Ram R. Miller

Statistical Analysis and Application of Quasi Experiments to Antimicrobial Resistance Intervention Studies

Quasi-experimental study designs are frequently used to assess interventions that aim to limit the emergence of antimicrobial-resistant pathogens. However, previous studies using these designs have often used suboptimal statistical methods, which may result in researchers making spurious conclusions. Methods used to analyze quasi-experimental data include 2-group tests, regression analysis, and time-series analysis, and they all have specific assumptions, data requirements, strengths, and limitations. An example of a hospital-based intervention to reduce methicillin-resistant Staphylococcus aureus infection rates and reduce overall length of stay is used to explore these methods.

Association of Low Vitamin D Levels With the Frailty Syndrome in Men and Women

BACKGROUND Although both vitamin D (25-hydroxyvitamin D [25(OH)D]) insufficiency and the frailty syndrome are more prevalent in women than men, sex-specific associations have not been explored. We estimated sex-specific associations of low 25(OH)D with frailty. Vitamin D insufficiency can result in hyperparathyroidism, and thus, parathyroid hormone (PTH) was explored as a potential mediator in the relationship between 25(OH)D levels and frailty. METHODS The sample included 444 male and 561 female participants aged 65 years and older from the InCHIANTI study for whom 25(OH)D levels and frailty information were available. Frailty was defined as the presence of at least three of the five following criteria: slowness, weakness, low energy expenditure, exhaustion, and weight loss. Logistic regression models estimated the association between serum levels of 25(OH)D and PTH with frailty, controlling for potential confounders. RESULTS Independent of covariates, men with 25(OH)D <50 nmol/L had greater odds of frailty than those with 25(OH)D > or =50 nmol/L (odds ratio [OR] = 4.94, 95% confidence interval [CI] = 1.80-13.61). In women, the adjusted OR for frailty (95% CI) was 1.43 (0.58-3.56). The 25(OH)D ORs differed between men and women (p = .041). ORs changed little after controlling for PTH. However, when low energy expenditure was excluded from the frailty definition, adjusted OR for frailty in men (95% CI) was 2.18 (0.59-8.04); controlling for PTH attenuated this OR by 32%. In women, the OR (95% CI) for frailty (low energy expenditure excluded) was 1.54 (0.31-7.58) and was attenuated by 6% after controlling for PTH. CONCLUSIONS Vitamin D insufficiency was associated with frailty in men, but not in women. Results suggest that PTH mediates the relationship between 25(OH)D and nonenergy expenditure aspects of frailty.

Absolute Strength and Loss of Strength as Predictors of Mobility Decline in Older Adults: The InCHIANTI Study

BACKGROUND Theoretical definitions of sarcopenia traditionally emphasize age-related loss of muscle strength; however, most analyses of the association between strength and mobility examine strength at a single time point. This study sought to identify sex-specific cutpoints for muscle strength and power (at one time point) and 3-year changes in strength and power that would maximize prediction of 3-year mobility decline. METHODS Longitudinal analysis of 934 adults aged ≥65 years enrolled in the Invecchiare in Chianti study was conducted. Grip strength, knee extension strength, and lower extremity power were measured at baseline and 3 years postenrollment. Mobility function (gait speed and self-reported mobility disability) was measured at 3 and 6 years postenrollment. Classification and regression tree analysis was used to predict mobility decline from Years 3 to 6. RESULTS Men with knee extension strength <19.2 kg and grip strength <39.0 kg had clinically meaningful declines in gait speed of .24 m/s. Furthermore, men with power <105 W were nearly nine times more likely to develop incident mobility disability (likelihood ratio = 8.68; 95% confidence interval = 3.91, 19.44). Among women, knee extension strength <18.0 kg was associated with a minimal gait speed decline of 0.06 m/s, and women with leg power <64 W were three times more likely to develop incident mobility disability (likelihood ratio = 3.01; 95% confidence interval = 1.79, 5.08). Three-year changes in strength and power did not predict mobility decline in either sex. CONCLUSIONS Findings suggest that strength and power measured at one time point are more predictive of mobility decline than 3-year changes and that low strength and power are particularly powerful risk factors in men.

Prevalence of methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii in a long-term acute care facility

BACKGROUND Patients in long-term acute care (LTAC) facilities often have many known risk factors for acquisition of antibiotic-resistant bacteria. However, the prevalence of resistance in these facilities has not been well described. METHODS We performed a single-day, point-prevalence study of a 180-bed, university-affiliated LTAC facility in Baltimore to assess the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii in the anterior nares, perirectal area, sputum, and wounds. RESULTS Among the 147 patients evaluated, we found a high prevalence of colonization by both MRSA (28%) and A baumannii (30%). Of the A baumannii isolates, 90% were susceptible to imipenem and 92% were susceptible to ampicillin-sulbactam. No isolates were resistant to both imipenem and ampicillin-sulbactam. CONCLUSION The high prevalence of resistance found in this study supports the need for increased surveillance of patients in the LTAC environment. The fact that these patients are often frequently transferred to tertiary care facilities also supports the need for coordination and collaboration among facilities within the same health care system and the broader geographic area.

Low-serum carotenoid concentrations and carotenoid interactions predict mortality in US adults: the Third National Health and Nutrition Examination Survey

Evidence regarding the health benefits of carotenoids is controversial. Effects of serum carotenoids and their interactions on mortality have not been examined in a representative sample of US adults. The objective was to examine whether serum carotenoid concentrations predict mortality among US adults. The study consisted of adults aged ≥20 years enrolled in the Third National Health and Nutrition Examination Survey, 1988 to 1994, with measured serum carotenoids and mortality follow-up through 2006 (N = 13,293). Outcomes were all-cause, cardiovascular disease, and cancer mortality. In adjusted Cox proportional hazards models, participants in the lowest total carotenoid quartile (<1.01 μmol/L) had significantly higher all-cause mortality (mortality rate ratio, 1.38; 95% confidence interval, 1.15-1.65; P = .005) than those in the highest total carotenoid quartile (>1.75 μmol/L). For α-carotene, the highest quartile (>0.11 μmol/L) had the lowest all-cause mortality rates (P < .001). For lycopene, the middle 2 quartiles (0.29-0.58 μmol/L) had the lowest all-cause mortality rates (P = .047). Analyses with continuous carotenoids confirmed associations of serum total carotenoids, α-carotene, and lycopene with all-cause mortality (P < .001). In a random survival forest analysis, very low lycopene was the carotenoid most strongly predictive of all-cause mortality, followed by very low total carotenoids. α-Carotene/β-cryptoxanthin, α-carotene/lutein+zeaxanthin and lycopene/lutein+zeaxanthin interactions were significantly related to all-cause mortality (P < .05). Low α-carotene was the only carotenoid associated with cardiovascular disease mortality (P = .002). No carotenoids were significantly associated with cancer mortality. Very low serum total carotenoid, α-carotene, and lycopene concentrations may be risk factors for mortality, but carotenoids show interaction effects on mortality. Interventions of balanced carotenoid combinations are needed for confirmation.

Associations Between Vitamin D Status and Pain in Older Adults: The Invecchiare in Chianti Study

OBJECTIVES: To examine cross‐sectional associations between vitamin D status and musculoskeletal pain and whether they differ by sex.

Treatment of Dementia in Community‐Dwelling and Institutionalized Medicare Beneficiaries

OBJECTIVES: To establish nationally representative estimates of the use of agents to treat Alzheimers disease and related dementias (ADRDs) and related behavioral symptoms in Medicare beneficiaries and to describe medication use according to residential status and other patient characteristics.

Delivery and Outcomes of a Yearlong Home Exercise Program After Hip Fracture: A Randomized Controlled Trial

BACKGROUND Hip fracture affects more than 1.6 million persons worldwide and causes substantial changes in body composition, function, and strength. Usual care (UC) has not successfully restored function to most patients, and prior research has not identified an effective restorative program. Our objective was to determine whether a yearlong home-based exercise program initiated following UC could be administered to older patients with hip fracture and improve outcomes. METHODS A randomized controlled trial of 180 community dwelling female patients with hip fracture, 65 years and older, randomly assigned to intervention (n = 91) or UC (n = 89). Patients were recruited within 15 days of fracture from 3 Baltimore-area hospitals from November 1998 through September 2004. Follow-up assessments were conducted at 2, 6, and 12 months after fracture. The Exercise Plus Program was administered by exercise trainers that included supervised and independently performed aerobic and resistive exercises with increasing intensity. Main outcome measures included bone mineral density of the contralateral femoral neck. Other outcomes included time spent and kilocalories expended in physical activity using the Yale Physical Activity Scale, muscle mass and strength, fat mass, activities of daily living, and physical and psychosocial functioning. The effect of intervention for each outcome was estimated by the difference in outcome trajectories 2 to 12 months after fracture. RESULTS More than 80% of participants received trainer visits, with the majority receiving more than 3 quarters (79%) of protocol visits. The intervention group reported more time spent in exercise activity during follow-up (P < .05). Overall, small effect sizes of 0 to 0.2 standard deviations were seen for bone mineral density measures, and no significant patterns of time-specific between-group differences were observed for the remaining outcome measures. CONCLUSION Patients with hip fracture who participate in a yearlong, in-home exercise program will increase activity level compared with those in UC; however, no significant changes in other targeted outcomes were detected. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00390741.

Serum 25-hydroxyvitamin D, transitions between frailty states, and mortality in older adults: the Invecchiare in Chianti Study

To assess whether serum 25‐hydroxyvitamin D (25(OH)D) concentrations relate to transitions between the states of robustness, prefrailty, and frailty and to mortality in older adults.

Frequent manual repositioning and incidence of pressure ulcers among bed-bound elderly hip fracture patients

Frequent manual repositioning is an established part of pressure ulcer prevention, but there is little evidence for its effectiveness. This study examined the association between repositioning and pressure ulcer incidence among bed‐bound elderly hip fracture patients, using data from a 2004–2007 cohort study in nine Maryland and Pennsylvania hospitals. Eligible patients (n=269) were age ≥65 years, underwent hip fracture surgery, and were bed‐bound at index study visits (during the first 5 days of hospitalization). Information about repositioning on the days of index visits was collected from patient charts; study nurses assessed presence of stage 2+ pressure ulcers 2 days later. The association between frequent manual repositioning and pressure ulcer incidence was estimated, adjusting for pressure ulcer risk factors using generalized estimating equations and weighted estimating equations. Patients were frequently repositioned (at least every 2 hours) on only 53% (187/354) of index visit days. New pressure ulcers developed at 12% of visits following frequent repositioning vs. 10% following less frequent repositioning; the incidence rate of pressure ulcers per person‐day did not differ between the two groups (incidence rate ratio 1.1, 95% confidence interval 0.5–2.4). No association was found between frequent repositioning of bed‐bound patients and lower pressure ulcer incidence, calling into question the allocation of resources for repositioning.