CD4+ cell count and outcomes among HIV-infected compared with uninfected medical ICU survivors in a national cohort.

BACKGROUND: People with HIV (PWH) with access to antiretroviral therapy (ART) experience excess morbidity and mortality compared with uninfected patients, particularly those with persistent viremia and without CD4+ cell recovery. We compared outcomes for medical intensive care unit (MICU) survivors with unsuppressed (>500 copies/ml) and suppressed (≤500 copies/ml) HIV-1 RNA and HIV-uninfected survivors, adjusting for CD4+ cell count. SETTING: We studied 4537 PWH [unsuppressed = 38%; suppressed = 62%; 72% Veterans Affairs-based (VA) and 10 531 (64% VA) uninfected Veterans who survived MICU admission after entering the Veterans Aging Cohort Study (VACS) between fiscal years 2001 and 2015. METHODS: Primary outcomes were all-cause 30-day and 6-month readmission and mortality, adjusted for demographics, CD4+ cell category (≥350 (reference); 200-349; 50-199; <50), comorbidity and prior healthcare utilization using proportional hazards models. We also adjusted for severity of illness using discharge VACS Index (VI) 2.0 among VA-based survivors. RESULTS: In adjusted models, CD4+ categories <350 cells/µl were associated with increased risk for both outcomes up to 6 months, and risk increased with lower CD4+ categories (e.g. 6-month mortality CD4+ 200-349 hazard ratio [HR] = 1.35 [1.12-1.63]; CD4+ <50 HR = 2.14 [1.72-2.66]); unsuppressed status was not associated with outcomes. After adjusting for VI in models stratified by HIV, VI quintiles were strongly associated with both outcomes at both time points. CONCLUSION: PWH who survive MICU admissions are at increased risk for worse outcomes compared with uninfected, especially those without CD4+ cell recovery. Severity of illness at discharge is the strongest predictor for outcomes regardless of HIV status. Strategies including intensive case management for HIV-specific and general organ dysfunction may improve outcomes for MICU survivors.

Corticosteroids in the Management of Severe Coccidioidomycosis.

BACKGROUND: There is limited data suggesting that recovery from severe pulmonary infection with Coccidioides may be hastened by the addition of systemic corticosteroids. METHODS: We present a case report of 2 patients with persistent and progressive coccidioidomycosis who demonstrated a dramatic response to adjunctive corticosteroid therapy. RESULTS: Both patients had Coccidioides immitis cultured from respiratory samples. One was a 69-year-old man who had been treated with combination fluconazole and liposomal amphotericin for over 6 weeks, with persistent fever and pneumonia. The other was a 61-year-old man treated with fluconazole and then amphotericin for 3 weeks, with progression to acute respiratory distress syndrome and shock. Both received short courses of intravenous methylprednisolone and recovered to be discharged home. CONCLUSIONS: As opposed to associated hypersensitivity, corticosteroid treatment in these cases was directed at modulating the ongoing destructive effects of unchecked inflammation. Rapid improvement was noted in both cases and raises the possibility that the addition of systemic corticosteroids may hasten recovery in patients with severe coccidioidomycosis.

Markers of chronic obstructive pulmonary disease are associated with mortality in people living with HIV.

OBJECTIVE: Aging people living with HIV (PLWH) face an increased burden of comorbidities, including chronic obstructive pulmonary disease (COPD). The impact of COPD on mortality in HIV remains unclear. We examined associations between markers of COPD and mortality among PLWH and uninfected study participants. DESIGN: Longitudinal analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) cohort study. METHODS: EXHALE includes 196 PLWH and 165 uninfected smoking-matched study participants who underwent pulmonary function testing and computed tomography (CT) to define COPD and were followed. We determined associations between markers of COPD with mortality using multivariable Cox regression models, adjusted for smoking and the Veterans Aging Cohort Study (VACS) Index, a validated predictor of mortality in HIV. RESULTS: Median follow-up time was 6.9 years; the mortality rate was 2.7/100 person-years among PLWH and 1.7/100 person-years among uninfected study participants (P = 0.11). The VACS Index was associated with mortality in both PLWH and uninfected study participants. In multivariable models, pulmonary function and CT characteristics defining COPD were associated with mortality in PLWH: those with airflow obstruction (forced expiratory volume in 1 s/ forced vital capacity <0.7) had 3.1 times the risk of death [hazard ratio 3.1 (95% confidence interval 1.4-7.1)], compared with those without; those with emphysema (>10% burden) had 2.4 times the risk of death [hazard ratio 2.4 (95% confidence interval 1.1-5.5)] compared with those with ≤ 10% emphysema. In uninfected subjects, pulmonary variables were not significantly associated with mortality, which may reflect fewer deaths limiting power. CONCLUSION: Markers of COPD were associated with greater mortality in PWLH, independent of the VACS Index. COPD is likely an important contributor to mortality in contemporary PLWH.

The Role of Noninvasive Ventilation in the Hospital and Outpatient Management of Chronic Obstructive Pulmonary Disease.

Positive pressure noninvasive ventilation (NIV) has become widely accepted in the treatment of both hospitalized and outpatient subjects with chronic obstructive pulmonary disease (COPD). The support has evolved over the past two decades to be part of first-line management in acute exacerbations of COPD and is also instrumental in discontinuing mechanical ventilation in COPD patients with acute respiratory failure. It is also suitable for treatment of COPD with other associated conditions including pneumonia, following lung resectional surgery, with concomitant obstructive sleep apnea and as part of end-of-life care. Short-term application can also facilitate some endoscopic procedures that may otherwise require endotracheal intubation. Outpatient use of NIV in COPD has garnered much attention, but the support has not been as robust as with NIV in hospitalized patients. However, an approach with higher pressures with a goal of significant reduction in daytime PaCO2 may be an effective strategy. NIV can also facilitate exercise training in pulmonary rehabilitation. A portable device which can augment tidal volume during ambulation and other activities of daily living may further expand the use of NIV in COPD patients.

Findings in asymptomatic HIV-infected patients undergoing chest computed tomography testing: implications for lung cancer screening.

BACKGROUND: HIV-infected persons have a two-fold to five-fold increased unadjusted risk of lung cancer. In the National Lung Screening Trial (NLST), computed tomography (CT) screening was associated with a reduction in lung cancer mortality among high-risk smokers. These results may not generalize to HIV-infected persons, particularly if they are more likely to have false-positive chest CT findings. METHODS: We utilized data including standardized chest CT scans from 160 HIV infected and 139 uninfected Veterans enrolled between 2009 and 2012 in the multicenter Examinations of HIV Associated Lung Emphysema (EXHALE) Study. Abnormal CT findings were abstracted from clinical interpretations of the scans and classified as positive by NLST criteria vs. other findings. Clinical evaluations and diagnoses that ensued were abstracted from the medical record. RESULTS: There was no significant difference by HIV in the proportion of CT scans classified as positive by NLST criteria (29% of HIV infected and 24% of HIV uninfected, P=0.3). However, HIV-infected participants with CD4 cell counts less than 200 cells/µl had significantly higher odds of positive scans, a finding that persisted in multivariable analysis. Evaluations triggered by abnormal CT scans were also similar in HIV-infected and uninfected participants (all P>0.05). CONCLUSION: HIV status was not associated with an increased risk of abnormal findings on CT or increased rates of follow-up testing in clinically stable outpatients with CD4 cell count more than 200. These data reflect favorably on the balance of benefits and harms associated with lung cancer screening for HIV-infected smokers with less severe immunodeficiency.

Real-time telehealth for COPD self-management using Skype™.

The utility of real-time interactive voice and video telehealth for teaching pursed-lips breathing (PLB) in chronic obstructive pulmonary disease (COPD) is unknown. This was a pilot study to determine its feasibility and efficacy on the key variables of social support and dyspnea. A randomized control study design with repeated measures (baseline, 4 and 12 weeks) was used. All participants in the control and intervention groups received PLB instruction at baseline, but only the intervention group received one weekly PLB reinforcement session for 4 weeks via home computer and Skype™ software. Outcome measures were Medical Outcomes Study Social Support Survey and dyspnea assessment (visual analogue scales for intensity and distress, modified Borg after six-minute walk distance, and Shortness of Breath Questionnaire for activity-associated dyspnea). A total of 22 participants with COPD (mean FEV(1)% predicted = 56) were randomized; 16 (9 telehealth, 7 control) completed the protocol. Intent-to-treat analysis at week 4, but not week 12, demonstrated significantly improved total social support (P = 0.02) and emotional/informational subscale (P = 0.03) scores. Dyspnea intensity decreased (P = 0.08) for the intervention group with a minimal clinical important difference of 10.4 units. Analysis of only participants who completed the protocol demonstrated a significant decrease in dyspnea intensity (P = < 0.01) for the intervention group at both week 4 and 12. Real-time telehealth is a feasible, innovative approach for PLB instruction in the home with outcomes of improved social support and decreased dyspnea.

Does a clinical decision rule using D-dimer level improve the yield of pulmonary CT angiography?

OBJECTIVE: The objective of our study was to evaluate the impact of incorporating a mandatory clinical decision rule and selective d-dimer use on the yield of pulmonary CT angiography (CTA). MATERIALS AND METHODS: Guidelines incorporating a clinical decision rule (Wells score: range, 0-12.5) and a highly sensitive d-dimer assay as decision points were placed into a computerized order entry menu. From December 2006 through November 2008, 261 pulmonary CTA examinations of 238 men and 14 women (mean age ± SD, 65 ± 12 years; range, 31-92 years) were performed. Eight patients underwent more than one pulmonary CTA examination. Charts were reviewed. The results of pulmonary CTA, the clinical decision rule, and d-dimer level (if obtained) were analyzed with the Student t test, chi-square test, or other comparisons using statistical software (MedCalc, version 11.0). RESULTS: Of the pulmonary CTA examinations, 16.5% (43/261) were positive for pulmonary embolism (PE) compared with 3.1% (6/196) during the previous 2 years. The mean clinical decision rule score and mean d-dimer level were 5.5 ± 2.4 (SD) and 4956 ± 2892 ng/mL, respectively, for those with PE compared with 4.5 ± 2.1 and 2398 ± 2100 ng/mL for those without PE (both, p < 0.01). The negative predictive value of a clinical decision rule score of 4 or less and d-dimer level of less than 1000 ng/mL was 1.0. A clinical decision rule of greater than 4 and a higher d-dimer level were better predictors for PE, especially a d-dimer level of greater than 3000 ng/mL (odds ratio = 6.69; 95% CI = 2.72-16.43). CONCLUSION: Guidelines combining a clinical decision rule with d-dimer level significantly improved the utilization of pulmonary CTA and positive yield for PE.

Intensive insulin therapy in critical care: a review of 12 protocols.

OBJECTIVE: To review performance characteristics of 12 insulin infusion protocols. RESEARCH DESIGN AND METHODS: We systematically identify and compare 12 protocols and then apply the protocols to generate insulin recommendations in the management of a patient with hyperglycemia. The main focus involves a comparison of insulin doses and patterns of insulin administration. RESULTS: There is great variability in protocols. Areas of variation include differences in initiation and titration of insulin, use of bolus dosing, requirements for calculation in adjustment of the insulin infusion, and method of insulin protocol adjustments. Insulin recommendations for a sample patient are calculated to highlight differences between protocols, including the patterns and ranges of insulin dose recommended (range 27-115 units [mean +/- SD 66.7 +/- 27.9]), amount recommended for glucose readings >200 mg/dl, and adjustments nearing target glucose. CONCLUSIONS: The lack of consensus in the delivery of intravenous insulin infusions is reflected in the wide variability of practice noted in this survey. This mandates close attention to the choice of a protocol. One protocol may not suffice for all patients.

Thrombolytic therapy for massive pulmonary embolism in a patient with a known intracranial tumor.

The objective was to describe and review the use of thrombolytic therapy in a patient with an intracranial tumor and massive pulmonary embolism. This is the first reported case of a patient with a known glioblastoma multiforme and massive pulmonary embolism who was successfully treated with alteplase. Pulmonary embolism was demonstrated by a ventilation-perfusion scan and transthoracic echocardiogram with repeat studies demonstrating resolution of the thromboembolism and reperfusion of pulmonary vasculature. A review of the literature revealed that the incidence of intracranial hemorrhage with thrombolysis is <3% and compares favorably with the much higher mortality rate of 25% to >/=50% in patients with hemodynamically unstable pulmonary emboli. The benefit of thrombolysis may outweigh the risks of intracranial hemorrhage in these patients, and careful consideration for its use in these patients is warranted.

Pulmonary hypertension in men with thyrotoxicosis.

Thyrotoxicosis has a myriad of respiratory symptoms including dyspnea. Pulmonary hypertension may contribute to the respiratory symptoms of thyrotoxicosis, but is often unrecognized. We describe 3 male patients with thyrotoxicosis and associated pulmonary hypertension. Case reports of an additional 15 patients are also reviewed. In patients with thyrotoxicosis and pulmonary hypertension, treatment of thyrotoxicosis alone is associated with improvement in pulmonary hypertension. Previous reports have consisted of mostly female patients, but we report 3 men. When all cases are considered, the typical patient is female (10/14 = 71%), middle-aged (48 years), with mean pulmonary artery systolic pressures improving from 56 to 32 mm Hg with treatment. Autoantibodies were detected in 10/14 (71%) patients. The response to treatment (medical or surgical) of thyrotoxicosis supports the hypothesis that hyperthyroidism is either a cause of pulmonary hypertension, or a factor that may unmask pulmonary hypertension. Recognition is important since treatment and response are very different compared to other patients with pulmonary hypertension. This association may not be readily considered in men, since most reports have been of women.

Nonpharmacologic adjuncts to training during pulmonary rehabilitation: the role of supplemental oxygen and noninvasive ventilation.

Exercise training is the cornerstone of pulmonary rehabilitation. However, patients may not be able to exercise at a level that produces a training effect because of limitations related to their underlying lung disease. Adjuncts during exercise training may increase their exercise capacity and increase the benefit of pulmonary rehabilitation. The pathophysiology of exercise associated limitation is reviewed, as well as the role of supplemental oxygen and noninvasive ventilatory support as nonpharmacologic adjuncts to training. While most studies demonstrate benefit during exercise, the evidence of an added benefit during pulmonary rehabilitation is mixed. Work is needed to better define the benefits and appropriate patient populations. The subgroups that may derive the most benefit from these adjuncts are those with oxygen desaturation during exercise and those with severe chronic obstructive pulmonary disease (defined as a forced expiratory volume in 1 s (FEV1) < 1.0 L). Nocturnal noninvasive ventilation during pulmonary rehabilitation seems to be an effective adjunct and merits further study.

Comparison of breathing patterns during exercise in patients with obstructive and restrictive ventilatory abnormalities.

Patients with obstructive and restrictive ventilatory abnormalities suffer from exercise intolerance and dyspnea. Breathing pattern components (volume, flow, and timing) during incremental exercise may provide further insight in the role played by dynamic hyperinflation in the genesis of dyspnea. This study analyzed the breathing patterns of patients with obstructive and restrictive ventilatory abnormalities during incremental exercise. It also explored breathing pattern components with dyspnea at maximum oxygen uptake (VO2 max). Twenty patients, thirteen obstructive patients (forced expiratory volume 38% +/- 13% predicted, forced expiratory volume in 1 s/forced vital capacity ratio 39 +/- 8%), and seven restrictive patients (forced vital capacity 55 +/- 16% predicted, forced expiratory volume in 1 s/forced vital capacity ratio 84% +/- 11%) performed symptom-limited incremental exercise tests on a cycle ergometer with breath-by-breath determination of ventilation and gas exchange parameters. Breathing patterns were analyzed at baseline, 20, 40, 60, 80, and 100 percent of VO2 max. Dyspnea was measured at end-exercise with a 100 mm visual analogue scale. The timing ratio of inspiratory to expiratory time (T(I)/T(E)) and the flow ratio of inspiratory flow to expiratory flow ratio (V(I)/V(E)) were different (p < 0.008) between obstructive and restrictive patients at all exercise intensity levels. The timing components of expiratory time (T(E)) and inspiratory time to total time (T(I)T(TOT)) were significantly different (p < 0.008) at baseline and maximum exercise. Dyspnea scores were not significantly different. For obstructive patients, correlations were noted between T(I)/T(E), V(I)/V(E), T(I)T(TOT) and dyspnea (p < 0.05). Breathing pattern-timing components, specifically T(I)/T(E), in patients with obstructive and restrictive ventilatory abnormalities during exercise provided further insight into the pathophysiology of the two conditions and the contribution of dynamic hyperinflation to dyspnea.