Publications

PURPOSE OF REVIEW

The purpose of this review is to summarize recent findings on the lung microbiome in HIV-infected patients and associated pulmonary diseases, and the relationship of airway microbial communities to metabolic and immune signatures within this patient population.

RECENT FINDINGS

The lung microbiome in HIV infection is a relatively new and rapidly developing field; early studies in the field produced inconclusive evidence as to whether HIV-infection changes the lower airway microbiome. More recent microbiome investigations have addressed these inconsistencies by incorporating systems biology approaches and laboratory models. Several investigations have now identified enrichment of Prevotella, Veillonella, and Streptococcus in the lower airways as consistent correlates of advanced HIV-infection and HIV-associated pulmonary diseases. These bacteria are associated with specific metabolic and immune profiles within the lung and circulation, providing the first indication that the lung microbiome may play a functional role in the pathogenesis of HIV-infection and HIV-associated pulmonary disease.

SUMMARY

This review summarizes knowledge to date on the lung microbiome in HIV infection, as well as challenges and accomplishments in the field within the last 2 years. Although the lung microbiome in HIV infection is still an emerging field, recent studies have formed a framework for future functional analysis of microbes in HIV pathogenesis.

Paclitaxel is an anticancer agent efficacious in the treatment of ovarian, breast, and lung cancer. Due to a strong link between the pharmacokinetics and therapeutic efficacy of paclitaxel, we reviewed the literature on paclitaxel pharmacokinetics. Systematic data mining was performed to extract the maximum concentration (C ), clearance (CL), and time of paclitaxel plasma concentration above 0.05 µmol/L (T > 0.05 µmol/L) following monotherapy of both the widely used cremophor-diluted paclitaxel and nanoparticle albumin-bound (nab-)paclitaxel. We identified a total of 53 studies yielding 121 aggregated pharmacokinetic profiles for paclitaxel monotherapy and extracted reported mean and median estimates of pharmacokinetic parameters. Paclitaxel has been studied formally at doses of 15-825 mg/m and infused over 0.5-96 h; included studies examined both weekly and every 3-weeks dosing cycles. The most widely used dose of cremophor-diluted paclitaxel, 175 mg/m given as a 3-h infusion, leads to an interstudy median C of 5.1 µmol/L [interquartile range (IQR) 4.5-5.7], CL of 12.0 L/h/m (IQR 10.9-12.9), and T > 0.05 µmol/L of 23.8 h (IQR 21.5-26.8). Importantly, the significant interindividual variation widely reported in the literature is not reflected in these interstudy estimates of pharmacokinetic parameters. Cremophor-diluted paclitaxel pharmacokinetics are non-linear following short (<6 h) but not long (>24 h) infusions. A similar pattern of non-linearity was observed for nab-paclitaxel, although the number of studies was limited. The pharmacokinetics of paclitaxel monotherapy have been widely studied at numerous dose levels of the Cremophor EL formulation, but are less well-characterized for the newer nab-paclitaxel formulation. In conclusion, paclitaxel pharmacokinetics are non-linear for short infusion times but not for longer infusions. Whether a similar conclusion can be drawn for nab-paclitaxel formulations requires further study.

Importance

Care planning is a critical function of palliative care teams, but the impact of advance care planning and goals of care discussions by palliative care teams has not been well characterized.

Objective

To describe the population of patients referred to inpatient palliative care consultation teams for care planning, the needs identified by palliative care clinicians, the care planning activities that occur, and the results of these activities.

Design, Setting, and Participants

This was a prospective cohort study conducted between January 1, 2013, and December 31, 2016. Seventy-eight inpatient palliative care teams from diverse US hospitals in the Palliative Care Quality Network, a national quality improvement collaborative. Standardized data were submitted for 73 145 patients.

Exposures

Inpatient palliative care consultation.

Results

Overall, 52 571 of 73 145 patients (71.9%) referred to inpatient palliative care were referred for care planning (range among teams, 27.5%-99.4% of patients). Patients referred for care planning were older (73.3 vs 67.9 years; F statistic, 1546.0; P < .001), less likely to have cancer (30.0% vs 41.1%; P < .001), and slightly more often had a clinical order of full code at the time of referral (54.6% vs 52.1%; P < .001). Palliative care teams identified care planning needs in 52 825 of 73 145 patients (72.2%) overall, including 42 467 of 49 713 patients (85.4%) referred for care planning and in 10 054 of 17 475 patients (57.5%) referred for other reasons. Through care planning conversations, surrogates were identified for 10 571 of 11 149 patients (94.8%) and 9026 patients (37.4%) elected to change their code status. Substantially more patients indicated that a status of do not resuscitate/do not intubate was consistent with their goals (7006 [32.1%] preconsultation to 13 773 [63.1%] postconsultation). However, an advance directive was completed for just 2160 of 67 955 patients (3.2%) and a Physicians Orders for Life-Sustaining Treatment form was completed for 8359 of 67 955 patients (12.3%) seen by palliative care teams.

Conclusions and Relevance

Care planning was the most common reason for inpatient palliative care consultation, and care planning needs were often found even when the consultation was for other reasons. Surrogates were consistently identified, and patients' preferences regarding life-sustaining treatments were frequently updated. However, a minority of patients completed legal forms to document their care preferences, highlighting an area in need of improvement.