Total body skeletal muscle mass estimated by magnetic resonance imaging and creatine (methyl-d3 ) dilution in athletes.

Creatine dilution (D3 -cr) is a technique for estimating total skeletal muscle mass (SMM) with practical utility, but has not been applied in athletic populations where body composition may differ to that in the normal population. This study aimed to assess the agreement between SMM derived from both D3 -cr and that obtained from whole-body magnetic resonance imaging (MRI) in 15 male and 5 female national level kayakers (stature: 182.0 ± 13.1 and 170.0 ± 9.0 cm; body mass: 80.6 ± 9.9 and 66.4 ± 6.0 kg; V̇O2 peak: 56.5 ± 7.0 and 49.6 ± 4.4 mL kg-1  min-1 , mean ± SD). SMM was determined following 60 mg of dosed D3 -cr and analysis of expelled urine collected on four subsequent days for creatine, creatinine, D3 -cr, and D3 -creatinine using liquid chromatography/mass spectroscopy. SMM was then estimated by assuming a creatine pool size of 4.3 g/kg. During the same time period, a whole-body MRI was undertaken to derive SMM from the analysis of multiple slices taken across the body. A strong positive correlation (F = 74.32; R = 0.90; P < .0001) between the two methods was observed, but the D3 -cr SMM was found to be significantly higher (43.3 ± 6.8 kg) when compared with MRI (36.3 ± 5.8 kg, P < .0001). However, the difference between the methods was removed when a higher intramuscular creatine pool (5.1 g/kg) was assumed. These data show that D3 -cr has potential utility in athletes, as referenced against MRI, but show that assumptions regarding creatine pool size need to be carefully considered.

Trunk Muscle Composition 2 Months After Hip Fracture: Findings From the Baltimore Hip Studies.

OBJECTIVE: To determine if hip fracture patients would have smaller cross-sectional area (CSA) and lower radiological attenuation (suggesting greater fat infiltration) in all trunk muscles as compared to older adults without hip fractures. DESIGN: Cross-sectional analysis of computed tomography (CT) scans. SETTING: Clinical imaging facility. PARTICIPANTS: Forty-one white participants (19 men, 22 women) from the Baltimore Hip Studies seventh cohort at 2 months postfracture were compared to 693 white participants (424 men, 269 women) from the Health, Aging and Body Composition (Health ABC) study at the year 6 visit (N=734). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Trunk muscle CSA and attenuation values were obtained from a single 10-mm, axial CT scan completed at the L4-L5 disc space in each participant. RESULTS: The hip fracture cohort had significantly smaller CSA for all trunk muscles (range: 12.1%-38% smaller) compared to the Health ABC cohort (P<.01), with the exception of the rectus abdominus muscle in men (P=.12). But, hip fracture patients, particularly female patients, had higher attenuation levels (lower intramuscular fat) in all trunk muscles (P<.0001). CONCLUSIONS: Findings are consistent with atrophy of the trunk muscles in the hip fracture population without a high level of intramuscular fat. Future work should evaluate the role of trunk muscle composition in the functional recovery of older adults after hip fracture.

Measurement of muscle mass in sarcopenia: from imaging to biochemical markers.

Sarcopenia encompasses the loss of muscle mass and strength/function during aging. Several methods are available for the estimation of muscle or lean body mass. Popular assessment tools include body imaging techniques (e.g., magnetic resonance imaging, computed tomography, dual X-ray absorptiometry, ultrasonography), bioelectric impedance analysis, anthropometric parameters (e.g., calf circumference, mid-arm muscle circumference), and biochemical markers (total or partial body potassium, serum and urinary creatinine, deuterated creatine dilution method). The heterogeneity of the populations to be evaluated as well as the setting in which sarcopenia is investigated impacts the definition of "gold standard" assessment techniques. The aim of this article is to critically review available methods for muscle mass estimation, highlighting strengths and weaknesses of each of them as well as their proposed field of application.

Biomarkers for physical frailty and sarcopenia.

Physical frailty (PF) and sarcopenia are major health issues in geriatric populations, given their high prevalence and association with several adverse outcomes. Nevertheless, the lack of an univocal operational definition for the two conditions has so far hampered their clinical implementation. Existing definitional ambiguities of PF and sarcopenia, together with their complex underlying pathophysiology, also account for the absence of robust biomarkers that can be used for screening, diagnostic and/or prognostication purposes. This review provides an overview of currently available biological markers for PF and sarcopenia, as well as a critical appraisal of strengths and weaknesses of traditional procedures for biomarker development in the field. A novel approach for biomarker identification and validation, based on multivariate methodologies, is also discussed. This strategy relies on the multidimensional modeling of complementary biomarkers to cope with the phenotypical and pathophysiological complexity of PF and sarcopenia. Biomarkers identified through the implementation of multivariate strategies may be used to support the detection of the two conditions, track their progression over time or in response to interventions, and reveal the onset of complications (e.g., mobility disability) at a very early stage.

Thigh Muscle Composition and Its Relationship to Functional Recovery Post Hip Fracture Over Time and Between Sexes.

BACKGROUND: Computed tomography (CT)-scan measures of muscle composition may be associated with recovery post hip fracture. METHODS: In an ancillary study to Baltimore Hip Studies Seventh cohort, older adults were evaluated at 2 and 6 months post hip fracture. CT-scan measures of muscle were acquired at 2 months. Short Physical Performance Battery (SPPB) was measured at 2 and 6 months. Generalized estimating equations were used to model the association of muscle measures and physical function, adjusting for age, sex, body mass index, and time postfracture. RESULTS: Seventy-one older adults (52% males, age 79.6 ± 7.3 years) were included. At 2-months, males had greater thigh cross-sectional area (CSA, p < .0001) and less low-density muscle (p = .047), and intermuscular adipose tissue (p = .007) than females on the side of the fracture, while females performed better on the SPPB (p = .05). Muscle measures on the fractured side were associated with function at 2 months in both sexes. Participants with the lowest tertile of muscle CSA difference at 2-months, indicating greater symmetry in CSA between limbs, performed better than the other 2 tertiles at 6-months. Males performed worse in functional measures at baseline and did not recover as well as females (p = .02). CONCLUSION: CT-scan measures of muscle CSA and fatty infiltration were associated with function at 2-months post hip fracture and with improvement in function by 6 months. Observed sex differences in these associations suggest that rehabilitation strategies may need to be adapted by sex after hip fracture.

Sex Differences in Recovery Across Multiple Domains Among Older Adults With Hip Fracture.

BACKGROUND: Hip fractures are a public health problem among older adults, but most research on recovery after hip fracture has been limited to females. With growing numbers of hip fractures among males, it is important to determine how recovery outcomes may differ between the sexes. METHODS: 168 males and 171 females were enrolled within 15 days of hospitalization with follow-up visits at 2, 6, and 12 months postadmission to assess changes in disability, physical performance, cognition, depressive symptoms, body composition, and strength, and all-cause mortality. Generalized estimating equations examined whether males and females followed identical outcome recovery assessed by the change in each outcome. RESULTS: The mean age at fracture was similar for males (80.4) and females (81.4), and males had more comorbidities (2.5 vs 1.6) than females. Males were significantly more likely to die over 12 months (hazard ratio 2.89, 95% confidence interval: 1.56-5.34). Changes in outcomes were significantly different between males and females for disability, gait speed, and depressive symptoms (p < .05). Both sexes improved from baseline to 6 months for these measures, but only males continued to improve between 6 and 12 months. There were baseline differences for most body composition measures and strength; however, there were no significant differences in change by sex. CONCLUSIONS: Findings confirm that males have higher mortality but suggest that male survivors have continued functional recovery over the 12 months compared to females. Research is needed to determine the underlying causes of these sex differences for developing future prognostic information and rehabilitative interventions.

Multicomponent intervention to prevent mobility disability in frail older adults: randomised controlled trial (SPRINTT project).

OBJECTIVE: To determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia. DESIGN: Evaluator blinded, randomised controlled trial. SETTING: 16 clinical sites across 11 European countries, January 2016 to 31 October 2019. PARTICIPANTS: 1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls). INTERVENTIONS: The multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months. MAIN OUTCOME MEASURES: The primary outcome was mobility disability (inability to independently walk 400 m in <15 minutes). Persistent mobility disability (inability to walk 400 m on two consecutive occasions) and changes from baseline to 24 and 36 months in physical performance, muscle strength, and appendicular lean mass were analysed as pre-planned secondary outcomes. Primary comparisons were conducted in participants with baseline SPPB scores of 3-7 (n=1205). Those with SPPB scores of 8 or 9 (n=314) were analysed separately for exploratory purposes. RESULTS: Mean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3-7, mobility disability occurred in 283/605 (46.8%) assigned to the multicomponent intervention and 316/600 (52.7%) controls (hazard ratio 0.78, 95% confidence interval 0.67 to 0.92; P=0.005). Persistent mobility disability occurred in 127/605 (21.0%) participants assigned to the multicomponent intervention and 150/600 (25.0%) controls (0.79, 0.62 to 1.01; P=0.06). The between group difference in SPPB score was 0.8 points (95% confidence interval 0.5 to 1.1 points; P<0.001) and 1.0 point (95% confidence interval 0.5 to 1.6 points; P<0.001) in favour of the multicomponent intervention at 24 and 36 months, respectively. The decline in handgrip strength at 24 months was smaller in women assigned to the multicomponent intervention than to control (0.9 kg, 95% confidence interval 0.1 to 1.6 kg; P=0.028). Women in the multicomponent intervention arm lost 0.24 kg and 0.49 kg less appendicular lean mass than controls at 24 months (95% confidence interval 0.10 to 0.39 kg; P<0.001) and 36 months (0.26 to 0.73 kg; P<0.001), respectively. Serious adverse events occurred in 237/605 (39.2%) participants assigned to the multicomponent intervention and 216/600 (36.0%) controls (risk ratio 1.09, 95% confidence interval 0.94 to 1.26). In participants with SPPB scores of 8 or 9, mobility disability occurred in 46/155 (29.7%) in the multicomponent intervention and 38/159 (23.9%) controls (hazard ratio 1.25, 95% confidence interval 0.79 to 1.95; P=0.34). CONCLUSIONS: A multicomponent intervention was associated with a reduction in the incidence of mobility disability in older adults with physical frailty and sarcopenia and SPPB scores of 3-7. Physical frailty and sarcopenia may be targeted to preserve mobility in vulnerable older people. TRIAL REGISTRATION: ClinicalTrials.gov NCT02582138.

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.

Semiparametric regression models for repeated measures of mortal cohorts with non-monotone missing outcomes and time-dependent covariates.

We propose a semiparametric marginal modeling approach for longitudinal analysis of cohorts with data missing due to death and non-response to estimate regression parameters interpreted as conditioned on being alive. Our proposed method accommodates outcomes and time-dependent covariates that are missing not at random with non-monotone missingness patterns via inverse-probability weighting. Missing covariates are replaced by consistent estimates derived from a simultaneously solved inverse-probability-weighted estimating equation. Thus, we utilize data points with the observed outcomes and missing covariates beyond the estimated weights while avoiding numerical methods to integrate over missing covariates. The approach is applied to a cohort of elderly female hip fracture patients to estimate the prevalence of walking disability over time as a function of body composition, inflammation, and age.

Pattern-mixture models for analyzing normal outcome data with proxy respondents.

Studies of older adults often involve interview questions regarding subjective constructs such as perceived disability. In some studies, when subjects are unable (e.g. due to cognitive impairment) or unwilling to respond to these questions, proxies (e.g. relatives or other care givers) are recruited to provide responses in place of the subject. Proxies are usually not approached to respond on behalf of subjects who respond for themselves; thus, for each subject, data from only one of the subject or proxy are available. Typically, proxy responses are simply substituted for missing subject responses, and standard complete-data analyses are performed. However, this approach may introduce measurement error and produce biased parameter estimates. In this paper, we propose using pattern-mixture models that relate non-identifiable parameters to identifiable parameters to analyze data with proxy respondents. We posit three interpretable pattern-mixture restrictions to be used with proxy data, and we propose estimation procedures using maximum likelihood and multiple imputation. The methods are applied to a cohort of elderly hip-fracture patients.

Bimagrumab vs Optimized Standard of Care for Treatment of Sarcopenia in Community-Dwelling Older Adults: A Randomized Clinical Trial.

Importance: The potential benefit of novel skeletal muscle anabolic agents to improve physical function in people with sarcopenia and other muscle wasting diseases is unknown. Objective: To confirm the safety and efficacy of bimagrumab plus the new standard of care on skeletal muscle mass, strength, and physical function compared with standard of care alone in community-dwelling older adults with sarcopenia. Design, Setting, and Participants: This double-blind, placebo-controlled, randomized clinical trial was conducted at 38 sites in 13 countries among community-dwelling men and women aged 70 years and older meeting gait speed and skeletal muscle criteria for sarcopenia. The study was conducted from December 2014 to June 2018, and analyses were conducted from August to November 2018. Interventions: Bimagrumab 700 mg or placebo monthly for 6 months with adequate diet and home-based exercise. Main Outcomes and Measures: The primary outcome was the change in Short Physical Performance Battery (SPPB) score after 24 weeks of treatment. Secondary outcomes included 6-minute walk distance, usual gait speed, handgrip strength, lean body mass, fat body mass, and standard safety parameters. Results: A total of 180 participants were recruited, with 113 randomized to bimagrumab and 67 randomized to placebo. Among these, 159 participants (88.3%; mean [SD] age, 79.1 [5.3] years; 109 [60.6%] women) completed the study. The mean SPPB score increased by a mean of 1.34 (95% CI, 0.90 to 1.77) with bimagrumab vs 1.03 (95% CI, 0.53 to 1.52) with placebo (P = .13); 6-minute walk distance increased by a mean of 24.60 (95% CI, 7.65 to 41.56) m with bimagrumab vs 14.30 (95% CI, -4.64 to 33.23) m with placebo (P = .16); and gait speed increased by a mean of 0.14 (95% CI, 0.09 to 0.18) m/s with bimagrumab vs 0.11 (95% CI, 0.05 to 0.16) m/s with placebo (P = .16). Bimagrumab was safe and well-tolerated and increased lean body mass by 7% (95% CI, 6% to 8%) vs 1% (95% CI, 0% to 2%) with placebo, resulting in difference of 6% (95% CI, 4% to 7%) (P < .001). Conclusions and Relevance: This randomized clinical trial found no significant difference between participants treated with bimagrumab vs placebo among older adults with sarcopenia who had 6 months of adequate nutrition and light exercise, with physical function improving in both groups. Bimagrumab treatment was safe, well-tolerated, increased lean body mass, and decreased fat body mass. The effects of sarcopenia, an increasing cause of disability in older adults, can be reduced with proper diet and exercise. Trial Registration: ClinicalTrials.gov Identifier: NCT02333331; EudraCT number: 2014-003482-25.

Hepatitis C in the elderly: epidemiology, natural history, and treatment.

Hepatitis C continues to be a major public health problem affecting approximately 3% of the global population. According to the World Health Organization, an estimated 170 million people have chronic hepatitis C. Ten percent to 20% of those who are chronically infected with hepatitis C will progress to cirrhosis and 5% will develop hepatocellular carcinoma. Although the safety and efficacy of hepatitis C therapies have been studied extensively in patients between the ages of 18 and 65, patients who are older than 65 still remain an understudied and difficult-to-treat population. This review discusses the epidemiology, natural history, and treatment of chronic hepatitis C in older adults.

Prevalence of antimicrobial-resistant bacteria isolated from older versus younger hospitalized adults: results of a two-centre study.

OBJECTIVES: To compare the proportion of antimicrobial-resistant strains among bacterial isolates from younger and older hospital patients and to quantify changes in the proportion of antimicrobial-resistant strains in both groups over time. PATIENTS AND METHODS: A retrospective analysis of microbiology data from two centres in Maryland and Chicago was performed. Adult hospital inpatients with positive clinical cultures for specific antimicrobial-resistant bacterial pathogens between 1999 and 2005 (55 427 isolates) were included. The proportions of isolates not susceptible to specific antimicrobial agents were compared between patients > or =65 and <65 years. Additional analyses examined temporal trends in the frequency of resistance and the frequency of resistance among the oldest patients (> or =80 years), in bacteria isolated from blood cultures and in bacteria obtained from intensive care unit patients. RESULTS: Heterogeneity was observed in the frequency of resistance among different bacteria between older and younger patients, between the two centres and over the study period. Staphylococcus aureus isolates were more likely to be resistant to methicillin when obtained from older patients at Chicago (50.9% versus 40.9%; P < 0.001). In contrast, younger patients yielded a greater proportion of enterococci resistant to vancomycin at Maryland (19.4% versus 16.5%; P = 0.009). Results were variable when resistance to fluoroquinolones, cephalosporins and imipenem were compared for Pseudomonas aeruginosa, Escherichia coli and Klebsiella spp. CONCLUSIONS: Overall, advanced patient age was not uniformly associated with a greater likelihood of antimicrobial resistance among all bacterial pathogens. Moreover, the frequency of resistance in older and younger patients varied considerably at the two sites over the study period. Variability in the frequency of resistance precludes simplistic conclusions regarding the relationship between age and resistance.

Repeat falls and the recovery of social participation in the year post-hip fracture.

BACKGROUND: although the majority of hip fractures are the result of a fall, whether repeated falls in the year post-fracture adversely influence recovery of social participation is not known. DESIGN: analysis of data from a longitudinal cohort study. SUBJECTS: community-dwelling women aged > or = 65 years, admitted to one of two hospitals in Baltimore with a new, non-pathological fracture of the proximal femur between 1992 and 1995. METHODS: information on falls was collected from a falls diary. At the baseline, 6- and 12-month evaluations, subjects were asked about the number of times in the 2 weeks prior to the evaluation they had participated in 10 categories of social activities. We examined the association of repeated falls with social participation using generalized estimating equations. The effect of physical and psychological functions was examined by including measures of lower extremity functional performance and depressive symptoms into the model. RESULTS: the analyses included 196 women, mean age = 80.2 years. Eighty-one subjects fell. The subjects with >1 fall between evaluations participated in a mean (95% CI) of 3.5 (0.12, 6.9) and 4.3 (0.9, 7.7) fewer social activities at 6 and 12 months post-fracture, respectively, compared to those who did not fall (P = 0.0003). These results were attenuated by adjustment for depressive symptoms, but not by lower extremity functional performance. CONCLUSIONS: in the year post-fracture, repeated falls in women were associated with decreased social participation independent of lower extremity function. Depressive symptoms in repeated fallers may partly explain this association.

Emerging Interventions for Elderly Patients-The Promise of Regenerative Medicine.

The impressive increase in lifespan that occurred in the 20th century has driven a boom in age-associated degeneration resulting from senescence. Geriatric syndromes, such as sarcopenia and frailty, do not fall neatly into classical medical definitions of disease because they result from subtle declines in physiological function that occur over many years instead of specific organ-related pathology. These conditions have become more clinically prominent with the aging population and are the focus of research in regenerative medicine. Two major approaches are being pursued: the first targets specific organs that are adversely affected by senescence, and the second targets senescence pathways themselves, with the goal of favorably altering the affected physiology. This review will highlight a few examples of recent applications of both of these approaches to illustrate the potential of the application of a regenerative medicine approach to improve the quality of life and independence in older adults.

Falls: epidemiology, pathophysiology, and relationship to fracture.

Falls are common in the elderly, and frequently result in injury and disability. Most falls result from an interaction between individual characteristics that increase an individual's propensity to fall and acute mediating risk factors that provide the opportunity to fall. Predisposing risk factors include age-associated changes in strength and balance, comorbidities such as osteoarthritis, visual impairment and dementia, psychotropic medications, and certain types of footwear. Fewer studies have focused on acute precipitating factors, but environmental and situational factors are clearly important to fall risk. Approximately 30% of falls result in an injury that requires medical attention, with fractures occurring in approximately 10%. In addition to the risk factors for falls, the fall descent, fall impact, and bone strength are all important determinants of whether a fall will result in a fracture. In recent years, numerous studies have been directed toward the development of effective fall and fall-related fracture prevention interventions.

Creatine ( methyl-d3) dilution in urine for estimation of total body skeletal muscle mass: accuracy and variability vs. MRI and DXA.

A noninvasive method to estimate muscle mass based on creatine ( methyl-d3) (D3-creatine) dilution using fasting morning urine was evaluated for accuracy and variability over a 3- to 4-mo period. Healthy older (67- to 80-yr-old) subjects ( n = 14) with muscle wasting secondary to aging and four patients with chronic disease (58-76 yr old) fasted overnight and then received an oral 30-mg dose of D3-creatine at 8 AM ( day 1). Urine was collected during 4 h of continued fasting and then at consecutive 4- to 8-h intervals through day 5. Assessment was repeated 3-4 mo later in 13 healthy subjects and 1 patient with congestive heart failure. Deuterated and unlabeled creatine and creatinine were measured using liquid chromatography-tandem mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by whole body MRI and 24-h urine creatinine, and lean body mass (LBM) was measured by dual-energy X-ray absorptiometry (DXA). D3-creatinine urinary enrichment from day 5 provided muscle mass estimates that correlated with MRI for all subjects ( r = 0.88, P < 0.0001), with less bias [difference from MRI = -3.00 ± 2.75 (SD) kg] than total LBM assessment by DXA, which overestimated muscle mass vs. MRI (+22.5 ± 3.7 kg). However, intraindividual variability was high with the D3-creatine dilution method, with intrasubject SD for estimated muscle mass of 2.5 kg vs. MRI (0.5 kg) and DXA (0.8 kg). This study supports further clinical validation of the D3-creatine method for estimating muscle mass. NEW & NOTEWORTHY Measurement of creatine ( methyl-d3) (D3-creatine) and D3-creatinine excretion in fasted morning urine samples may be a simple, less costly alternative to MRI or dual-energy X-ray absorptiometry (DXA) to calculate total body muscle mass. The D3-creatine enrichment method provides estimates of muscle mass that correlate well with MRI, and with less bias than DXA. However, intraindividual variability is high with the D3-creatine method. Studies to refine the spot urine sample method for estimation of muscle mass may be warranted.

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.

A systematic review of the methods used to assess the association between appropriate antibiotic therapy and mortality in bacteremic patients.

Studies of the association between inappropriate antibiotic therapy and mortality among bacteremic patients have generated conflicting findings. We systematically reviewed these studies to identify methodological heterogeneity that may explain the lack of agreement. We identified 51 articles that met the inclusion criteria, and we extracted the following data: study design, definition and measurement of variables, and statistical methods. Only 8 studies (16%) defined inappropriate antibiotic therapy as that which was inactive in vitro against the isolated organism(s) and not consistent with current clinical practice recommendations and distinguished between empiric and definitive treatment. Thirty-four studies (67%) measured the severity of illness, but only 6 (12%) specified the time at which it was measured. The methodological recommendations suggested in this article are intended to improve the validity and generalizability of future research. In brief, future studies should define "inappropriate" therapy on the basis of in vitro susceptibility data, should separately evaluate empiric and definitive therapy, and should control for the baseline severity of illness.

Association of serum vitamin D levels with inflammatory response following hip fracture: the Baltimore Hip Studies.

BACKGROUND: Vitamin D, known for its role in calcium homeostasis, may also regulate immune function. Whether vitamin D deficiency at the time of hip fracture is associated with the inflammatory response postfracture is not known. METHODS: In a cohort from the Baltimore Hip Studies, women aged >or= 65 years were evaluated at baseline and 2, 6, and 12 months after hip fracture repair. Serum at baseline was analyzed for 25-hydroxyvitamin D [25(OH)D], and serum from all time points was analyzed for interleukin-6 (IL-6). Participants were divided into two groups based on their baseline 25(OH)D levels. Vitamin D deficiency was defined as a 25(OH)D level of