Multi-state Markov model for time to treatment changes for HIV/AIDS patients: a retrospective cohort national datasets, Ethiopia.

BACKGROUND: Virological failure, drug resistance, toxicities, and other issues make it difficult for ART to maintain long-term sustainability. These issues would force a modification in the patient's treatment plan. The aim of this research was to determine whether first-line antiretroviral therapy is durable and to identify the factors that lead to patients on HAART changing their first highly active antiretroviral therapy regimen. METHODS: A retrospective cohort study was conducted from October, 2019-March, 2020 across all regional states including Addis Ababa and Dire Dawa administrative cities. The target population is from all health facilities that have been providing ART service for at least the past 6 months as of October 2019. Multi-stage clustered sampling method was used to select study facilities and participants. Simple random selected ART medical records of patients ever enrolled in ART treatment services. We adopted a multi-state survival modelling (msm) approach assuming each treatment regimen as state. We estimate the transition probability of patients to move from one regimen to another for time to treatment change/switch. We estimated the transition probability, prediction probabilities and length of stay and factor associated with treatment modification of patients to move from one regimen to another. RESULTS: Any of the six therapy combinations (14.4%) altered their treatment at least once during the follow-up period for a variety of reasons. Of the patients, 4,834 (13.26%) changed their treatments just once, while 371 (1.1%) changed it more than once. For 38.6% of the time, a treatment change was undertaken due to toxicity, another infection or comorbidity, or another factor, followed by New drugs were then made accessible and other factors 18.3% of the time, a drug was out of supply; 2.6% of those instances involved pregnancy; and 43.1% involved something else. Highly active anti-retroviral therapy (HAART) combinations TDF + 3TC + NVP, d4T + 3TC + NVP, and TDF + 3TC + EFV were high to treatment alterations in all reasons of treatment modifications, with 29.74%, 26.52%, and 19.52% treatment changes, respectively. Early treatment modification or regime change is one of the treatment combinations that include the d4T medication that creates major concern. The likelihood of staying and moving at the the start of s = 0 and 30-month transitions increased, but the likelihood of staying were declined. For this cohort dataset, the presence of opportunistic disease, low body weight, baseline CD4 count, and baseline TB positive were risk factors for therapy adjustment. CONCLUSION: Given that the current study took into account a national dataset, it provides a solid basis for ART drug status and management. The patient had a higher likelihood of adjusting their treatment at some point during the follow-up period due to drug toxicity, comorbidity, drug not being available, and other factors, according to the prediction probability once more. Baseline TB positivity, low CD4 count, opportunistic disease, and low body weight were risk factors for therapy adjustment in this cohort dataset.

Associations of abdominal obesity with different types of bone fractures in adults: A systematic review and dose-response meta-analysis of prospective cohort studies.

Findings on the association between abdominal obesity and hip fracture were summarized in a meta-analysis in 2017; however, no study has examined the dose-response association between abdominal fat indices and hip fracture. Also, we found no meta-analysis investigating other types of bone fractures including any vertebral fractures in relation to abdominal obesity. Therefore, the present systematic review and dose-response meta-analysis of prospective cohort studies were conducted to examine the association between abdominal obesity and different types of bone fractures. A comprehensive literature search was done by searching PubMed, Scopus, Web of Science, and Google Scholar until October 2021. In total, 23 articles from prospective cohort studies with a total sample size of 3,456,631 participants were included. During the follow-up periods ranging between 4 and 26 years, 137,989 cases of bone fracture were recorded. After comparing the highest and lowest categories of abdominal fat indices, the summary relative risks (RRs) of any, hip, and vertebral fractures were 0.99 (95% CI: 0.81-1.20), 1.09 (95% CI: 0.82-1.43), and 1.18 (95% CI: 1.05-1.33), respectively, indicating a significant positive association between abdominal obesity and risk of vertebral fracture. In the non-linear dose-response analysis, abdominal obesity based on the waist-to-hip ratio (WHR) was positively associated with an increased risk of hip fracture from 0.7 to 1.1 units of WHR. In the linear analysis, a 10 cm increase in waist circumference (WC) was associated with a 3% higher risk of vertebral fracture. We found no other dose-response association for other types of bone fractures. In conclusion, abdominal obesity may be associated with a higher risk of hip and vertebral fractures.

Do Psychological and Behavioural Factors Change Over Pregnancy?

OBJECTIVES: To investigate how psychological and behavioural factors change from the first to the last half of pregnancy. METHODS: In this prospective cohort study, we assessed the changes in psychological and behavioural factors across 10 domains among 445 women (mean age = 30.9 years) in Ontario, Canada. We collected data using 2 standardized questionnaires administered at <21 and 32-36 weeks of gestation. We computed intraclass correlation coefficients, percentages of no change, decrease, and increase, and mean differences between the 2 surveys. RESULTS: Most psychological and behavioural factors had intraclass correlation coefficients < 0.50 between the first and the second half of pregnancy, suggesting remarkable changes over the course of pregnancy. We observed significant decreases in self-efficacy, compensatory health beliefs, guilt regarding binge eating, emotional eating, dietary restriction, pregnancy-related nausea and food cravings, sleep duration, and physical activity. We also found increases in anxious and depressive symptoms and the tendency to accept friends' and family's beliefs regarding pregnancy. CONCLUSIONS: In the first prospective analysis, we found that many psychological and behavioural factors changed significantly over pregnancy.

Resistance training prescription for muscle strength and hypertrophy in healthy adults: a systematic review and Bayesian network meta-analysis.

OBJECTIVE: To determine how distinct combinations of resistance training prescription (RTx) variables (load, sets and frequency) affect muscle strength and hypertrophy. DATA SOURCES: MEDLINE, Embase, Emcare, SPORTDiscus, CINAHL, and Web of Science were searched until February 2022. ELIGIBILITY CRITERIA: Randomised trials that included healthy adults, compared at least 2 predefined conditions (non-exercise control (CTRL) and 12 RTx, differentiated by load, sets and/or weekly frequency), and reported muscle strength and/or hypertrophy were included. ANALYSES: Systematic review and Bayesian network meta-analysis methodology was used to compare RTxs and CTRL. Surface under the cumulative ranking curve values were used to rank conditions. Confidence was assessed with threshold analysis. RESULTS: The strength network included 178 studies (n=5097; women=45%). The hypertrophy network included 119 studies (n=3364; women=47%). All RTxs were superior to CTRL for muscle strength and hypertrophy. Higher-load (>80% of single repetition maximum) prescriptions maximised strength gains, and all prescriptions comparably promoted muscle hypertrophy. While the calculated effects of many prescriptions were similar, higher-load, multiset, thrice-weekly training (standardised mean difference (95% credible interval); 1.60 (1.38 to 1.82) vs CTRL) was the highest-ranked RTx for strength, and higher-load, multiset, twice-weekly training (0.66 (0.47 to 0.85) vs CTRL) was the highest-ranked RTx for hypertrophy. Threshold analysis demonstrated these results were extremely robust. CONCLUSION: All RTx promoted strength and hypertrophy compared with no exercise. The highest-ranked prescriptions for strength involved higher loads, whereas the highest-ranked prescriptions for hypertrophy included multiple sets. PROSPERO REGISTRATION NUMBER: CRD42021259663 and CRD42021258902.

HIV infection and multidrug resistant tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) in HIV infected individuals is a serious threat to global efforts to combat tuberculosis. Inconsistent findings on the association between HIV infection and MDR-TB were present in many studies. We aimed to review existing data on the relationship between HIV infection and MDR-TB systematically to assess the contribution of HIV on MDR-TB worldwide. We also investigated the patterns of MDR-TB by age, country-wise income, study designs, and global regions. METHODS: We utilized PubMed, Google Scholar, and ScienceDirect databases to select eligible studies for meta-analysis that were published between January 12,010, and July 30, 2020. The random-effects model was used to obtain the pooled odds ratio of the crude association between HIV and MDR-TB with a 95% confidence interval. We investigated the potential publication-bias by checking funnel plot asymmetry and using the Egger's test. Moreover, we assessed the heterogeneity using the I2 statistic. Sensitivity analysis was performed based on sample size and adjustment factors. The protocol was registered with PROSPERO-CRD42019132752. RESULTS: We identified 1603 studies through a database search, and after subsequent eliminations we selected 54 studies including 430,534 TB patients. The pooled odds of MDR-TB was 1.42 times higher in HIV-positive patients than HIV-negative patients (OR=1.42,CI=1.17-1.71, I2=75.8%). Subgroup analysis revealed that the estimated pooled odds for South-East Asian countries was 1.86, which is the highest in WHO regions (OR=1.86,CI=1.30-2.67, I2=0.00%), followed by Europe and Africa. The effect estimate was found to be higher for primary MDR-TB (OR=2.76,CI=1.70-4.46, I2=0.00%). There was also a trend towards increased odds of MDR-TB for HIV patients older than 40 years (OR=1.56,CI=1.17-2.06). The association was found to be significant in high-burden TB countries (OR=1.75, CI=1.39-2.19) and in high-income countries (OR=1.55, CI=1.06-2.27). CONCLUSION: Such findings indicate that HIV infection raises the risk of MDR-TB, and after contrasting it with the results of the earlier pooled study, it appeared to be an upward risk trend. Moreover, we found that the risk is the highest in the South-East Asian region. A balanced allocation of resources is needed to halt both primary and secondary MDR-TB, particularly in HIV infected people with 40 years of age and older.

Gestational weight gain outside the 2009 Institute of Medicine recommendations: novel psychological and behavioural factors associated with inadequate or excess weight gain in a prospective cohort study.

BACKGROUND: Previous studies have noted traditional physical, demographic, and obstetrical predictors of inadequate or excess gestational weight gain, but the roles of psychological and behavioral factors are not well established. Few interventions targeting traditional factors of gestational weight gain have been successful, necessitating exploration of new domains. The objective of this study was to identify novel psychological and behavioral factors, along with physical, demographic, and obstetrical factors, associated with gestational weight gain that is discordant with the 2009 Institute of Medicine guidelines (inadequate or excess gain). METHODS: We recruited English-speaking women with a live singleton fetus at 8 to 20 weeks of gestation who received antenatal care from 12 obstetrical, family medicine, and midwifery clinics. A questionnaire was used to collect information related to demographic, physical, obstetrical, psychological, and behavioural factors anticipated to be related to weight gain. The association between these factors and total gestational weight gain, classified as inadequate, appropriate, and excess, was examined using stepwise multinomial logistic regression. RESULTS: Our study population comprised 970 women whose baseline data were obtained at a mean of 14.8 weeks of gestation ±3.4 weeks (standard deviation). Inadequate gestational weight gain was associated with obesity, planned gestational weight gain (below the guidelines or not reported), anxiety, and eating sensibly when with others but overeating when alone, while protective factors were frequent pregnancy-related food cravings and preferring an overweight or obese body size image. Excess gestational weight gain was associated with pre-pregnancy overweight or obese body mass index, planned gestational weight gain (above guidelines), frequent eating in front of a screen, and eating sensibly when with others but overeating when alone, while a protective factor was being underweight pre-pregnancy. CONCLUSIONS: In addition to commonly studied predictors, this study identified psychological and behavioral factors associated with inadequate or excess gestational weight gain. Factors common to both inadequate and excessive gestational weight gain were also identified, emphasizing the multidimensional nature of the contributors to guideline-discordant weight gain.

Neonatal and Maternal Outcomes of Lower Versus Standard Doses of Antenatal Corticosteroids for Women at Risk of Preterm Delivery: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: Our objective was to systematically review randomized and quasi-randomized trials on the neonatal and maternal effects of lower doses of antenatal corticosteroids (<24 mg of betamethasone or dexamethasone) compared with standard double doses of antenatal corticosteroids (24 mg of betamethasone or dexamethasone) administered to women at risk of preterm delivery. DATA SOURCES: Medline, Embase, CINAHL, Web of Science, Cochrane CENTRAL, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and the Australia New Zealand Clinical Trials Registry were searched from inception to December 8, 2019. STUDY SELECTION: A total of 2401 titles, abstracts, and protocols were independently screened by two reviewers, and subsequently 113 full-text articles were reviewed. DATA EXTRACTION: Our primary outcomes were perinatal death and severe respiratory distress syndrome. DATA SYNTHESIS: We identified one large in-progress trial comparing 11.4 mg versus 22.8 mg betamethasone and one published randomized controlled trial that compared a lower dose of dexamethasone (16 mg) to a standard dose of betamethasone (24 mg). The only relevant data from the published trial suggests minor changes in fetal heart rate variability between baseline and 24- to 48-hour follow-up between the two groups. Data for other outcomes had to be excluded due to the administration of weekly courses of antenatal corticosteroids. CONCLUSIONS: Randomized trial data comparing lower doses of antenatal corticosteroids to standard double doses are scarce. Given concerns regarding current antenatal corticosteroids dosing patterns, there is an urgent need for randomized controlled trials examining lower versus standard double doses of antenatal corticosteroids.

Admissions and Emergency Visits by Late Preterm Singletons and Twins in the First 5 Years: A Population-Based Cohort Study.

OBJECTIVE: To compare admission and emergency visits of late preterm (340/7-366/7 weeks) versus term infants (370/7-416/7 weeks) in the first 5 years. STUDY DESIGN: This population-based cohort study included all singletons and twins born alive at 340/7 to 416/7 weeks' gestation registered in a health administrative database in Ontario, Canada, between April 1, 2002 and December 31, 2012. Admissions and emergency visits from initial postnatal discharge to 5 years were compared between late preterm and term infants adjusting for maternal and infant characteristics. RESULTS: A total of 1,316,931 infants (75,364 late preterm infants) were included. Late preterm infants had more frequent admissions than term infants in the first 5 years in both singletons (adjusted incidence rate ratio [95% confidence interval] = 1.46 [1.42-1.49]) and twins (1.21 [1.11-1.31]). The difference in admissions between late preterm and term infants were smaller in twins than singletons and decreased with children's ages. Twins had less frequent admissions than singletons for late preterm infants, but not for term infants. The emergency visits were more frequent in late preterm than term infants in all the periods. CONCLUSION: Admissions and emergency visits were more frequent in late preterm than term infants through the first 5 years. Admissions were less frequent in late preterm twins than singletons.

Subnational mapping for targeting anaemia prevention in women of reproductive age in Ethiopia: A coverage-equity paradox.

Anaemia in women of reproductive age (WRA) can be effectively addressed if supported by a better understanding of the spatial variations, magnitude, severity and distribution of anaemia. This study aimed to map the subnational spatial distribution of anaemia (any, moderate and severe forms) among WRA in Ethiopia. We identified and mapped (any, moderate and severe) anaemia hotspots in WRA (n = 14,923) at the subnational level and identified risk factors using multilevel logistic regression. Kulldorff scan statistics were used to identify hotspot regions. Ordinary kringing was used to predict the anaemia prevalence in unmeasured areas. The overall anaemia prevalence increased from 16.6% in 2011 to 23.6% in 2016, a rise that was mostly related to the widening of existing hotspot areas. The primary clusters of (any) anaemia were in Somali and Afar regions. The horn of the Somali region represented a cluster of 330 km where 10% of WRA were severely anaemic. The Oromia-Somali border represented a significant cluster covering 247 km, with 9% severe anaemia. Population-dense areas with low anaemia prevalence had high absolute number of cases. Women education, taking iron-folic-acid tablets during pregnancy and birth-delivery in health facilities reduced the risk of any anaemia (P < 0.05). The local-level mapping of anaemia helped identify clusters that require attention but also highlighted the urgent need to study the aetiology of anaemia to improve the effectiveness and safety of interventions. Both relative and absolute anaemia estimates are critical to determine where additional attention is needed.

Hospital Care Cost and Resource Use of Early Discharge of Healthy Late Preterm and Term Singletons: A Population-based Cohort Study and Cost Analysis.

OBJECTIVE: To assess the hospital care cost and resource use associated with discharge timings after late preterm and term births. STUDY DESIGN: This population-based cohort study and cost analysis included all healthy singleton late preterm (35-36 weeks gestational age) and term infants (37-41 weeks gestational age) born vaginally in hospitals in Ontario, Canada, from 2003 to 2012. Early, late, and very late discharge (<48, 48-71, and 72-95 hours after birth, respectively) were compared using generalized linear models. The primary outcome was the total hospital care cost (hospitalizations and emergency department visits) per infant within 28 days of birth. RESULTS: Among 860 693 singletons (3.7% late preterm), early discharge increased significantly over 10 years for term infants (from 69% to 82%; P < .001), but not late preterm infants (from 32% to 35%; P = .75). The mean total cost within 28 days after birth was not significantly different for late preterm infants between early discharge and late discharge after adjustment. However, for term infants, the adjusted cost was higher with early discharge than late discharge (aMCD $311 [95% CI, $211-$412] per infant; $366 [95% CI, $355-$377] per mother-infant dyad). The neonatal readmission rates were higher after early than late discharge for late preterm and term infants. CONCLUSIONS: Early discharge was not associated with cost savings for vaginally born healthy singleton late preterm infants, and instead was associated with a cost increase for term infants. Early discharge was associated with higher neonatal readmission rates. Individualized approach balancing the risk and benefit is appropriate to determine the discharge timings.

Spatial patterns and associated factors of HIV Seropositivity among adults in Ethiopia from EDHS 2016: a spatial and multilevel analysis.

BACKGROUND: HIV is a major public health issue, especially in developing countries. It is important to track and design successful intervention programs to explore the spatial pattern, distribution, and associated factors of HIV Seropositivity. This study therefore showed the spatial variation of HIV Seropositivity and related factors in Ethiopia. METHODS: A total sample of 25,774 individual data collected from the 2016 EDHS data were primarily HIV biomarkers, IR, MR, and GPS. Spatial heterogeneity analysis was used with methods such as Morans I, Interpolation, and Kulldorff 's scan statistic. Spatial analysis was conducted using open source tools (QGIS, GeoDa, SaTScan). Multilevel logistic regression analysis was performed using Stata14 to identify HIV-associated factors. Finally, the AOR with a 95% confidence interval was used to report the mixed-effect logistic regression result in the full model. RESULT: The prevalence of HIV / AIDS at national level was 0.93%. The highest prevalence regions were Gambela, Addis Abeba, Harari and Diredawa, accounting for 4.79, 3.36, 2.65 and 2.6%, respectively. Higher HIV seropositive spatial clusters have been established in the Gambela and Addis Ababa regions. Multilevel analysis at the individual level being married [AOR = 2.19 95% CI: (1.11-4.31)] and previously married [AOR = 6.45, 95% CI: (3.06-13.59)], female [AOR = 1.8, 95% CI: (1.19-2.72)], first-sex at age ≤15 [AOR = 4.39, 95% CI: (1.70-11.34)], 18-19 [AOR = 2.67 95% CI: (1.05-6.8)], middle age group (25-34) [AOR = 6.53, 95% CI: (3.67-11.75)], older age group (>34) [AOR = 2.67 95% CI: (1.05-6.8)], primary school [AOR = 3.03, 95% CI: (1.92-4.79)], secondary school [AOR = 3.37, 95% CI: (1.92-5.92) were significantly associated with serropositivity. Regarding household level, place of residence [urban: AOR = 6.13 CI: (3.12, 12.06)], female-headed households (AOR = 2.24 95% CI: (1.57-3.73), media exposure [low exposure (AOR = 0.53 95% CI: (0.33-0.86), no exposure AOR = 0.39 95% CI: (0.23-0.65)] and increased household size [AOR = 0.72 95% CI: (0.65-0.8)] were associated with HIV Seropositivity. CONCLUSION: High cluster HIV cases were found in Gambela, Addis Abeba, Harari, and Diredawa. Having a history of married, start sex at a younger age, female-headed household, urban residence, and lower household size is more affected by HIV/AIDS. So any concerned body work around this risk group and area can be effective in the reduction of transmission.

Skew-normal random-effects model for meta-analysis of diagnostic test accuracy (DTA) studies.

Hierarchical models are recommended for meta-analyzing diagnostic test accuracy (DTA) studies. The bivariate random-effects model is currently widely used to synthesize a pair of test sensitivity and specificity using logit transformation across studies. This model assumes a bivariate normal distribution for the random-effects. However, this assumption is restrictive and can be violated. When the assumption fails, inferences could be misleading. In this paper, we extended the current bivariate random-effects model by assuming a flexible bivariate skew-normal distribution for the random-effects in order to robustly model logit sensitivities and logit specificities. The marginal distribution of the proposed model is analytically derived so that parameter estimation can be performed using standard likelihood methods. The method of weighted-average is adopted to estimate the overall logit-transformed sensitivity and specificity. An extensive simulation study is carried out to investigate the performance of the proposed model compared to other standard models. Overall, the proposed model performs better in terms of confidence interval width of the average logit-transformed sensitivity and specificity compared to the standard bivariate linear mixed model and bivariate generalized linear mixed model. Simulations have also shown that the proposed model performed better than the well-established bivariate linear mixed model in terms of bias and comparable with regards to the root mean squared error (RMSE) of the between-study (co)variances. The proposed method is also illustrated using a published meta-analysis data.

Correction to: Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial.

In contrast to statements made in the above paper, measurements of waist and hip circumference were in fact available.

Phenotypic Classification of preterm Birth Among Multiparous Women: A Population-Based Cohort Study.

OBJECTIVE: The Global Alliance to Prevent Prematurity and Stillbirth developed a phenotypic classification for preterm birth using clinical presentation (rather than risk factors) to improve surveillance. The objective of this study was to determine distributions of preterm birth phenotypes and associations with Caesarean section, low Apgar score, and neonatal death in multiparous women, stratifying by first versus recurrent preterm births. METHODS: This population-based cohort study used the Better Outcomes Registry and Network (BORN) of multiparous women giving birth in hospital with a singleton after 20 weeks in Ontario from 2012 to 2014 (Canadian Task Force Classification II-2). RESULTS: In multiparous women with preterm birth, 29.6% had a history of recurrence, of whom 66.2% had at least one clinical condition associated with the phenotypic model, compared with 63.5% of first preterm births. In recurrent preterm births, criteria for maternal, fetal, and placental conditions were met in 44.5%, 37.9%, and 8.2%, respectively, compared with 36.8%, 39.0%, and 10.4%, respectively, of first preterm births. Associations of preterm birth with Caesarean section, low Apgar score, and neonatal death varied across clinical conditions but were similar between first and recurrent preterm births; for example, for recurrent preterm birth, Caesarean section for maternal, fetal, and placental conditions had odds ratios of 1.66 (95% confidence interval [CI] 1.32-2.07), 1.09 (95% CI 0.80-1.49), and 3.92 (95% CI 1.98-7.78), compared with first preterm birth odds ratios of 1.21 (95% CI 1.03-1.41), 0.92 (95% CI 0.77-1.10), and 6.24 (95% CI 4.07-9.56). CONCLUSION: This study provides novel evidence of the utility of the preterm birth phenotypic classification model by using stratification for previous preterm birth, a robust predictor-with variation in phenotypes in initial and recurrent preterm births.

Phenotypic Classification of Preterm Birth Among Nulliparous Women: A Population-Based Cohort Study.

OBJECTIVE: A classification model based on preterm birth clinical presentations (phenotypes) was proposed at the International Conference on Prematurity and Stillbirth, with calls for validation. This study sought to determine the distribution of clinical phenotypes of preterm birth among nulliparous women, their corresponding associations with maternal characteristics, and the odds ratios (ORs) of preterm Caesarean section and other adverse outcomes. METHODS: A population-based cohort study was performed of all nulliparous women with singleton pregnancies (>20 weeks) who gave birth in a hospital in Ontario between 2012 and 2014. Logistic regression models were used to estimate adjusted ORs (Canadian Task Force Classification II-2). RESULTS: Among 113 942 nulliparous women, 6.1% delivered at <37 weeks, at a mean gestational age of 33.9 weeks. Of those women, 34.1% did not meet the criteria for the presence of any clinical phenotype; 42.3% had one maternal, fetal, or placental condition; 22.3% had two clinical conditions; and 1.3% had three clinical conditions. The most common preterm birth phenotypes were worsening of maternal diseases (24.0%), intrauterine growth restriction (23.5%), and fetal distress (23.0%). Compared with preterm births without any significant clinical phenotype, those with maternal, fetal, or placental phenotypes were associated with increased odds of Caesarean section (adjusted ORs 2.70 [95% confidence interval [CI] 2.30-3.17], 1.66 [95% CI 1.36-2.03], and 6.49 [95% CI 4.29-9.80], respectively). CONCLUSION: Approximately two thirds of nulliparous preterm births were grouped into distinct clinical phenotypes. This study demonstrated that outcomes varied across phenotypes, thus providing evidence of benefit for the phenotypic classification model.

Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial.

AIMS/HYPOTHESIS: In line with current advice, we assessed the effect of replacing carbohydrate consumption with mixed nut consumption, as a source of unsaturated fat, on cardiovascular risk factors and HbA1c in type 2 diabetes. The data presented here are from a paper that was retracted at the authors' request ( https://doi.org/10.2337/dc16-rt02 ) owing to lack of adjustment for repeated measures in the same individual. Our aim, therefore, was to fix the error and add new complementary data of interest, including information on clotting factors and LDL particle size. METHODS: A total of 117 men and postmenopausal women with type 2 diabetes who were taking oral glucose-lowering agents and with HbA1c between 47.5 and 63.9 mmol/mol (6.5-8.0%) were randomised after stratification by sex and baseline HbA1c in a parallel design to one of three diets for 3 months: (1) 'full-dose nut diet' (n = 40): a diet with 2.0 MJ (477 kcal) per 8.4 MJ (2000 kcal) energy provided as mixed nuts (75 g/day); (2) 'full-dose muffin diet' (n = 39): a diet with 1.97 MJ (471 kcal) per 8.4 MJ (2000 kcal) energy provided as three whole-wheat muffins (188 g/day), with a similar protein content to the nuts, and the same carbohydrate-derived energy content as the monounsaturated fatty acid-derived energy content in the nuts; or (3) 'half-dose nut diet' (n = 38): a diet with 1.98 MJ (474 kcal) per 8.4 MJ (2000 kcal) energy provided as half portions of both the nuts and muffins. The primary outcome was change in HbA1c. The study was carried out in a hospital clinical research centre and concluded in 2008. Only the statistician, study physicians and analytical technicians could be blinded to the group assessment. RESULTS: A total of 108 participants had post-intervention data available for analysis (full-dose nut group, n = 40; full-dose muffin group, n = 35; half-dose nut group, n = 33). Compared with the full-dose muffin diet, the full-dose nut diet provided 9.2% (95% CI 7.1, 11.3) greater total energy intake from monounsaturated fat. The full-dose nut diet (median intake, 75 g/day) also reduced HbA1c compared with the full-dose muffin diet by -2.0 mmol/mol (95% CI -3.8, -0.3 mmol/mol) (-0.19% [95% CI -0.35%, -0.02%]), (p = 0.026). Estimated cholesterol levels in LDL particles with a diameter <255 ångström [LDL-c<255Å]) and apolipoprotein B were also significantly decreased after the full-dose nut diet compared with the full-dose muffin diet. According to the dose response, the full-dose nut diet is predicted to reduce HbA1c (-2.0 mmol/mol [-0.18%]; p = 0.044), cholesterol (-0.25 mmol/l; p = 0.022), LDL-cholesterol (-0.23 mmol/l; p = 0.019), non-HDL-cholesterol (-0.26 mmol/l; p = 0.020), apolipoprotein B (-0.06 g/l, p = 0.013) and LDL-c<255Å (-0.42 mmol/l; p < 0.001). No serious study-related adverse events occurred, but one participant on the half-dose nut diet was hospitalised for atrial fibrillation after shovelling snow. CONCLUSIONS/INTERPRETATION: Nut intake as a replacement for carbohydrate consumption improves glycaemic control and lipid risk factors in individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00410722 FUNDING: The study was funded by the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Loblaw Companies and the Canada Research Chairs Program of the Government of Canada.

MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer: the hOrmone and Diet in the ETiology of breast cancer prospective study.

MicroRNAs (miRNAs) might be considered both predictors and players of cancer development. The aim of the present report was to investigate whether many years before the diagnosis of breast cancer miRNA expression is already disregulated. In order to test this hypothesis, we compared miRNAs extracted from leukocytes in healthy women who later developed breast cancer and in women who remain healthy during the whole 15-year follow-up time. Accordantly, we used a case-control study design nested in the hOrmone and Diet in the ETiology of breast cancer (ORDET) prospective cohort study addressing the possibility that miRNAs can serve as both early biomarkers and components of the hormonal etiological pathways leading to breast cancer development in premenopausal women. We compared leukocyte miRNA profiles of 191 incident premenopausal breast cancer cases and profiles of 191 women who remained healthy over a follow-up period of 20 years. The analysis identified 20 differentially expressed miRNAs in women candidate to develop breast cancer versus control women. The upregulated miRNAs, miR-513-a-5p, miR-513b-5p and miR-513c-5p were among the most significantly deregulated miRNAs. In multivariate analysis, miR-513a-5p upregulation was directly and statistically significant associated with breast cancer risk (OR = 1.69; 95% CI 1.08-2.64; P = 0.0293). In addition, the upregulation of miR-513-a-5p displayed the strongest direct association with serum progesterone and testosterone levels. The experimental data corroborated the inhibitory function of miR-513a-5p on progesterone receptor expression confirming that progesterone receptor is a target of miR-513a-5p. The identification of upregulated miR-513a-5p with its oncogenic potential further validates the use of miRNAs as long-term biomarker of breast cancer risk.

Statistical models and computational algorithms for discovering relationships in microbiome data.

Microbiomes, populations of microscopic organisms, have been found to be related to human health and it is expected further investigations will lead to novel perspectives of disease. The data used to analyze microbiomes is one of the newest types (the result of high-throughput technology) and the means to analyze these data is still rapidly evolving. One of the distributions that have been introduced into the microbiome literature, the Dirichlet-Multinomial, has received considerable attention. We extend this distribution's use uncover compositional relationships between organisms at a taxonomic level. We apply our new method in two real microbiome data sets: one from human nasal passages and another from human stool samples.

Comparing the performance of linear and nonlinear principal components in the context of high-dimensional genomic data integration.

Linear principal component analysis (PCA) is a widely used approach to reduce the dimension of gene or miRNA expression data sets. This method relies on the linearity assumption, which often fails to capture the patterns and relationships inherent in the data. Thus, a nonlinear approach such as kernel PCA might be optimal. We develop a copula-based simulation algorithm that takes into account the degree of dependence and nonlinearity observed in these data sets. Using this algorithm, we conduct an extensive simulation to compare the performance of linear and kernel principal component analysis methods towards data integration and death classification. We also compare these methods using a real data set with gene and miRNA expression of lung cancer patients. First few kernel principal components show poor performance compared to the linear principal components in this occasion. Reducing dimensions using linear PCA and a logistic regression model for classification seems to be adequate for this purpose. Integrating information from multiple data sets using either of these two approaches leads to an improved classification accuracy for the outcome.

Pregnancy outcomes in women taking probiotics or prebiotics: a systematic review and meta-analysis.

BACKGROUND: Probiotics are living microorganisms that, when administered in adequate amounts, confer a health benefit. It has been speculated that probiotics might help prevent preterm birth, but in two previous systematic reviews possible major increases in this risk have been suggested. Our objective was to perform a systematic review and meta-analysis of the risk of preterm birth and other adverse pregnancy outcomes in pregnant women taking probiotics, prebiotics or synbiotics. METHODS: We searched six electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Web of Science's Core collection and BIOSIS Preview) up to September 2016 and contacted authors for additional data. We included randomized controlled trials in which women with a singleton pregnancy received a probiotic, prebiotic or synbiotic intervention. Two independent reviewers extracted data using a piloted form and assessed the risk of bias using the Cochrane risk of bias tool. We used random-effects meta-analyses to pool the results. RESULTS: We identified 2574 publications, screened 1449 non-duplicate titles and abstracts and read 160 full text articles. The 49 publications that met our inclusion criteria represented 27 studies. No study used synbiotics, one used prebiotics and the rest used probiotics. Being randomized to take probiotics during pregnancy neither increased nor decreased the risk of preterm birth < 34 weeks (RR 1.03, 95% CI 0.29-3.64, I2 0%, 1017 women in 5 studies), preterm birth < 37 weeks (RR 1.08, 95% CI 0.71-1.63, I2 0%, 2484 women in 11 studies), or most of our secondary outcomes, including gestational diabetes mellitus. CONCLUSIONS: We found no evidence that taking probiotics or prebiotics during pregnancy either increases or decreases the risk of preterm birth or other infant and maternal adverse pregnancy outcomes. TRIAL REGISTRATION: We prospectively published the protocol for this study in the PROSPERO database ( CRD42016048129 ).