Publications

OBJECTIVE

Many healthcare systems employ population-based risk scores to prospectively identify patients at high risk of poor outcomes, but it is unclear whether single point-in-time scores adequately represent future risk. We sought to identify and characterize latent subgroups of high-risk patients based on risk score trajectories.

STUDY DESIGN

Observational study of 7289 patients discharged from Veterans Health Administration (VA) hospitals during a 1-week period in November 2012 and categorized in the top 5th percentile of risk for hospitalization.

METHODS

Using VA administrative data, we calculated weekly risk scores using the validated Care Assessment Needs model, reflecting the predicted probability of hospitalization. We applied the non-parametric k-means algorithm to identify latent subgroups of patients based on the trajectory of patients' hospitalization probability over a 2-year period. We then compared baseline sociodemographic characteristics, comorbidities, health service use, and social instability markers between identified latent subgroups.

RESULTS

The best-fitting model identified two subgroups: moderately high and persistently high risk. The moderately high subgroup included 65% of patients and was characterized by moderate subgroup-level hospitalization probability decreasing from 0.22 to 0.10 between weeks 1 and 66, then remaining constant through the study end. The persistently high subgroup, comprising the remaining 35% of patients, had a subgroup-level probability increasing from 0.38 to 0.41 between weeks 1 and 52, and declining to 0.30 at study end. Persistently high-risk patients were older, had higher prevalence of social instability and comorbidities, and used more health services.

CONCLUSIONS

On average, one third of patients initially identified as high risk stayed at very high risk over a 2-year follow-up period, while risk for the other two thirds decreased to a moderately high level. This suggests that multiple approaches may be needed to address high-risk patient needs longitudinally or intermittently.

OBJECTIVE

It remains unknown whether high-functioning teams can compensate for poor continuity of care to support important patient outcomes.

DATA SOURCE

Linked VA administrative and Medicare claims data to measure the relationship of team-based care and continuity of care with high-cost utilization.

STUDY DESIGN

Retrospective cohort study of 1.2 million VA-Medicare dual eligible Veterans assigned to a VA primary care provider (PCP) in 2012. Continuity was the proportion of primary care visits to the assigned VA provider of care. Clinics were categorized as low, average, or high-team functioning based on survey data. Our primary outcomes were the number of all-cause hospitalizations, ambulatory care sensitive (ACSC) hospitalizations, and emergency department (ED) visits in 2013.

PRINCIPAL FINDINGS

A 10-percentage point increase in continuity with a VA PCP was associated with 4.5 fewer hospitalizations (p < .001), 3.2 fewer ACSC hospitalizations (p < .001), and 2.6 more ED visits (p = .07) per 1,000 patients. Team-based care was not significantly associated with any high-cost utilization category. Associations were heterogeneous across VA-reliant and nonreliant Veterans. Finally, the interaction results demonstrated that the quality of team-based care functioning could not compensate for poor continuity on hospitalizations, ACSC hospitalizations, or ED visits.

CONCLUSIONS

In Veterans who were reliant on the VA for services, increasing continuity with a VA PCP and high-functioning team-based care clinics was associated with fewer ED visits and hospitalizations. Furthermore, leveraging combined data from VA and Medicare allowed to better measure continuity and assess high-cost utilization among Veterans who are and are not reliant on the VA for services.

BACKGROUND

Cytomegalovirus (CMV) infection is a risk factor for chronic lung allograft dysfunction (CLAD), which limits survival in lung allograft recipients. Natural killer (NK) cells that express the NKG2C receptor mediate CMV-specific immune responses. We hypothesized that NKG2C NK cells responding to CMV in the lung allograft would reduce CMV-related inflammation and would improve CLAD-free survival.

METHODS

We prospectively followed 130 subjects who underwent lung transplantation from 2012 to 2016. Bronchoalveolar lavage (BAL) NK cells were immunophenotyped for NKG2C, maturation, and proliferation markers. CMV viral load, serologies, serial spirometry, and mortality were recorded from medical records. Natural killer cell subset association with CMV endpoints were made using generalized estimating equation-adjusted linear models. BAL NKG2C NK cell association with CLAD-free survival was assessed by Cox proportional hazards modeling.

RESULTS

NKG2C NK cells were more mature and proliferative than NKG2C NK cells and represented a median of 7.8% of BAL NK cells. The NKG2C NK cell proportion increased prior to the first detection of viremia and was nearly tripled in subjects with high level viremia (>1000 copies/mL) compared with no detected viremia. Subjects with increased BAL NKG2C NK cells, relative to the median, had a significantly increased risk for CLAD or death (hazard ratio, 4.2; 95% confidence interval, 1.2-13.3).

CONCLUSIONS

The BAL NKG2C NK cell proportion may be a relevant biomarker for assessing risk of CMV viremia and quantifying potential CMV-related graft injury that can lead to CLAD or death.

BACKGROUND

Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis.

METHODS

In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration.

FINDINGS

Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses.

INTERPRETATION

Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition.

FUNDING

American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.