Nevin Manimala

Endocrine. 2022 Sep 17. doi: 10.1007/s12020-022-03184-8. Online ahead of print.

ABSTRACT

OBJECTIVES: The sensitivities of the pituitary to thyroxine feedback, and the thyroid to thyrotropin stimulation determine the free thyroxine /thyrotropin feedback loop and can be described mathematically by two curves. It is not well understood how the two curves combine in a healthy population with normal thyroid function to express the individual balance points that are observed. This study was directed at this issue testing the possibilities of random combination and directed linkage between the two curves.

METHODS: We reverse-engineered two sets of population data, on the assumption of independent combinations of thyroid and pituitary sensitivities, to obtain estimates of the curve describing thyroid sensitivity. Sensitivity studies were performed.

RESULTS: No analysis resulted in a physiologically feasible estimate of the curve describing thyroid sensitivity. There was evidence of linkage of the two curves in terms of their combination throughout the normal range. Thyroid response curves reflecting a low free thyroxine response to thyrotropin tended to be combined in individuals with thyrotropin curves reflecting a high thyrotropin response to free thyroxine, and vice versa.

CONCLUSIONS: Thyroid and pituitary sensitivities are linked, being combined in individuals in a non-random directed pattern. Direct mutual interaction may contribute to this linkage. This linkage precludes the derivation of the curves describing these sensitivities from population data of the free thyroxine and thyrotropin relationship and complicates their derivation by physiological experimentation. This linkage and probable interaction may also bestow evolutionary advantage by minimising inter-individual variation in free thyroxine levels and by augmenting homeostasis.

PMID:36115005 | DOI:10.1007/s12020-022-03184-8

Qual Life Res. 2022 Sep 17. doi: 10.1007/s11136-022-03252-6. Online ahead of print.

ABSTRACT

PURPOSE: A joint modeling approach is recommended for analysis of longitudinal health-related quality of life (HRQoL) data in the presence of potentially informative dropouts. However, the linear mixed model modeling the longitudinal HRQoL outcome in a joint model often assumes a linear trajectory over time, an oversimplification that can lead to incorrect results. Our aim was to demonstrate that a more flexible model gives more reliable and complete results without complicating their interpretation.

METHODS: Five dimensions of HRQoL in patients with esophageal cancer from the randomized clinical trial PRODIGE 5/ACCORD 17 were analyzed. Joint models assuming linear or spline-based HRQoL trajectories were applied and compared in terms of interpretation of results, graphical representation, and goodness of fit.

RESULTS: Spline-based models allowed arm-by-time interaction effects to be highlighted and led to a more precise and consistent representation of the HRQoL over time; this was supported by the martingale residuals and the Akaike information criterion.

CONCLUSION: Linear relationships between continuous outcomes (such as HRQoL scores) and time are usually the default choice. However, the functional form turns out to be important by affecting both the validity of the model and the statistical significance.

TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number NCT00861094.

PMID:36115002 | DOI:10.1007/s11136-022-03252-6

Int J Clin Pharm. 2022 Sep 17. doi: 10.1007/s11096-022-01447-y. Online ahead of print.

ABSTRACT

BACKGROUND: Of all hospital admissions in older patients, 10-30% seem to be medication-related. However, medication-related admissions are often unidentified in clinical practice. To increase the identification of medication-related hospital admissions in older patients a triggerlist is published in the Dutch guideline for polypharmacy.

AIM: To assess whether the triggerlist has value as selection criterion to identify patients at high risk of medication-related hospital admissions.

METHOD: This retrospective cohort study was carried out in 100 older (≥ 60 years) patients with polypharmacy and having two triggers from the triggerlist. The admissions were assessed as either possibly or unlikely medication-related according to the Assessment Tool for identifying Hospital Admissions Related to Medications.

RESULTS: Of all the admissions 48% were classified as possibly medication-related. Patients with a possible medication-related hospital admission were more likely to have an impaired renal function (p = 0.015), but no differences with regard to age, sex, comorbidity or number of medicines were found.

CONCLUSION: The high prevalence of medication-related hospital admissions, suggests the triggerlist may have added value as selection criterion in a cohort of older patients with polypharmacy and can be used to improve the identification of a population at high risk of medication-related hospital admissions.

PMID:36115001 | DOI:10.1007/s11096-022-01447-y

Neurol Sci. 2022 Sep 17. doi: 10.1007/s10072-022-06386-0. Online ahead of print.

ABSTRACT

BACKGROUND: Age-related declines in cognitive function may begin in midlife.

PURPOSE: To determine whether blood-based biomarkers of inflammation, metabolic dysregulation and neurotoxins are associated with risk of cognitive decline and impairment.

METHODS: Baseline blood samples from the longitudinal Beaver Dam Offspring Study (2005-2008) were assayed for markers of inflammation, metabolic dysregulation, and environmental neurotoxins. Cognitive function was measured at baseline, 5-year (2010-2013) and 10-year (2015-2017) examinations. Participants without cognitive impairment at baseline and with cognitive data from at least one follow-up were included. Cox proportional hazards models were used to evaluate associations between baseline blood biomarkers and the 10-year cumulative incidence of cognitive impairment. Poisson models were used to estimate the relative risk (RR) of 5-year decline in cognitive function by baseline blood biomarkers. Models were adjusted for age, sex, education, and cardiovascular related risk factors.

RESULTS: Participants (N = 2421) were a mean age of 49 years and 55% were women. Soluble vascular cell adhesion molecule-1 (sVCAM-1_{Tertile(T)3 vs T1-2} hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.05,2.82) and hemoglobin A1C (HR = 1.75, 95% CI = 1.18,2.59, per 1% in women) were associated with the 10-year cumulative incidence of cognitive impairment. sVCAM-1 (RR_T3 vs _T1-2 = 1.45, 95% CI = 1.06,1.99) and white blood cell count (RR = 1.10, 95% CI = 1.02,1.19, per 10³/μL) were associated with 5-year cognitive decline.

CONCLUSIONS: Biomarkers related to inflammation and metabolic dysregulation were associated with an increased risk of developing cognitive decline and impairment. These results extend previous research in cognitive aging to early markers of cognitive decline in midlife, a time when intervention methods may be more efficacious.

PMID:36114981 | DOI:10.1007/s10072-022-06386-0

Matern Child Health J. 2022 Sep 17. doi: 10.1007/s10995-022-03492-5. Online ahead of print.

ABSTRACT

BACKGROUND: The relationship between housing instability and reproductive healthcare is understudied. We examined the association between housing insecurity and access and utilization of general healthcare, contraceptive healthcare, and abortion care.

METHODS: Using data from a population-representative survey of adult reproductive-age Ohio women (N = 2,529), we assessed housing insecurity (not paying rent/mortgage on time in the past year). We examined associations between housing insecurity and the following outcomes: (1) not being able to access general healthcare in the past year; (2) experiencing delays or difficulties in accessing contraceptive healthcare in the past year; and (3) ever having an abortion. We used unadjusted and adjusted logistic regression models. We selected confounders a priori and included age, socioeconomic status, and healthcare status.

RESULTS: Overall, 10.6% of Ohio women of adult reproductive age experienced housing insecurity. Approximately 27.5% of respondents were not able to access general healthcare and 10.4% experienced delays or difficulties in accessing contraceptive care. Compared to housing-secure respondents, housing-insecure women were less able to access general healthcare (adjusted odds ratio [aOR]:2.16; 95% confidence interval [CI]:1.45-3.23) and more likely to experience delays or difficulties when accessing contraceptive care (aOR:1.74; 95% CI:1.00-3.04). Insecure housing was not statistically associated with ever having an abortion (aOR:1.76; 95% CI:0.93-3.34).

CONCLUSIONS: In this study, recent housing insecurity was associated with poorer access to general and contraceptive healthcare. Studies utilizing multidimensional measures of housing insecurity and other material insecurity measures are needed to further explore the relationship between material insecurity and access to general and contraceptive care.

PMID:36114977 | DOI:10.1007/s10995-022-03492-5

Breast Cancer Res Treat. 2022 Sep 17. doi: 10.1007/s10549-022-06744-8. Online ahead of print.

ABSTRACT

PURPOSE: The impact of elevated body mass index (BMI) on overall survival (OS) in patients receiving modern anthracycline-taxane chemotherapy for early breast cancer (EBC) has not yet been well established. The purpose of our study was to examine overall survival (OS) by BMI category in women with EBC receiving either doxorubicin (A), cyclophosphamide (C) + paclitaxel (P) or fluorouracil (F), epirubicin (E), cyclophosphamide (C) + docetaxel (D).

METHODS: This was a retrospective cohort study in patients ≥ 18 years with resected stage I-III BC diagnosed between 2007 and 2017 in Ontario, identified through linkage of administrative databases. Patients were classified according to baseline BMI into underweight (< 18.5 kg/m²), normal (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), and obese (≥ 30 kg/m²) World Health Organization (WHO) categories. The primary outcome was OS. Univariable and multivariable analyses were used to examine the association between clinico-pathologic characteristics and OS among BMI categories.

RESULTS: Our cohort included 11,601 women, of whom 3890 (33.5%) were normal weight, 3696 (31.9%) overweight, and 3847 (33.1%) obese. Median OS was 7.9 years. There were no statistically significant differences in OS according to BMI (p = 0.66) in the overall study cohort or among the BMI categories after adjusting for age, nodal status, stage, grade, ER and HER2 status for either AC-P or FEC-D- treated patients (p = 0.45 and p = 0.97, respectively).

CONCLUSIONS: Our large population-based retrospective cohort analysis of EBC patients receiving adjuvant anthracycline-taxane chemotherapy found no significant impact of BMI on OS. Further investigation is warranted to confirm these findings in prospective patient cohorts.

PMID:36114940 | DOI:10.1007/s10549-022-06744-8

Breast Cancer Res Treat. 2022 Sep 17. doi: 10.1007/s10549-022-06689-y. Online ahead of print.

ABSTRACT

PURPOSE: To present an overview of the management of male patients with Ductal Carcinoma In Situ of the breast (male DCIS).

METHODS: We retrospectively studied all male patients with a diagnosis of pure DCIS from January 1999 to December 2018: 20 patients were identified in our cancer referral center. We collected data regarding clinical presentation, age of onset, radiological features, receptor status of the neoplasm, histological type, and the follow-up of those patients.

RESULTS: The median age was 62 years (range 21-80). All patients underwent surgery, in 15/20 (75%) cases a mastectomy was carried out. Two patients (10%) underwent endocrine treatment and 1/20 (5%) underwent radiotherapy. The receptor status for 15/20 patients was documented: 13/15 patients were ER+/Pr+. In 3 cases the Ki 67% was positive (i.e., > 20%). All cases were negative for Her2. The median follow-up time was 9.0 years (IQR 4.0-13.7). Only one patient had an ipsilateral recurrence with the finding of an infiltrating carcinoma in the same breast after 14 years. The 5-year disease-free survival was 92.9%.

CONCLUSION: Pure DCIS in men is an extremely rare disease: proper diagnosis and management allow an excellent prognosis.

PMID:36114939 | DOI:10.1007/s10549-022-06689-y

Ir J Med Sci. 2022 Sep 17. doi: 10.1007/s11845-022-03152-1. Online ahead of print.

ABSTRACT

BACKGROUND: Kisspeptin has recently emerged as a key regulator of the reproductive axis in women. Kisspeptin, acting centrally via the kisspeptin receptor, stimulates the secretion of the gonadotrophin-releasing hormone (GnRH).

AIMS: To investigate serum kisspeptin levels in infertility patients for its clinical utilisation in management and understanding of the pathophysiology of infertility in a wide array of patients.

METHODS: This prospective case-control study analysis involved 92 primary infertile women with PCOS, diminished ovarian reserve (DOR), unexplained infertility (UEI), and male factor infertility between 20 and 42 years of age. Serum samples were collected between the second and fifth day of the menstrual cycle. The kisspeptin level was determined using a human kisspeptin ELISA kit according to the manufacturer’s procedure.

RESULTS: The median value of serum kisspeptin in the PCOS infertility group was significantly higher than that in the UEI group (p = 0.011). There was a statistically significant (p = 0.015, r = -0.182) negative weak correlation found between serum kisspeptin levels and age. The optimal cutoff value obtained to differentiate the UEI from others (PCOS infertility + DOR + male factor infertility) according to the serum kisspeptin level was 214.3 ng/L with a sensitivity of 55% and specificity of 80.9%.

CONCLUSIONS: Understanding the role of kisspeptin may lead to its use as a biomarker in infertility diagnosis in UEI patients and might guide the use of kisspeptin analogues in selected patients for infertility management.

PMID:36114933 | DOI:10.1007/s11845-022-03152-1

Radiol Med. 2022 Sep 17. doi: 10.1007/s11547-022-01546-w. Online ahead of print.

ABSTRACT

PURPOSE: To assess the role of 2D-shear wave elastography (2D-SWE) in differentiating benign from malignant focal breast lesions (FBLs), providing new vendor-specific cutoff values.

METHODS: 158 FBLs (size: 3.5-50 mm) detected in 151 women (age: 21-87 years) were prospectively evaluated by means 2D-SWE. For each lesion, an expert radiologist assessed US BI-RADS category and calculated the following four 2D-SWE parameters: (1) elasticity maximum (E_max); (2) mean elasticity (E_mean); (3) minimum elasticity (E_min); (4) elasticity ratio (E_ratio). US-guided core-biopsy was considered as standard of reference for all the FBLs classified as BI-RADS 4 or 5. For each 2D-SWE parameter, the optimal cutoff value for a diagnostic test was calculated using the Youden method. Diagnostic performance of the US BI-RADS and 2D-SWE parameters was calculated accordingly.

RESULTS: 83/158 (52.5%) FBLs were benign and 75/158 (47.5%) were malignant. Statistically significant higher stiffness values were observed in malignant FBLs for all 2D-SWE parameters than in benign ones (p < 0.001). 2D-SWE cutoff values were 82.6 kPa, 66.0 kPa and 53.6 kPa, respectively, for E_max, E_mean, E_min and 330.8% for E_ratio. The 2D-SWE parameter showing the best diagnostic accuracy was E_max (85.44%). Considering US BI-RADS 3 (n = 60) and 4a (n = 32) FBLs, E_max and E_mean showed the best diagnostic accuracy (85.87% for both), without a statistically significant decrease in sensitivity (p = 0.7003 and p = 1, respectively).

CONCLUSION: Our study provides new vendor-specific cutoff values for 2D-SWE, suggesting its possible clinical use in the adjunctive assessment of category US-BI-RADS 3 and 4a breast masses.

PMID:36114930 | DOI:10.1007/s11547-022-01546-w

J Math Biol. 2022 Sep 17;85(4):31. doi: 10.1007/s00285-022-01788-2.

ABSTRACT

We introduce a model in the context of ecology that can be used to describe the distribution and abundance of individuals when data from field work is extremely limited (for example, in the case of endangered species). Our procedure is based on an intuitive understanding of the physical properties of phenomena. The idea is that individuals have the tendency to be attracted (or repulsed) to certain properties of the environment. At the same time, they are spread in such a way that if there is no reason for them to be in some specific locations, then they are uniformly distributed throughout the region. Our model draws from quantum mechanics, by using quantum Hamiltonians in the context of classical statistical mechanics. The equilibrium between the spreading and the attractive (or repulsive) forces determines the behavior of the species that we model, and this is expressed in terms of a global control problem of an energy operator which is the sum of a kinetic term (spreading) and a potential (attraction or repulsion). We focus on the full probability measure and a global control of the model (instead of looking at conditional measures that generate a global measure). Furthermore, we propose a numerical solution to this global control problem that overcomes the well-known major difficulty of Gibbs sampling (annealing) which is the fact that a global control is hardly reachable when the number of variables is large (the algorithms get stuck in non-optimal states).

PMID:36114925 | DOI:10.1007/s00285-022-01788-2