Nevin Manimala

Eur J Heart Fail. 2021 Dec 10. doi: 10.1002/ejhf.2397. Online ahead of print.

ABSTRACT

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been recently recommended as a foundational therapy for patients with heart failure (HF) and reduced ejection fraction (HFrEF) because of their favourable effects on mortality, clinical events and quality of life. While clinical practice guidelines have recommended the use of dapagliflozin and empagliflozin regardless of diabetes history in patients with HFrEF, or sotagliflozin in those with HFrEF and concomitant type 2 diabetes mellitus (T2DM), the timing and practical integration of this class of therapies in practice is less well defined. We propose that these drugs are candidates for early, upfront administration to patients with newly diagnosed HFrEF and for patients hospitalized with HF. Growing evidence has established early benefits, with clinically meaningful reductions in clinical events that reach statistical significance within days to weeks, following dapagliflozin, empagliflozin or, in diabetic patients, sotagliflozin initiation. Secondly, although major clinical trials have tested these drugs in patients already receiving background HF therapy, secondary analyses showed that their efficacy is independent of that. Third, SGLT2 inhibitors are generally safe and well tolerated, with clinical trial data reporting minimal effects on blood pressure, glycaemia-related adverse events, and no excess in acute kidney injury. Rather, they exert renal protective effects and reduce risk of hyperkalaemia, properties that favour initiation, tolerance and persistence of renin-angiotensin-system inhibitors and mineralocorticoid receptor antagonists. This review, therefore, supports the early initiation of dapagliflozin and empagliflozin (or sotagliflozin limited to patients with T2DM) to rapidly improve clinical outcome and quality of life of HFrEF patients.

PMID:34894038 | DOI:10.1002/ejhf.2397

Wound Repair Regen. 2021 Dec 11. doi: 10.1111/wrr.12987. Online ahead of print.

ABSTRACT

Adjuvants to compression are sought for treating venous ulceration. There is animal, observational and trial evidence that suggests statins increase venous ulcer healing. The objective of this study was to conduct secondary analyses investigating the association of statin use with healing in three randomised trials that recruited people with venous ulceration. The difference in healing rates was modest but higher in the statins group. Crude analyses found no significant difference between the groups, but when adjusted for the trial effect and potential confounders (age, diabetes, first ever ulcer, ulcer area and ulcer duration), significantly more participants healed among those taking statins. The analyses were robust to method of analysis (fixed effects or random effects models). A definitive trial is required to evaluate the effect of statins versus placebo on venous ulcer healing, but until then patients needing to take statins seem unlikely to be disadvantaged by this treatment.

PMID:34894034 | DOI:10.1111/wrr.12987

Microsc Res Tech. 2021 Dec 10. doi: 10.1002/jemt.24010. Online ahead of print.

ABSTRACT

The pollen morphology, with special reference to exine sculpture, of some species of the gymnosperms was assessed for the first time from the subalpine and alpine zones of western Himalayas northern Pakistan. The pollen of all these species is airborne and allergenic, so pollen morphology helps for identification of this allergenic pollen at specific level. Different morpho-palynological characteristics were analyzed including size range of pollen, polar and equatorial diameter ratio, exine ornamentation, sculpturing, exine thickness, pollen type, and shape. For accurate and quick identification of species, taxonomic key was made based on different morpho-palynological characteristics. The quantitative data were processed using SPSS software. Gymnospermal pollen includes inaperturate, rarely 1-colpate observed in (Cupressaceae), hexazonocolpate in (Ephedraceae), vesiculate, bissacate in (Pinaceae), and inaperturate in (Taxaceae). Different pollen shapes observed were prolate (4 spp), sub-spheroidal (7 spp), and oblate (1 spp). Variation was observed in exine sculpturing granular (4 spp), reticulate (1 spp), areolate-punctate (3 spp), and psilate (2 spp). This is based on the analysis of 10 plants belonging to four families of gymnosperms. Distinct pollen shape has emerged as the most diagnostic feature to separate some genera such as spheroidal in (Cupressaceae, Taxaceae), prolate and radiosymmetrical in (Ephedraceae), and bilateral in (Pinaceae). Exine thickness and sculpturing proved to be helpful at generic and specific levels. The results reinforced the significance of gymnospermal pollen morphological features which were used as aid for valuable taxonomic tool in plant systematics.

PMID:34894029 | DOI:10.1002/jemt.24010

Psychogeriatrics. 2021 Dec 11. doi: 10.1111/psyg.12795. Online ahead of print.

ABSTRACT

BACKGROUND: Age-related changes in cognitive and behavioural functions, although common, may vary considerably across individuals and cognitive domains. There is limited evidence focusing on the benefits of training based on cognitive/social learning principles in the elderly. The aim of this study is to investigate the effects of Assertive Social Skill Training (ASST) in improving cognitive and mood outcomes in a sample of older patients living in a Sicilian nursing home.

METHODS: Forty-seven older subjects were enrolled in this case-control study. Each participant was evaluated by a neuropsychologist, through the administration of a short psychometric battery using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Geriatric Depression Scale (GDS), at three time points: before (T0), immediately following (T1), and 6 months after the end of the training (T2). Both groups received cognitive behavioural therapy and psychological support, but the experimental group received the ASST protocol (60 sessions, five times a week, for 12 weeks, each session lasting about 60 min), whilst the control group participated in group meetings with recreational activities.

RESULTS: Post-hoc analysis showed that only patients receiving ASST presented a statistically significant improvement in global cognitive functions (MMSE: P < 0.001), frontal abilities (FAB: P < 0.001), and mood (GDS: P < 0.001); these positive outcomes were maintained at T2.

CONCLUSIONS: Promising treatments, like the ASST, aimed at potentiating cognitive, behavioural, and social skills, are needed to improve older people’s quality of life, especially when they live in nursing homes.

PMID:34894028 | DOI:10.1111/psyg.12795

J Gastrointest Cancer. 2021 Dec 10. doi: 10.1007/s12029-021-00779-8. Online ahead of print.

ABSTRACT

BACKGROUND: Some quality indicators of proper health care in patients with colorectal cancer have been established.

AIMS: Our goal was to evaluate the relationship between performing of certain procedures or treatments, included as quality indicators, and some outcomes of indicators in the follow-up of colorectal cancer patients.

METHODS: This was a prospective cohort study of patients diagnosed with colorectal cancer that underwent surgery and were followed at 1, 2, 3, and 5 years. CT scanning, colonoscopy, chemotherapy, and radiotherapy were evaluated in relation to various clinical outcomes and PROM changes over 5 years. Multivariable generalized linear mixed models were used to evaluate their effect on mortality, complications, recurrence, and PROM changes (HAD, EQ-5D, EORTC-Q30) at the next follow-up.

RESULTS: CT scanning or colonoscopy was related to a decrease in the risk of dying, while chemotherapy at a specified moment was related to an increased risk. In the case of recurrence, CT scanning and chemotherapy showed statistically increased the risk, while all the procedures and treatments influenced complications. Regarding PROM scales, CT scanning, colonoscopy, and radiotherapy showed statistically significant results with respect to an increase in anxiety and decrease in quality of life measured by the EORTC. However, undergoing radiotherapy at a specified moment increased depression levels, and overall, receiving radiotherapy decreased the quality of life of the patients, as measured by the EuroQol-5d.

CONCLUSIONS: After adjustment for sociodemographic factors, comorbidities, and severity of the disease, performing certain quality indicators of proper health care in patients with colorectal cancer was related to less mortality but higher adverse outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02488161.

PMID:34893952 | DOI:10.1007/s12029-021-00779-8

Environ Monit Assess. 2021 Dec 10;194(1):21. doi: 10.1007/s10661-021-09671-1.

ABSTRACT

This study supplements previous research focused on environmental condition in the vicinity of waste ash material. The main aim of our study was the comparative analysis of lead levels in soil, plant, and animal organisms in the area of the tailings pond and surroundings, using x-ray. Findings confirm that the level of Pb in the top layer of soil is in the range of 20-135 ppm. Lead content in Calamagrostis plant tissues was confirmed only at the tailings pond area, with the highest lead concentrations measured in above-ground components; stems with blooms followed by roots and ground floor sheats. The livers, kidneys, and hearts of Apodemus flavicollis were examined, with findings of higher values in the tailings pond area than in the reference site, and average values of 14.5 ppm for livers, 16.0 ppm for kidneys, and 16.6 ppm for hearts. No significant differences were discovered based on sex and body length/body weight of A. flavicollis individuals. Values for Bombina variegata liver tissue reached an average of 12.3 ppm for individuals caught in a water reservoir without ash sediments, versus 15.7 ppm in those trapped by the edge of then tailings pond area. Females had lower concentrations of lead than males, but with no statistically significant differences found. Despite lower lead levels in soil and ash than expected, concentrations in mammalian and amphibian organs suggest a possible transition of this element into the food chain, and therefore further research in this area is recommended.

PMID:34893947 | DOI:10.1007/s10661-021-09671-1

AAPS J. 2021 Dec 10;24(1):11. doi: 10.1208/s12248-021-00660-3.

ABSTRACT

We developed an integrated population pharmacokinetic model to investigate loncastuximab tesirine pharmacokinetics (PK) and exposure-response relationships for relapsed/refractory B cell non-Hodgkin lymphoma, including diffuse large B cell lymphoma (DLBCL). The model, based on the recommended dosing schedule (150 µg/kg every 3 weeks [Q3W] for 2 cycles; 75 µg/kg Q3W thereafter) and drug concentrations in phase 1 and 2 studies (DLBCL [n = 284], non-DLBCL [n = 44]), was used to characterize loncastuximab tesirine PK and evaluate exposure covariates. Relationships between exposure (pyrrolobenzodiazepine-conjugated antibody [cAb] cycle 1 average concentration) and (1) efficacy (including overall response rate [ORR; primary endpoint] and overall survival [OS]) and (2) grade ≥ 2 treatment-emergent adverse events were explored. Statistical analyses included univariate and multivariate logistic regression, Kaplan-Meier analysis, and Cox proportional hazard regression. cAb and total Ab were best described by a two-compartment linear model with time-dependent clearance. The cAb steady-state half-life increased to 20.6 days by ~ 15 weeks. cAb exposure was lower for low albumin, mild/moderate hepatic impairment, non-DLBCL subtypes, and Eastern Cooperative Oncology Group scores > 1. Significant positive associations were reported between exposure and ORR (p = 3.21E-6), OS (p = 0.0016), grade ≥ 2 increased gamma-glutamyltransferase, liver function test abnormalities, pain, and skin/nail reactions (p < 0.05). Low albumin, bulky disease, and mild/moderate hepatic impairment had a significant negative effect on OS (p < 0.01). Modeling supports the recommended loncastuximab tesirine dosing schedule. Although reduced exposure and efficacy were predicted for specific covariates (e.g., low albumin, mild/moderate hepatic impairment), dose increases are not recommended. Trial registration: NCT02669017 and NCT03589469.

PMID:34893942 | DOI:10.1208/s12248-021-00660-3

Clin Oral Investig. 2021 Dec 10. doi: 10.1007/s00784-021-04338-0. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the effectiveness of different fiber post removal techniques and to correlate dentinal loss with microcrack formation.

MATERIALS AND METHODS: Forty-five extracted single-rooted teeth were root canal treated and fiber posts were adhesively luted. Specimens were divided into three groups (n = 15) according to the removal technique: long-shaft round bur (EndoTracer #08, Komet, Lemgo, Germany), SonicFlex Endo (KaVo, Biberach, Germany), DT Post Removal Kit (VDW, Munich, Germany). Roots were scanned before post cementation and after post removal using micro-computed tomography. Dentin loss, residual luting material, working time, and the induction of microcracks were assessed. Statistical analysis was performed by using multiple contrast tests (max-t tests, α = 0.05). Correlations between parameters dentin loss/new microcracks and dentin loss/residual material were calculated using Kendall’s tau.

RESULTS: Post removal with SonicFlex Endo resulted in the highest amount of removed dentin with significant differences to the round bur and the DT Post Removal Kit. No technique was found to completely remove the post and luting material. All techniques induced microcracks with the DT Post Removal Kit presenting the highest number of new defects. No correlation between dentin loss and new microcracks was observed. Deviations from the original root canal occurred in all groups, but no perforation was observed.

CONCLUSIONS: All techniques resulted in dentin loss, residual luting material, and the formation of microcracks. However, no correlation between dentin loss and the induction of microcracks was observed.

CLINICAL RELEVANCE: As all techniques resulted in microcrack formation and dentin loss, this study emphasizes the risk of iatrogenic damage due to post removal procedures.

PMID:34893941 | DOI:10.1007/s00784-021-04338-0

Arch Osteoporos. 2021 Dec 10;17(1):4. doi: 10.1007/s11657-021-01046-w.

ABSTRACT

PURPOSE: To investigate the time and effort needed to perform vertebral morphometry, as well as inter-observer agreement for identification of vertebral fractures on vertebral fracture assessment (VFA) images.

METHODS: Ninety-six images were retrospectively selected, and three radiographers independently performed semi-automatic 6-point morphometry. Fractures were identified and graded using the Genant classification. Time needed to annotate each image was recorded, and reader fatigue was assessed using a modified Simulator Sickness Questionnaire (SSQ). Inter-observer agreement was assessed per-patient and per-vertebra for detecting fractures of all grades (grades 1-3) and for grade 2 and 3 fractures using the kappa statistic. Variability in measured vertebral height was evaluated using the intraclass correlation coefficient (ICC).

RESULTS: Per-patient agreement was 0.59 for grades 1-3 fracture detection, and 0.65 for grades 2-3 only. Agreement for per-vertebra fracture classification was 0.92. Vertebral height measurements had an ICC of 0.96. Time needed to annotate VFA images ranged between 91 and 540 s, with a mean annotation time of 259 s. Mean SSQ scores were significantly lower at the start of a reading session (1.29; 95% CI: 0.81-1.77) compared to the end of a session (3.25; 95% CI: 2.60-3.90; p < 0.001).

CONCLUSION: Agreement for detection of patients with vertebral fractures was only moderate, and vertebral morphometry requires substantial time investment. This indicates that there is a potential benefit for automating VFA, both in improving inter-observer agreement and in decreasing reading time and burden on readers.

PMID:34893935 | DOI:10.1007/s11657-021-01046-w

Eur Arch Otorhinolaryngol. 2021 Dec 10. doi: 10.1007/s00405-021-07209-2. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of the study was to determine the influence of oral, oropharyngeal, laryngeal and hypopharyngeal dysplasia and cancer diagnosis on motivation to smoking cessation in patients. Consecutively, we assessed the competence of ENT specialists in counseling anti-smoking therapies.

METHODS: Questionnaire of expected support, Schneider motivation test and Fagerström Test for Nicotine Dependence (FTND) were administered to 50 smoking patients. The online survey was collected from 152 ENT doctors.

RESULTS: Mean FTND score was 4.58 and Heaviness of Smoking Index (HSI) was 3.1. Patients with oral cavity and oropharyngeal cancer showed the greatest dependence to nicotine 7.67 and 5.25, respectively, and with hypopharyngeal cancer had the lowest 3.5, (p = 0.039). The ranges of HSI were significantly higher for younger patients (p = 0.036). 35 patients were adequately motivated to quit smoking, and their mean age was statistically higher (p = 0.05). Self-reported motivation to smoking cessation was 76%. Of 152 surveyed doctors, only 39% declared knowledge of the diagnostic and therapeutic cessation interventions. 75% showed interest in the training programs.

PMID:34893934 | DOI:10.1007/s00405-021-07209-2