Nevin Manimala

Pacing Clin Electrophysiol. 2021 Dec 7. doi: 10.1111/pace.14416. Online ahead of print.

ABSTRACT

AIMS: Goal of Transvenous Lead Extraction (TLE) is complete removal of all targeted leads, without complications. Despite counter traction manoeuvres, efficacy rates are often hampered by broken right ventricle lead (RV-lead) tips. Mechanically powered lead extraction (Evolution sheath) is effective, however safety of dissection up to the lead tip is unclear. Therefore, we examined the feasibility and safety of RV-lead extraction requiring dissection up to the myocardium.

METHODS AND RESULTS: From 2009 to 2018, all TLE in the Isala Heart Centre (Zwolle, The Netherlands) requiring the hand-powered mechanical Evolution system to extract RV-leads (n = 185) were examined from a prospective registry. We assessed 4 groups: TLE with the first generation Evolution (n = 43) with (A1,n = 18) and without (A2,n = 25) adhesions up to the myocardium and TLE with the Novel R/L type (n = 142) of sheath with (B1, n = 59) and without (B2, n = 83) adhesions up to the myocardium. Complete success rate in Group B was significantly higher than group A (96.5 vs 76.7%, p = 0.0354). When comparing the patients with adhesions up to the myocardium, total complete success is higher in the R/L group (61.1% vs 90.5%, p = 0.0067). There were no deaths. Overall major complication rates were low (2/185; 1.1%) and there was no statistically significant difference in major and minor complications between the two groups.

CONCLUSION: Extraction strategy with the bidirectional Evolution R/L sheath for right ventricular leads with adhesions up to the myocardium is safe and feasible. This article is protected by copyright. All rights reserved.

PMID:34875112 | DOI:10.1111/pace.14416

J Travel Med. 2021 Dec 7:taab188. doi: 10.1093/jtm/taab188. Online ahead of print.

ABSTRACT

BACKGROUND: Currently, there is limited data on long-term persistence of antibodies and boostability of intradermal (ID) rabies pre-exposure prophylaxis (PrEP) schedules. This study investigated travellers who received a primary ID PrEP schedule at least 5 years previously to determine persistence of antibodies and subsequent antibody response after one 0.1 mL ID booster dose.

METHODS: Adults (age ≥ 18 years) who had previously received ID PrEP at a specialist travel medicine clinic in Brisbane, Australia were included. At day 0, blood was collected for serology and one dose of 0.1 mL ID rabies vaccine (Verorab®) was administered. At day 7, serology was repeated. At day 14, participants were given results and enquired if they experienced adverse events following immunisation (AEFIs). Antibodies were measured using Platelia Rabies II ELISA, levels ≥0.5 EU/mL were considered antibody-positive.

RESULTS: 158 participants were included (64.6% female, median age at enrolment 56.4 years, IQR [interquartile range] 42.4-65.2 years), and median time since the primary ID PrEP was 8.5 years (IQR 6.9-11.7 years). The majority of participants (82.3%) were antibody-positive at day 0. The proportion of participants who were antibody-positive at day 0 was higher among those who were younger at primary vaccination (87.0% if aged<50 years, 75.8% of aged ≥50 years). The proportion of participants who were antibody-positive declined as median time since primary vaccination increased, though the trend was not statistically significant (p-trend = 0.187). All except one participant (99.4%) were antibody-positive after one ID booster dose. AEFIs were reported by 42.4% of participants and were mainly mild.

CONCLUSIONS: Rabies antibodies persist for many years after ID PrEP and can be rapidly boosted with a single ID dose. Future studies are needed to confirm that ID PrEP primes the immune system sufficiently so that boosters are not routinely needed, and only given in the event of a rabies-prone exposure.

PMID:34875078 | DOI:10.1093/jtm/taab188

J Public Health (Oxf). 2021 Dec 6:fdab385. doi: 10.1093/pubmed/fdab385. Online ahead of print.

ABSTRACT

BACKGROUND: During a pandemic, non-pharmaceutical interventions (NPIs) play an important role in protecting oneself and others from infection. There are large regional differences in COVID-19 infection rates in Japan. We hypothesized that the local infection incidence may affect adherence to individual NPIs.

METHODS: This cross-sectional study was conducted online among full-time workers in Japan in December 2020. The questionnaire asked the respondents to identify their habits regarding seven common NPIs (wearing masks, washing hands after the bathroom, disinfecting hands when entering indoors, gargling when returning home, ventilating the room, disinfecting or washing hands after touching frequently touched surfaces, carrying alcohol sanitizers when outdoors).

RESULTS: A total of 27 036 participants were analyzed. Compared with the region with the lowest infection rate, five of the seven NPIs showed statistically significant trends across regional infection levels, the two exceptions being wearing masks and washing hands after the bathroom. Multivariate adjustment did not change these trends.

CONCLUSIONS: This study found that NPIs were more prevalent in regions with higher incidence rates of COVID-19 in Japanese workers. The findings suggest that the implementation of NPIs was influenced not only by personal attributes but also by contextual effects of the local infection level.

PMID:34875074 | DOI:10.1093/pubmed/fdab385

Hum Reprod. 2021 Dec 7:deab264. doi: 10.1093/humrep/deab264. Online ahead of print.

ABSTRACT

STUDY QUESTION: What is the predictive performance of a currently recommended prediction model in an external Dutch cohort of couples with unexplained recurrent pregnancy loss (RPL)?

SUMMARY ANSWER: The model shows poor predictive performance on a new population; it overestimates, predicts too extremely and has a poor discriminative ability.

WHAT IS KNOWN ALREADY: In 50-75% of couples with RPL, no risk factor or cause can be determined and RPL remains unexplained. Clinical management in RPL is primarily focused on providing supportive care, in which counselling on prognosis is a main pillar. A frequently used prediction model for unexplained RPL, developed by Brigham et al. in 1999, estimates the chance of a successful pregnancy based on number of previous pregnancy losses and maternal age. This prediction model has never been externally validated.

STUDY DESIGN, SIZE, DURATION: This retrospective cohort study consisted of 739 couples with unexplained RPL who visited the RPL clinic of the Leiden University Medical Centre between 2004 and 2019.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Unexplained RPL was defined as the loss of two or more pregnancies before 24 weeks, without the presence of an identifiable cause for the pregnancy losses, according to the ESHRE guideline. Obstetrical history and maternal age were noted at intake at the RPL clinic. The outcome of the first pregnancy after intake was documented. The performance of Brigham’s model was evaluated through calibration and discrimination, in which the predicted pregnancy rates were compared to the observed pregnancy rates.

MAIN RESULTS AND THE ROLE OF CHANCE: The cohort included 739 women with a mean age of 33.1 years (±4.7 years) and with a median of three pregnancy losses at intake (range 2-10). The mean predicted pregnancy success rate was 9.8 percentage points higher in the Brigham model than the observed pregnancy success rate in the dataset (73.9% vs 64.0% (95% CI for the 9.8% difference 6.3-13.3%)). Calibration showed overestimation of the model and too extreme predictions, with a negative calibration intercept of -0.46 (95% CI -0.62 to -0.31) and a calibration slope of 0.42 (95% CI 0.11-0.73). The discriminative ability of the model was very low with a concordance statistic of 0.55 (95% CI 0.51-0.59). Recalibration of the Brigham model hardly improved the c-statistic (0.57; 95% CI 0.53-0.62).

LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study in which only the first pregnancy after intake was registered. There was no time frame as inclusion criterium, which is of importance in the counselling of couples with unexplained RPL. Only cases with a known pregnancy outcome were included.

WIDER IMPLICATIONS OF THE FINDINGS: This is the first study externally validating the Brigham prognostic model that estimates the chance of a successful pregnancy in couples with unexplained RPL. The results show that the frequently used model overestimates the chances of a successful pregnancy, that predictions are too extreme on both the high and low ends and that they are not much more discriminative than random luck. There is a need for revising the prediction model to estimate the chance of a successful pregnancy in couples with unexplained RPL more accurately.

STUDY FUNDING/COMPETING INTEREST(S): No external funding was used and no competing interests were declared.

TRIAL REGISTRATION NUMBER: N/A.

PMID:34875054 | DOI:10.1093/humrep/deab264

J Gerontol A Biol Sci Med Sci. 2021 Dec 7:glab362. doi: 10.1093/gerona/glab362. Online ahead of print.

ABSTRACT

Forkhead box O3 (FOXO3A) is a candidate longevity gene. Urban residents are also positively associated with longer life expectancy. We conducted a gene-environment interaction to assess the synergistic effect of FOXO3A and urban/rural environments on mortality. We included 3085 older adults from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We used single nucleotide polymorphisms (SNPs) rs2253310, rs2802292, and rs4946936 to identify the FOXO3A gene and classified residential locations as “urban” and “rural.” Given the open cohort design, we used the Cox-proportional hazard regression models to assess the mortality risk. We found the minor allele homozygotes of FOXO3A to have a protective effect on mortality [HR (95% CI) for rs4946936 TT vs. CC: 0.807 (0.653, 0.996); rs2802292 GG vs TT: 0.812 (0.67, 0.985); rs2253310 CC vs. GG: 0.808 (0.667, 0.978)]. Participants living in urban areas had a lower risk of mortality [HR of the urban vs. the rural: 0.854 (0.759, 0.962)]. The interaction between FOXO3A and urban and rural regions was statistically significant (pinteraction<0.01). Higher air pollution (fine particulate matter: PM2.5) and lower residential greenness (Normalized Difference Vegetation Index: NDVI) both contributed to higher mortality. After adjusting for NDVI and PM2.5, the protective effect size of FOXO3A SNPs was slightly attenuated while the protective effect size of living in an urban environment increased. The effect size of the beneficial effect of FOXO3 on mortality is roughly equivalent to that of living in urban areas. Our research findings indicate the effect of places of residence and genetic predisposition of longevity are intertwined.

PMID:34875051 | DOI:10.1093/gerona/glab362

Cereb Cortex. 2021 Dec 7:bhab415. doi: 10.1093/cercor/bhab415. Online ahead of print.

ABSTRACT

Although the neural scaffolding for language is putatively present before birth, the maturation of functional connections among the key nodes of the language network, Broca’s and Wernicke’s areas, is less known. We leveraged longitudinal and cross-sectional data from three sites collected through six studies to track the development of functional circuits between Broca’s and Wernicke’s areas from 30 weeks of gestation through 30 months of age in 127 unique participants. Using resting-state fMRI data, functional connectivity was calculated as the correlation between fMRI time courses from pairs of regions, defined as Broca’s and Wernicke’s in both hemispheres. The primary analysis evaluated 23 individuals longitudinally imaged from 30 weeks postmenstrual age (fetal) through the first postnatal month (neonatal). A secondary analysis in 127 individuals extended these curves into older infants and toddlers. These data demonstrated significant growth of interhemispheric connections including left Broca’s and its homolog and left Wernicke’s and its homolog from 30 weeks of gestation through the first postnatal month. In contrast, intrahemispheric connections did not show significant increases across this period. These data represent an important baseline for language systems in the developing brain against which to compare those neurobehavioral disorders with the potential fetal onset of disease.

PMID:34875024 | DOI:10.1093/cercor/bhab415

Am J Epidemiol. 2021 Dec 7:kwab285. doi: 10.1093/aje/kwab285. Online ahead of print.

ABSTRACT

There are unique challenges to identifying causes and developing strategies for prevention of rare cancers, driven by the difficulty in estimating incidence, prevalence, and survival due to their small numbers. Using a Poisson modeling approach, Salmerón et al. (Am J Epidemiol. 2021) built upon their previous work to estimate incidence rates of rare cancers in Europe using a Bayesian framework, establishing a uniform prior for a measure of variability for country-specific incidence rates. They offer a methodology with potential transferability to other settings with similar cancer surveillance infrastructure. However, the approach does not consider the spatio-temporal correlation of rare cancer case counts and other, potentially more appropriate, non-normal probability distributions. In this commentary, we discuss the implications of future work from cancer and spatial epidemiology perspectives. We describe the possibility of developing prediction models tailored to each type of rare cancer; incorporating the spatial heterogeneity in at-risk populations, surveillance coverage, and risk factors in these predictions; and considering a modeling framework to address the inherent spatio-temporal components of these data. We note that extension of this methodology to estimate sub-country rates at provincial, state, or smaller levels of geography would be useful but pose additional statistical challenges.

PMID:34875003 | DOI:10.1093/aje/kwab285

Am J Epidemiol. 2021 Dec 7:kwab286. doi: 10.1093/aje/kwab286. Online ahead of print.

NO ABSTRACT

PMID:34874996 | DOI:10.1093/aje/kwab286

PLoS One. 2021 Dec 7;16(12):e0260632. doi: 10.1371/journal.pone.0260632. eCollection 2021.

ABSTRACT

Strategies adopted globally to mitigate the threat of COVID-19 have primarily involved lockdown measures with substantial economic and social costs with varying degrees of success. Morbidity patterns of COVID-19 variants have a strong association with age, while restrictive lockdown measures have association with negative mental health outcomes in some age groups. Reduced economic prospects may also afflict some age cohorts more than others. Motivated by this, we propose a model to describe COVID-19 community spread incorporating the role of age-specific social interactions. Through a flexible parameterisation of an age-structured deterministic Susceptible Exposed Infectious Removed (SEIR) model, we provide a means for characterising different forms of lockdown which may impact specific age groups differently. Social interactions are represented through age group to age group contact matrices, which can be trained using available data and are thus locally adapted. This framework is easy to interpret and suitable for describing counterfactual scenarios, which could assist policy makers with regard to minimising morbidity balanced with the costs of prospective suppression strategies. Our work originates from an Irish context and we use disease monitoring data from February 29th 2020 to January 31st 2021 gathered by Irish governmental agencies. We demonstrate how Irish lockdown scenarios can be constructed using the proposed model formulation and show results of retrospective fitting to incidence rates and forward planning with relevant “what if / instead of” lockdown counterfactuals. Uncertainty quantification for the predictive approaches is described. Our formulation is agnostic to a specific locale, in that lockdown strategies in other regions can be straightforwardly encoded using this model.

PMID:34874981 | DOI:10.1371/journal.pone.0260632

PLoS One. 2021 Dec 7;16(12):e0261002. doi: 10.1371/journal.pone.0261002. eCollection 2021.

ABSTRACT

Somatic mutations have a central role in cancer but their role in other diseases such as common autoimmune disorders is not clear. Previously we and others have demonstrated that especially CD8+ T cells in blood can harbor persistent somatic mutations in some patients with multiple sclerosis (MS) and rheumatoid arthritis. Here we concentrated on CD8+ cells in more detail and tested (i) how commonly somatic mutations are detectable, (ii) does the overall mutation load differ between MS patients and controls, and (iii) do the somatic mutations accumulate non-randomly in certain genes? We separated peripheral blood CD8+ cells from newly diagnosed relapsing MS patients (n = 21) as well as matched controls (n = 21) and performed next-generation sequencing of the CD8+ cells’ DNA, limiting our search to a custom panel of 2524 immunity and cancer related genes, which enabled us to obtain a median sequencing depth of over 2000x. We discovered nonsynonymous somatic mutations in all MS patients’ and controls’ CD8+ cell DNA samples, with no significant difference in number between the groups (p = 0.60), at a median allelic fraction of 0.5% (range 0.2-8.6%). The mutations showed statistically significant clustering especially to the STAT3 gene, and also enrichment to the SMARCA2, DNMT3A, SOCS1 and PPP3CA genes. Known activating STAT3 mutations were found both in MS patients and controls and overall 1/5 of the mutations were previously described cancer mutations. The detected clustering suggests a selection advantage of the mutated CD8+ clones and calls for further research on possible phenotypic effects.

PMID:34874980 | DOI:10.1371/journal.pone.0261002