Individual Organ Failure and Concomitant Risk of Mortality Differs According to the Type of Admission to ICU – A Retrospective Study of SOFA Score of 23,795 Patients

Introduction

Organ dysfunction or failure after the first days of ICU treatment and subsequent mortality with respect to the type of intensive care unit (ICU) admission is poorly elucidated. Therefore we analyzed the association of ICU mortality and admission for medical (M), scheduled surgery (ScS) or unscheduled surgery (US) patients mirrored by the occurrence of organ dysfunction/failure (OD/OF) after the first 72h of ICU stay.

Methods

For this retrospective cohort study (23,795 patients; DIVI registry; German Interdisciplinary Association for Intensive Care Medicine (DIVI)) organ dysfunction or failure were derived from the Sequential Organ Failure Assessment (SOFA) score (excluding the Glasgow Coma Scale). SOFA scores were collected on admission to ICU and 72h later. For patients with a length of stay of at least five days, a multivariate analysis was performed for individual OD/OF on day three.

Results

M patients had the lowest prevalence of cardiovascular failure (M 31%; ScS 35%; US 38%), and the highest prevalence of respiratory (M 24%; ScS 13%; US 17%) and renal failure (M 10%; ScS 6%; US 7%). Risk of death was highest for M- and ScS-patients in those with respiratory failure (OR; M 2.4; ScS 2.4; US 1.4) and for surgical patients with renal failure (OR; M 1.7; ScS 2.7; US 2.4).

Conclusion

The dynamic evolution of OD/OF within 72h after ICU admission and mortality differed between patients depending on their types of admission. This has to be considered to exclude a systematic bias during multi-center trials.     

Frequency of False Positive Rapid HIV Serologic Tests in African Men and Women Receiving PrEP for HIV Prevention: Implications for Programmatic Roll-Out of Biomedical Interventions

Background

Rapid HIV assays are the mainstay of HIV testing globally. Delivery of effective biomedical HIV prevention strategies such as antiretroviral pre-exposure prophylaxis (PrEP) requires periodic HIV testing. Because rapid tests have high (>95%) but imperfect specificity, they are expected to generate some false positive results.

Methods

We assessed the frequency of true and false positive rapid results in the Partners PrEP Study, a randomized, placebo-controlled trial of PrEP. HIV testing was performed monthly using 2 rapid tests done in parallel with HIV enzyme immunoassay (EIA) confirmation following all positive rapid tests.

Results

A total of 99,009 monthly HIV tests were performed; 98,743 (99.7%) were dual-rapid HIV negative. Of the 266 visits with ≥1 positive rapid result, 99 (37.2%) had confirmatory positive EIA results (true positives), 155 (58.3%) had negative EIA results (false positives), and 12 (4.5%) had discordant EIA results. In the active PrEP arms, over two-thirds of visits with positive rapid test results were false positive results (69.2%, 110 of 159), although false positive results occurred at <1% (110/65,945) of total visits.

Conclusions

When HIV prevalence or incidence is low due to effective HIV prevention interventions, rapid HIV tests result in a high number of false relative to true positive results, although the absolute number of false results will be low. Program roll-out for effective interventions should plan for quality assurance of HIV testing, mechanisms for confirmatory HIV testing, and counseling strategies for persons with positive rapid test results.     

Leukocyte Subtype Counts and Its Association with Vascular Structure and Function in Adults with Intermediate Cardiovascular Risk. MARK Study

Objectives

We investigated the relationship between leukocyte subtype counts and vascular structure and function based on carotid intima-media thickness, pulse wave velocity, central augmentation index and cardio-ankle vascular index by gender in intermediate cardiovascular risk patients.

Methods

This study analyzed 500 subjects who were included in the MARK study, aged 35 to 74 years (mean: 60.3±8.4), 45.6% women. Measurement: Brachial ankle Pulse Wave Velocity (ba-PWV) estimate by equation, Cardio-AnkleVascular Index (CAVI) using the VaSera device and Carotid ultrasound was used to measure carotid Intima Media Thickness (IMT). The Mobil-O-Graph was used to measure the Central Augmentation Index (CAIx).

Results

Total leukocyte, neutrophil and monocyte counts were positively correlated with IMT (p < 0.01) in men. Monocyte count was positively correlated with CAIx in women (p < 0.01). In a multiple linear regression analysis, the IMT mean maintained a positive association with the neutrophil count (β = 1.500, p = 0.007) in men. CAIx maintained a positive association with the monocyte count (β = 2.445, p = 0.022) in women.

Conclusion

The results of this study suggest that the relationship between subtype circulating leukocyte counts and vascular structure and function, although small, may be different by gender. In men, the neutrophil count was positively correlated with IMT and in women, the monocyte count with CAIx, in a large sample of intermediate-risk patients. These association were maintained after adjusting for age and other confounders.

Trial Registration

ClinicalTrials.gov NCT01428934     

Persistence of Transmitted HIV-1 Drug Resistance Mutations Associated with Fitness Costs and Viral Genetic Backgrounds

Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM) can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare.Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS). All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR) determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities) and were included in the survival models as explanatory variables.In 857 sequential samples from 168 treatment-naïve patients, 17 TDRM were analyzed. RR varied substantially and ranged from 174.0/100-person-years;CI=[51.4, 588.8] (for 184V) to 2.7/100-person-years;[0.7, 10.9] (for 215D). RR increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs). When subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background, we found that both components were significantly associated with reversion-rates.Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation.     

The Impact of the Thai Motorcycle Transition on Road Traffic Injury: Thai Cohort Study Results

Objectives

The aim of this study was to investigate the impact of motorcycle to car transitioning and urbanisation on traffic injury rates in Thailand.

Design

Analysis of two consecutive surveys of a large national cohort study.

Setting

Thailand.

Participants

The data derived from 57,154 Thai Cohort Study (TCS) participants who provided relevant data on both the 2005 and 2009 surveys.

Primary and secondary outcome measures

Motorcycle and car traffic crash injury self-reported in 2009, with twelve months’ recall.

Results

In 2009, 5608(10%) participants reported a traffic crash injury. Most crashes involved a motorcycle (74%). Car access increased and motorcycle use decreased between 2005 and 2009. Among those who used a motorcycle at both time points, traffic injury incidence was 2.8 times greater compared to those who did not use a motorcycle at either time point. Multivariable logistic regression models were used to test longitudinal and cross sectional factors associated with traffic crash injury: in the adjusted model, cars were negatively and motorcycles positively associated with injury. Living in an urban area was not injury protective in the adjusted model of traffic crash injury.

Conclusions

Ongoing urbanisation in Thailand can be expected to lead to further reductions in road traffic injuries based on transition from motorcycles to cars in urban areas. Cities, however, do not provide an intrinsically safer traffic environment. To accommodate a safe transition to car use in Thailand, traffic infrastructural changes anticipating the growing car density in urban areas is warranted.     

Intra-Rater and Inter-Rater Reliability of a Medical Record Abstraction Study on Transition of Care after Childhood Cancer

BackgroundThe abstraction of data from medical records is a widespread practice in epidemiological research. However, studies using this means of data collection rarely report reliability. Within the Transition after Childhood Cancer Study (TaCC) which is based on a medical record abstraction, we conducted a second independent abstraction of data with the aim to assess a) intra-rater reliability of one rater at two time points; b) the possible learning effects between these two time points compared to a gold-standard; and c) inter-rater reliability.MethodWithin the TaCC study we conducted a systematic medical record abstraction in the 9 Swiss clinics with pediatric oncology wards. In a second phase we selected a subsample of medical records in 3 clinics to conduct a second independent abstraction. We then assessed intra-rater reliability at two time points, the learning effect over time (comparing each rater at two time-points with a gold-standard) and the inter-rater reliability of a selected number of variables. We calculated percentage agreement and Cohen’s kappa.FindingsFor the assessment of the intra-rater reliability we included 154 records (80 for rater 1; 74 for rater 2). For the inter-rater reliability we could include 70 records. Intra-rater reliability was substantial to excellent (Cohen’s kappa 0-6-0.8) with an observed percentage agreement of 75%-95%. In all variables learning effects were observed. Inter-rater reliability was substantial to excellent (Cohen’s kappa 0.70-0.83) with high agreement ranging from 86% to 100%.ConclusionsOur study showed that data abstracted from medical records are reliable. Investigating intra-rater and inter-rater reliability can give confidence to draw conclusions from the abstracted data and increase data quality by minimizing systematic errors.     

Effect of Cytomegalovirus Co-Infection on Normalization of Selected T-Cell Subsets in Children with Perinatally Acquired HIV Infection Treated with Combination Antiretroviral Therapy

Background

We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithm study.

Methods

Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry.

Results

Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets.

Conclusions

In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system.