Category: Nevin Manimala

ESC Heart Fail. 2021 Mar 17. doi: 10.1002/ehf2.13306. Online ahead of print.

ABSTRACT

AIMS: We applied the restricted mean survival time (RMST) to analyse the survival data reported in the PARADIGM-HT trial in which sacubitril + valsartan was studied in comparison with enalapril in patients with heart failure. The estimates of this parameter were compared with the published values of hazard ratio (HR).

METHODS: Two endpoints were evaluated: a composite of death or hospitalization and cardiovascular death. Our analyses were performed by considering the original follow-up of 41.4 months and on the basis of a lifetime perspective. All statistical calculations were carried out using specific packages developed under the R-platform.

RESULTS: According to our RMST analysis, the results for the composite endpoint in the comparison of sacubitril + valsartan vs. enalapril showed an improvement from 32.9 to 34.2 months (gain of 1.25 months). This result is based on a time horizon of 41.4 months. The results for the cardiovascular mortality endpoint showed a RMST of 37.2 months for sacubitril + valsartan vs. 36.2 for enalapril (gain of 0.96 months). In the two lifetime analyses, the improvements were much more relevant and yielded a gain of 25.8 months for the composite endpoint and 27.6 months for survival free from cardiovascular death.

CONCLUSIONS: Using the data of the PARADIGM-HT trial, our analysis confirmed that the RMST has documented advantages over the HR, particularly when the clinical study is characterized by a long follow-up. The number needed to treat (NNT) has a more specific methodological role and cannot be replaced by the RMST.

PMID:33733623 | DOI:10.1002/ehf2.13306

Allergy Asthma Immunol Res. 2021 May;13(3):420-434. doi: 10.4168/aair.2021.13.3.420.

ABSTRACT

PURPOSE: Minimizing the future risk of asthma exacerbation (AE) is one of the main goals of asthma management. We investigated prognostic factors for risk of severe AE (SAE) in a real-world clinical setting.

METHODS: This is an observational study evaluating subjects who were diagnosed with asthma and treated with anti-asthmatic medications from January 1995 to June 2018. Risk factors for SAE were analyzed in 2 treatment periods (during the initial 2 years and the following 3-10 years of treatment) using the big data of electronic medical records.

RESULTS: In this study, 5,058 adult asthmatics were enrolled; 1,335 (28.64%) experienced ≥ 1 SAE during the initial 2 years of treatment. Female sex, higher peripheral eosinophil/basophil counts, and lower levels of forced expiratory volume in 1 second (FEV1; %) were factors predicting the risk of SAEs (P < 0.001 for all). Higher serum total immunoglobulin E levels increased the risk of SAEs among the patients having ≤ 2 SAEs (P = 0.025). Patients with more frequent SAEs during the initial 2 years of treatment had significantly higher risks of SAEs during the following years of treatment (P < 0.001, for all) (patients with ≥ 4 SAEs, odds ratio [OR], 29.147; those with 3 SAEs, OR, 14.819; those with 2 SAEs, OR, 9.867; those with 1 SAE, OR, 5.116), had higher maintenance doses of systemic steroids, and showed more gradual decline in FEV1 (%) and FEV1/forced vital capacity levels maintained during the following years of treatment (P < 0.001 for all).

CONCLUSIONS: Asthmatics having risk factors for SAEs (female sex, higher peripheral eosinophil/basophil counts, and lower FEV1) should be strictly monitored to prevent future risk and improve clinical outcomes.

PMID:33733637 | DOI:10.4168/aair.2021.13.3.420

Allergy Asthma Immunol Res. 2021 May;13(3):468-478. doi: 10.4168/aair.2021.13.3.468.

ABSTRACT

PURPOSE: Evidence supporting a link between indoor formaldehyde exposure and atopic dermatitis (AD) in humans is limited. The purpose of this longitudinal study was to investigate whether AD symptoms in children could be affected by indoor formaldehyde levels in ordinary households.

METHODS: Fifty-five children with moderate-to-severe AD aged under 18 years were enrolled as a panel. They were followed up from February 2019 through February 2020. Indoor formaldehyde levels of patients’ houses and their AD symptoms were repeatedly measured on a daily basis. The generalized linear mixed model was utilized for statistical analysis. Subdivision analysis was performed by stratifying patients by sex, body mass index, presence of parental allergy, and indoor environments including mold/dampness, temperature, and relative humidity (RH).

RESULTS: A total of 4,789 person-days of AD symptom data were collected. The average concentration of formaldehyde was 13.6 ± 16.4 ppb, with the highest value found in spring (18.1 ± 20.6 ppb). Higher levels of formaldehyde were observed when there was parental smoking, increased indoor temperature over 25.5°C, or RH over 60% (P < 0.0001). When the effect size was compared between each season after controlling for ambient particulate matter, temperature, and RH, an increase in 10 ppb of formaldehyde increased AD symptoms by 79.2% (95% confidence interval [CI], 19.6-168.4) in spring and by 39.9% (95% CI, 14.3-71.2) in summer. AD symptoms in children aged 6-18 years appeared to increase significantly, whereas there was no significant increase in children under 6 years. When indoor temperature was over 25.5°C, an increase in formaldehyde by 10 ppb increased AD symptoms by 17.8% (95% CI, 3.9-33.6).

CONCLUSIONS: Indoor formaldehyde can exacerbate AD symptom in children with moderate-to-severe AD, particularly in spring and summer, even at allowable levels. Thus, minimizing exposure to indoor formaldehyde may be needed for the proper management of AD in children.

PMID:33733640 | DOI:10.4168/aair.2021.13.3.468

Int Wound J. 2021 Mar 17. doi: 10.1111/iwj.13583. Online ahead of print.

ABSTRACT

This study aimed to explore the treatment effect of Z-plasty on a non-healing wound. A total of 72 patients diagnosed with a chronic non-healing wound in Peking University Third Hospital from November 2009 to August 2019 were retrospectively analysed. Among them, 27 patients were treated with Z-plasty, and 45 patients were treated with the general method. Detailed patient information was retrieved from medical records, including age, gender, body mass index (BMI), alcohol, smoking, and comorbidities (diabetes mellitus, hypertension, heart disease). Surgical parameters included operation time and intraoperative blood loss. Wound swelling, epidermal blisters, wound edge colour, and skin temperature at 1 day after surgery were assessed to evaluate the blood supply of the wound. Surgical complications included infection, haematoma, dehiscence, and non-healing within 2 weeks postoperatively. Student t test (for continuous data) and Chi-square test (for categorical data) were conducted to determine the statistical difference. We found no significant differences in age, gender, BMI, alcohol, smoking, and comorbidities between the two groups. Z-plasty did not show any advantages in the surgical time, invasive blood loss, hospital days, and hospitalisation expenses. The incidence of abnormal wound edge colour with Z-plasty was significantly lower than that with the general treatment (P < .05), and the Z-plasty enables better healing of the patient’s wound (P < .05). Z-plasty promoted better recovery of chronic non-healing wounds than direct suturing.

PMID:33733609 | DOI:10.1111/iwj.13583

Matern Child Nutr. 2021 Mar 17:e13165. doi: 10.1111/mcn.13165. Online ahead of print.

ABSTRACT

Rapid household food insecurity (HFI) tracking has been identified as a priority in the context of the COVID-19 pandemic and its aftermath. We report the validation of the Latin American and Caribbean Food Security Scale (Escala Latinoamericana y Caribena de Seguridad Alimentaria [ELCSA]) among pregnant women in Sri Lanka. The eight-item adult version of the ELCSA was translated from English to Sinhala and Tamil. Cognitive testing (on 10 pregnant women and five local experts) and psychometric validation of the self-administered HFI tool were conducted among pregnant women (n = 269) attending the special clinics of the Rajarata Pregnancy Cohort (RaPCo) in Anuradhapura in February 2020. We assessed the psychometric properties and fit using a one parameter logistic model (Rasch model analysis) using STATA Version 14 and WINSTEP software Version 4.3.4. Concurrent validity was tested using psychological distress. The scale was internally consistent (Cronbach’s alpha = 0.79) and had a good model fit (Rasch items infit statistic range: 0.85 to 1.07). Item 8 (‘did not eat for the whole day’) was removed from the model fit analysis, as it was not affirmed by respondent. Item severity scores ranged from -2.15 for ‘not eating a diverse diet’ to 4.43 for ‘not eating during the whole day’. Concurrent validity between HFI and psychological distress was confirmed (r = 0.15, p < 0.05). The self-applied version of ELCSA-pregnancy in Sri Lanka (ELCSA-P-SL) is a valid and feasible valid tool. We recommend it to track HFI among pregnant women in lower income countries during the COVID-19 pandemic.

PMID:33733618 | DOI:10.1111/mcn.13165

J Biophotonics. 2021 Mar 18:e202000377. doi: 10.1002/jbio.202000377. Online ahead of print.

ABSTRACT

Monte Carlo (MC) modeling is a valuable tool to gain fundamental understanding of light-tissue interactions, provide guidance and assessment to optical instrument designs, and help analyze experimental data. It has been a major challenge to efficiently extend MC towards modeling of bulk-tissue Raman spectroscopy (RS) due to the wide spectral range, relatively sharp spectral features, and presence of background autofluorescence. Here, we report a computationally efficient MC approach for RS by adapting the massively-parallel Monte Carlo eXtreme (MCX) simulator. Simulation efficiency is achieved through “isoweight”, a novel approach that combines the statistical generation of Raman scattered and Fluorescence emission with a lookup-table-based technique well-suited for parallelization. The MC model uses a graphics processor to produce dense Raman and fluorescence spectra over a range of 800-2000cm^-1 with an approximately 100x increase in speed over prior RS Monte Carlo methods. The simulated RS signals are compared against experimentally collected spectra from gelatin phantoms, showing a strong correlation. This article is protected by copyright. All rights reserved.

PMID:33733621 | DOI:10.1002/jbio.202000377

Eur J Haematol. 2021 Mar 18. doi: 10.1111/ejh.13624. Online ahead of print.

ABSTRACT

OBJECTIVES: The impact of conventional treatment for acute myeloid leukemia (AML) on the nutritional, cognitive, and functional status of elderly patients is seldom studied. This assessment was performed in the context of the LAMSA 2007 trial.

METHODS: The trial enrolled 424 patients with de novo AML. Among them, 316 benefited from geriatric assessment (GA) including nutritional, cognitive and functional status and were scored according to Eastern Cooperative Oncology Group (ECOG) and SORROR for the prediction of treatment toxicity, morbidity and mortality. Patients were investigated at diagnosis and three times during follow-up.

RESULTS: This study showed that AML and its treatment have no impact on cognitive (p=0.554) nor functional status (p=0.842 for Activity of Daily Living and p=0.087 for Instrumental Activities of Daily Living). The nutritional status improved over time (p=0.041). None of these three parameters at baseline, associated or not with ECOG and SORROR scores, impacted survivals or toxicities.

CONCLUSIONS: The cognitive, functional and nutritional status had no impact in this cohort of fit elderly AML patients without unfavorable cytogenetics. The GA tools used provided no additional information compared to ECOG and SORROR scores, to predict toxicity, morbidity, or mortality due to intensive chemotherapy.

PMID:33733520 | DOI:10.1111/ejh.13624

J Neuroendocrinol. 2021 Mar;33(3):e12963. doi: 10.1111/jne.12963.

ABSTRACT

Oxytocin (OT) is a neuropeptide hormone. Single and repetitive administration of OT increases social interaction and maternal behaviour in humans and mammals. Recently, it was found that the receptor for advanced glycation end-products (RAGE) is an OT-binding protein and plays a critical role in the uptake of OT to the brain after peripheral OT administration. Here, we address some unanswered questions on RAGE-dependent OT transport. First, we found that, after intranasal OT administration, the OT concentration increased in the extracellular space of the medial prefrontal cortex (mPFC) of wild-type male mice, as measured by push-pull microperfusion. No increase of OT in the mPFC was observed in RAGE knockout male mice. Second, in a reconstituted in vitro blood-brain barrier system, inclusion of the soluble form of RAGE (endogenous secretory RAGE [esRAGE]), an alternative splicing variant, in the luminal (blood) side had no effect on the transport of OT to the abluminal (brain) chamber. Third, OT concentrations in the cerebrospinal fluid after i.p. OT injection were slightly higher in male mice overexpressing esRAGE (esRAGE transgenic) compared to those in wild-type male mice, although this did not reach statistical significance. Although more extensive confirmation is necessary because of the small number of experiments in the present study, the reported data support the hypothesis that RAGE may be involved in the transport of OT to the mPFC from the circulation. These results suggest that the soluble form of RAGE in the plasma does not function as a decoy in vitro.

PMID:33733541 | DOI:10.1111/jne.12963

Crim Behav Ment Health. 2021 Mar 18. doi: 10.1002/cbm.2191. Online ahead of print.

ABSTRACT

BACKGROUND: Previous research with non-offenders has linked a higher dispositional cognition of hope to lower levels of psychological symptoms and demonstrated mediating effects of attentional biases on the relationship between hope and psychological symptoms, but this has not been explored among offenders.

AIMS: Our aim was to investigate associations between a dispositional cognition of hope and habitual attentional processing styles and distress among women in prison. We hypothesised that higher levels of hope would be associated with more attention to positive information and less to negative information in the surroundings and, in turn, lower levels of depression, anxiety and stress symptoms in women in prison.

METHOD: In a cross-sectional study, we recruited consenting women serving a prison sentence who had been referred to psychological services. Participants completed a set of self-rating inventories individually, which scaled their levels of hope, attention to positive and negative information and symptoms of anxiety, stress and depression.

RESULTS: Two hundred and three women participated. Their average age was 35.68 years (range 21-67 years). Over half were recidivists (170, 58%). Overall, the higher the level of hope they had, the lower were the ratings of their psychological symptoms. Positive attentional bias was associated with higher hope and lower psychological distress. In contrast, negative attentional bias was related to lower hope and higher psychological distress ratings. In statistical models, both attentional biases appeared to be partial mediators of the relationship between hope and psychological distress.

CONCLUSIONS: Our findings among women in prison were consistent with those in non-forensic populations and not previously studied among prisoners. They suggest that it would be worth evaluating interventions to modify attentional styles as they may have value in increasing hope and reducing psychological symptoms and perhaps also harmful behaviours in this vulnerable population.

PMID:33733563 | DOI:10.1002/cbm.2191

Addict Biol. 2021 Mar 17:e13030. doi: 10.1111/adb.13030. Online ahead of print.

ABSTRACT

Cannabis use is associated with a number of psychiatric disorders; however, the causal nature of these associations has been difficult to establish. Mendelian randomization (MR) offers a way to infer causality between exposures with known genetic predictors (genome-wide significant single nucleotide polymorphisms [SNPs]) and outcomes of interest. MR has previously been applied to investigate the relationship between lifetime cannabis use (having ever used cannabis) and schizophrenia, depression, and attention deficit hyperactivity disorder (ADHD), but not bipolar disorder, representing a gap in the literature. We conducted a two-sample bidirectional MR study on the relationship between bipolar disorder and lifetime cannabis use. Genetic instruments (SNPs) were obtained from the summary statistics of recent large genome-wide association studies (GWAS). We conducted a two-sample bidirectional MR study on the relationship between bipolar disorder and lifetime cannabis use using inverse variance weighted regression, weighted median regression, and Egger regression. Genetic liability to bipolar disorder was significantly associated with an increased risk of lifetime cannabis use; however, genetic liability to lifetime cannabis use showed no association with the risk of bipolar disorder. The sensitivity analyses showed no evidence for pleiotropic effects. The present findings support a causal effect of liability to bipolar disorder on the risk of using cannabis at least once. No evidence was found for a causal effect of liability to cannabis use on the risk of bipolar disorder. These findings add important new knowledge to the understanding of the complex relationship between cannabis use and psychiatric disorders.

PMID:33733564 | DOI:10.1111/adb.13030