Antiretroviral therapy optimisation without genotype resistance testing: a perspective on treatment history based models

Background

Although genotypic resistance testing (GRT) is recommended to guide combination antiretroviral therapy (cART), funding and/or facilities to perform GRT may not be available in low to middle income countries. Since treatment history (TH) impacts response to subsequent therapy, we investigated a set of statistical learning models to optimise cART in the absence of GRT information.

Methods and Findings

The EuResist database was used to extract 8-week and 24-week treatment change episodes (TCE) with GRT and additional clinical, demographic and TH information. Random Forest (RF) classification was used to predict 8- and 24-week success, defined as undetectable HIV-1 RNA, comparing nested models including (i) GRT+TH and (ii) TH without GRT, using multiple cross-validation and area under the receiver operating characteristic curve (AUC). Virological success was achieved in 68.2% and 68.0% of TCE at 8- and 24-weeks (n = 2,831 and 2,579), respectively. RF (i) and (ii) showed comparable performances, with an average (st.dev.) AUC 0.77 (0.031) vs. 0.757 (0.035) at 8-weeks, 0.834 (0.027) vs. 0.821 (0.025) at 24-weeks. Sensitivity analyses, carried out on a data subset that included antiretroviral regimens commonly used in low to middle income countries, confirmed our findings. Training on subtype B and validation on non-B isolates resulted in a decline of performance for models (i) and (ii).

Conclusions

Treatment history-based RF prediction models are comparable to GRT-based for classification of virological outcome. These results may be relevant for therapy optimisation in areas where availability of GRT is limited. Further investigations are required in order to account for different demographics, subtypes and different therapy switching strategies.     

Predictors of Costs in Dementia in a Longitudinal Perspective

Objective

To analyse predictors of costs in dementia from a societal perspective in a longitudinal setting.

Method

Healthcare resource use and costs were assessed retrospectively using a questionnaire in four waves at 6-month intervals in a sample of dementia patients (N = 175). Sociodemographic data, dementia severity and comorbidity at baseline, cognitive impairment and impairment in basic and instrumental activities of daily living were also recorded. Linear mixed regression models with random intercepts for individuals were used to analyse predictors of total and sector-specific costs.

Results

Impairment in activities of daily living significantly predicted total costs in dementia patients, with associations between basic activities of daily living and formal care costs on the one and instrumental activities of daily living and informal care costs on the other hand. Nursing home residence was associated with lower total costs than residence in the community. There was no effect of cognition on total or sector-specific costs.

Conclusion

Cognitive deficits in dementia are associated with costs only via their effect on the patients'' capacity for activities of daily living. Transition into a nursing home may reduce total costs from a societal perspective, owing to the fact that a high amount of informal care required by severely demented patients prior to transition into a nursing home may cause higher costs than inpatient nursing care.     

Definition of miRNAs Expression Profile in Glioblastoma Samples: The Relevance of Non-Neoplastic Brain Reference

Glioblastoma is the most aggressive brain tumor that may occur in adults. Regardless of the huge improvements in surgery and molecular therapy, the outcome of neoplasia remains poor. MicroRNAs are small molecules involved in several cellular processes, and their expression is altered in the vast majority of tumors. Several studies reported the expression of different miRNAs in glioblastoma, but one of the most critical point in understanding glioblastoma miRNAs profile is the comparison of these studies. In this paper, we focused our attention on the non-neoplastic references used for determining miRNAs expression. The aim of this study was to investigate if using three different non-neoplastic brain references (normal adjacent the tumor, commercial total RNA, and epileptic specimens) could provide discrepant results. The analysis of 19 miRNAs was performed using Real-Time PCR, starting from the set of samples described above and the expression values compared. Moreover, the three different normal RNAs were used to determine the miRNAs profile in 30 glioblastomas. The data showed that different non-neoplastic controls could lead to different results and emphasize the importance of comparing miRNAs profiles obtained using the same experimental condition.     

Economic Impact of Maternal Death on Households in Rural China: A Prospective Cohort Study

Objective

To assess the economic impact of maternal death on rural Chinese households during the year after maternal death.

Methods

A prospective cohort study matched 183 households who had suffered a maternal death to 346 households that experienced childbirth without maternal death in rural areas of three provinces in China. Surveys were conducted at baseline (1–3 months after maternal death or childbirth) and one year after baseline using the quantitative questionnaire. We investigated household income, expenditure, accumulated debts, and self-reported household economic status. Difference-in-Difference (DID), linear regression, and logistic regression analyses were used to compare the economic status between households with and without maternal death.

Findings

The households with maternal death had a higher risk of self-reported “household economy became worse” during the follow-up period (adjusted OR = 6.04, p<0.001). During the follow-up period, at the household level, DID estimator of income and expenditure showed that households with maternal death had a significant relative reduction of US$ 869 and US$ 650, compared to those households that experienced childbirth with no adverse event (p<0.001). Converted to proportions of change, an average of 32.0% reduction of annual income and 24.9% reduction of annual expenditure were observed in households with a maternal death. The mean increase of accumulated debts in households with a maternal death was 3.2 times as high as that in households without maternal death (p = 0.024). Expenditure pattern of households with maternal death changed, with lower consumption on food (p = 0.037), clothes and commodity (p = 0.003), traffic and communication (p = 0.022) and higher consumption on cigarette or alcohol (p = 0.014).

Conclusion

Compared with childbirth, maternal death had adverse impact on household economy, including higher risk of self-reported “household economy became worse”, decreased income and expenditure, increased debts and changed expenditure pattern.     

Effects of Multidisciplinary Rehabilitation on Chronic Fatigue in Multiple Sclerosis: A Randomized Controlled Trial

Background

Several rehabilitation programmes aim at reducing the impact of fatigue in MS patients. Acute and chronic fatigue should require different management.

Objectives

To assess the effects of individually tailored, multidisciplinary outpatient rehabilitation (MDR) on chronic fatigue.

Methods

Forty-eight ambulatory MS patients with chronic fatigue were randomized to MDR or to MS–nurse consultation. Fatigue was assessed by the Checklist Individual Strength (CIS-20R). Secondary outcomes included the Modified Fatigue Impact Scale, Fatigue Severity Scale, Functional Independence Measure, Disability and Impact Profile (DIP), Multiple Sclerosis Impact Scale and the Impact on Participation and Autonomy (IPA).

Results

The primary outcome measure CIS-20R overall score showed no significant differences between groups at 12 weeks (P = 0.39) and 24 weeks follow-up (P = 0.14), nor for subscales (t = 12 and t = 24, 0.19≤P≤0.88). No significant within-group effects were found for both groups with respect to the primary (0.57≤p≤0.97) and secondary (0.11≤p≤0.92) outcome measures from baseline to 12 or 24 weeks.

Conclusion

Multidisciplinary rehabilitation was not more effective in terms of reducing self-reported fatigue in MS patients compared to MS-nurse consultation. Our results suggest that chronic fatigue in patients with MS may be highly invariant over time, irrespective of interventions.

Trial Registration

controlled-trials.com ISRCTN05017507     

Body Mass Index and Mortality in Korean Intensive Care Units: A Prospective Multicenter Cohort Study

Background

The level of body mass index (BMI) that is associated with the lowest mortality in critically ill patients in Asian populations is uncertain. We aimed to examine the association of BMI with hospital mortality in critically ill patients in Korea.

Methods

We conducted a prospective multicenter cohort study of 3,655 critically ill patients in 22 intensive care units (ICUs) in Korea. BMI was categorized into five groups: <18.5, 18.5 to 22.9, 23.0 to 24.9 (the reference category), 25.0 to 29.9, and ≥30.0 kg/m².

Results

The median BMI was 22.6 (IQR 20.3 to 25.1). The percentages of patients with BMI<18.5, 18.5 to 22.9, 23.0 to 24.9, 25.0 to 29.9, and ≥30.0 were 12, 42.3, 19.9, 22.4, and 3.3%, respectively. The Cox-proportional hazard ratios with exact partial likelihood to handle tied failures for hospital mortality comparing the BMI categories <18.5, 18.5 to 22.9, 25.0 to 29.9, and ≥30.0 with the reference category were 1.13 (0.88 to 1.44), 1.03 (0.84 to 1.26), 0.96 (0.76 to 1.22), and 0.68 (0.43 to 1.08), respectively, with a highly significant test for trend (p = 0.02).

Conclusions

A graded inverse association between BMI and hospital mortality with a strong significant trend was found in critically ill patients in Korea.     

Tobacco Smoking in HIV-Infected versus General Population in France: Heterogeneity across the Various Groups of People Living with HIV

Background

Although the various groups of people living with HIV (PLWHIV) considerably differ regarding socioeconomic and behavioral characteristics, their specificities regarding tobacco smoking have been poorly investigated. We aimed to assess patterns of tobacco consumption across the various groups of PLWHIV and to compare them to the general population, accounting for the specific socioeconomic profile of PLWHIV.

Methods

We used data of the ANRS-Vespa2 study, a national representative survey on PLWHIV conducted in France in 2011. Prevalence of past and current tobacco consumption, heavy smoking and strong nicotine dependence were assessed among the various groups of PLWHIV as defined by transmission category, gender and geographic origin, and compared to the French general population using direct standardization and multivariate Poisson regression models, accounting for gender, age, education and geographic origin.

Results

Among the 3,019 participants aged 18–85 years (median time since HIV diagnosis: 12 years), 37.5% were current smokers and 22.1% were past smokers, with marked differences across the various groups of PLWHIV. Compared to the general population, the prevalence of regular smoking was increased among HIV-infected men who have sex with men (MSM) (adjusted prevalence rate ratio (aPRR): 1.19, 95% confidence interval (95% CI): 1.07–1.32), French-native women (aPRR: 1.32, 95% CI: 1.10–1.57), and heterosexual French-native men (although not significantly, aPRR: 1.19, 95% CI: 0.98–1.45). Additionally, HIV-infected MSM were significantly less likely to be ex-smokers (aPRR: 0.73, 95% CI: 0.64–0.82) than the general population and similar trends were observed among heterosexual French-native men (aPRR: 0.89, 95% CI: 0.78–1.02) and women (aPRR: 0.84, 95% CI: 0.70–1.01). HIV-infected sub-Saharan African migrants were less likely to be regular smokers than the general population.

Conclusions

Smoking constitutes a major concern in various groups of PLWHIV in France including MSM and heterosexual French-natives, probably resulting from PLWHIV being less likely to quit smoking than their counterparts in the general population.     

The effect of ponderal index at birth on the relationships between common LEP and LEPR polymorphisms and adiposity in adolescents

This study examined the effect of ponderal index (PI) at birth on the relationships between eight common polymorphisms of the leptin (LEP) and leptin receptor (LEPR) genes and adiposity in adolescents. A total of 823 European adolescents (45.4% girls) aged 14.8 ± 1.4 years were genotyped for the LEP (rs2167270, rs12706832, rs10244329, rs2071045, and rs3828942) and LEPR (rs1137100, rs1137101, and rs8179183) polymorphisms. The PI was calculated from parental reports of birth weight and length. Fat mass index (FMI) was calculated. Analyses were adjusted for relevant confounders. An "adiposity-risk-allele score" based on genotypes at the three single-nucleotide polymorphisms (SNPs) associated with adolescents' FMI in adolescents within the lower tertile of PI was calculated. The LEP rs10244329 and rs3828942 polymorphisms were associated with higher FMI only in adolescents within the lower PI tertile (+0.55 kg/m(2) per minor T allele, P = 0.040, and +0.58 kg/m(2) per major G allele, P = 0.028, respectively). The LEPR rs8179183 polymorphism was significantly associated with higher FMI in adolescents within the lower PI tertile (+0.87 kg/m(2) per minor C allele, P = 0.006). After correction for multiple comparisons, only the association between the LEPR rs8179183 and FMI persisted. However, each additional risk allele conferred 0.53 kg/m(2) greater FMI in adolescents within the lower tertile of PI (P = 0.008). In conclusion, our results suggest that those adolescents born with lower PI could be more vulnerable to the influence of the LEP rs10244329 and rs3828942 polymorphisms and LEPR rs8179183 polymorphism on total adiposity content. Due to the relatively small sample size, these findings should be replicated in further larger population samples.     

Influence of marital status and employment status on long-term adherence with continuous positive airway pressure in sleep apnea patients

Background

Long-term adherence is a major issue in patients receiving home continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea-hypopnea syndrome (OSAHS). In a multicenter prospective cohort (the Institut de Recherche en Santé Respiratoire des Pays de la Loire [IRSR] sleep cohort) of consecutive OSAHS patients in whom CPAP had been prescribed for at least 90 days, we studied the impact on long-term treatment adherence of socioeconomic factors, patients and disease characteristics prior to CPAP initiation.

Methods and Principal Findings

Among 1,141 patients in whom CPAP had been prescribed for an average of 504±251 days (range: 91 to 1035), 674 (59%) were adherent with a mean daily use of CPAP≥4 h (mean: 6.42±1.35 h). Stepwise regression analysis identified 4 independent factors of CPAP adherence including apnea-hypopnea index (AHI) (OR: 1.549, 95%CI 1.163 to 2.062 for AHI≥30 vs. AHI<30; p = 0.003), body mass index (BMI) (OR: 1.786, 95%CI 1.131 to 2.822 for BMI≥25 and <30 kg/m², p = 0.01; OR: 1.768, 95%CI 1.145–2.731 for BMI≥30 kg/m², p = 0.01 vs. BMI<25 kg/m²), employment status (OR: 1.414, 95%CI 1.097–1.821 for retired vs. employed; p = 0.007) and marital status (OR: 1.482, 95%CI 1.088–2.019 for married or living as a couple vs. living alone; p = 0.01). Age, gender, Epworth sleepiness scale, depressive syndrome, associated cardiovascular morbidities, educational attainment and occupation category did not influence CPAP adherence.

Conclusions

Marital status and employment status are independent factors of CPAP adherence in addition to BMI and disease severity. Patients living alone and/or working patients are at greater risk of non-adherence, whereas adherence is higher in married and retired patients. These findings suggest that the social context of daily life should be taken into account in risk screening for CPAP non-adherence. Future interventional studies targeting at-risk patients should be designed to address social motivating factors and work-related barriers to CPAP adherence.