Marginal structural model to evaluate the association between cumulative osteoporosis medication and infection using claims data.

Due to the suboptimal persistence to osteoporosis (OP) treatment, factors triggering treatment discontinuation/switching may be causing time-varying confounding. BP treatment was associated with the risk of overall infection in opposite directions in the unweighted Cox model versus the weighted MSM. The discrepancy of effect estimates for overall infection in the MSM suggested there may be time-varying confounding. INTRODUCTION: Due to the suboptimal persistence to osteoporosis (OP) treatment, factors triggering treatment discontinuation/switching may be affected by prior treatment and confound the subsequent treatment effect, causing time-varying confounding. METHODS: In a US insurance database, the association between joint treatment of bisphosphonates (BP) and other OP medication and the incidence of infections among postmenopausal women was assessed using a marginal structural model (MSM). Stabilized weights were estimated by modeling treatment and censoring processes conditioning on past treatment, and baseline and time-varying covariates. RESULTS: BP treatment was associated with the risk of overall infection in opposite directions in the unweighted Cox model {incidence rate ratio [IRR] [95% confidence interval (CI)] = 1.15 [1.14-1.17]} versus the weighted MSM [IRR (95% CI) = 0.79 (0.77-0.81)], but was consistently associated with a lower risk of serious infection in both the unweighted Cox model [IRR (95% CI] = 0.79 (0.78-0.81)) and the weighted MSM [IRR (95% CI) = 0.71 (0.68-0.75)]. Similar results were found when current and past treatments were simultaneously assessed. CONCLUSIONS: The discrepancy of effect estimates for overall but not serious infection comparing unweighted models and MSM suggested analyses of composite outcomes with a wide range of disease severity may be more susceptible to time-varying confounding.

Pentagonal Bipyramid FeII Complexes: Robust Ising-Spin Units towards Heteropolynuclear Nanomagnets.

Pentagonal bipyramid FeII complexes have been investigated to evaluate their potential as Ising-spin building units for the preparation of heteropolynuclear complexes that are likely to behave as single-molecule magnets (SMMs). The considered monometallic complexes were prepared from the association of a divalent metal ion with pentadentate ligands that have a 2,6-diacetylpyridine bis(hydrazone) core (H2 LN3O2R ). Their magnetic anisotropy was established by magnetometry to reveal their zero-field splitting (ZFS) parameter D, which ranged between -4 and -13 cm-1 and was found to be modulated by the apical ligands (ROH versus Cl). The alteration of the D value by N-bound axial CN ligands, upon association with cyanometallates, was also assessed for heptacoordinated FeII as well as for related NiII and CoII derivatives. In all cases, N-coordinated cyanide ligands led to large magnetic anisotropy (i.e., -8 to -18 cm-1 for Fe and Ni, +33 cm-1 for Co). Ab initio calculations were performed on three FeII complexes, which enabled one to rationalize the role of the ligand on the nature and magnitude of the magnetic anisotropy. Starting from the pre-existing heptacoordinated complexes, a series of pentanuclear compounds were obtained by reactions with paramagnetic [W(CN)8 ]3- . Magnetic studies revealed the occurrence of ferromagnetic interactions between the spin carriers in all the heterometallic systems. Field-induced slow magnetic relaxation was observed for mononuclear FeII complexes (Ueff /kB up to 53 K (37 cm-1 ), τ0 =5×10-9  s), and SMM behavior was evidenced for a heteronuclear [Fe3 W2 ] derivative (Ueff /kB =35 K and τ0 =4.6 10-10  s), which confirmed that the parent complexes were robust Ising-type building units. High-field EPR spectroscopic investigation of the ZFS parameters for a Ni derivative is also reported.

Hetero-tri-spin [2p-3d-4f] chain compounds based on nitronyl nitroxide lanthanide metallo-ligands: synthesis, structure, and magnetic properties.

Employing nitronyl nitroxide lanthanide(III) complexes as metallo-ligands allowed the efficient and highly selective preparation of three series of unprecedented hetero-tri-spin (Cu-Ln-radical) one-dimensional compounds. These 2p-3d-4f spin systems, namely [Ln3Cu(hfac)11(NitPhOAll)4] (Ln(III) = Gd 1Gd, Tb 1Tb, Dy 1Dy; NitPhOAll = 2-(4'-allyloxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), [Ln3Cu(hfac)11(NitPhOPr)4] (Ln(III) = Gd 2Gd, Tb 2Tb, Dy 2Dy, Ho 2Ho, Yb 2Yb; NitPhOPr = 2-(4'-propoxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) and [Ln3Cu(hfac)11(NitPhOBz)4] (Ln(III) = Gd 3Gd, Tb 3Tb, Dy 3Dy; NitPhOBz=2-(4'-benzyloxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) involve O-bound nitronyl nitroxide radicals as bridging ligands in chain structures with a [Cu-Nit-Ln-Nit-Ln-Nit-Ln-Nit] repeating unit. The dc magnetic studies show that ferromagnetic metal-radical interactions take place in these hetero-tri-spin chain complexes, these and the next-neighbor interactions have been quantified for the Gd derivatives. Complexes 1Tb and 2Tb exhibit frequency dependence of ac magnetic susceptibilities, indicating single-chain magnet behavior.

Uncovering the Uncommon: Institutional Insights Into the Clinical and Epidemiological Characteristics of Rarer Forms of Bladder Cancer Beyond Transitional Cell Carcinoma.

Introduction Non-transitional cell carcinomas of the bladder (NTCCB) represent a significant clinical challenge due to their rarity, heterogeneity, and poor prognosis. Despite their poor prognosis, the treatment of NTCCB has historically been based on the same principles used for transitional cell carcinomas (TCCs). Our study focuses on the management of non-transitional cell carcinomas and aims to identify areas where treatment outcomes can be improved based on our institutional experience. Materials and methods A retrospective analysis of patients with NTCCB who presented at Kasturba Hospital Manipal was conducted between 2012 to 2021. Patient data were collected, and demographic characteristics, presenting symptoms, history of other primary malignancies, comorbidities, location of the tumour, stage at presentation, histopathological subtype, site of systemic metastasis, and primary treatment given were analyzed descriptively. Median overall survival was determined by calculating the time from the initial diagnosis to the date of death. Results Among 31 patients with NTCCB, 15 (48%) presented with metastatic disease, five (16%) with locally advanced disease, and 11 (36%) with localized disease. The most common histopathological subtypes were squamous cell carcinoma and adenocarcinoma, as noted in 14 (45.2%) and 13 (41.9%) patients, respectively, followed by neuroendocrine tumours in two (6.5%), extra-adrenal phaeochromocytoma in one (3.3%), and sarcomatoid carcinoma in one (3.3%) patient, respectively. The lung was the most frequent site of systemic metastasis as noted in six (40%) patients, followed by the liver and skeletal system in three (20%) patients each, peritoneum in two (13.3%), cerebral cortex in one (6.7%), and non-regional lymph nodes in one (6.7%) patient. The primary treatment given included palliative chemotherapy in 14 (45.2%) patients, radical cystectomy with ileal conduit in 10 (32.3%), neoadjuvant chemotherapy only in four (12.9%), partial cystectomy in one (3.2%), pelvic exenteration with ileal conduit in one (3.2%), and peritoneal debulking with palliative chemotherapy in one (3.2%) patient. The overall median survival was 15 months, with a one-year survival rate of 67.4%. Conclusion NTCCB exhibits aggressive clinical behaviour and presents with nonspecific clinical features in the early stages, often leading to late diagnosis and an advanced tumour stage at presentation. Multi-institutional studies with larger patient cohorts are needed to recommend best clinical practices for early detection and optimal treatment strategies to improve patient survival.

Above-Room-Temperature Ferromagnetism in Thin van der Waals Flakes of Cobalt-Substituted Fe5GeTe2.

Two-dimensional (2D) magnetic van der Waals materials provide a powerful platform for studying the fundamental physics of low-dimensional magnetism, engineering novel magnetic phases, and enabling thin and highly tunable spintronic devices. To realize high-quality and practical devices for such applications, there is a critical need for robust 2D magnets with ordering temperatures above room temperature that can be created via exfoliation. Here, the study of exfoliated flakes of cobalt-substituted Fe5GeTe2 (CFGT) exhibiting magnetism above room temperature is reported. Via quantum magnetic imaging with nitrogen-vacancy centers in diamond, ferromagnetism at room temperature was observed in CFGT flakes as thin as 16 nm corresponding to 16 layers. This result expands the portfolio of thin room-temperature 2D magnet flakes exfoliated from robust single crystals that reach a thickness regime relevant to practical spintronic applications. The Curie temperature Tc of CFGT ranges from 310 K in the thinnest flake studied to 328 K in the bulk. To investigate the prospect of high-temperature monolayer ferromagnetism, Monte Carlo calculations were performed, which predicted a high value of Tc of ∼270 K in CFGT monolayers. Pathways toward further enhancing monolayer Tc are discussed. These results support CFGT as a promising platform for realizing high-quality room-temperature 2D magnet devices.

Design and optimization of film-forming gel of etoricoxib using research surface methodology.

The present investigation is focused on the development of transdermal film-forming gel (FFG) loaded with etoricoxib employing research surface methodology (RSM). Box-Behnken surface design method was used to develop experimental run using different concentrations of etoricoxib, hydroxypropyl methylcellulose (HPMC K100M), and eudragit RL100 as independent variables, and Derringer's optimization tool was employed to optimize best possible formulation. The dependent variables considered in this study were viscosity and drug permeation at 24 h (Q24, µg/cm2). Anti-inflammatory study was performed on Wistar albino rats for 8 h. Skin irritation studies and accelerated stability studies were performed for validated FFG formulations. Quadratic model was found to be best fit model (p < 0.0001) for both the responses. The influence of HPMC concentration on the viscosity was found to be highest whereas concentration of etoricoxib was maximum for Q24. The optimum composition of the FFG was observed to be 4% of etoricoxib, 1.1246% of HPMC, and 0.4% of eudragit. Above composition resulted in viscosity of 1549.5 mPa.s and maximum Q24 of 4639.11 µg/cm2 with desirability 0.918. The in vivo anti-inflammatory study demonstrated better sustained release effect (for 8 h) of optimized FFG compared to orally administered drug suspension. An average irritation score of 0.555 was observed on Draize scoring system. The validated FFG formulation was found to be stable for the 3 months in accelerated conditions. It can be concluded from the above investigations that the validated FFG formulation of etoricoxib is well tolerated and could provide sustained drug release for 8 h. Graphical abstract.

Doppler echocardiographic profiles in obstructive right and left atrial myxomas.

Previous reports have suggested that atrioventricular (AV) flow disturbances accompanying atrial myxomas mimic mitral stenosis. Two patients complaining of orthostatic syncope and positional intolerance had a large right and left atrial myxoma, respectively. Doppler flow records showed abrupt early diastolic flow cessation and normal velocity half-times, unlike AV valve stenosis. Large, obstructing atrial myxomas may behave as ball valves.

Noninvasive evaluation of aortic stenosis severity utilizing Doppler ultrasound and electrical bioimpedance.

Aortic valve area was calculated noninvasively in 30 patients with aortic stenosis undergoing cardiac catheterization. Continuous wave Doppler ultrasound was employed to estimate the mean transvalvular pressure gradient. The mean left ventricular outflow tract flow velocity and cross-sectional area were determined from pulsed Doppler and two-dimensional ultrasound recordings. Electrical transthoracic bioimpedance cardiography performed simultaneously with the ultrasonic study and repeated at the time of catheterization measured heart rate, systolic ejection period and cardiac output. These noninvasive data permitted calculation of aortic valve area using the Gorlin equation (range 0.21 to 1.75 cm2) and the continuity equation (range 0.25 to 1.9 cm2). Subsequent cardiac catheterization showed valve area to range from 0.21 to 1.75 cm2. The mean Doppler pressure gradient estimate was highly predictive of the gradient measured at catheterization (r = +0.92, SEE = 10). Bioimpedance cardiac output measurements agreed with the average of Fick and indicator dye estimates (r = +0.90, SEE = 0.52). Valve area estimates utilizing continuous wave Doppler ultrasound and electrical bioimpedance were superior (r = +0.91, SEE = 0.12) to estimates obtained utilizing the continuity equation (r = +0.76, SEE = 0.29) and were more reliable in the detection of patients with severe aortic stenosis (9 of 11 versus 6 of 11). These data show that 1) electrical bioimpedance methods accurately estimate cardiac output in the presence of aortic stenosis; 2) the hybridized bioimpedance-Doppler ultrasound method yields accurate estimates of aortic stenosis area; and 3) the speed, accuracy and cost-effectiveness of aortic stenosis evaluation may be improved by this hybridized approach.

Religious coping and depression among elderly, hospitalized medically ill men.

OBJECTIVE: The investigators examined the frequency of religious coping among older medical inpatients, the characteristics of those who use it, and the relation between this behavior and depression. METHOD: The subjects were 850 men aged 65 years and over, without psychiatric diagnoses, who were consecutively admitted to the medical or neurological services of a southern Veterans Administration medical center. Religious coping was assessed with a three-item index. Depressive symptoms were assessed by self-rating (the Geriatric Depression Scale) and observer rating (the Hamilton Rating Scale for Depression). RESULTS: One out of every five patients reported that religious thought and/or activity was the most important strategy used to cope with illness. Variables that were associated with religious coping included black race, older age, being retired, religious affiliation, high level of social support, infrequent alcohol use, a prior history of psychiatric problems, and higher cognitive functioning. Depressive symptoms were inversely related to religious coping, an association which persisted after other sociodemographic and health correlates were controlled. When 202 men were reevaluated during their subsequent hospital admissions an average of 6 months later, religious coping was the only baseline variable that predicted lower depression scores at follow-up. CONCLUSIONS: These findings suggest that religious coping is a common behavior that is inversely related to depression in hospitalized elderly men.

Major depressive disorder in hospitalized medically ill patients: an examination of young and elderly male veterans.

OBJECTIVE: To study the epidemiology of depressive disorder in younger and older medical inpatients. DESIGN, PATIENTS, & SETTING: Depressive disorders were examined using the Diagnostic Interview Schedule in 116 young and 332 elderly medically ill men hospitalized in a VA medical center. RESULTS: Major depressive disorder was diagnosed in 22.4% of men under 40 and 13.3% of those age 70 or over; minor depression was found in 18.1% of young and 29.2% of older men. Besides age, other risk factors for major depression were impaired social support, severe medical illness or functional disability in older men, and history of psychiatric problems primarily in younger men; specific medical diagnosis was not a risk factor. Major depression was associated with more severe symptomatology in younger patients; in both age groups, however, symptoms were of prolonged duration and frequently included suicidal thoughts. CONCLUSIONS: Depressive disorder in hospitalized male veterans is common, varies with age, severity of medical illness, degree of social support, and history of psychiatric problems and is associated with considerable psychological morbidity.

Survival and health care utilization in elderly medical inpatients with major depression.

Forty-one elderly medical inpatients with active major depression were matched with nondepressed controls from the same population. Survival and health care utilization were examined during a mean follow-up period of five months. Cases and controls were matched by age, functional status, severity and type of medical illness, and extent of disease. In-hospital mortality was significantly higher among depressed compared with nondepressed controls (6 vs 0 deaths, P = .03). For patients discharged from the hospital alive, however, depression did not have a substantial impact on mortality (31.4% cases, 31.7% controls). Health care utilization--in terms of days of inpatient care--was significantly higher both during the index admission (25 vs 14 days, P less than .005) and during the follow-up period (16 vs 7 days, P less than .05) for depressed patients compared with controls. Hence, older medically ill patients with major depression consume more healthcare resources and experience greater mortality during their initial hospital stay. After discharge, while survival is little affected, excess resource utilization persists among those with depression.

Predictors of response to pain management treatment. The role of family environment and changes in cognitive processes.

OBJECTIVE: The purpose of the present study was to examine factors that influence individual differences in treatment response after multidisciplinary pain management. DESIGN: Pre-post assessment design. PATIENTS: 119 chronic pain inpatients. MAIN MEASURES: Outcome measures included pain report from the McGill Pain Questionnaire, emotional distress from the Symptom Checklist-90 Revised, and activity discomfort from the Activity Discomfort Scale. Process measures included the Family Environment Scale, the Coping Strategies Questionnaire, and the Inventory of Negative Thoughts in Response to Pain. RESULTS: Results indicated that pretreatment family environment, cognitive coping strategies, and negative thinking accounted for small yet significant proportions of the variance in outcome. The proportion of variance accounted for by the changes in cognitive coping and negative thinking was somewhat higher. An increase in pain control and rational thinking was related to decreases in depression and anxiety, pain report, and activity discomfort. Decreases in negative social cognitions were related to decreased depression at posttreatment. CONCLUSIONS: Changes in coping strategies and negative thinking may be important mechanisms related to improvement, or lack of improvement, in a range of outcome measures. Patients from families who are controlling and disorganized, and patients high on negative thinking at pretreatment may represent high-risk groups in need of further individually tailored interventions.

Studies on a frustrated Heisenberg spin chain with alternating ferromagnetic and antiferromagnetic exchanges.

We study Heisenberg spin-1/2 and spin-1 chains with alternating ferromagnetic (J(F)(1)) and antiferromagnetic (J(A)(1)) nearest-neighbor interactions and a ferromagnetic next-nearest-neighbor interaction (J(F)(2)). In this model frustration is present due to the non-zero J(F)(2). The model with site spin s behaves like a Haldane spin chain, with site spin 2s in the limit of vanishing J(F)(2)and large J(F)(1)/J(A)(1). We show that the exact ground state of the model can be found along a line in the parameter space. For fixed J(F)(1), the phase diagram in the space of J(A)(1)-J(F)(2) is determined using numerical techniques complemented by analytical calculations. A number of quantities, including the structure factor, energy gap, entanglement entropy and zero temperature magnetization, are studied to understand the complete phase diagram. An interesting and potentially important feature of this model is that it can exhibit a macroscopic magnetization jump in the presence of a magnetic field; we study this using an effective Hamiltonian.

Quantum phases of dimerized and frustrated Heisenberg spin chains with s = 1/2, 1 and 3/2: an entanglement entropy and fidelity study.

We study here different regions in phase diagrams of the spin-1/2, spin-1 and spin-3/2 one-dimensional antiferromagnetic Heisenberg systems with frustration (next-nearest-neighbor interaction J2) and dimerization (δ). In particular, we analyze the behaviors of the bipartite entanglement entropy and fidelity at the gapless to gapped phase transitions and across the lines separating different phases in the J2-δ plane. All the calculations in this work are based on numerical exact diagonalizations of finite systems.

Exact entanglement studies of strongly correlated systems: role of long-range interactions and symmetries of the system.

We study the bipartite entanglement of strongly correlated systems using exact diagonalization techniques. In particular, we examine how the entanglement changes in the presence of long-range interactions by studying the Pariser-Parr-Pople model with long-range interactions. We compare the results for this model with those obtained for the Hubbard and Heisenberg models with short-range interactions. This study helps us to understand why the density matrix renormalization group (DMRG) technique is so successful even in the presence of long-range interactions. To better understand the behavior of long-range interactions and why the DMRG works well with it, we study the entanglement spectrum of the ground state and a few excited states of finite chains. We also investigate if the symmetry properties of a state vector have any significance in relation to its entanglement. Finally, we make an interesting observation on the entanglement profiles of different states (across the energy spectrum) in comparison with the corresponding profile of the density of states. We use isotropic chains and a molecule with non-Abelian symmetry for these numerical investigations.

Study on clinical presentation of ear and nose foreign bodies.

Ear and nose foreign bodies are common problems affecting the children but adults are not an exception. A prospective study involving 87 patients is undertaken concentrating on presentation of patients with various types of ear or nasal foreign bodies. In the present study common presenting complaints and uncommon presentation scenarios encountered by us like a nasal foreign body with intra cranial complications, an impacted middle ear foreign body with mastoiditis is discussed. The present article emphasizes the need of considering presence of foreign bodies even in the absence of appropriate clinical signs and symptoms suggestive of a foreign body in ear or nose.

Obsessive Compulsive Disorder: Improving prognosis through therapy and drug treatment.

An estimated three to seven million Americans suffer from obsessive compulsive disorder at some time in their lives. Until recently, obsessive compulsive disorder was considered refractory to most treatments. However, recent studies indicate a better prognosis with behavioral therapy, antidepressant medications, or both. Behavioral treatment is generally more effective for compulsions than for obsessions.