Restrictive left ventricular filling pattern and risk of new-onset atrial fibrillation after acute myocardial infarction

Mechanisms for atrial arrhythmias that occur in the context of acute myocardial infarction (AMI) have not been well characterized. AMI often leads to alterations in left ventricular (LV) filling dynamics, which may result in advanced diastolic dysfunction. Diastolic dysfunction may produce increased left atrial (LA) pressure and initiate LA remodeling, promoting the progression to atrial fibrillation (AF). We studied 1,169 patients admitted with AMI. Advanced diastolic dysfunction was defined as a restrictive filling pattern (RFP), defined as ratio of early to late transmitral velocity of mitral inflow >1.5 or deceleration time <130 ms. The relation between RFP and the primary end point of new-onset AF occurring within 6 months was analyzed using multivariable Cox models. Of 1,169 patients (70% men, mean ± SD 64 ± 10 years of age), 110 (9.4%) developed new-onset AF (19.6% and 7.5% in patients with and without RFP, respectively, p <0.0001). RFP was associated with a hazard ratio of 2.72 for AF (95% confidence interval 1.83 to 4.05, p <0.0001). After multivariable adjustments for clinical variables, LV ejection fraction (EF) and LA size, RFP remained an independent predictor of AF (hazard ratio 2.17, 95% confidence interval 1.42 to 3.32, p <0.0001). Risk of AF was higher in patients with RFP for preserved (≥45%, hazard ratio 2.14, 95% confidence interval 1.09 to 4.20, p = 0.03) or decreased (hazard ratio 2.80, 95% confidence interval 1.63 to 4.82, p <0.0001) LVEF. In contrast, decreased LVEF in the absence of RFP was similar to that of patients with preserved LVEF and without RFP. In conclusion, in patients with AMI, presence of advanced diastolic dysfunction was independently associated with new-onset AF, suggesting that increased filling pressures may contribute to the development of AF after AMI.     

Future strategies for the treatment of diastolic heart failure

It is estimated that 30% to 50% of heart failure patients have preserved systolic left ventricular (LV) function, often referred to as diastolic heart failure (DHF). Mortality is high in this patient population, and morbidity and rate of hospitalization are similar to those of patients with systolic heart failure. The management of patients with diastolic heart failure is essentially empirical, limited, and disappointing. New drugs, devices, and gene therapy based treatment options are currently under investigation. In this review, future strategies for the treatment of diastolic heart failure are discussed.     

Tolerance induction by third-party "off-the-shelf" CD4+CD25+ Treg cells

OBJECTIVE: Recent reports have shown that donor or host CD4(+)CD25(+) Treg cells can be used to control GVHD or graft rejection following allogeneic BMT in mice. In the present study we investigated the potential of third-party Treg cells compared to donor-type cells to facilitate BM allografting. METHODS: Graft rejection is assessed in a mouse model of T cell-mediated BM allograft rejection. Lethally irradiated C3H mice are transplanted at day 2 after irradiation with T cell-depleted Balb/Nude BM. Graft rejection is induced by purified host-type T cells infused one day prior to BMT. Cells tested for their facilitating activity are added to the T cell-depleted BM allograft. RESULTS: Na?ve or ex vivo-expanded third-party Treg cells can effectively enhance engraftment of T cell-depleted BM allografts, exhibiting reactivity in vitro and in vivo similar to that found for donor-type Treg cells. CONCLUSION: The use of third-party Treg cells in contrast to donor-type cells could allow advanced preparation of a large bank of Treg cells (off-the-shelf), with all the appropriate quality controls required for cell therapy.     

Algorithms to qualify respiratory data collected during the transport of trauma patients

We developed a quality indexing system to numerically qualify respiratory data collected by vital-sign monitors in order to support reliable post-hoc mining of respiratory data. Each monitor-provided (reference) respiratory rate (RR(R)) is evaluated, second-by-second, to quantify the reliability of the rate with a quality index (QI(R)). The quality index is calculated from: (1) a breath identification algorithm that identifies breaths of 'typical' sizes and recalculates the respiratory rate (RR(C)); (2) an evaluation of the respiratory waveform quality (QI(W)) by assessing waveform ambiguities as they impact the calculation of respiratory rates and (3) decision rules that assign a QI(R) based on RR(R), RR(C) and QI(W). RR(C), QI(W) and QI(R) were compared to rates and quality indices independently determined by human experts, with the human measures used as the 'gold standard', for 163 randomly chosen 15 s respiratory waveform samples from our database. The RR(C) more closely matches the rates determined by human evaluation of the waveforms than does the RR(R) (difference of 3.2 +/- 4.6 breaths min(-1) versus 14.3 +/- 19.3 breaths min(-1), mean +/- STD, p < 0.05). Higher QI(W) is found to be associated with smaller differences between calculated and human-evaluated rates (average differences of 1.7 and 8.1 breaths min(-1) for the best and worst QI(W), respectively). Establishment of QI(W) and QI(R), which ranges from 0 for the worst-quality data to 3 for the best, provides a succinct quantitative measure that allows for automatic and systematic selection of respiratory waveforms and rates based on their data quality.     

The association between vital signs and major hemorrhagic injury is significantly improved after controlling for sources of measurement variability

Purpose

Measurement error and transient variability affect vital signs. These issues are inconsistently considered in published reports and clinical practice. We investigated the association between major hemorrhagic injury and vital signs, successively applying analytic techniques that excluded unreliable measurements, reduced transient variation, and then controlled for ambiguity in individual vital signs through multivariate analysis.

Methods

Vital sign data from 671 adult prehospital trauma patients were analyzed retrospectively. Computer algorithms were used to identify and exclude unreliable data and to apply time averaging. An ensemble classifier was developed and tested by cross-validation. Primary outcome was hemorrhagic injury plus red cell transfusion. Areas under receiver operating characteristic curves (ROC AUCs) were compared by the test of DeLong et al.

Results

Of initial vital signs, systolic blood pressure (BP) had the highest ROC AUC of 0.71 (95% confidence interval, 0.64-0.78). The ROC AUCs improved after excluding unreliable data, significantly for heart rate and respiratory rate but not significantly for BP. Time averaging to reduce temporal variability further increased AUCs, significantly for BP and not significantly for heart rate and respiratory rate. The ensemble classifier yielded a final ROC AUC of 0.84 (95% confidence interval, 0.80-0.89) in cross-validation.

Conclusions

Techniques to reduce variability in vital sign data can lead to significantly improved diagnostic performance. Failure to consider such variability could significantly reduce clinical effectiveness or confound research investigations.     

Alcohol use and HIV sexual risk among MSM in Chennai, India

Men who have sex with men (MSM) in India are a core risk group for HIV. Heavy alcohol consumption is associated with increased sexual risk-taking behaviours in many cultures, in particular among MSM. However, no studies to date have explored alcohol use and HIV risk among MSM in India. MSM in Chennai, India (n = 210) completed an interviewer-administered behavioural and psychosocial assessment. Bivariate and multivariable logistic regression procedures examined behavioural and demographic associations with weekly alcohol consumption. Twenty-eight percent of the sample (n = 58) reported using alcohol at least weekly to the point of being buzzed/intoxicated, which was associated with older age, being married to a woman, being panthi (masculine appearing, predominantly insertive partners) versus kothi (feminine acting/appearing and predominantly receptive partners), weekly tobacco use, unprotected anal sex and unprotected vaginal sex in the three months prior to study enrollment (all P < 0.05). In a multivariable model, unprotected vaginal sex in the previous three months and being married to a women were unique variables associated with weekly alcohol use (all P < 0.01). Further investigation of alcohol use within the context of sexual risk taking is warranted among Indian MSM. Panthis and MSM who are married to women may be particularly likely to benefit from interventions to decrease alcohol intake and concurrent unsafe sex.     

Burden of HIV among young transgender women: factors associated with HIV infection and HIV treatment engagement

Young transgender women (YTW) are disproportionately affected by HIV, however, little is known about the factors associated with HIV infection and treatment engagement. We examined correlates of HIV infection and the steps of the HIV treatment cascade, specifically, being aware of their HIV infection, linked to care, on ART, and adherent to ART. We analyzed the baseline data of Project LifeSkills, a randomized control trial of sexually active YTW recruited from Chicago, Illinois and Boston, Massachusetts. We conducted multivariable Poisson regressions to evaluate correlates of HIV infection and the steps of the HIV treatment cascade. Nearly a quarter (24.7%) of YTW were HIV-infected. Among HIV-infected YTW, 86.2% were aware of their HIV status, 72.3% were linked to care, 56.9% were on ART, and 46.2% were adherent to ART. Having avoided healthcare due to cost in the past 12 months and not having a primary care provider were associated with suboptimal engagement in HIV care. Our results suggest that improving linkage and retention in care by addressing financial barriers and improving access to primary care providers could significantly improve health outcomes of YTW as well as reduce forward transmission of HIV.