Recent advances in bacterial whole-genome sequencing have resulted in a comprehensive catalog of antibiotic resistance genomic signatures in Mycobacterium tuberculosis. With a view to pre-empt the ...emergence of resistance, we hypothesized that pre-existing polymorphisms in susceptible genotypes (pre-resistance mutations) could increase the risk of becoming resistant in the future. We sequenced whole genomes from 3135 isolates sampled over a 17-year period. After reconstructing ancestral genomes on time-calibrated phylogenetic trees, we developed and applied a genome-wide survival analysis to determine the hazard of resistance acquisition. We demonstrate that M. tuberculosis lineage 2 has a higher risk of acquiring resistance than lineage 4, and estimate a higher hazard of rifampicin resistance evolution following isoniazid mono-resistance. Furthermore, we describe loci and genomic polymorphisms associated with a higher risk of resistance acquisition. Identifying markers of future antibiotic resistance could enable targeted therapy to prevent resistance emergence in M. tuberculosis and other pathogens.
Understanding how pathogen genetic factors contribute to pathology in TB could enable tailored treatments to the most pathogenic and infectious strains. New strategies are needed to control ...drug-resistant TB, which requires longer and costlier treatment. We hypothesised that the severity of radiological pathology on the chest radiograph in TB disease was associated with variants arising independently, multiple times (homoplasies) in the
genome.
We performed whole genome sequencing (Illumina HiSeq2000 platform) on
isolates from 103 patients with drug-resistant TB in Lima between 2010 and 2013. Variables including age, sex, HIV status, previous TB disease and the percentage of lung involvement on the pretreatment chest radiograph were collected from health posts of the national TB programme. Genomic variants were identified using standard pipelines.
Two mutations were significantly associated with more widespread radiological pathology in a multivariable regression model controlling for confounding variables (Rv2828c.141, RR 1.3, 95% CI 1.21 to 1.39, p<0.01; rpoC.1040 95% CI 1.77 to 2.16, RR 1.9, p<0.01). The rpoB.450 mutation was associated with less extensive radiological pathology (RR 0.81, 95% CI 0.69 to 0.94, p=0.03), suggestive of a bacterial fitness cost for this mutation in vivo. Patients with a previous episode of TB disease and those between 10 and 30 years of age also had significantly increased radiological pathology.
This study is the first to compare the
genome to radiological pathology on the chest radiograph. We identified two variants significantly positively associated with more widespread radiological pathology and one with reduced pathology. Prospective studies are warranted to determine whether mutations associated with increased pathology also predict the spread of drug-resistant TB.
The COVID-19 pandemic has significantly disrupted tuberculosis (TB) programs, making it urgent to focus TB elimination efforts on key populations. People experiencing incarceration are at high risk ...for TB, however, how COVID-19-related disruptions have impacted incarcerated populations with TB is unknown.
Using Peruvian National TB Program data from Jan 2018 to Dec 2021, an interrupted time series of drug-susceptible (DS) TB case notifications pre- and during COVID-19 was conducted (cut-off date: COVID-19 emergency declaration in Peru, 16 March 2020). The effect of TB care occurring pre-vs. during COVID-19 on TB treatment success in the incarcerated and non-incarcerated populations was explored using logistic regression.
DS-TB cases notified in prisons from Jan 2018 to Dec 2021 (n = 10,134) represented 10% of all cases notified in the country (n = 101,507). In the first week of COVID-19, DS-TB case notifications dropped by 61.2% (95% CI: 59.9–62.7%) in the non-incarcerated population and 17.7% (95% CI: 17.5–17.9%) among the incarcerated population. TB treatment success was significantly lower in people receiving TB care entirely during the COVID-19 pandemic vs. before COVID-19 in the non-incarcerated population (OR: 0.81, 95% CI: 0.78–0.85), but not statistically significantly lower in the incarcerated population (OR: 0.88, 95% CI: 0.76–1.01). Incarceration status was not found to modify the effect of COVID-19 period on TB treatment outcomes (OR: 1.07, 95% CI: 0.92–1.25), although treatment success was higher in the incarcerated population (OR incarcerated vs. not incarcerated, pre-COVID: 1.52, 95% CI: 1.39–1.67).
Both incarcerated and non-incarcerated populations experienced a large drop in DS-TB case notifications (although higher in the non-incarcerated population). Lower TB treatment success among those receiving care during COVID-19 indicates significant TB service disruptions in the overall population. The finding that incarceration at time of diagnosis was associated with treatment success is plausible in Peru given increased screening and stricter treatment monitoring in prisons.
Canadian Institutes of Health Research (Funding Reference Number: 179418) .
Background: The COVID-19 pandemic has significantly disrupted tuberculosis (TB) programs, making it urgent to focus TB elimination efforts on key populations. People experiencing incarceration are at ...high risk for TB, however, how COVID-19-related disruptions have impacted incarcerated populations with TB is unknown. Methods: Using Peruvian National TB Program data from Jan 2018 to Dec 2021, an interrupted time series of drug-susceptible (DS) TB case notifications pre- and during COVID-19 was conducted (cut-off date: COVID-19 emergency declaration in Peru, 16 March 2020). The effect of TB care occurring pre-vs. during COVID-19 on TB treatment success in the incarcerated and non-incarcerated populations was explored using logistic regression. Findings: DS-TB cases notified in prisons from Jan 2018 to Dec 2021 (n = 10,134) represented 10% of all cases notified in the country (n = 101,507). In the first week of COVID-19, DS-TB case notifications dropped by 61.2% (95% CI: 59.9–62.7%) in the non-incarcerated population and 17.7% (95% CI: 17.5–17.9%) among the incarcerated population. TB treatment success was significantly lower in people receiving TB care entirely during the COVID-19 pandemic vs. before COVID-19 in the non-incarcerated population (OR: 0.81, 95% CI: 0.78–0.85), but not statistically significantly lower in the incarcerated population (OR: 0.88, 95% CI: 0.76–1.01). Incarceration status was not found to modify the effect of COVID-19 period on TB treatment outcomes (OR: 1.07, 95% CI: 0.92–1.25), although treatment success was higher in the incarcerated population (OR incarcerated vs. not incarcerated, pre-COVID: 1.52, 95% CI: 1.39–1.67). Interpretation: Both incarcerated and non-incarcerated populations experienced a large drop in DS-TB case notifications (although higher in the non-incarcerated population). Lower TB treatment success among those receiving care during COVID-19 indicates significant TB service disruptions in the overall population. The finding that incarceration at time of diagnosis was associated with treatment success is plausible in Peru given increased screening and stricter treatment monitoring in prisons. Funding: Canadian Institutes of Health Research (Funding Reference Number: 179418) .
The development and implementation of effective physical activity (PA) intervention programs is challenging, particularly in older adults. After the first year of the intervention program used in the ...ongoing PREvención con DIeta MEDiterránea (PREDIMED)-Plus trial, we assessed the initial effectiveness of the PA component.
PREDIMED-Plus is an ongoing randomized clinical trial including 6874 participants randomized to an intensive weight-loss lifestyle intervention based on an energy-restricted Mediterranean diet (MedDiet), physical activity promotion and behavioral support and to a control group using MedDiet recommendations but without calorie restriction or PA advice. Body mass index (BMI) and waist circumference (WC) are measured by standard clinical protocols. Duration and intensity of PA is self-reported using the validated REGICOR Short Physical Activity Questionnaire. The primary endpoint of the PREDIMED-Plus trial is a combined cardiovascular outcome: myocardial infarction (acute coronary syndromes with positive troponin test), stroke, or cardiovascular mortality. The present study involved secondary analysis of PA data (n = 6059; mean age 65 ± 4.9 years) with one-year changes in total, light, and moderate-to-vigorous PA within and between intervention groups as the outcome. Generalized estimating equation models were fitted to evaluate time trends of PA, BMI, and WC within groups and differences between intervention and control groups.
After 12 months, average daily MVPA increased by 27.2 (95%CI 5.7;48.7) METs-min/day and 123.1 (95%CI 109.7-136.6) METs-min/day in the control and intervention groups, respectively. Total-PA, light-PA, and MVPA increased significantly (p < 0.01) in both groups. A significant (p < 0.001) time*intervention group interaction was found for Total-PA and MVPA, meaning the PA trajectory over time differed between the intervention and control groups. Age, sex, education level, and BMI did not moderate the effectiveness of the PA intervention. BMI and WC decreased significantly with increasing MVPA, compared with participants who reported no changes in MVPA.
After one year of follow-up, the PREDIMED-Plus PA intervention has been effective in increasing daily PA in older adults.
Retrospectively registered at the International Standard Randomized Controlled Trial ( http://www.isrctn.com/ISRCTN89898870 ), registration date: 24 July 2014.
Physical activity (PA) has been hypothesized to be effective to maintaining cognitive function and delay cognitive decline in the elderly, but physical fitness (PF) could be a better predictor of ...cognitive function. We aimed to study the association between PA and PF with cognitive function and quality of life using cross-sectional data from 6874 participants of the PREDIMED-Plus trial (64.9 ± 4.9 years, 48.5% female). PF and PA were measured with a Chair Stand Test, the REGICOR and Rapid Assessment Physical Activity questionnaires. Cognitive function was measured with Mini-mental State Examination, Control Oral Word Association Test, Trail Making Test and Digit Span tests; whereas health-related quality of life was assessed with the SF36-HRQL test. Cognitive and quality of life scores were compared among PF quartiles and PA levels (low, moderate and high) with ANCOVA and with Chair Stand repetitions and energy expenditure from total PA with multivariable linear regression adjusted for confounding factors. PF associated with higher scores in phonemic and semantic verbal fluency tests and with lower TMT A time. However, PA was not associated with the neurocognitive parameters evaluated. Both PF and PA levels were strongly associated with a better quality of life. We concluded that PF, but not PA, is associated with a better cognitive function. This trial was retrospectively registered at the International Standard Randomized Controlled Trial (ISRCTN89898870, https://www.isrctn.com/ISRCTN89898870?q=ISRCTN89898870&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search) on 07/24/2014.
The association between ultra-processed food (UPF) and risk of cardiometabolic disorders is an ongoing concern. Different food processing-based classification systems have originated discrepancies in ...the conclusions among studies. To test whether the association between UPF consumption and cardiometabolic markers changes with the classification system, we used baseline data from 5636 participants (48.5% female and 51.5% male, mean age 65.1 ± 4.9) of the PREDIMED-Plus (“PREvention with MEDiterranean DIet”) trial. Subjects presented with overweight or obesity and met at least three metabolic syndrome (MetS) criteria. Food consumption was classified using a 143-item food frequency questionnaire according to four food processing-based classifications: NOVA, International Agency for Research on Cancer (IARC), International Food Information Council (IFIC) and University of North Carolina (UNC). Mean changes in nutritional and cardiometabolic markers were assessed according to quintiles of UPF consumption for each system. The association between UPF consumption and cardiometabolic markers was assessed using linear regression analysis. The concordance of the different classifications was assessed with intra-class correlation coefficients (ICC3, overall = 0.51). The highest UPF consumption was obtained with the IARC classification (45.9%) and the lowest with NOVA (7.9%). Subjects with high UPF consumption showed a poor dietary profile. We detected a direct association between UPF consumption and BMI (p = 0.001) when using the NOVA system, and with systolic (p = 0.018) and diastolic (p = 0.042) blood pressure when using the UNC system. Food classification methodologies markedly influenced the association between UPF consumption and cardiometabolic risk markers.
Choline and betaine intakes have been related to cardiovascular health.
We aimed to explore the relation between 1-y changes in dietary intake of choline or betaine and 1-y changes in cardiometabolic ...and renal function traits within the frame of the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial.
We used baseline and 1-y follow-up data from 5613 participants (48.2% female and 51.8% male; mean ± SD age: 65.01 ± 4.91 y) to assess cardiometabolic traits, and 3367 participants to assess renal function, of the Spanish PREDIMED-Plus trial. Participants met ≥3 criteria of metabolic syndrome and had overweight or obesity BMI (in kg/m2) ≥27 and ≤40. These criteria were similar to those of the PREDIMED parent study. Dietary intakes of choline and betaine were estimated from the FFQ.
The greatest 1-y increase in dietary choline or betaine intake (quartile 4) was associated with improved serum glucose concentrations (−3.39 and −2.72 mg/dL for choline and betaine, respectively) and HbA1c levels (−0.10% for quartile 4 of either choline or betaine intake increase). Other significant changes associated with the greatest increase in choline or betaine intake were reduced body weight (−2.93 and −2.78 kg, respectively), BMI (−1.05 and −0.99, respectively), waist circumference (−3.37 and −3.26 cm, respectively), total cholesterol (−4.74 and −4.52 mg/dL, respectively), and LDL cholesterol (−4.30 and −4.16 mg/dL, respectively). Urine creatinine was reduced in quartile 4 of 1-y increase in choline or betaine intake (−5.42 and −5.74 mg/dL, respectively).
Increases in dietary choline or betaine intakes were longitudinally related to improvements in cardiometabolic parameters. Markers of renal function were also slightly improved, and they require further investigation.
This trial was registered at https://www.isrctn.com/ as ISRCTN89898870.
Background and Aims. To control the COVID-19 spread, in March 2020, a forced home lockdown was established in Spain. In the present study, we aimed to assess the effect of mobility and social ...COVID-19-established restrictions on depressive symptomatology in older adults with metabolic syndrome. We hypothesize that severe restrictions might have resulted in detrimental changes in depressive symptomatology. Methods. 2,312 PREDIMED-Plus study participants (men=53.9%; mean age=64.9±4.8 years) who completed a COVID-19 lockdown questionnaire to assess the severity of restrictions/lockdown and the validated Spanish version of the Beck Depression Inventory-II (BDI-II) during the three established phases concerning the COVID-19 lockdown in Spain (prelockdown, lockdown, and postlockdown) were included in this longitudinal analysis. Participants were categorized according to high or low lockdown severity. Analyses of covariance were performed to assess changes in depressive symptomatology across lockdown phases. Results. No significant differences in participant depression symptomatology changes were observed between lockdown severity categories (low/high) at the studied phases. During the lockdown phase, participants showed a decrease in BDI-II score compared to the prelockdown phase (mean (95% CI), -0.48 (-0.24, -0.72), P<0.001); a nonsignificantly larger decrease was observed in participants allocated in the low-lockdown category (low: -0.59 (-0.95, -0.23), high: -0.43 (-0.67, -0.19)). Similar decreases in depression symptomatology were found for the physical environment dimension. The post- and prelockdown phase BDI-II scores were roughly similar. Conclusions. The COVID-19 pandemic lockdown was associated with a decrease in depressive symptomatology that returned to prelockdown levels after the lockdown. The degree of lockdown was not associated with depressive symptomatology. The potential preventive role of the physical environment and social interactions on mental disorders during forced home lockdown should be further studied. This trial is registered with ISRCTN89898870. Retrospectively registered on 24 July 2014.
To examine independent and combined associations of sleep duration and sleep variability with body composition, obesity and type 2 diabetes (T2D) in elders at high cardiovascular risk.
...Cross-sectional analysis of 1986 community-dwelling elders with overweight/obesity and metabolic syndrome from PREDIMED-Plus trial. Associations of accelerometry-derived sleep duration and sleep variability with body mass index (BMI), waist circumference (WC) and body composition were assessed fitting multivariable-adjusted linear regression models. Prevalence ratios (PR) and 95% confidence intervals (CI) for obesity and T2D were obtained using multivariable-adjusted Cox regression with constant time. "Bad sleepers" (age-specific non-recommended sleep duration plus sleep variability above the median) and "good sleepers" (age-specific recommended sleep duration plus sleep variability below the median) were characterized by combining sleep duration and sleep variability, and their associations with these outcomes were examined.
One hour/night increment in sleep duration was inversely associated with BMI (β -0.38 kg/m2 95% CI -0.54, -0.23), WC (β -0.86 cm 95% CI -1.25, -0.47), obesity (PR 0.96 95% CI 0.93, 0.98), T2D (PR 0.93 95% CI 0.88, 0.98) and other DXA-derived adiposity-related measurements (android fat and trunk fat, all p < .05). Each 1-hour increment in sleep variability was positively associated with T2D (PR 1.14 95% CI 1.01, 1.28). Compared with "good sleepers," "bad sleepers" were positively associated with obesity (PR 1.12 95% CI 1.01, 1.24) and T2D (PR 1.62 95% CI 1.28, 2.06).
This study revealed cross-sectional associations of sleep duration with adiposity parameters and obesity. Sleep duration and sleep variability were associated with T2D. Considering simultaneously sleep duration and sleep variability could have additional value, particularly for T2D, as they may act synergistically.
PDF
