Category: Nevin Manimala

AIDS. 2021 Apr 15. doi: 10.1097/QAD.0000000000002920. Online ahead of print.

ABSTRACT

BACKGROUND: HIV and HCV have each been linked with cardiac dysfunction. Studies of HIV have often lacked appropriate controls and primarily involved men, while data for HCV are sparse.

METHODS: We performed repeat echocardiography over a median interval of 12 years in participants from the Women’s Interagency HIV Study in order to evaluate the relationships of HIV and HCV with incident left ventricular (LV) dysfunction (systolic or diastolic).

RESULTS: Of the 311 women included (age 39 ± 9), 70% were HIV and 20% HCV positive. Forty three participants (13.8%) developed LV dysfunction, of which 79.1% was diastolic. Compared to participants with neither infection, the group with HIV-HCV coinfection showed a significantly increased risk of incident LV dysfunction after adjustment for risk factors (RR = 2.96 [95% CI = 1.05-8.31]), but associations for the HCV monoinfected and HIV monoinfected groups were not statistically significant (RR = 2.54 [0.83-7.73] and RR = 1.66 [0.65-4.25], respectively). Comparison of HCV-positive and HCV-negative women showed a significantly increased risk independent of covariates (RR = 1.96 [1.02-3.77]), but this was not the case for HIV-positive vs. HIV-negative women (RR = 1.43 [0.76-2.69]). There was no evidence of HCV-by-HIV interaction. A more restrictive definition of LV diastolic dysfunction led to fewer incident cases, but a similar, though non-significant, risk estimate for HCV.

CONCLUSIONS: Among middle-aged women, HCV but not HIV infection was associated with a pronounced risk of incident LV dysfunction. Although the influence of residual confounding cannot be excluded, these findings bolster the potential benefits that could be realized by adopting recent recommendations for expanding HCV screening and treatment.

PMID:33859109 | DOI:10.1097/QAD.0000000000002920

J Dev Behav Pediatr. 2021 Apr 13. doi: 10.1097/DBP.0000000000000951. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to characterize the association between maternal pregnancy intention and socioemotional developmental outcomes in a Brazilian sample of preschool-aged children.

METHODS: Data from children aged 4 to 5 years and their primary caregivers in Embu das Artes, a Brazilian municipality in the state of São Paulo, were collected in 2016. Maternal pregnancy intention was defined as intended or unintended, which was then further stratified as mistimed or unwanted. Outcomes included socioemotional developmental delay, internalizing and externalizing behaviors, and school readiness. We estimated risk ratios (RRs) for unadjusted and inverse-probability-weighted regression adjustment (IPWRA) analyses using 2-level (intended vs unintended) and 3-level (intended vs mistimed vs unwanted) exposure definitions.

RESULTS: Of 1,034 total mothers, 40.7% reported their pregnancy as intended, 46.0% as mistimed, and 13.4% as unwanted. In both unadjusted and IPWRA analyses comparing intended and unintended pregnancies, all associations failed to reach statistical significance. In the IPWRA analysis using the 3-level exposure definition, unwanted pregnancies were associated with higher risk of socioemotional developmental delay (RR = 1.14; 95% confidence interval [CI], 1.01-1.28) and co-occurring internalizing and externalizing behaviors (RR = 1.11, 95% CI, 1.00-1.22), compared with intended pregnancies.

CONCLUSION: There was higher risk of poor child outcomes among unwanted compared with intended pregnancies, whereas mistimed pregnancies were not associated with poor outcomes. Further research using standardized definitions of pregnancy intention along with targeted interventions that increase access to family planning services and counseling for parents of children born after unintended pregnancies is needed.

PMID:33859123 | DOI:10.1097/DBP.0000000000000951

Am J Dermatopathol. 2021 Apr 13. doi: 10.1097/DAD.0000000000001953. Online ahead of print.

ABSTRACT

Cutaneous malignant melanoma is an aggressive cancer that contributes significantly to cancer-related mortality. Over the years, a deeper scrutiny of melanoma biology has led to identification of diverse evolutionary patterns involving various genetic pathways. This study attempts to further understand the genetic landscape of cutaneous malignant melanoma in terms of loco-regional variations and malignant potential. Thirty-five cases of cutaneous malignant melanoma were retrieved from the archives and were classified based on location of the primary tumor and presence or absence of metastatic disease. Next-generation sequencing data consisting of base substitutions, copy number variations, indels, and rearrangements in a total of 324 genes were analyzed for recurrent genetic alterations. Statistical analysis was performed using IBM SPSS26 software. Mutations in KDM gene family were found in 62.5% of the melanomas in the head and neck as compared with 10% in melanomas of the extremity and trunk (P = 0.03). Mutations in the RAS gene family were found in 70% of melanomas in the extremities as compared to 12.5% in melanomas of the head and neck (P = 0.003). BTK gene mutations were found exclusively in melanomas of the head and neck (P = 0.032). CREBBP mutations were seen in 50% of the nonmetastatic melanomas as compared with 3.57% of metastatic melanomas (P = 0.005). This study highlights the loco-regional variations in cutaneous malignant melanoma for genetic alterations involving the KDM, RAS, and BTK gene family. In addition, the CREBBP mutational status is identified as a potential prognostic marker for predicting metastatic potential in cutaneous malignant melanomas.

PMID:33859081 | DOI:10.1097/DAD.0000000000001953

Thorax. 2021 Apr 15:thoraxjnl-2020-216368. doi: 10.1136/thoraxjnl-2020-216368. Online ahead of print.

ABSTRACT

Diagnosing cystic fibrosis (CF) when sweat chloride is not in the CF range and less than 2 disease-causing CFTR mutations are found requires physiological CFTR assays, which are not always feasible or available. We developed a new physiological CFTR assay based on the morphological differences between rectal organoids from subjects with and without CF. In organoids from 167 subjects with and 22 without CF, two parameters derived from a semi-automated image analysis protocol (rectal organoid morphology analysis, ROMA) fully discriminated CF subjects with two disease-causing mutations from non-CF subjects (p<0.001). ROMA, feasible at all ages, can be centralised to improve standardisation.

PMID:33859053 | DOI:10.1136/thoraxjnl-2020-216368

Science. 2021 Apr 16;372(6539):eabf1941. doi: 10.1126/science.abf1941.

ABSTRACT

Abruzzi et al argue that transcriptome oscillations found in our study in the absence of Bmal1 are of low amplitude, statistical significance, and consistency. However, their conclusions rely solely on a different statistical algorithm than we used. We provide statistical measures and additional analyses showing that our original analyses and observations are accurate. Further, we highlight independent lines of evidence indicating Bmal1-independent 24-hour molecular oscillations.

PMID:33859003 | DOI:10.1126/science.abf1941

Thorax. 2021 Apr 15:thoraxjnl-2020-216098. doi: 10.1136/thoraxjnl-2020-216098. Online ahead of print.

ABSTRACT

PURPOSE: To determine the effect of depth of sedation on intensive care mortality, duration of mechanical ventilation, and other clinically important outcomes.

METHODS: We searched MEDLINE, Embase, Cochrane Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, PsycINFO from 2000 to 2020. Randomised controlled trials (RCTs) and cohort studies that examined the effect of sedation depth were included. Two reviewers independently screened, selected articles, extracted data and appraised quality. Data on study design, population, setting, patient characteristics, study interventions, depth of sedation and relevant outcomes were extracted. Quality was assessed using Critical Appraisal Skills Programme tools.

RESULTS: We included data from 26 studies (n=7865 patients): 8 RCTs and 18 cohort studies. Heterogeneity of studies was substantial. There was no significant effect of lighter sedation on intensive care mortality. Lighter sedation did not affect duration of mechanical ventilation in RCTs (mean difference (MD): -1.44 days (95% CI -3.79 to 0.91)) but did in cohort studies (MD: -1.52 days (95% CI -2.71 to -0.34)). No statistically significant benefit of lighter sedation was identified in RCTs. In cohort studies, lighter sedation improved time to extubation, intensive care and hospital length of stay and ventilator-associated pneumonia. We found no significant effects for hospital mortality, delirium or adverse events.

CONCLUSION: Evidence of benefit from lighter sedation is limited, with inconsistency between observational and randomised studies. Positive effects were mainly limited to low quality evidence from observational studies, which could be attributable to bias and confounding factors.

PMID:33859048 | DOI:10.1136/thoraxjnl-2020-216098

Tob Control. 2021 Apr 15:tobaccocontrol-2020-056386. doi: 10.1136/tobaccocontrol-2020-056386. Online ahead of print.

ABSTRACT

BACKGROUND: Concerns about the magnitude of illicit cigarette trade have prevented the Government of Pakistan from increasing tobacco taxes. We estimated the proportion of illicit cigarettes sold in Pakistani cities. Moreover, we compared two methods for collecting cigarette packs and investigated if the illicit cigarette trade equates to tax evasion.

METHOD: We analysed cigarette packs collected from 10 cities of Pakistan using two methods: consumer survey based on a two-stage random sampling strategy to recruit adult smokers and photograph their cigarette packs and waste recycle store survey to purchase used cigarette packs. Cigarettes were considered illicit if any one of the following was absent from their packs: text and pictorial health warning, underage sale prohibition warning, retail price and manufacturer’s name. From the consumer survey, we also estimated the proportion of smokers who purchased loose cigarettes (illegal) and packs below the minimum retail price. Taxation officers (n=4) were consulted to assess their level of confidence in judging tax evasion using the above criteria.

RESULTS: Out of 2416 cigarette packs in the consumer survey, 454 (17.8%; 95% CI 15.4% to 20.2%) were illicit. Similarly, out of 6213 packs from waste recycle shops, 1046 (16.8%; 95% CI 15.9% to 17.7%) were illicit; the difference was not statistically significant (p=0.473). Among consumers, 29.5% bought loose cigarettes and 13.8% paid less than the minimum retail price. The taxation officers considered the manufacturer’s name and retail price on cigarette packs as the most relevant criteria to detect tax evasion.

CONCLUSIONS: One in six cigarette packs consumed in Pakistan could be illicit. These figures are far less than those propagated by the tobacco industry. Collecting packs from waste recycle stores is an efficient and valid method to estimate illicit cigarette trade.

PMID:33858966 | DOI:10.1136/tobaccocontrol-2020-056386

Learn Mem. 2021 Apr 15;28(5):148-152. doi: 10.1101/lm.053306.120. Print 2021 May.

ABSTRACT

Humans and others primates are highly attuned to temporal consistencies and regularities in their sensory environment and learn to predict such statistical structure. Moreover, in several instances, the presence of temporal structure has been found to facilitate procedural learning and to improve task performance. Here we extend these findings to visual object recognition and to presentation sequences in which mutually predictive objects form distinct clusters or “communities.” Our results show that temporal community structure accelerates recognition learning and affects the order in which objects are learned (“onset of familiarity”).

PMID:33858967 | DOI:10.1101/lm.053306.120

J Neurointerv Surg. 2021 Apr 15:neurintsurg-2021-017487. doi: 10.1136/neurintsurg-2021-017487. Online ahead of print.

ABSTRACT

BACKGROUND: A direct aspiration first pass thrombectomy (ADAPT) is a fast-growing technique for which a broad catalog of catheters that provide a wide range of aspiration forces can be used. We aimed to characterize different catheters’ aspiration performance on stiff clots in an in vitro vascular model. We hypothesized that labeled catheter inner diameter (labeled-ID) is not the only parameter that affects the aspiration force (asp-F) and that thrombus-catheter tip interaction and distensibility also play a major role.

METHODS: We designed an experimental setup consisting of a 3D-printed carotid artery immersed in a water deposit. We measured asp-F and distensibility of catheter tips when performing ADAPT on a stiff clot analog larger than catheter labeled-ID. Correlations between asp-F, catheter ID, and tip distensibility were statistically assessed.

RESULTS: Experimental asp-F and catheter labeled-ID were correlated (r=0.9601; P<0.01). The relative difference between experimental and theoretical asp-F (obtained by the product of the tip’s section area by the vacuum pressure) correlated with tip’s distensibility (r=0.9050; P<0.01), evidencing that ADAPT performance is highly influenced by catheter tip shape-adaptability to the clot and that the effective ID (eff-ID) may differ from the labeled-ID specified by manufacturers. Eff-ID showed the highest correlation with experimental asp-F (r=0.9944; P<0.01), confirming that eff-ID rather than labeled-ID should be considered to better estimate the device efficiency.

CONCLUSIONS: Catheter tip distensibility can induce a significant impact on ADAPT performance when retrieving a stiff clot larger than the device ID. Our findings might contribute to optimizing thrombectomy strategies and the design of novel aspiration catheters.

PMID:33858973 | DOI:10.1136/neurintsurg-2021-017487

BMJ Open. 2021 Apr 15;11(4):e046331. doi: 10.1136/bmjopen-2020-046331.

ABSTRACT

INTRODUCTION: Screening programmes represent a considerable amount of healthcare activity. As complex interventions, they require careful delivery to generate net benefit. Much screening work occurs in primary care. Despite intensive study of intervention delivery in primary care, there is currently no synthesis of the delivery of screening programmes in this setting. The purpose of this review is to describe and critically evaluate the delivery of screening programmes in general practice and community services.

METHODS AND ANALYSIS: We will use scoping review methods to explore which components of screening programmes are delivered in primary care and systematic review methods to locate and synthesise evidence on how screening programmes can be delivered in primary care, including barriers, facilitators and strategies. We will include empirical studies of any design which consider screening programmes in high-income countries, based in part or whole in primary care. We will search 20 information sources from 1 January 2000, including those relating to health (eg, MEDLINE, Embase, CINAHL), management (eg, Rx for change database) and grey literature (eg, OpenGrey, screening committee websites). Two reviewers will screen citations and full texts of potentially eligible studies and assess these against inclusion criteria. Qualitative and quantitative data will be extracted in duplicate and synthesised using a best fit framework approach. Within the systematic review, the mixed methods appraisal tool will be used to assess risk of bias.

ETHICS AND DISSEMINATION: No ethics approval is required. We will disseminate findings to academics through publication and presentation, to decision-makers through national screening bodies, to practitioners through professional bodies, and to the public through social media.

PROSPERO REGISTRATION NUMBER: CRD42020215420.

PMID:33858873 | DOI:10.1136/bmjopen-2020-046331