Tag: pubmed

J Travel Med. 2021 Jun 9:taab071. doi: 10.1093/jtm/taab071. Online ahead of print.

ABSTRACT

BACKGROUND: In recent years, multiple outbreaks of measles associated with vaccine hesitancy occurred in high-income countries, where measles incidence had previously been low. Most safety data about the measles, mumps and rubella (MMR) vaccine are derived from studies conducted among children, whereas evidence regarding the safety profile of the vaccine in adults is scarce.

METHODS: In 2017, during an outbreak of measles in Europe, Israeli travellers to high-risk locations who were incompletely vaccinated, were urged to complete the two MMR vaccination schedule before their travel. In this prospective cohort study, we analysed adverse events (AEs) of MMR and MMRV (measles, mumps, rubella and varicella) vaccines among these travellers. All participants were followed up using structured questionnaires 2-4 weeks after vaccination.

RESULTS: Seven hundred and eighty-five adult travellers whose median age was 49.2 years were vaccinated and followed up. Any AEs were reported by 25.2% of all participants; 11.6% reported local AEs, and 18.6% reported systemic AEs, none of which were severe. In general, AEs were much more common among female travellers (19.4% of males vs 30.1% of females (P < 0.001)). Local AEs, overall systemic AEs, headache and arthralgia were much more common among females, whereas rates of general malaise and fever were not statistically different between genders. We did not observe any significant differences in the rates of total, local or systemic AEs between the MMR and MMRV vaccines. Higher rates of systemic AEs were observed among participants who were younger and probably immunized once with MMR compared to older vaccines immunized once to measles only and to those who were never immunized.

CONCLUSIONS: The current study demonstrated low rates of systemic AEs and no serious AEs following either MMR or MMRV administration. More AEs were reported among females, and rates of AEs were similar after either MMR or MMRV.

PMID:34101817 | DOI:10.1093/jtm/taab071

Cancer. 2021 Jun 8. doi: 10.1002/cncr.33503. Online ahead of print.

ABSTRACT

BACKGROUND: Defining workup beyond usual clinical practice that may improve treatment outcomes in men with a prostate-specific antigen (PSA) level of ≤4 ng/mL (vs >4 ng/mL) and Gleason score (GS) 9 to 10 prostate cancer (PC) remains to be determined.

METHODS: Between February 25, 1992, and February 25, 2016, 17,632 men with clinical T1-4 PC with a biopsy GS of 6 to 10 underwent radical prostatectomy at a single academic center. Multivariable Fine and Gray regressions were used to evaluate the risk of prostate cancer-specific mortality (PCSM) with an interaction model evaluating the prognostic significance of PSA ≤ 4 ng/mL versus PSA > 4 ng/mL among men with PC with a biopsy GS of 9 to 10 versus ≤8, with adjustments made for the time-dependent use of adjuvant and/or salvage radiation therapy and androgen deprivation therapy (ADT) in addition to known PC prognostic factors.

RESULTS: There was a significant interaction in men with a biopsy GS of 9 to 10 versus ≤8 and a PSA level of ≤4 ng/mL versus >4 ng/mL (adjusted hazard ratio [AHR], 2.87; 95% confidence interval [CI], 1.02-8.08; P = .046). Specifically, among men with a biopsy GS of 9 to 10 and a PSA level of ≤4 ng/mL versus >4 ng/mL, there was a significantly higher rate of PCSM (AHR, 2.59; 95% CI, 1.19-5.67; P = .017); however, there was no significant difference in the risk of PCSM in men with a biopsy GS ≤ 8 and a PSA level of ≤4 ng/mL versus >4 ng/mL (AHR, 0.90; 95% CI, 0.46-1.78; P = .771). Moreover, the time-dependent use of postoperative ADT was also associated with an increased risk of PCSM (AHR, 10.76; 95% CI, 6.88-16.81; P < .0001).

CONCLUSIONS: Some men with PSA ≤ 4 ng/mL and a biopsy GS of 9 to 10 may have pathologic or genetic variants that make them less amenable to a cure with current standards of care. Additional workup assessing for small cell, neuroendocrine, and genetic variants should be considered.

PMID:34101827 | DOI:10.1002/cncr.33503

J Gerontol B Psychol Sci Soc Sci. 2021 Jun 8;76(Supplement_1):S86-S96. doi: 10.1093/geronb/gbab004.

ABSTRACT

OBJECTIVE: To study the role of gender and marital status as risk factors for nursing home entry in the United States.

METHOD: The paper uses data from the Health and Retirement Study, a nationally representative survey of the older population in the United States. Multivariate logit models of the risk of nursing home entry over a 2-year follow-up period were estimated for noninstitutionalized individuals over the age of 65. A multiple imputation procedure was used to explore the sensitivity of the results to alternative assumptions about the data-generating process of missing outcome values.

RESULTS: In an analysis based on complete observations, women exhibited the same risk of nursing home entry as men (risk ratio [RR] = 1.01; CI: 0.90, 1.13). However, after expanding the sample to include information on nursing home use for individuals who died during the follow-up period, women were found to have a statistically lower risk of nursing home entry (RR = 0.85; CI: 0.79, 0.92). The latter result was robust to alternative assumptions about the nature of missing data. The type of sample used in the analysis did not affect the conclusions regarding the role of marital status. Divorced and widowed individuals were found to be at higher risk of nursing home admissions than married individuals in all specifications.

DISCUSSION: The findings clarify the role of gender as a predictor of nursing home admissions and may provide useful prognostic information for clinicians and caregivers regarding nursing home entry risk. The study also sheds light on how conclusions about predictors of nursing home risk obtained from prospective studies with long follow-up periods can be affected by the treatment of missing outcomes due to death or attritions.

PMID:34101810 | DOI:10.1093/geronb/gbab004

Microscopy (Oxf). 2021 Jun 8:dfab021. doi: 10.1093/jmicro/dfab021. Online ahead of print.

ABSTRACT

An automated hologram acquisition system for big-data analysis and for improving the statistical precision of phase analysis has been upgraded with automated particle detection technology. The coordinates of objects in low-magnification images are automatically detected using zero-mean normalized cross-correlation with preselected reference images. In contrast with the conventional scanning acquisitions from the whole area of a microgrid and/or a thin specimen, the new method allows efficient data collections only from the desired fields of view including the particles. The acquisition time of the cubic/triangular nanoparticles that were observed was shortened by about 1/58 that of the conventional scanning acquisition method because of the efficient data collections. The developed technology can improve statistical precision in electron holography with shorter acquisition time and is applicable to the analysis of electromagnetic fields for various kinds of nanoparticles.

PMID:34101814 | DOI:10.1093/jmicro/dfab021

PLoS One. 2021 Jun 8;16(6):e0251338. doi: 10.1371/journal.pone.0251338. eCollection 2021.

ABSTRACT

Cognitive impairment is a common symptom in individuals with Multiple Sclerosis (MS), but meaningful, reliable biomarkers relating to cognitive decline have been elusive, making evaluation of the impact of therapeutics on cognitive function difficult. Here, we combine pathway-based MRI measures of structural and functional connectivity to construct a metric of functional decline in MS. The Structural and Functional Connectivity Index (SFCI) is proposed as a simple, z-scored metric of structural and functional connectivity, where changes in the metric have a simple statistical interpretation and may be suitable for use in clinical trials. Using data collected at six time points from a 2-year longitudinal study of 20 participants with MS and 9 age- and sex-matched healthy controls, we probe two common symptomatic domains, motor and cognitive function, by measuring structural and functional connectivity in the transcallosal motor pathway and posterior cingulum bundle. The SFCI is significantly lower in participants with MS compared to controls (p = 0.009) and shows a significant decrease over time in MS (p = 0.012). The change in SFCI over two years performed favorably compared to measures of brain parenchymal fraction and lesion volume, relating to follow-up measures of processing speed (r = 0.60, p = 0.005), verbal fluency (r = 0.57, p = 0.009), and score on the Multiple Sclerosis Functional Composite (r = 0.67, p = 0.003). These initial results show that the SFCI is a suitable metric for longitudinal evaluation of functional decline in MS.

PMID:34101741 | DOI:10.1371/journal.pone.0251338

PLoS One. 2021 Jun 8;16(6):e0252533. doi: 10.1371/journal.pone.0252533. eCollection 2021.

ABSTRACT

Recent technological advances in the field of big data have increased our capabilities to query large databases and combine information from different domains and disciplines. In the area of preclinical studies, initiatives like SEND (Standard for Exchange of Nonclinical Data) will also contribute to collect and present nonclinical data in a consistent manner and increase analytical possibilities. With facilitated access to preclinical data and improvements in analytical algorithms there will surely be an expectation for organisations to ensure all the historical data available to them is leveraged to build new hypotheses. These kinds of analyses may soon become as important as the animal studies themselves, in addition to being critical components to achieve objectives aligned with 3Rs. This article proposes the application of meta-analyses at large scale in corporate databases as a tool to exploit data from both preclinical studies and in vitro pharmacological activity assays to identify associations between targets and tissues that can be used as seeds for the development of causal hypotheses to characterise of targets. A total of 833 in-house preclinical toxicity studies relating to 416 compounds reported to be active (pXC50 ≥ 5.5) against a panel of 96 selected targets of interest for potential off-target non desired effects were meta-analysed, aggregating the data in tissue-target pairs. The primary outcome was the odds ratio (OR) of the number of animals with observed events (any morphology, any severity) in treated and control groups in the tissue analysed. This led to a total of 2139 meta-analyses producing a total of 364 statistically significant associations (random effects model), 121 after adjusting by multiple comparison bias. The results show the utility of the proposed approach to leverage historical corporate data and may offer a vehicle for researchers to share, aggregate and analyse their preclinical toxicological data in precompetitive environments.

PMID:34101743 | DOI:10.1371/journal.pone.0252533

PLoS One. 2021 Jun 8;16(6):e0252140. doi: 10.1371/journal.pone.0252140. eCollection 2021.

ABSTRACT

BACKGROUND: The widely-used estimates of completeness of birth registration collected by Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) and published by UNICEF primarily rely on registration status of children as reported by respondents. However, these self-reported estimates may be inaccurate when compared with completeness as assessed from nationally-reported official birth registration statistics, for several reasons, including over-reporting of registration due to concern about penalties for non-registration. This study assesses the concordance of self-reported birth registration and certification completeness with completeness calculated from civil registration and vital statistics (CRVS) systems data for 57 countries.

METHODS: Self-reported estimates of birth registration and certification completeness, at ages less than five years and 12-23 months, were compiled and calculated from the UNICEF birth registration database, DHS and MICS. CRVS birth registration completeness was calculated as birth registrations reported by a national authority divided by estimates of live births published in the United Nations (UN) World Population Prospects or the Global Burden of Disease (GBD) Study. Summary measures of concordance were used to compare completeness estimates.

FINDINGS: Birth registration completeness (based on ages less than five years) calculated from self-reported data is higher than that estimated from CRVS data in most of the 57 countries (31 countries according to UN estimated births, average six percentage points (p.p.) higher; 43 countries according to GBD, average eight p.p. higher). For countries with CRVS completeness less than 95%, self-reported completeness was higher in 26 of 28 countries, an average 13 p.p. and median 9-10 p.p. higher. Self-reported completeness is at least 30 p.p. higher than CRVS completeness in three countries. Self-reported birth certification completeness exhibits closer concordance with CRVS completeness. Similar results are found for self-reported completeness at 12-23 months.

CONCLUSIONS: These findings suggest that self-reported completeness figures over-estimate completeness when compared with CRVS data, especially at lower levels of completeness, partly due to over-reporting of registration by respondents. Estimates published by UNICEF should be viewed cautiously, especially given their wide usage.

PMID:34101745 | DOI:10.1371/journal.pone.0252140

PLoS One. 2021 Jun 8;16(6):e0252004. doi: 10.1371/journal.pone.0252004. eCollection 2021.

ABSTRACT

OBJECTIVE: To characterize the microbial communities of the anterior nares (nose) and posterior pharynx (throat) of adults dwelling in the community and in nursing homes before and after treatment with intranasal mupirocin.

METHODS: Staphylococcus aureus-colonized adults were recruited from the community (n = 25) and from nursing homes (n = 7). S. aureus colonization was confirmed using cultures. Participants had specimens taken from nose and throat for S. aureus quantitation using quantitative PCR for the nuc gene and bacterial profiling using 16S rRNA gene sequencing over 12 weeks. After two baseline study visits 4 weeks apart, participants received intranasal mupirocin for 5 days with 3 further visits over a 8 week follow-up period.

RESULTS: We found a decrease in the absolute abundance of S. aureus in the nose for 8 weeks after mupirocin (1693 vs 141 fg/ul, p = 0.047). Mupirocin caused a statistically significant disruption in bacterial communities of the nose and throat after 1 week, which was no longer detected after 8 weeks. Bacterial community profiling demonstrated that there was a decrease in the relative abundance of S. aureus (8% vs 0.3%, p<0.01) 8 weeks after mupirocin and a transient decrease in the relative abundance of Staphylococcus epidermidis in the nose (21% vs 5%, p<0.01) 1 week after mupirocin.

CONCLUSIONS: Decolonization with mupirocin leads to a sustained effect on absolute and relative abundance of S. aureus but not for other bacteria in the nose. This demonstrates that a short course of mupirocin selectively decreases S. aureus in the nose for up to 8 weeks.

PMID:34101737 | DOI:10.1371/journal.pone.0252004

Nat Commun. 2021 Jun 7;12(1):3411. doi: 10.1038/s41467-021-23627-6.

ABSTRACT

Tree-ring chronologies underpin the majority of annually-resolved reconstructions of Common Era climate. However, they are derived using different datasets and techniques, the ramifications of which have hitherto been little explored. Here, we report the results of a double-blind experiment that yielded 15 Northern Hemisphere summer temperature reconstructions from a common network of regional tree-ring width datasets. Taken together as an ensemble, the Common Era reconstruction mean correlates with instrumental temperatures from 1794-2016 CE at 0.79 (p < 0.001), reveals summer cooling in the years following large volcanic eruptions, and exhibits strong warming since the 1980s. Differing in their mean, variance, amplitude, sensitivity, and persistence, the ensemble members demonstrate the influence of subjectivity in the reconstruction process. We therefore recommend the routine use of ensemble reconstruction approaches to provide a more consensual picture of past climate variability.

PMID:34099683 | DOI:10.1038/s41467-021-23627-6

Nat Commun. 2021 Jun 7;12(1):3417. doi: 10.1038/s41467-021-22491-8.

ABSTRACT

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.

PMID:34099642 | DOI:10.1038/s41467-021-22491-8