Publications

BACKGROUND

Little is known about hospitalization-associated disability (HAD) in older adults who receive care in safety-net hospitals.

OBJECTIVES

To describe HAD and to examine its association with age in adults aged 55 and older hospitalized in a safety-net hospital.

DESIGN

Secondary post hoc analysis of a prospective cohort from a discharge intervention trial, the Support from Hospital to Home for Elders.

SETTING

Medicine, cardiology, and neurology inpatient services of San Francisco General Hospital, a safety-net hospital.

PARTICIPANTS

A total of 583 participants 55 and older who spoke English, Spanish, or Chinese. We determined the incidence of HAD 30 days post-hospitalization and ORs for HAD by age group.

MEASUREMENTS

The outcome measure was death or HAD at 30 days after hospital discharge. HAD is defined as a new or additional disability in one or more activities of daily living (ADL) that is present at hospital discharge compared to baseline. Participants' functional status at baseline (2 weeks prior to admission) and 30 days post-discharge was ascertained by self-report of ADL function.

RESULTS

Many participants (75.3 %) were functionally independent at baseline. By age group, HAD occurred as follows: 27.4 % in ages 55-59, 22.2 % in ages 60-64, 17.4 % in ages 65-69, 30.3 % in ages 70-79, and 61.7 % in ages 80 or older. Compared to the youngest group, only the adjusted OR for HAD in adults over 80 was significant, at 2.45 (95 % CI 1.17, 5.15).

CONCLUSIONS

In adults at a safety-net hospital, HAD occurred in similar proportions among adults aged 55-59 and those aged 70-79, and was highest in the oldest adults, aged ≥ 80. In safety-net hospitals, interventions to reduce HAD among patients 70 years and older should consider expanding age criteria to adults as young as 55.

RATIONALE

Improved understanding of the lung microbiome in HIV-infected individuals could lead to better strategies for diagnosis, therapy, and prophylaxis of HIV-associated pneumonias. Differences in the oral and lung microbiomes in HIV-infected and HIV-uninfected individuals are not well defined. Whether highly active antiretroviral therapy influences these microbiomes is unclear.

OBJECTIVES

We determined whether oral and lung microbiomes differed in clinically healthy groups of HIV-infected and HIV-uninfected subjects.

METHODS

Participating sites in the Lung HIV Microbiome Project contributed bacterial 16S rRNA sequencing data from oral washes and bronchoalveolar lavages (BALs) obtained from HIV-uninfected individuals (n = 86), HIV-infected individuals who were treatment naive (n = 18), and HIV-infected individuals receiving antiretroviral therapy (n = 38).

MEASUREMENTS AND MAIN RESULTS

Microbial populations differed in the oral washes among the subject groups (Streptococcus, Actinomyces, Rothia, and Atopobium), but there were no individual taxa that differed among the BALs. Comparison of oral washes and BALs demonstrated similar patterns from HIV-uninfected individuals and HIV-infected individuals receiving antiretroviral therapy, with multiple taxa differing in abundance. The pattern observed from HIV-infected individuals who were treatment naive differed from the other two groups, with differences limited to Veillonella, Rothia, and Granulicatella. CD4 cell counts did not influence the oral or BAL microbiome in these relatively healthy, HIV-infected subjects.

CONCLUSIONS

The overall similarity of the microbiomes in participants with and without HIV infection was unexpected, because HIV-infected individuals with relatively preserved CD4 cell counts are at higher risk for lower respiratory tract infections, indicating impaired local immune function.

Asthma is a common chronic disease without cure. Our understanding of asthma onset, pathobiology, classification, and management has evolved substantially over the past decade; however, significant asthma-related morbidity and excess healthcare use and costs persist. To address this important clinical condition, the NHLBI convened a group of extramural investigators for an Asthma Research Strategic Planning workshop on September 18-19, 2014, to accelerate discoveries and their translation to patients. The workshop focused on (1) in utero and early-life origins of asthma, (2) the use of phenotypes and endotypes to classify disease, (3) defining disease modification, (4) disease management, and (5) implementation research. This report summarizes the workshop and produces recommendations to guide future research in asthma.

BACKGROUND

Primary amoebic meningoencephalitis (PAM) is a rare, often lethal, cause of encephalitis, for which early diagnosis and prompt initiation of combination antimicrobials may improve clinical outcomes.

METHODS

In this study, we sequenced a full draft assembly of the Balamuthia mandrillaris genome (44.2 Mb in size) from a rare survivor of PAM, and recovered the mitochondrial genome from six additional Balamuthia strains. We also used unbiased metagenomic next-generation sequencing (NGS) and SURPI bioinformatics analysis to diagnose an ultimately fatal case of Balamuthia mandrillaris encephalitis in a 15-year-old girl.

RESULTS AND DISCUSSION

Comparative analysis of the mitochondrial genome and high-copy number genes from six additional Balamuthia mandrillaris strains demonstrated remarkable sequence variation, and the closest Balamuthia homologs corresponded to other amoebae, hydroids, algae, slime molds, and peat moss. Real-time NGS testing of hospital day 6 CSF and brain biopsy samples detected Balamuthia on the basis of high-quality hits to 16S and 18S ribosomal RNA sequences present in the National Center for Biotechnology Information (NCBI) nt reference database. The presumptive diagnosis of PAM by visualization of amoebae on brain biopsy histopathology and NGS analysis was subsequently confirmed at the US Centers for Disease Control and Prevention (CDC) using a Balamuthia-specific PCR assay. Retrospective analysis of a day 1 CSF sample revealed that more timely identification of Balamuthia by metagenomic NGS, potentially resulting in a better clinical outcome, would have required availability of the complete genome sequence.

CONCLUSIONS

These results underscore the diverse evolutionary origins of Balamuthia mandrillaris, provide new targets for diagnostic assay development, and will facilitate further investigations of the biology and pathogenesis of this eukaryotic pathogen. The failure to identify PAM from a day 1 sample without a fully sequenced Balamuthia genome in the database highlights the critical importance of whole-genome reference sequences for microbial detection by metagenomic NGS.

IMPORTANCE

There has been limited surveillance for acute flaccid paralysis in North America since the regional eradication of poliovirus. In 2012, the California Department of Public Health received several reports of acute flaccid paralysis cases of unknown etiology.

OBJECTIVE

To quantify disease incidence and identify potential etiologies of acute flaccid paralysis cases with evidence of spinal motor neuron injury.

DESIGN, SETTING, AND PARTICIPANTS

Case series of acute flaccid paralysis in patients with radiological or neurophysiological findings suggestive of spinal motor neuron involvement reported to the California Department of Public Health with symptom onset between June 2012 and July 2015. Patients meeting diagnostic criteria for other acute flaccid paralysis etiologies were excluded. Cerebrospinal fluid, serum samples, nasopharyngeal swab specimens, and stool specimens were submitted to the state laboratory for infectious agent testing.

MAIN OUTCOMES AND MEASURES

Case incidence and infectious agent association.

RESULTS

Fifty-nine cases were identified. Median age was 9 years (interquartile range [IQR], 4-14 years; 50 of the cases were younger than 21 years). Symptoms that preceded or were concurrent included respiratory or gastrointestinal illness (n = 54), fever (n = 47), and limb myalgia (n = 41). Fifty-six patients had T2 hyperintensity of spinal gray matter on magnetic resonance imaging and 43 patients had cerebrospinal fluid pleocytosis. During the course of the initial hospitalization, 42 patients received intravenous steroids; 43, intravenous immunoglobulin; and 13, plasma exchange; or a combination of these treatments. Among 45 patients with follow-up data, 38 had persistent weakness at a median follow-up of 9 months (IQR, 3-12 months). Two patients, both immunocompromised adults, died within 60 days of symptom onset. Enteroviruses were the most frequently detected pathogen in either nasopharynx swab specimens, stool specimens, serum samples (15 of 45 patients tested). No pathogens were isolated from the cerebrospinal fluid. The incidence of reported cases was significantly higher during a national enterovirus D68 outbreak occurring from August 2014 through January 2015 (0.16 cases per 100,000 person-years) compared with other monitoring periods (0.028 cases per 100,000 person-years; P <.001).

CONCLUSIONS AND RELEVANCE

In this series of patients identified in California from June 2012 through July 2015, clinical manifestations indicated a rare but distinct syndrome of acute flaccid paralysis with evidence of spinal motor neuron involvement. The etiology remains undetermined, most patients were children and young adults, and motor weakness was prolonged.

BACKGROUND

In the context of orthotopic liver transplantation (OLT), renal dysfunction is used as a criterion for simultaneous liver-kidney transplantation. Changes in glomerular filtration rate (GFR) the year before and after OLT have not been well defined.

METHODS

In a cohort of 416 OLT patients from 1996 to 2009, estimated GFR (eGFR) was assessed during the 12 months before OLT (period A), at time of OLT (period B), and the 12 months after OLT (period C). Outcomes included progression to end stage renal disease (ESRD), length of stay, and mortality.

RESULTS

The overall rate of progression to ESRD over 15 years of follow-up was 0.155/person-year and was strongly associated with eGFR <60 (hazard ratio [HR] = 2.7; P < 0.001), diabetes (HR = 2.6; P < 0.001), and with a combination of the 2 (HR = 5.5; P < 0.0001). Mean eGFR decreased from period A (86 mL/min per 1.73 m) to period B (77; P < 0.001) to period C (71; P < 0.001), with similar decreases in eGFR across subgroups of clinical variables. Patients with eGFR less than 60 mL/min per 1.73 m at OLT had acute and large decreases in eGFR from periods A to B, then increases to period C. Length of stay was associated with eGFR at OLT, hepatorenal syndrome, dialysis requirement, model for end-stage liver disease score, and alcoholic liver disease. Twelve-month mortality was strongly associated with time-dependent change in eGFR, hepatorenal syndrome, dialysis requirement, hepatitis C, and model for end-stage liver disease era transplantation but was not associated with eGFR at OLT.

CONCLUSIONS

Among OLT patients, renal function worsened in all subgroups from before to after OLT, but the association of progression to ESRD was particularly high among patients with both diabetes and eGFR less than 60 at the time of OLT. This suggests that diabetes could be considered as a criterion when making decisions regarding simultaneous liver-kidney transplantation.

RATIONALE

Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation.

OBJECTIVES

To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates.

METHODS

In a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case-control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively.

MEASUREMENTS AND MAIN RESULTS

Of 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24-33%) and 10% based on the SPPB (95% CI, 7-14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01-1.67) for FFP and 1.53 (95% CI, 1.19-1.59) for SPPB.

CONCLUSIONS

Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.