Mycobacterium tuberculosis Subculture Results in Loss of Potentially Clinically Relevant Heteroresistance.

Multidrug-resistant tuberculosis (TB) presents a major public health dilemma. Heteroresistance, the coexistence of drug-resistant and drug-susceptible strains or of multiple drug-resistant strains with discrete haplotypes, may affect accurate diagnosis and the institution of effective treatment. Subculture, or passage of cells onto fresh growth medium, is utilized to preserve Mycobacterium tuberculosis cell lines and is universally employed in TB diagnostics. The impact of such passages, typically performed in the absence of drug, on drug-resistant subpopulations is hypothesized to vary according to the competitive costs of genotypic resistance-associated variants. We applied ultradeep next-generation sequencing to 61 phenotypically rifampin-monoresistant (n = 17) and preextensively (n = 41) and extensively (n = 3) drug-resistant isolates with presumptive heteroresistance at two time points in serial subculture. We found significant dynamic loss of minor-variant resistant subpopulations across all analyzed resistance-determining regions, including eight isolates (13%) whose antibiogram data would have transitioned from resistant to susceptible for at least one drug through subculture. Surprisingly, some resistance-associated variants appeared to be selected for in subculture.

Risk adjustment for health care financing in chronic disease: what are we missing by failing to account for disease severity?

BACKGROUND: Adjustment for differing risks among patients is usually incorporated into newer payment approaches, and current risk models rely on age, sex, and diagnosis codes. It is unknown the extent to which controlling additionally for disease severity improves cost prediction. Failure to adjust for within-disease variation may create incentives to avoid sicker patients. We address this issue among patients with chronic obstructive pulmonary disease (COPD). METHODS: Cost and clinical data were collected prospectively from 1202 COPD patients at Kaiser Permanente. Baseline analysis included age, sex, and diagnosis codes (using the Diagnostic Cost Group Relative Risk Score) in a general linear model predicting total medical costs in the following year. We determined whether adding COPD severity measures-forced expiratory volume in 1 second, 6-Minute Walk Test, dyspnea score, body mass index, and BODE Index (composite of the other 4 measures)-improved predictions. Separately, we examined household income as a cost predictor. RESULTS: Mean costs were $12,334/y. Controlling for Relative Risk Score, each ½ SD worsening in COPD severity factor was associated with $629 to $1135 in increased annual costs (all P<0.01). The lowest stratum of forced expiratory volume in 1 second (<30% normal) predicted $4098 (95% confidence interval, $576-$8773) additional costs. Household income predicted excess costs when added to the baseline model (P=0.038), but this became nonsignificant when also incorporating the BODE Index. CONCLUSIONS: Disease severity measures explain significant cost variations beyond current risk models, and adding them to such models appears important to fairly compensate organizations that accept responsibility for sicker COPD patients. Appropriately controlling for disease severity also accounts for costs otherwise associated with lower socioeconomic status.

Exposure to polycyclic aromatic hydrocarbons and volatile organic compounds among recently pregnant rural Guatemalan women cooking and heating with solid fuels.

BACKGROUND: Household air pollution is a major contributor to death and disability worldwide. Over 95% of rural Guatemalan households use woodstoves for cooking or heating. Woodsmoke contains carcinogenic or fetotoxic polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs). Increased PAHs and VOCs have been shown to increase levels of oxidative stress. OBJECTIVE: We examined PAH and VOC exposures among recently pregnant rural Guatemalan women exposed to woodsmoke and compared exposures to levels seen occupationally or among smokers. METHODS: Urine was collected from 23 women who were 3 months post-partum three times over 72h: morning (fasting), after lunch, and following dinner or use of wood-fired traditional sauna baths (samples=68). Creatinine-adjusted urinary concentrations of metabolites of four PAHs and eight VOCs were analyzed by liquid chromatography-mass spectrometry. Creatinine-adjusted urinary biomarkers of oxidative stress, 8-isoprostane and 8-OHdG, were analyzed using enzyme-linked immunosorbent assays (ELISA). Long-term (pregnancy through 3 months prenatal) exposure to particulate matter and airborne PAHs were measured. RESULTS: Women using wood-fueled chimney stoves are exposed to high levels of particulate matter (median 48h PM2.5 105.7µg/m3; inter-quartile range (IQR): 77.6-130.4). Urinary PAH and VOC metabolites were significantly associated with woodsmoke exposures: 2-naphthol (median (IQR) in ng/mg creatinine: 295.9 (74.4-430.9) after sauna versus 23.9 (17.1-49.5) fasting; and acrolein: 571.7 (429.3-1040.7) after sauna versus 268.0 (178.3-398.6) fasting. Urinary PAH (total PAH: ρ=0.89, p<0.001) and VOC metabolites of benzene (ρ=0.80, p<0.001) and acrylonitrile (ρ=0.59, p<0.05) were strongly correlated with long-term exposure to particulate matter. However urinary biomarkers of oxidative stress were not correlated with particulate matter (ρ=0.01 to 0.05, p>0.85) or PAH and VOC biomarkers (ρ=-0.20 to 0.38, p>0.07). Urinary metabolite concentrations were significantly greater than those of heavy smokers (mean cigarettes/day=18) across all PAHs. In 15 (65%) women, maximum 1-hydroxypyrene concentrations exceeded the occupational exposure limit of coke-oven workers. CONCLUSIONS: The high concentrations of urinary PAH and VOC metabolites among recently pregnant women is alarming given the detrimental fetal and neonatal effects of prenatal PAH exposure. As most women used chimney woodstoves, cleaner fuels are critically needed to reduce smoke exposure.

From the closest observers of patient care: a thematic analysis of online narrative reviews of hospitals.

OBJECTIVE: Patient-centred care has become a priority in many countries. It is unknown whether current tools capture aspects of care patients and their surrogates consider important. We investigated whether online narrative reviews from patients and surrogates reflect domains in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) and we described additional potential domains. DESIGN: We used thematic analysis to assess online narrative reviews for reference to HCAHPS domains and salient non-HCAHPS domains and compared results by reviewer type (patient vs surrogate). SETTING: We identified hospitals for review from the American Hospital Association database using a stratified random sampling approach. This approach ensured inclusion of reviews of a diverse set of hospitals. We searched online in February 2013 for narrative reviews from any source for each hospital. PARTICIPANTS: We included up to two narrative reviews for each hospital. EXCLUSIONS: Outpatient or emergency department reviews, reviews from self-identified hospital employees, or reviews of <10 words. RESULTS: 50.0% (n=122) of reviews (N=244) were from patients and 38.1% (n=93) from friends or family members. Only 57.0% (n=139) of reviews mentioned any HCAHPS domain. Additional salient domains were: Financing, including unexpected out-of-pocket costs and difficult interactions with billing departments; system-centred care; and perceptions of safety. These domains were mentioned in 51.2% (n=125) of reviews. Friends and family members commented on perceptions of safety more frequently than patients. CONCLUSIONS: A substantial proportion of consumer reviews do not mention HCAHPS domains. Surrogates appear to observe care differently than patients, particularly around safety.

Genetic modification of the effect of maternal household air pollution exposure on birth weight in Guatemalan newborns.

Low birth weight is associated with exposure to air pollution during pregnancy. The purpose of this study was to evaluate whether null polymorphisms of Glutathione S-transferases (GSTs), specifically GSTM1 and GSTT1 genes in infants or mothers, modify the association between high exposures to household air pollution (HAP) from cooking fires and birth weight. Pregnant women in rural Guatemala were randomized to receive a chimney stove or continue to use open fires for cooking. Newborns were measured within 48 h of birth. 132 mother-infant pairs provided infant genotypes (n=130) and/or maternal genotypes (n=116). Maternal null GSTM1 was associated with a 144 g (95% CI, -291, 1) and combined maternal/infant null GSTT1 was associated with a 155 g (95% CI, -303, -8) decrease in birth weight. Although there was a trend toward higher birth weights with increasing number of expressed GST genes, the effect modification by chimney stove use was not demonstrated.

National patterns of codeine prescriptions for children in the emergency department.

BACKGROUND AND OBJECTIVES: National guidelines have recommended against codeine use in children, but little is known about prescribing patterns in the United States. Our objectives were to assess changes over time in pediatric codeine prescription rates in emergency departments nationally and to determine factors associated with codeine prescription. METHODS: We performed a serial cross-sectional analysis (2001-2010) of emergency department visits for patients ages 3 to 17 years in the nationally representative National Hospital Ambulatory Medical Care Survey. We determined survey-weighted annual rates of codeine prescriptions and tested for linear trends over time. We used multivariate logistic regression to identify characteristics associated with codeine prescription and interrupted time-series analysis to assess changes in prescriptions for upper respiratory infection (URI) or cough associated with two 2006 national guidelines recommending against its use for these indications. RESULTS: The proportion of visits (N = 189 million) with codeine prescription decreased from 3.7% to 2.9% during the study period (P = .008). Odds of codeine prescription were higher for children ages 8 to 12 years (odds ratio [OR], 1.42; 95% confidence interval [1.21-1.67]) and among providers outside the northeast. Odds were lower for children who were non-Hispanic black (OR, 0.67 [0.56-0.8]) or with Medicaid (OR, 0.84 [0.71-0.98]). The 2006 guidelines were not associated with a decline in codeine prescriptions for cough or URI visits. CONCLUSIONS: Although there was a small decline in codeine prescription over 10 years, use for cough or URI did not decline after national guidelines recommending against its use. More effective interventions are needed to prevent codeine prescription to children.

The relationship between commercial website ratings and traditional hospital performance measures in the USA.

BACKGROUND: Our goal was to compare hospital scores from the most widely used commercial website in the USA to hospital scores from more systematic measures of patient experience and outcomes, and to assess what drives variation in the commercial website scores. METHODS: For a national sample of US hospitals, we compared scores on Yelp.com, which aggregates website visitor ratings (1-5 stars), with traditional measures of hospital quality. We calculated correlations between hospital Yelp scores and the following: hospital percent high ratings (9 or 10, scale 0-10) on the 'Overall' item on the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey; hospital individual HCAHPS domain scores (eg, nurse communication, pain control); hospital 30-day mortality; and hospital 30-day readmission rates. RESULTS: Of hospitals reporting HCAHPS (n=3796), 962 (25%) had scores on Yelp. Among hospitals with >5 Yelp ratings, the correlation of percent high ratings between Yelp and HCAHPS was 0.49 (p<0.001). The percent high ratings within each HCAHPS domain increased monotonically with increasing Yelp scores (p≤0.001 for all domains). Percent high ratings in Yelp and HCAHPS were statistically significantly correlated with lower mortality for myocardial infarction (MI; -0.19 for Yelp and -0.13 for HCAHPS) and pneumonia (-0.14 and -0.18), and fewer readmissions for MI (-0.17 and -0.39), heart failure (-0.31 and -0.39), and pneumonia (-0.18 and -0.27). CONCLUSIONS: These data suggest that rater experiences for Yelp and HCAHPS may be similar, and that consumers posting ratings on Yelp may observe aspects of care related to important patient outcomes.

Measuring hospital quality using pediatric readmission and revisit rates.

OBJECTIVE: To assess variation among hospitals on pediatric readmission and revisit rates and to determine the number of high- and low-performing hospitals. METHODS: In a retrospective analysis using the State Inpatient and Emergency Department Databases from the Healthcare Cost and Utilization Project with revisit linkages available, we identified pediatric (ages 1-20 years) visits with 1 of 7 common inpatient pediatric conditions (asthma, dehydration, pneumonia, appendicitis, skin infections, mood disorders, and epilepsy). For each condition, we calculated rates of all-cause readmissions and rates of revisits (readmission or presentation to the emergency department) within 30 and 60 days of discharge. We used mixed logistic models to estimate hospital-level risk-standardized 30-day revisit rates and to identify hospitals that had performance statistically different from the group mean. RESULTS: Thirty-day readmission rates were low (<10.0%) for all conditions. Thirty-day rates of revisit to the inpatient or emergency department setting ranged from 6.2% (appendicitis) to 11.0% (mood disorders). Study hospitals (n = 958) had low condition-specific visit volumes (37.0%-82.8% of hospitals had <25 visits). The only condition with >1% of hospitals labeled as different from the mean on 30-day risk-standardized revisit rates was mood disorders (4.2% of hospitals [n = 15], range of hospital performance 6.3%-15.9%). CONCLUSIONS: We found that when comparing hospitals' performances to the average, few hospitals that care for children are identified as high- or low-performers for revisits, even for common pediatric diagnoses, likely due to low hospital volumes. This limits the usefulness of condition-specific readmission or revisit measures in pediatric quality measurement.