Increasing prevalence of cirrhosis among insured adults in the United States, 2012-2018.

BACKGROUND: Liver cirrhosis is a chronic disease that is known as a "silent killer" and its true prevalence is difficult to describe. It is imperative to accurately characterize the prevalence of cirrhosis because of its increasing healthcare burden. METHODS: In this retrospective cohort study, trends in cirrhosis prevalence were evaluated using administrative data from one of the largest national health insurance providers in the US. (2011-2018). Enrolled adult (≥18-years-old) patients with cirrhosis defined by ICD-9 and ICD-10 were included in the study. The primary outcome measured in the study was the prevalence of cirrhosis 2011-2018. RESULTS: Among the 371,482 patients with cirrhosis, the mean age was 62.2 (±13.7) years; 53.3% had commercial insurance and 46.4% had Medicare Advantage. The most frequent cirrhosis etiologies were alcohol-related (26.0%), NASH (20.9%) and HCV (20.0%). Mean time of follow-up was 725 (±732.3) days. The observed cirrhosis prevalence was 0.71% in 2018, a 2-fold increase from 2012 (0.34%). The highest prevalence observed was among patients with Medicare Advantage insurance (1.67%) in 2018. Prevalence increased in each US. state, with Southern states having the most rapid rise (2.3-fold). The most significant increases were observed in patients with NASH (3.9-fold) and alcohol-related (2-fold) cirrhosis. CONCLUSION: Between 2012-2018, the prevalence of liver cirrhosis doubled among insured patients. Alcohol-related and NASH cirrhosis were the most significant contributors to this increase. Patients living in the South, and those insured by Medicare Advantage also have disproportionately higher prevalence of cirrhosis. Public health interventions are important to mitigate this concerning trajectory of strain to the health system.

Where you live matters: Area deprivation predicts poor survival and liver transplant waitlisting.

Social determinants of health (SDOH) are important predictors of poor clinical outcomes in chronic diseases, but their associations among the general cirrhosis population and liver transplantation (LT) are limited. We conducted a retrospective, multiinstitutional analysis of adult (≥18-years-old) patients with cirrhosis in metropolitan Chicago to determine the associations of poor neighborhood-level SDOH on decompensation complications, mortality, and LT waitlisting. Area deprivation index and covariates extracted from the American Census Survey were aspects of SDOH that were investigated. Among 15 101 patients with cirrhosis, the mean age was 57.2 years; 6414 (42.5%) were women, 6589 (43.6%) were non-Hispanic White, 3652 (24.2%) were non-Hispanic Black, and 2662 (17.6%) were Hispanic. Each quintile increase in area deprivation was associated with poor outcomes in decompensation (sHR [subdistribution hazard ratio] 1.07; 95% CI 1.05-1.10; P < .001), waitlisting (sHR 0.72; 95% CI 0.67-0.76; P < .001), and all-cause mortality (sHR 1.09; 95% CI 1.06-1.12; P < .001). Domains of SDOH associated with a lower likelihood of waitlisting and survival included low income, low education, poor household conditions, and social support (P < .001). Overall, patients with cirrhosis residing in poor neighborhood-level SDOH had higher decompensation, and mortality, and were less likely to be waitlisted for LT. Further exploration of structural barriers toward LT or optimizing health outcomes is warranted.

Brief PROMIS Assessment Screens for Frailty and Predicts Hospitalizations in Liver Transplant Candidates.

BACKGROUND: Frailty is prevalent in patients with end-stage liver disease and predicts waitlist mortality, posttransplant mortality, and frequency of hospitalizations. The Liver Frailty Index (LFI) is a validated measure of frailty in liver transplant (LT) candidates but requires an in-person assessment. METHODS: We studied the association between patient-reported physical function and LFI in a single-center prospective study of adult patients with cirrhosis undergoing LT evaluation from October 2020 to December 2021. Frailty was assessed with the LFI and 4-m gait speed. Patient-reported physical function was evaluated using a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey. RESULTS: Eighty-one LT candidates were enrolled, with a mean model of end-stage liver disease-sodium of 17.6 (±6.3). The mean LFI was 3.7 (±0.77; 15% frail and 59% prefrail) and the mean PROMIS Physical Function score was 45 (±8.6). PROMIS Physical Function correlated with LFI ( r = -0.54, P < 0.001) and 4-m gait speed ( r = 0.48, P < 0.001). The mean hospitalization rate was 1.1 d admitted per month. After adjusting for age, sex, and model of end-stage liver disease-sodium, patient-reported physical function-predicted hospitalization rate ( P = 0.001). CONCLUSIONS: This study suggests that a brief patient-reported outcome measure can be used to screen for frailty and predict hospitalizations in patients with cirrhosis.

Home-Based Walking Exercise and Supervised Treadmill Exercise in Patients With Peripheral Artery Disease: An Individual Participant Data Meta-Analysis.

Importance: Few people with lower extremity peripheral artery disease (PAD) participate in supervised treadmill exercise covered by the Center for Medicare and Medicaid Services. In people with PAD, the benefits of home-based walking exercise, relative to supervised exercise, remain unclear. Objective: To study whether home-based walking exercise improves 6-minute walk (6MW) more than supervised treadmill exercise in people with PAD (defined as Ankle Brachial Index ≤0.90). Data Sources: Data were combined from 5 randomized clinical trials of exercise therapy for PAD using individual participant data meta-analyses, published from 2009 to 2022. Study Selection: Of the 5 clinical trials, 3 clinical trials compared supervised treadmill exercise to nonexercise control (N = 370) and 2 clinical trials compared an effective home-based walking exercise intervention to nonexercise control (N = 349). Data Extraction and Synthesis: Individual participant-level data from 5 randomized clinical trials led by 1 investigative team were combined. The 5 randomized clinical trials included 3 clinical trials of supervised treadmill exercise and 2 effective home-based walking exercise interventions. Main Outcomes and Measures: Change in 6MW distance, maximum treadmill walking distance, and Walking Impairment Questionnaire at 6-month follow-up. The supervised treadmill exercise intervention consisted of treadmill exercise in the presence of an exercise physiologist, conducted 3 days weekly for up to 50 minutes per session. Home-based walking exercise consisted of a behavioral intervention in which a coach helped participants walk for exercise in or around home for up to 5 days per week for 50 minutes per session. Results: A total of 719 participants with PAD (mean [SD] age, 68.8 [9.5] years; 46.5% female) were included (349 in a home-based exercise clinical trial and 370 in a supervised exercise trial). Compared with nonexercise control, supervised treadmill exercise was associated with significantly improved 6MW by 32.9 m (95% CI, 20.6-45.6; P < .001) and home-based walking exercise was associated with significantly improved 6MW by 50.7 m (95% CI, 34.8-66.7; P < .001). Compared with supervised treadmill exercise, home-based walking exercise was associated with significantly greater improvement in 6MW distance (between-group difference: 23.8 m [95% CI, 3.6, 44.0; P = .02]) but significantly less improvement in maximum treadmill walking distance (between-group difference:-132.5 m [95% CI, -192.9 to -72.1; P < .001]). Conclusions and Relevance: In this individual participant data meta-analyses, compared with supervised exercise, home-based walking exercise was associated with greater improvement in 6MW in people with PAD. These findings support home-based walking exercise as a first-line therapy for walking limitations in PAD.

Barriers to participation in supervised exercise therapy reported by people with peripheral artery disease.

OBJECTIVE: This study identified barriers to participation in supervised exercise therapy covered by the Centers for Medicare and Medicaid Services (CMS), reported by people with lower extremity peripheral artery disease (PAD). METHODS: People with PAD participating in research studies of walking impairment due to PAD in the Chicagoland area were asked to complete a questionnaire between March 15, 2019, and July 12, 2022, assessing their experience and attitudes about supervised exercise therapy. Participants were identified using mailed postcards to people aged 50 and older in Chicagoland, from medical centers in Chicago, and using bus and train advertisements. The questionnaire was developed based on focus group feedback from people with PAD. RESULTS: Of 516 participants with PAD approached, 489 (94.8%) completed the questionnaire (mean age: 71.0 years [standard deviation: 8.7], mean ankle-brachial index: 0.71 [standard deviation: 0.25]; 204 [41.7%] women and 261 [53.4%] Black). Of the 489 participants, 416 (85.1%) reported that their physician had never prescribed or recommended supervised exercise therapy. Overall, 357 (73.2%) reported willingness to travel three times weekly to the medical center for supervised exercise participation. However, of these, 214 (59.9%) reported that they were unwilling or unable to pay the $11 per exercise session copay required for supervised exercise covered by CMS. Of 51 people with PAD who reported prior participation in supervised exercise, only 5 (9.8%) completed the 12 weeks of supervised exercise therapy covered by CMS and 29 (56.9%) completed 6 or fewer weeks. Of 131 (26.8%) unwilling to travel three times weekly to a center for supervised exercise, the most common reasons for unwillingness to participate were "too time-consuming" (55.0%), "too inconvenient" (45.8%), and "lack of interest in treadmill exercise" (28.2%). CONCLUSIONS: Approximately 2 to 4 years after CMS began covering supervised exercise for PAD, most people with PAD in this study from a large urban area had not participated in supervised exercise therapy. Of those who participated, most completed fewer than half of the sessions covered by CMS. The required CMS copayment was a common barrier to supervised exercise participation by people with PAD.

Association of Body Mass Index in Midlife With Morbidity Burden in Older Adulthood and Longevity.

Importance: Abundant evidence links obesity with adverse health consequences. However, controversies persist regarding whether overweight status compared with normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with longer survival and whether this occurs at the expense of greater long-term morbidity and health care expenditures. Objective: To examine the association of BMI in midlife with morbidity burden, longevity, and health care expenditures in adults 65 years and older. Design, Setting, and Participants: Prospective cohort study at the Chicago Heart Association Detection Project in Industry, with baseline in-person examination between November 1967 and January 1973 linked with Medicare follow-up between January 1985 and December 2015. Participants included 29 621 adults who were at least age 65 years in follow-up and enrolled in Medicare. Data were analyzed from January 2020 to December 2021. Exposures: Standard BMI categories. Main Outcomes and Measures: (1) Morbidity burden at 65 years and older assessed with the Gagne combined comorbidity score (ranging from -2 to 26, with higher score associated with higher mortality), which is a well-validated index based on International Classification of Diseases, Ninth Revision codes for use in administrative data sets; (2) longevity (age at death); and (3) health care costs based on Medicare linkage in older adulthood (aged ≥65 years). Results: Among 29 621 participants, mean (SD) age was 40 (12) years, 57.1% were men, and 9.1% were Black; 46.0% had normal BMI, 39.6% were overweight, and 11.9% had classes I and II obesity at baseline. Higher cumulative morbidity burden in older adulthood was observed among those who were overweight (7.22 morbidity-years) and those with classes I and II obesity (9.80) compared with those with a normal BMI (6.10) in midlife (P < .001). Mean age at death was similar between those who were overweight (82.1 years [95% CI, 81.9-82.2 years]) and those who had normal BMI (82.3 years [95% CI, 82.1-82.5 years]) but shorter in those who with classes I and II obesity (80.8 years [95% CI, 80.5-81.1 years]). The proportion (SE) of life-years lived in older adulthood with Gagne score of at least 1 was 0.38% (0.00%) in those with a normal BMI, 0.41% (0.00%) in those with overweight, and 0.43% (0.01%) in those with classes I and II obesity. Cumulative median per-person health care costs in older adulthood were significantly higher among overweight participants ($12 390 [95% CI, $10 427 to $14 354]) and those with classes I and II obesity ($23 396 [95% CI, $18 474 to $28 319]) participants compared with those with a normal BMI (P < .001). Conclusions and Relevance: In this cohort study, overweight in midlife, compared with normal BMI, was associated with higher cumulative burden of morbidity and greater proportion of life lived with morbidity in the context of similar longevity. These findings translated to higher total health care expenditures in older adulthood for those who were overweight in midlife.

Black Patients With Cirrhosis Have Higher Mortality and Lower Transplant Rates: Results From a Metropolitan Cohort Study.

BACKGROUND AND AIMS: Estimates of racial disparity in cirrhosis have been limited by lack of large-scale, longitudinal data, which track patients from diagnosis to death and/or transplant. APPROACH AND RESULTS: We analyzed a large, metropolitan, population-based electronic health record data set from seven large health systems linked to the state death registry and the national transplant database. Multivariate competing risk analyses, adjusted for sex, age, insurance status, Elixhauser score, etiology of cirrhosis, HCC, portal hypertensive complication, and Model for End-Stage Liver Disease-Sodium (MELD-Na), examined the relationship between race, transplant, and cause of death as defined by blinded death certificate review. During the study period, 11,277 patients met inclusion criteria, of whom 2,498 (22.2%) identified as Black. Compared to White patients, Black patients had similar age, sex, MELD-Na, and proportion of alcohol-associated liver disease, but higher comorbidity burden, lower rates of private insurance, and lower rates of portal hypertensive complications. Compared to White patients, Black patients had the highest rate all-cause mortality and non-liver-related death and were less likely to be listed or transplanted (P < 0.001 for all). In multivariate competing risk analysis, Black patients had a 26% increased hazard of liver-related death (subdistribution HR, 1.26; 95% CI, [1.15-1.38]; P < 0.001). CONCLUSIONS: Black patients with cirrhosis have discordant outcomes. Further research is needed to determine how to address these real disparities in the field of hepatology.

Microeconomic Costs, Insurance, and Catastrophic Health Spending Among Patients With Acute Myocardial Infarction in India: Substudy of a Randomized Clinical Trial.

Importance: Ischemic heart disease is the leading cause of death in India, and treatment can be costly. Objective: To evaluate individual- and household-level costs and impoverishing effects of acute myocardial infarction among patients in Kerala, India. Design, Setting, and Participants: This investigation was a prespecified substudy of the Acute Coronary Syndrome Quality Improvement in Kerala study, a stepped-wedge, cluster randomized clinical trial conducted between November 2014 and November 2016 across 63 hospitals in Kerala, India. In this cross-sectional substudy, individual- and household-level cost data were collected 30 days after hospital discharge from a sample of 2114 respondents from November 2014 to July 2016. Data were analyzed from July through October 2018 and in March 2019. Exposures: Health insurance status. Main Outcomes and Measures: The primary outcomes were detailed direct and indirect cost data associated with acute myocardial infarction and respondent ability to pay as well as catastrophic health spending and distress financing. Catastrophic health spending was defined as 40% or more of household expenditures minus food costs spent on health, and distress financing was defined as borrowing money or selling assets to cover health costs. Hierarchical regression models were used to evaluate the association between health insurance and measures of financial risk. Costs were converted from Indian rupees to international dollars (represented herein as "$"). Results: Among 2114 respondents, the mean (SD) age was 62.3 (12.7) years, 1521 (71.9%) were men, 1144 (54.1%) presented with an ST-segment elevation myocardial infarction, and 1600 (75.7%) had no health insurance. The median (interquartile range) expenditure among respondents was $480.4 ($112.5-$1733.0) per acute myocardial infarction encounter, largely driven by in-hospital expenditures. There was greater than 15-fold variability between the 25th and 75th percentiles. Individuals with or without health insurance had similar monthly incomes and annual household expenditures, yet individuals without health insurance had approximately $400 higher out-of-pocket cardiovascular health care costs (median [interquartile range] total cardiovascular expenditures among uninsured, $560.3 [$134.1-$1733.6] vs insured, $161.4 [$23.2-$1726.9]; P < .001). Individuals without health insurance also had a 24% higher risk of catastrophic health spending (adjusted risk ratio, 1.24; 95% CI, 1.07-1.43) and 3-fold higher risk of distress financing (adjusted risk ratio; 3.05; 95% CI, 1.45-6.44). Conclusions and Relevance: The results of this study indicate that acute myocardial infarction carries substantial financial risk for patients in Kerala. Expansion of health insurance may be an important strategy for financial risk protection to disrupt the poverty cycle associated with cardiovascular diseases in India.

Cardiovascular health in young and middle adulthood and medical care utilization and costs at older age - The Chicago Heart Association Detection Project Industry (CHA).

It is unclear how long-term medical utilization and costs from diverse care settings and their age-related patterns may differ by cardiovascular health (CVH) status earlier in adulthood. We followed 17,195 participants of the Chicago Heart Association Detection Project Industry (1967-1973) with linked Medicare claims (1992 to 2010). Baseline CVH is a composite measure of blood pressure, body mass index, diabetes, cholesterol, and smoking and includes four mutually exclusive strata: all factors were favorable (5.5%), one or more factors were elevated but none high (20.3%), one factor was high (40.9%), and two or more factors were high (33.2%). We assessed differences in the quantities (using negative binomial models) of and costs (using quantile regressions) for inpatient admissions, ambulatory care, home health care, and others between less favorable and all favorable CVH. All analyses adjusted for baseline age, race, sex, education, age at follow-up, year, state of residence, and death. We found that all favorable CVH in earlier adulthood was associated with lower long-term utilization and costs in all settings and the gap widened with age. Compared to all favorable CVH, the annual number of acute inpatient admissions per person was 79% greater (p-value < 0.001) for poor CVH, the median annual Medicare payment per person was $640 greater (41%, p-value < 0.001), and the mean was $4628 greater (67%, p-value < 0.001). The cost differences were greatest for acute inpatient, followed by ambulatory, post-acute inpatient, home health, and other. Early prevention efforts may potentially result in compressed all-cause morbidity in later years of age, along with reductions in resource use and health care costs for associated conditions.

Effect of Ongoing Assessment of Resident Operative Autonomy on the Operating Room Environment.

OBJECTIVE: We have previously demonstrated the feasibility and validity of a smartphone-based system called Procedural Autonomy and Supervision System (PASS), which uses the Zwisch autonomy scale to facilitate assessment of the operative performances of surgical residents and promote progressive autonomy. To determine whether the use of PASS in a general surgery residency program is associated with any negative consequences, we tested the null hypothesis that PASS implementation at our institution would not negatively affect resident or faculty satisfaction in the operating room (OR) nor increase mean OR times for cases performed together by residents and faculty. METHODS: Mean OR times were obtained from the electronic medical record at Northwestern Memorial Hospital for the 20 procedures most commonly performed by faculty members with residents before and after PASS implementation. OR times were compared via two-sample t-test. The OR Educational Environment Measure tool was used to assess OR satisfaction with all clinically active general surgery residents (n = 31) and full-time general surgery faculty members (n = 27) before and after PASS implementation. Results were compared using the Mann-Whitney rank sum test. RESULTS: A significant prolongation in mean OR time between control and study period was found for only 1 of the 20 operative procedures performed at least 20 times by participating faculty members with residents. Based on the overall survey score, no significant differences were found between resident and faculty responses to the OR Educational Environment Measure survey before and after PASS implementation. When individual survey items were compared, while no differences were found with resident responses, differences were noted with faculty responses for 7 of the 35 items addressed although after Bonferroni correction none of these differences remained significant. CONCLUSIONS: Our data suggest that PASS does not increase mean OR times for the most commonly performed procedures. Resident OR satisfaction did not significantly change during PASS implementation, whereas some changes in faculty satisfaction were noted suggesting that PASS implementation may have had some negative effect with them. Although the effect on faculty satisfaction clearly requires further investigation, our findings support that use of an autonomy-based OR performance assessment system such as PASS does not appear to have a major negative influence on OR times nor OR satisfaction.

Favorable Cardiovascular Health, Compression of Morbidity, and Healthcare Costs: Forty-Year Follow-Up of the CHA Study (Chicago Heart Association Detection Project in Industry).

BACKGROUND: We examined the association of cardiovascular health at younger ages with the proportion of life lived free of morbidity, the cumulative burden of morbidity, and average healthcare costs at older ages. METHODS: The CHA study (Chicago Heart Association Detection Project in Industry) is a longitudinal cohort of employed men and women 18 to 74 years of age at baseline examination in 1967 to 1973. Baseline measurements included blood pressure, cholesterol, diabetes mellitus, body mass index, and smoking. Individuals were classified into 1 of 4 strata of cardiovascular health: favorable levels of all factors, 0 factors high but ≥1 elevated risk factors, 1 high risk factor, and ≥2 high risk factors. Linked Medicare and National Death Index data from 1984 to 2010 were used to determine morbidity in older age. An individual's all-cause morbidity score and cardiovascular morbidity score were calculated from International Classification of Disease, Ninth Revision codes for each year of follow-up. RESULTS: We included 25 804 participants who became ≥65 years of age by 2010, representing 65% of all original CHA participants (43% female; 90% white; mean age, 44 years at baseline); 6% had favorable levels of all factors, 19% had ≥1 risk factors at elevated levels, 40% had 1 high risk factor, and 35% had ≥2 high risk factors. Favorable cardiovascular health at younger ages extended survival by almost 4 years and postponed the onset of all-cause and cardiovascular morbidity by 4.5 and 7 years, respectively, resulting in compression of morbidity in both absolute and relative terms. This translated to lower cumulative and annual healthcare costs for those in favorable cardiovascular health (P<0.001) during Medicare eligibility. CONCLUSIONS: Individuals in favorable cardiovascular health in early middle age live a longer, healthier life free of all types of morbidity. These findings provide strong support for prevention efforts earlier in life aimed at preserving cardiovascular health and reducing the burden of disease in older ages.

Racial differences in functional decline in peripheral artery disease and associations with socioeconomic status and education.

OBJECTIVE: The objective of this study was to determine whether blacks with lower extremity peripheral artery disease (PAD) have faster functional decline than whites with PAD. METHODS: Participants with ankle-brachial index <0.90 were identified from Chicago medical centers and observed longitudinally. Mobility impairment and the 6-minute walk were assessed at baseline and every 6 to 12 months. Mobility loss was defined as becoming unable to walk up and down a flight of stairs or to walk » mile without assistance. RESULTS: Of 1162 PAD participants, 305 (26%) were black. Median follow-up was 46.0 months. Among 711 PAD participants who walked 6 minutes continuously at baseline, black participants were more likely to become unable to walk 6 minutes continuously during follow-up (64/171 [37.4%] vs 156/540 [28.9%]; log-rank, P = .006). Black race was associated with becoming unable to walk 6 minutes continuously, adjusting for age, sex, ankle-brachial index, comorbidities, and other confounders (hazard ratio, 1.45; 95% confidence interval, 1.05-1.99; P = .022). This association was attenuated after adjustment for income and education (P = .229). Among 844 participants without baseline mobility impairment, black participants had a higher rate of mobility loss (64/209 [30.6%] vs 164/635 [25.8%]; log-rank, P = .009). Black race was associated with increased mobility loss, adjusting for potential confounders (hazard ratio, 1.42; 95% confidence interval, 1.04-1.94; P = .028). This association was attenuated after additional adjustment for income and education (P = .392) and physical activity (P = .113). There were no racial differences in average annual declines in 6-minute walk, usual-paced 4-meter walking velocity, or fast-paced 4-meter walking velocity. CONCLUSIONS: Black PAD patients have higher rates of mobility loss and becoming unable to walk for 6 minutes continuously. These differences appear related to racial differences in socioeconomic status and physical activity.

Estimating and testing high-dimensional mediation effects in epigenetic studies.

MOTIVATION: High-dimensional DNA methylation markers may mediate pathways linking environmental exposures with health outcomes. However, there is a lack of analytical methods to identify significant mediators for high-dimensional mediation analysis. RESULTS: Based on sure independent screening and minimax concave penalty techniques, we use a joint significance test for mediation effect. We demonstrate its practical performance using Monte Carlo simulation studies and apply this method to investigate the extent to which DNA methylation markers mediate the causal pathway from smoking to reduced lung function in the Normative Aging Study. We identify 2 CpGs with significant mediation effects. AVAILABILITY AND IMPLEMENTATION: R package, source code, and simulation study are available at https://github.com/YinanZheng/HIMA CONTACT: lei.liu@northwestern.edu.

Estimation with Right-Censored Observations Under A Semi-Markov Model.

The semi-Markov process often provides a better framework than the classical Markov process for the analysis of events with multiple states. The purpose of this paper is twofold. First, we show that in the presence of right censoring, when the right end-point of the support of the censoring time is strictly less than the right end-point of the support of the semi-Markov kernel, the transition probability of the semi-Markov process is nonidentifiable, and the estimators proposed in the literature are inconsistent in general. We derive the set of all attainable values for the transition probability based on the censored data, and we propose a nonparametric inference procedure for the transition probability using this set. Second, the conventional approach to constructing confidence bands is not applicable for the semi-Markov kernel and the sojourn time distribution. We propose new perturbation resampling methods to construct these confidence bands. Different weights and transformations are explored in the construction. We use simulation to examine our proposals and illustrate them with hospitalization data from a recent cancer survivor study.

On the covariate-adjusted estimation for an overall treatment difference with data from a randomized comparative clinical trial.

To estimate an overall treatment difference with data from a randomized comparative clinical study, baseline covariates are often utilized to increase the estimation precision. Using the standard analysis of covariance technique for making inferences about such an average treatment difference may not be appropriate, especially when the fitted model is nonlinear. On the other hand, the novel augmentation procedure recently studied, for example, by Zhang and others (2008. Improving efficiency of inferences in randomized clinical trials using auxiliary covariates. Biometrics 64, 707-715) is quite flexible. However, in general, it is not clear how to select covariates for augmentation effectively. An overly adjusted estimator may inflate the variance and in some cases be biased. Furthermore, the results from the standard inference procedure by ignoring the sampling variation from the variable selection process may not be valid. In this paper, we first propose an estimation procedure, which augments the simple treatment contrast estimator directly with covariates. The new proposal is asymptotically equivalent to the aforementioned augmentation method. To select covariates, we utilize the standard lasso procedure. Furthermore, to make valid inference from the resulting lasso-type estimator, a cross validation method is used. The validity of the new proposal is justified theoretically and empirically. We illustrate the procedure extensively with a well-known primary biliary cirrhosis clinical trial data set.