aims to propose an approximation of the sample median distribution with a normal parent distribution. Although the mean is usually used as the central tendency measure for normal samples, the median has also been used in engineering, process control in particular. The proposed method approximates the normal sample median distribution only using the normal distribution function. It outperforms Castagliola’s method for small samples and serves as an alternative approximation for trading off accuracy against computational complexity for large samples.

Activin A correlates with the worst outcomes in COVID-19 patients, and can be induced by cytokines via the IKK/NF-kappa B pathway

SummaryA fraction of COVID-19 patients develop the most severe form, characterized by Acute Respiratory Disease Syndrome (ARDS). The molecular mechanisms causing COVID-19-induced ARDS have yet to be defined, though many studies have documented an increase in cytokines known as a “cytokine storm.” Here, we demonstrate that cytokines that activate the NF-kappaB pathway can induce Activin A and its downstream marker, FLRG. In hospitalized COVID-19 patients elevated Activin A/FLRG at baseline were predictive of the most severe longitudinal outcomes of COVID-19, including the need for mechanical ventilation, lack of clinical improvement and all-cause mortality. Patients with Activin A/FLRG above the sample median were 2.6/2.9 times more likely to die, relative to patients with levels below the sample median, respectively. The study indicates high levels of Activin A and FLRG put patients at risk of ARDS, and blockade of Activin A may be beneficial in treating COVID-19 patients experiencing ARDS.