Nevin Manimala

Circulation. 2022 Jun 28:101161CIRCULATIONAHA122059785. doi: 10.1161/CIRCULATIONAHA.122.059785. Online ahead of print.

ABSTRACT

BACKGROUND: Empagliflozin improves outcomes in patients with heart failure with a preserved ejection fraction, but whether the effects are consistent in patients with and without diabetes remains to be elucidated.

METHODS: Patients with class II through IV heart failure and a left ventricular ejection fraction >40% were randomized to receive empagliflozin 10 mg or placebo in addition to usual therapy. We undertook a prespecified analysis comparing the effects of empagliflozin versus placebo in patients with and without diabetes.

RESULTS: Of the 5988 patients enrolled, 2938 (49%) had diabetes. The risk of the primary outcome (first hospitalization for heart failure or cardiovascular death), total hospitalizations for heart failure, and estimated glomerular filtration rate decline was higher in patients with diabetes. Empagliflozin reduced the rate of the primary outcome irrespective of diabetes status (hazard ratio, 0.79 [95% CI, 0.67, 0.94] for patients with diabetes versus hazard ratio, 0.78 [95% CI, 0.64, 0.95] in patients without diabetes; P_interaction=0.92). The effect of empagliflozin to reduce total hospitalizations for heart failure was also consistent in patients with and without diabetes. The effect of empagliflozin to attenuate estimated glomerular filtration rate decline during double-blind treatment was also present in patients with and without diabetes, although more pronounced in patients with diabetes (1.77 in diabetes versus 0.98 mL/min per 1.73 m² in patients without diabetes; P_interaction=0.01). Across these 3 end points, the effect of empagliflozin did not differ in patients with prediabetes or normoglycemia (33% and 18% of the patient population, respectively). When investigated as a continuous variable, baseline hemoglobin A1c did not modify the effects on the primary outcome (P_interaction=0.26). There was no increased risk of hypoglycemic events in either subgroup as compared with placebo.

CONCLUSIONS: In patients with heart failure and a preserved ejection fraction enrolled in EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), empagliflozin significantly reduced the risk of heart failure outcomes irrespective of diabetes status at baseline.

REGISTRATION: URL: https://www.

CLINICALTRIALS: gov; Unique identifier: NCT03057951.

PMID:35762322 | DOI:10.1161/CIRCULATIONAHA.122.059785

Dermatol Ther. 2022 Jun 28:e15668. doi: 10.1111/dth.15668. Online ahead of print.

ABSTRACT

BACKGROUND: Striae Distensae (SD) are quite common complaint in dermatology practice. They are linear lesions of variable length and width according to the site and the causative condition. Several treatment modalities have been tried. To achieve satisfactory results, a combination therapy is often needed.

OBJECTIVES: To evaluate the efficacy and safety of fractional CO₂ laser versus carboxytherapy in the treatment of Striae Distensae clinically and radiologically.

METHODS: Thirty Egyptian patients with striae distensae, received a split body therapy: the left side was treated by fractional CO₂ laser and the right side was treated by carboxytherapy in the same session. Six sessions were done with 4 weeks apart. Clinical evaluation by measurement of the width of widest striae on both sides, global aesthetic improvement scale (GAIS) and Likert satisfaction scale. Radiological evaluation by measurement of cutaneous thickness of widest striae on both sides by ultrasonography.

RESULTS: There was a highly statistically significant decrease in the median width of the widest striae distensae on both sides after the last session (P < 0.01). Regarding GAIS, satisfaction scale and ultrasound, there was highly statistically significant improvement on laser side than carboxytherapy side (P < 0.01) after last session.

CONCLUSION: Both fractional CO₂ laser and carboxytherapy may be considered as safe and effective lines of treatment for striae distensae, but fractional CO₂ laser showed excellent improvement clinically, radiologically when compared with carboxytherapy which made it a promising module in treatment of striae distensae. This article is protected by copyright. All rights reserved.

PMID:35762297 | DOI:10.1111/dth.15668

Epigenomics. 2022 Jun 28. doi: 10.2217/epi-2022-0055. Online ahead of print.

ABSTRACT

Aim: We systematically reviewed and evaluated current literature on alcohol consumption and DNA methylation (DNAm) at the genome-wide and probe-wise level in blood of adults. Materials & methods: Five databases (PubMed, Embase, Web of Science, CINAHL and PsycInfo) were searched until 20 December 2020. Studies assessing the effect of alcohol dependence on DNAm were not eligible. Results: 11 cross-sectional studies were included with 88 to 9643 participants. Overall, all studies had a risk of bias criteria unclear or unmet. Epigenome-wide association studies identified between 0 and 5458 differentially methylated positions, and 15 were observed in at least four studies. Conclusion: Potential methylation markers for alcohol consumption have been identified, but further validation in large cohorts is needed.

PMID:35762294 | DOI:10.2217/epi-2022-0055

Liver Int. 2022 Jun 28. doi: 10.1111/liv.15348. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: The immunologic features involved in the immune-tolerant phase of chronic hepatitis B (CHB) virus (HBV) infection are unclear. The hepatitis B virus X (HBx) protein disrupts IFN-β induction by downregulating MAVS and may destroy subsequent HBV-specific adaptive immunity. We aimed to analyze the impacts of genetic variability of HBx in CHB patients on the immune-tolerant phase during long-term follow-up.

METHODS: Children with CHB in the immune-tolerant phase were recruited and followed longitudinally. HBx gene sequencing of infecting HBV strains was performed, and the effects of HBx mutations on the immune-tolerant phase were assessed. Restoration of the host immune response to end the immune-tolerant phase was investigated by immunoblotting, immunostaining, ELISA and reporter assays of MAVS/IFN-β signaling in liver cell lines, patient liver tissues and the HBV plasmid replication system.

RESULTS: A total of 173 children (median age, 6.92 years) were recruited. Patients carrying HBx R87G, I127V, and R87G+I127V double mutations exhibited higher cumulative incidences of immune-tolerant phase breakthrough (p=0.011, p=0.006, and p=0.017, respectively). Cells transfected with HBx R87G and I127V mutants and pHBV1.3-B6.3 replicons containing the HBx R87G and I127V mutations exhibited statistically increased level of IFN-β, especially under poly(I:C) stimulation or Flag-MAVS cotransfection. HA-HBx wild-type interacted with Flag-MAVS and enhanced its ubiquitination, but this ability was diminished in the R87G and I127V mutants.

CONCLUSIONS: HBx suppresses IFN-β induction. R87G and I127V mutation restored IFN-β production by preventing MAVS degradation, contributing to curtailing the HBV immune-tolerant phase in CHB patients.

PMID:35762289 | DOI:10.1111/liv.15348

Eur J Pain. 2022 Jun 28. doi: 10.1002/ejp.1998. Online ahead of print.

ABSTRACT

BACKGROUND: For pediatric chronic pain patients, intensive interdisciplinary pain treatment (IIPT) is a well-established treatment. The treatment’s short-term effectiveness can be improved by an additive psychosocial aftercare (PAC). However, neither the program’s long-term effectiveness nor the patients in particular need have been investigated yet.

METHODS: This study aimed at determining the long-term effects of PAC and detecting predictors of treatment outcome within a multicenter randomized controlled trial measured at five time points up to twelve months after discharge. At inpatient admission to IIPT, patients (N=419, 14.3 years of age, 72.3% female) were randomly assigned to intervention or control group. After IIPT discharge, the intervention group received PAC, whereas the control group received treatment as usual (TAU). Patient-reported outcomes included pain and emotional characteristics. Clinicians assessed potential psychosocial risk factors and their prognosis of treatment outcome. Statistical analyses included mixed-models and univariable logistic regressions.

RESULTS: Data at the 12-month follow-up (n=288) showed a significant benefit of PAC compared with TAU; the majority (59.0%) of patients in the PAC-group reported no chronic pain compared to 29.2% of TAU-patients (p<.001). Patients with a single parent specifically benefited from PAC compared to TAU. Clinicians were able to make a reliable prognosis of treatment outcome, but did not successfully predict which patients would benefit the most from PAC.

CONCLUSIONS: Study results suggest that PAC is highly effective irrespective of patient characteristics, but particularly for patients with single parents. Its broad implementation could help to improve the long-term outcomes of youth with severely disabling chronic pain.

PMID:35762280 | DOI:10.1002/ejp.1998

BJU Int. 2022 Jun 28. doi: 10.1111/bju.15839. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop a nomogram that could predict spontaneous stone passage (SSP) in patients presenting with acute ureteric colic who are suitable for conservative management.

SUBJECT/PATIENTS: A 2517 patient dataset was utilised from an international multi-centre cohort study (MIMIC, A Multi-centre Cohort Study Evaluating the role of Inflammatory Markers In Patients Presenting with Acute Ureteric Colic) of patients presenting with acute ureteric colic across 71 secondary care hospitals in the United Kingdom, Ireland, Australia, and New Zealand. Inclusion criteria mandated a non-contrast CT-KUB.

METHODS: SSP was defined as the ‘absence of the need for intervention’. The model was developed using logistic regression and backwards selection (to achieve lowest AIC) in a subset from 2009-2015 (n=1728) and temporally validated on a subset from 2016-2017 (n=789).

RESULTS: Of the 2517 patients, 1874 had SSP (74.5%). Mean age (±[SD]) was 47 (±14.7) years and 1892 were male (75.2%). At the end of the modelling process, gender: male (OR 0.8, 95%CI 0.64-1.01, p=0.07), neutrophil count (OR 1.03, 95%CI 1.00-1.06, p = 0.08), hydronephrosis (OR 0.79, 95%CI 0.59-1.05, p=0.1), hydroureter (OR 1.3, 95%CI 0.97-1.75, p =0.08), stone size >5-7mm (OR 0.2, 95%CI 0.16-0.25, p<0.0001), stone size >7mm (OR 0.11, 95%CI 0.08-0.15, p<0.001), middle ureter stone position (OR 0.59, 95%CI 0.43-0.81, p=0.001), upper ureter stone position (OR 0.31, 95%CI 0.25-0.39, p<0.001) ), medical expulsive therapy use (OR 1.36, 95%CI 1.1 – 1.67, p = 0.001), oral NSAID use (OR 1.3, 95%CI 0.99 – 1.71, p=0.06), and rectal NSAID use (OR1.17, 95%CI 0.9 – 1.53, p=0.24) remained. Concordance-statistic (C-statistic) was 0.77 (95%CI 0.75 – 0.80) and a nomogram was developed based on these.

CONCLUSION: The presented nomogram is available to use as an online calculator via www.BURSTurology.com and could allow clinicians and patients to make a more informed decision on pursuing conservative management versus early intervention.

PMID:35762278 | DOI:10.1111/bju.15839

Cytometry A. 2022 Jun 28. doi: 10.1002/cyto.a.24666. Online ahead of print.

NO ABSTRACT

PMID:35762261 | DOI:10.1002/cyto.a.24666

Biometrics. 2022 Jun 28. doi: 10.1111/biom.13710. Online ahead of print.

ABSTRACT

Randomized clinical trials with time-to-event endpoints are frequently stopped after a pre-specified number of events has been observed. This practice leads to dependent data and non-random censoring, which can in general not be solved by conditioning on the underlying baseline information. In case of staggered study entry, matters are complicated substantially. The present paper demonstrates that the study design at hand entails general independent censoring in the counting process sense, provided that the analysis is based on study time information only. To illustrate that the filtrations must not use abundant information, we simulated data of event-driven trials and evaluated them by means of Cox regression models with covariates for the calendar times. The Breslow curves of the cumulative baseline hazard showed considerable deviations, which implies that the analysis is disturbed by conditioning on the calendar time variables. A second simulation study further revealed that Efron’s classical bootstrap, unlike the (martingale-based) wild bootstrap, may lead to biased results in the given setting, as the assumption of random censoring is violated. This is exemplified by an analysis of data on immunotherapy in patients with advanced, previously treated non-small cell lung cancer.

PMID:35762259 | DOI:10.1111/biom.13710

Indoor Air. 2022 Jun;32(6):e13065. doi: 10.1111/ina.13065.

ABSTRACT

Heating and cooling requirement differences across climates not only have carbon emissions and energy efficiency implications but also impact indoor air quality (IAQ) and health. Energy and IAQ building simulation models help understand tradeoffs or co-benefits, but these have not been applied to evaluate climate zone or multi-family home differences. We modeled a four-story multi-family home in six U.S. climate zones and quantified energy, IAQ, and health outcomes with EnergyPlus, CONTAM, and a pediatric asthma systems science model. Pollutant sources included cooking and ambient. Outputs were daily PM_2.5 and NO₂ indoor concentrations, infiltration, energy for heating and cooling, and asthma exacerbations, which were compared across climate zones, apartment units, and resident behaviors. Daily ambient-sourced PM_2.5 decreased and cooking-sourced PM_2.5 increased with higher ambient temperatures. Infiltration air changes per hour were higher on the first versus the fourth floor and in colder climates. Window opening during cooking led to decreases in total pollutant concentrations (11%-18% for PM_2.5 and 9%-15% for NO₂ ), 3%-4% decreases in asthma exacerbations within climate zones, and minimal impacts on cooling, but led to increased heating demand (4%-8%). Our results demonstrate the influence of meteorology, multi-family building characteristics, and resident behavior on IAQ, energy, and health, focused on multi-zone methodology.

PMID:35762242 | DOI:10.1111/ina.13065

Indoor Air. 2022 Jun;32(6):e13069. doi: 10.1111/ina.13069.

ABSTRACT

Secondhand smoke (SHS) remains a common health threat in densely populated, urban settings. We estimated the prevalence of exposure and associated respiratory symptoms, knowledge, attitudes, and behaviors in a multi-ethnic, weighted sample of Singapore residents using a cross-sectional survey of 1806 adults. We weighted data to match the national population in terms of gender, ethnicity, and education level and analyzed data using descriptive statistics, bivariate analyses, multiple linear and logistic regressions, and a multinomial logistic regression model. About 88% of respondents reported regular SHS exposure. Nearly 57% reported exposure to neighbors’ SHS at home. Respiratory symptoms were reported by 32.5% and significantly associated with exposure to daily (AOR = 2.63, 95% CI = 1.62-4.36), non-daily (AOR = 1.75, 95% CI = 1.14-2.77), and neighbors’ (AOR = 1.37, 95% CI = 1.07-1.76) SHS. More knowledge of SHS was associated with male gender (β = 0.28, p = 0.0009) and higher household income (linear trend; p = 0.0400). More negative attitudes to SHS were associated with older age (linear trend; p < 0.0001). Engaging in behaviors to avoid SHS was associated with a more negative attitude to SHS (AOR = 1.09-1.23). SHS exposure is common in Singapore’s densely populated setting and associated with respiratory symptoms, even if exposure is non-daily or from neighboring homes.

PMID:35762238 | DOI:10.1111/ina.13069