Bassett Healthcare Network

CONTEXT: Television (TV) viewing is associated with obesity among school-aged children, adolescents, and adults, but this relationship has not been evaluated in preschool-aged children. OBJECTIVE: To describe the TV/video viewing habits of a multiethnic, low-income preschool population of children and to determine whether TV/video viewing is related to their adiposity. DESIGN: Cross-sectional survey of parents/guardians with measurements of children's height and weight. SETTING AND PARTICIPANTS: Two thousand seven hundred sixty-one adults with children, 1 through <5 years, from 49 New York State agencies of the Supplemental Nutrition Program for Women, Infants, and Children. OUTCOME MEASURES: Cross-sectional relationships between the amount of time the child spends viewing TV/video and the presence of a TV set in the child's bedroom, with the prevalence of overweight children (body mass index [BMI] >85th percentile) after adjustment for potential confounders. RESULTS: Mean TV/video viewing times were higher among black children and Hispanic children than white children and increased with the child's age. In multiple logistic regression, the odds ratio of children having a BMI >85th percentile was 1.06 (95% confidence interval [CI]: 1.004-1.11) for each additional hour per day of TV/video viewed, independent of child age, child sex, parental educational attainment, and race/ethnicity. Almost 40% of children had a TV set in their bedroom; they were more likely to be overweight and spent more time (4.6 hours per week) watching TV/video than children without a TV in their bedroom. In multiple logistic regression, the odds ratio of having a BMI >85th percentile was 1.31 (95% CI: 1.01-1.69) among those with a TV in their bedroom versus those without a TV, after statistical adjustment for child age, child sex, child TV/video viewing hours per week, maternal BMI, maternal education, and race/ethnicity. CONCLUSIONS: This study extends the association between TV viewing and risk of being overweight to younger, preschool-aged children. A TV in the child's bedroom is an even stronger marker of increased risk of being overweight. Because most children watch TV by age 2, educational efforts about limiting child TV/video viewing and keeping the TV out of the child's bedroom need to begin before then.

Because cobalamin deficiency is routinely treated with parenteral cobalamin, we investigated the efficacy of oral therapy. We randomly assigned 38 newly diagnosed cobalamin deficient patients to receive cyanocobalamin as either 1 mg intramuscularly on days 1, 3, 7, 10, 14, 21, 30, 60, and 90 or 2 mg orally on a daily basis for 120 days. Therapeutic effectiveness was evaluated by measuring hematologic and neurologic improvement and changes in serum levels of cobalamin (normal, 200 to 900 pg/mL) methylmalonic acid (normal, 73 to 271 nmol/L), and homocysteine (normal, 5.1 to 13.9 micromol/L). Five patients were subsequently found to have folate deficiency, which left 18 evaluable patients in the oral group and 15 in the parenteral group. Correction of hematologic and neurologic abnormalities was prompt and indistinguishable between the 2 groups. The mean pretreatment values for serum cobalamin, methylmalonic acid, and homocysteine were, respectively, 93 pg/mL, 3,850 nmol/L, and 37. 2 micromol/L in the oral group and 95 pg/mL, 3,630 nmol/L, and 40.0 micromol/L in the parenteral therapy group. After 4 months of therapy, the respective mean values were 1,005 pg/mL, 169 nmol/L, and 10.6 micromol/L in the oral group and 325 pg/mL, 265 nmol/L, and 12.2 micromol/L in the parenteral group. The higher serum cobalamin and lower serum methylmalonic acid levels at 4 months posttreatment in the oral group versus the parenteral group were significant, with P < .0005 and P < .05, respectively. In cobalamin deficiency, 2 mg of cyanocobalamin administered orally on a daily basis was as effective as 1 mg administered intramuscularly on a monthly basis and may be superior.

Cytochrome P450 phenotyping provides valuable information about real-time activity of these important drug-metabolizing enzymes through the use of specific probe drugs. Despite more than 20 years of research, few conclusions regarding optimal phenotyping methods have been reached. Caffeine offers many advantages for CYP1A2 phenotyping, but the widely used caffeine urinary metabolic ratios may not be the optimal method of measuring CYP1A2 activity. Several probes of CYP2C9 activity have been suggested, but little information exists regarding their use, largely due to the narrow therapeutic index of most CYP2C9 probes. Mephenytoin has long been considered the standard CYP2C19 phenotyping probe, but problems such as sample stability and adverse effects have prompted the investigation of potential alternatives, such as omeprazole. Several well-validated CYP2D6 probes are available, including dextromethorphan, debrisoquin and sparteine, but, in most cases, dextromethorphan may be preferred due to its wide safety margin and availability. Chlorzoxazone remains the only CYP2E1 probe that has received much study. However, questions concerning phenotyping method and involvement of other enzymes have impaired its acceptance as a suitable CYP2E1 phenotyping probe. CYP3A phenotyping has been the subject of numerous investigations, reviews and commentaries. Nevertheless, much controversy regarding the selection of an ideal CYP3A probe remains. Of all the proposed methods, midazolam plasma clearance and the erythromycin breath test have been the most rigorously studied and appear to be the most reliable of the available methods. Despite the limitations of many currently available probes, with continued research, phenotyping will become an even more valuable research and clinical resource.

BACKGROUND: It has been recognized for more than 20 years that the macrolides have immunomodulatory effects that are beneficial for those suffering from chronic pulmonary inflammatory syndromes, such as diffuse panbronchiolitis, cystic fibrosis, asthma and bronchiectasis. The macrolides have consistently been associated with decreased length of stay and mortality when used alone or in combination with beta-lactam antibiotics. This effect can be demonstrated against combinations consisting of beta-lactams and other antibiotics active against 'atypical chest pathogens' when treating community-acquired pneumonia (CAP) in hospitalized patients. As such, it appears that the macrolides' effects in CAP patients are more than just antibacterial in nature. AIMS OF THIS REVIEW: This review aims: to give the reader information on the background areas described, as well as related areas; to review the CAP benefits with macrolides and how they may be related to the immunomodulatory properties they demonstrate, albeit in a shorter period of time than previously demonstrated with chronic pulmonary disorders; to use ex vivo data to support these extrapolations. LITERATURE SEARCH: A literature search using Medline was conducted from 1966 onwards, searching for articles with relevant key words such as macrolide, diffuse panbronchiolitis, community-acquired pneumonia, biofilm, immunomodulation, cystic fibrosis, erythromycin, clarithromycin, roxithromycin and azithromycin, bronchiectasis and asthma. When appropriate, additional references were found from the bibliographies of identified papers of interest. Any relevant scientific conference proceedings or medical texts were checked when necessary. CONCLUSIONS: (1) Research into macrolide immunomodulation for chronic pulmonary disorders demonstrates consistent positive effects, although of types other than seen with diffuse panbronchiolitis. These effects, together with their inhibitory activity on biofilms, have the potential to make them a useful option. (2) The benefits for CAP are consistent, and higher when a macrolide is given with another atypical agent than if the other atypical agent is given alone, suggesting a non-antibacterial benefit. (3) Recent research of the immunomodulatory properties of azithromycin imply that azithromycin may have a previously unknown short-term biphasic effect on inflammation modulation: enhancement of host defence mechanisms shortly after initial administration followed by curtailment of local infection/inflammation in the following period. (4) Additional in vivo research is needed prior to developing any firm conclusions.

OBJECTIVE: The population subgroups with the highest proportion of overweight and obese women often are characterized by the lowest rates of initiation and shortest durations of breastfeeding. We previously documented that these 2 population-level trends may be related. In a population of white women who lived in a rural area, we observed that prepregnant overweight and obesity were associated with failure to initiate and also to sustain lactation. The means by which being overweight or obese negatively affect lactational performance is unknown and likely to be multifactorial in origin, including the simple mechanical difficulties of latching on and proper positioning of the infant. In addition, we have shown that prepregnant body mass index (BMI) is negatively associated with the timing of lactogenesis II, the onset of copious milk secretion. Although the effects of obesity on the prolactin response to infant suckling have never been studied, we postulated that maternal obesity could compromise this important response. We proposed that this might occur because obesity alters the 24-hour spontaneous release of prolactin and also because prolactin secretion is blunted in response to various stimuli among obese subjects. The fall in progesterone concentration that occurs immediately postpartum is the trigger for the onset of copious milk secretion, but maintenance of prolactin and cortisol concentrations is necessary for this trigger to be effective. Adipose tissue concentrates progesterone. We proposed that this additional source of progesterone would lead to consistently higher progesterone concentrations among obese compared with normal-weight women. This, in turn, would lead to a delay in reaching the appropriate concentration to trigger the onset of lactogenesis II. We tested the hypotheses that a reduced prolactin response to suckling and higher-than-normal progesterone concentration in the first week after delivery might be among the means by which maternal overweight could compromise early lactation. METHODS: We enrolled 40 mothers of term infants from the same population that we studied previously. We measured serum prolactin and progesterone concentrations by radioimmunoassay before and 30 minutes after the beginning of a suckling episode at 48 hours and 7 days after delivery. We used path analysis to develop a parsimonious multivariate prediction of the prolactin response to suckling at 48 hours and 7 days postpartum. RESULTS: As expected, prolactin values decreased from 48 hours to 7 days postpartum. Women who were overweight or obese (using the Institute of Medicine's cutoff for women of a BMI >26 kg/m2) before conception had a lower prolactin response to suckling than normal-weight women at 48 hours but not at day 7. In multivariate analyses, overweight/obesity, primiparity, and birth weight were negatively associated with the prolactin response to suckling at 48 hours. After adjustment for confounding by time since delivery and the duration of the nursing episode, only overweight/obesity remained a significant negative predictor of prolactin response to suckling at day 7. Concentrations of progesterone decreased dramatically from 48 hours to 7 days postpartum but did not differ between normal-weight and overweight/obese women at either time. In addition, the decreases in progesterone concentrations from 48 hours to 7 days postpartum did not differ between the prepregnant BMI groups. CONCLUSION: The unique and important finding from this study is that overweight/obese women had a lower prolactin response to suckling. This would be expected to compromise the ability of overweight/obese women to produce milk and, over time, could lead to premature cessation of lactation. These findings are important because, during our observation period (just before and after lactogenesis II, the time of onset of copious milk secretion), the prolactin response to suckling is more important for milk production than it is later in lactation. We have previously shown that a high proportion of the overweight and obese women in women in this population who give up on breastfeeding do so at this time. This finding thus provides evidence of a biological basis for this association, and additional study of it is likely to be informative. We postulated that there would be consistently higher progesterone concentrations in the early postpartum period among obese compared with normal-weight women because adipose tissue is an extraplacental source of this hormone. This hypothesis was not supported in this study because there were no significant differences between normal-weight and overweight/obese women in progesterone concentrations at either 48 hours or 7 days postpartum. The values that we observed at these times were similar to those reported by others in the early postpartum period. The findings from this study add plausibility to our observation that initiation, not just duration of breastfeeding, is negatively affected by maternal overweight/obesity. Although women should begin pregnancy at a healthy weight and gain reasonably during gestation, not all will. Pediatricians can help overweight/obese women to succeed at breastfeeding by targeting them for contact with a lactation consultant before discharge from the hospital to be sure that they have received optimal advice on breastfeeding techniques. In addition, early contact with the mother after discharge--by calling her at home to offer her support and counseling for breastfeeding, by scheduling the first pediatric visit earlier than for other patients, or by enlisting the assistance of public health nurses for a home visit if this is possible--would help overweight/obese women to continue to breastfeed. Being overweight or obese is negatively associated with the prolactin response to suckling in the first week postpartum and, thus, may contribute to early lactation failure.

Only a fraction of the clinical complications of atherosclerosis are explained by known risk factors. Animal studies have shown that plasma sphingomyelin (SM) levels are closely related to the development of atherosclerosis. SM carried into the arterial wall on atherogenic lipoproteins may be locally hydrolyzed by sphingomyelinase, promoting lipoprotein aggregation and macrophage foam cell formation. A novel, high-throughput, enzymatic method to measure plasma SM levels has been developed. Plasma SM levels were related to the presence of coronary artery disease (CAD) in a biethnic angiographic case-control study (279 cases and 277 controls). Plasma SM levels were higher in CAD patients than in control subjects (60+/-29 versus 49+/-21 mg/dL, respectively; P:<0. 0001). Moreover, the ratio of SM to SM+phosphatidylcholine (PC) was also significantly higher in cases than in controls (0.33+/-0.13 versus 0.29+/-0.10, respectively; P:<0.0001). Similar relationships were observed in African Americans and whites. Plasma SM levels showed a significant correlation with remnant cholesterol levels (r=0.51, P:<0.0001). By use of multivariate logistic regression analysis, plasma SM levels and the SM/(SM+PC) ratio were found to have independent predictive value for CAD after adjusting for other risk factors, including remnants. The odds ratio (OR) for CAD was significantly higher for the third and fourth quartiles of plasma SM levels (OR 2.81 [95% CI 1.66 to 4.80] and OR 2.33 [95% CI 1.38 to 3. 92], respectively) as well as the SM/(SM+PC) ratio (OR 1.95 [95% CI 1.10 to 3.45] and OR 2.33 [95% CI 1.34 to 4.05], respectively). The findings indicate that human plasma SM levels are positively and independently related to CAD. Plasma SM levels could be a marker for atherogenic remnant lipoprotein accumulation and may predict lipoprotein susceptibility to arterial wall sphingomyelinase.

Nosocomial pneumonia is a notable cause of morbidity and mortality and leads to increases in lengths of hospital stays and institutional expenditures. Aminoglycosides are used to treat patients with these infections, but few data on the doses and schedules required to achieve optimal therapeutic outcomes exist. We analyzed aminoglycoside treatment data for 78 patients with nosocomial pneumonia to determine if optimization of aminoglycoside pharmacodynamic parameters results in a more rapid therapeutic response (defined by outcome and days to leukocyte count resolution and temperature resolution). Cox proportional hazards, Classification and Regression Tree (CART), and logistic regression analyses were applied to the data. By all analyses, the first measured maximum concentration of drug in serum (Cmax)/MIC predicted days to temperature resolution and the second measured Cmax/MIC predicted days to leukocyte count resolution. For days to temperature resolution and leukocyte count resolution, CART analyses produced breakpoints, with an 89% success rate at 7 days of therapy for a Cmax/MIC of > 4.7 and an 86% success rate at 7 days of therapy for a Cmax/MIC of > 4.5, respectively. Logistic regression analyses predicted a 90% probability of temperature resolution and leukocyte count resolution by day 7 if a Cmax/MIC of > or = 10 is achieved within the first 48 h of aminoglycoside therapy. Aggressive aminoglycoside dosing immediately followed by individualized pharmacokinetic monitoring would ensure that Cmax/MIC targets are achieved early in therapy. This would increase the probability of a rapid therapeutic response for pneumonia caused by gram-negative bacteria and potentially decreasing durations of parenteral antibiotic therapy, lengths of hospitalization, and institutional expenditures, a situation in which both the patient and the institution benefit.

BACKGROUND: In a referral population of young children, excessive fruit juice consumption has been reported to be a contributing factor in nonorganic failure to thrive. OBJECTIVE: To evaluate, in a population-based sample of healthy children, fruit juice consumption and its effects on growth parameters during early childhood. DESIGN: Cross-sectional study. SETTING: General primary care health center in upstate New York. PARTICIPANTS: One hundred sixteen 2-year-old children and one hundred seven 5-year-old children, who were scheduled for a nonacute visit, and their primary care taker/parent were recruited over a 2-year period. MEASUREMENTS: For 168 children (ninety-four 2-year-old children and seventy-four 5-year-old children), mean dietary intake was calculated from 7 days of written dietary records, entered, and analyzed using the Minnesota Nutrition Data System. Height was measured using a Harpenden Stadiometer. Weight was measured using a standard balance beam scale. RESULTS: The 2-year-old and 5-year-old children consumed, on average, 5.9 and 5.0 fl oz/day of fruit juice and 9.8 and 11.0 fl oz/day of milk, respectively. Nineteen children (11%) consumed > or = 12 fl oz/day of juice. Forty-two percent of children consuming > or = 12 fl oz/day of juice had short stature (height less than 20th sex-specific percentile for age) vs 14% of children drinking less than 12 fl oz/day of juice. Obesity was more common among children drinking > or = 12 fl oz/day of juice compared with those drinking less juice: 53% vs 32% had a body mass index > or = 75th age- and sex-specific percentile; 32% vs 9% had a body mass index > or = 90th age- and sex-specific percentile; and 32% vs 5% had a ponderal index > or = 90th age-specific percentile. After adjustment for maternal height, child age, child sex, and child age-sex interaction, children consuming > or = 12 fl oz/day of juice, compared with those drinking less than 12 fl oz/day of juice, were shorter (86.5 vs 89.3 cm and 106.5 vs 111.2 cm for the 2-year-old and 5-year-old children, respectively) and more overweight (body mass index = 17.2 vs 16.3 kg/m2 and ponderal index = 18.4 vs 16.8 kg/m3). CONCLUSIONS: Consumption of > or = 12 fl oz/day of fruit juice by young children was associated with short stature and with obesity. Parents and care takers should limit young children's consumption of fruit juice to less than 12 fl oz/day.

BACKGROUND: Television viewing has been associated with increased violence in play and higher rates of obesity. Although there are interventions to reduce television viewing by school-aged children, there are none for younger children. OBJECTIVE: To develop and evaluate an intervention to reduce television viewing by preschool children. DESIGN: Randomized controlled trial conducted in 16 preschool and/or day care centers in rural upstate New York. PATIENTS: Children aged 2.6 through 5.5 years. INTERVENTION: Children attending intervention centers received a 7-session program designed to reduce television viewing as part of a health promotion curriculum, whereas children attending the control centers received a safety and injury prevention program. OUTCOME MEASUREMENTS: Change in parent-reported child television/video viewing and measured growth variables. RESULTS: Before the intervention, the intervention and control groups viewed 11.9 and 14.0 h/wk of television/videos, respectively. Afterward, children in the intervention group decreased their television/video viewing 3.1 h/wk, whereas children in the control group increased their viewing by 1.6 h/wk, for an adjusted difference between the groups of -4.7 h/wk (95% confidence interval, -8.4 to -1.0 h/wk; P =.02). The percentage of children watching television/videos more than 2 h/d also decreased significantly from 33% to 18% among the intervention group, compared with an increase of 41% to 47% among the control group, for a difference of -21.5% (95% confidence interval, -42.5% to -0.5%; P =.046). There were no statistically significant differences in children's growth between groups. CONCLUSIONS: This study is the first to show that a preschool-based intervention can lead to reductions in young children's television/video viewing. Further research is needed to determine the long-term effects associated with reductions in young children's television viewing.

The absolute bioavailability of oral melatonin tablets was studied in 12 normal healthy volunteers. Subjects were administered, in a randomized crossover fashion, melatonin 2 mg intravenously and 2 and 4 mg orally. Blood was sampled over approximately eight (estimated) half-lives. Both the 2 and the 4 mg oral dosages showed an absolute bioavailability of approximately 15%. No difference in serum half-life was seen in any of the study phases. Oral melatonin tablets in dosages of 2 and 4 mg show poor absolute bioavailability, either due to poor oral absorption, large first-pass metabolism, or a combination of both. Further studies examining larger doses, in an attempt to saturate first-pass metabolism if it occurs, may be warranted.

OBJECTIVE: Our goal was to test the hypothesis that increased fruit juice intake and parental restriction of children's eating are associated with increased adiposity gain and whether exposure to nutritional counseling predicted reduced adiposity gain among children. PATIENTS AND METHODS: A sample of parents or guardians of children aged 1 to 4 years who attended 1 of 49 Special Supplemental Nutrition Program for Women, Infants, and Children agencies in New York State were surveyed in 1999 or 2000 (N = 2801). The survey addressed children's dietary intake, parental feeding practices, and parental exposure to nutritional counseling messages to increase fruit, vegetable, and low-fat milk intakes. Each child's height and weight were measured approximately every 6 months for up to 48 months. A prospective cohort design was used in which survey variables were the predictors and the outcome was change in children's adiposity, defined as change in age- and gender-standardized BMI per month (ie, BMI z-score slope). RESULTS: Controlling for gender and ethnicity, the relationship between juice intake and adiposity gain depended on children's initial overweight status. Among children who were initially either at risk for overweight or overweight, increased fruit juice intake was associated with excess adiposity gain, whereas parental offerings of whole fruits were associated with reduced adiposity gain. Each additional daily serving of fruit juice was associated with an excess adiposity gain of 0.009 SD per month. Feeding restriction was greater among parents whose children were initially at risk for overweight or overweight compared with those at a healthy weight. Parental exposure to nutritional messages was not associated with reduced child adiposity gain. CONCLUSION: This study supports the Institute of Medicine recommendations to reduce fruit juice intake as a strategy for overweight prevention in high-risk children.

OBJECTIVE: To determine among a contemporary cohort whether rapid weight gain between birth and 6 months is associated with risk of childhood overweight and if this risk differs by ethnicity and/or breast-feeding history. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional survey in 1999 to 2000 of parents/guardians of children participating in the Special Supplemental Nutrition Program for Women, Infants, and Children in New York State. Measurements were abstracted by chart review, including weight at birth and 6 months, and height and weight at time of survey and every 6 months subsequently. Overweight at 4 years of age was defined as a BMI > or = 95th age- and sex-specific percentiles. RESULTS: The study sample was 32% Hispanic, 19% black, and 49% white; 17% of children were overweight. Rate of infant weight gain (expressed in terms of 100 g/mo) was significantly associated with being overweight at 4 years (odds ratio, 1.4; 95% confidence interval, 1.3 to 1.6 after adjusting for history of breast-feeding, birth weight, and ethnicity). The odds of being overweight at 4 years of age for Hispanic children were twice those of non-Hispanic children (odds ratio, 2.2; 95% confidence interval, 1.5 to 3.3). The population-attributable risk of overweight at 4 years of age was 19% for children in the highest quintile of infant weight gain. DISCUSSION: Among this contemporary, multi-ethnic cohort, rapid infant weight gain was associated with increased risk of being overweight at 4 years of age, independently of potential confounders. Identification of the risk factors contributing to rapid weight gain during infancy might improve early recognition and guide strategies for optimal nutrition to prevent the development of childhood overweight.

PURPOSE: Previous studies of the impact of renal cell carcinoma histopathology on survival are conflicting and generally limited to institutional analyses. Thus, we determined the role of renal cell carcinoma histopathology on the stage specific survival rate in a large population based cohort. MATERIALS AND METHODS: We used the 2000 to 2005 National Cancer Institute SEER (Surveillance, Epidemiology and End Results) database to identify 17,605 patients who underwent surgery for renal cell carcinoma and met study inclusion criteria. Patients were stratified by histological subtype (clear cell, papillary, chromophobe, collecting duct and sarcomatoid differentiation) and pathological stage. We performed Cox proportional hazard modeling and Kaplan-Meier survival analysis to determine overall and cancer specific survival. RESULTS: Patients with papillary and chromophobe pathology were less likely to present with T3 or greater disease (17.6% and 16.9%, respectively) while patients with collecting duct and sarcomatoid variants were more likely to present with T3 or greater disease (55.7% and 82.8%, respectively) compared to those with clear cell histology (p <0.001). On multivariate analysis histology was significantly associated with overall and cancer specific survival. Patients with chromophobe pathology had improved survival (HR 0.56, 95% CI 0.40-0.78) while those with collecting duct and sarcomatoid variants had worse survival (HR 2.07, 95% CI 1.44-2.97 and 2.26, 95% CI 1.93-2.64, respectively). CONCLUSIONS: Renal cell carcinoma histological subtype predicts overall and cancer specific survival. Patients with collecting duct and sarcomatoid variants of renal cell carcinoma have poor survival, even those who present with low stage disease. These data suggest inherent differences in renal cell carcinoma biology and may ultimately form the basis of future histologically targeted therapies.

There is no doubt that owing to the prolific use of the macrolides and azithromycin over the past several years, resistance has developed and is increasing in incidence. I believe we should re-evaluate the use of these antibiotics for our patients and consider parameters other than the negative in-vitro results. Firstly, microbiology laboratories should return to the habit of providing the clinician with MIC values for pathogenic isolates rather than generic susceptibility reports ((S)usceptible, (I)ntermediate, (R)esistant) that are based on standard disc diffusion testing. Although agar dilution MIC testing is a bulky and labour intensive practice, it provides the best data when conducted in the appropriate environment. Secondly, and more importantly, these MIC values need to be compared with in-vivo antibiotic pharmacokinetics and pharmacodynamics. Although it is possible to compare MIC values directly with serum concentrations of beta-lactams and aminoglycosides, this is not a valid practice for azithromycin or the macrolides. MICs of azithromycin and the macrolides must be compared with the infection site and phagocytic cell concentrations to determine the utility, or lack thereof, of one of these agents. Whereas azithromycin cellular penetration allows maximal pharmacodynamics potentially even against moderately or highly resistant pneumococci, the macrolides do so less optimally. Although there are no reports of widespread clinical failures resulting from macrolide/azalide resistance in pneumococci, it is expected that such reports will appear once the isolates become consistently highly resistant. This is likely to affect the macrolides, erythromycin and clarithromycin, before the azalide, azithromycin owing to the differences in pharmacokinetics of these drugs. Until then, it will be important to determine the MICs of not just one macrolide, but of all macrolides and azalides for the isolates. This will allow the clinician to make a pharmacokinetically and pharmacodynamically sound choice. By choosing clinical MIC breakpoints of 4-8 mg/L for oral macrolides and < or = 32 mg/L for oral azithromycin, rather than the present standard breakpoints, the clinician can make a macrolide/azalide choice that will optimize the pharmacodynamics of the drug against the isolated pathogen and result in the best possible clinical outcome. Once data concerning the cellular penetration of intravenous formulations of these drugs becomes available, it will be possible to develop clinical breakpoints for these formulations as well. Only through utilizing good antibiotic prescribing practices and by using the drugs appropriately when they are used, can resistance trends be stemmed. In this way, not only does a clinician treat the patient more effectively, but they also extend the antibiotic's useful life.

Musculoskeletal disorders (MSDs) are increasingly recognized as a significant hazard of agricultural occupation. In agricultural jobs with significant physical labor, MSDs are typically the most frequently reported injury. Although not as lethal as tractor roll-overs, MSDs can result in disability, lost work time, and increased production costs. MSDs increase production costs as a result of worker absence, medical and insurance costs, decreased work capacity, and loss of employees to turnover and competition from other less physically demanding industries. This paper will provide an overview of what is currently known about MSDs in agriculture, including high-risk commodities, tasks and work practices, and the related regulatory factors and workers' compensation costs. As agricultural production practices evolve, the types of MSDs also change, as do ergonomic risk factors. One example is the previous higher rates of knee and hip arthritis identified in farmers in stanchion dairies evolving into upper extremity tendonitis, arthritis, and carpal tunnel syndrome now found in milking technicians in dairy milking parlors. This paper summarizes the presentation, "Musculoskeletal Disorders in Labor-Intensive Operations," at the Agricultural Safety and Health Council of America/National Institute for Occupational Safety and Health conference, "Be Safe, Be Profitable: Protecting Workers in Agriculture," January 27-28, 2010, Dallas/Fort Worth, Texas. The primary focus of the paper is to address current research on ergonomic solutions for MSDs in agriculture. These include improved tools, carts or equipment, as well as work practices. One of the key challenges in this area pertains to measurement, due to the fact that musculoskeletal strain is a chronic condition that can come and go, with self-reported pain as its only indicator. Alternative measurement methods will be discussed. Finally, the implementation of research into practice is reviewed, with an emphasis on best practices that have been demonstrated to be effective in the agricultural setting, based on worker acceptance and comfort, improved productivity, and decreased MSDs. The paper will provide an overview for agricultural stakeholders as to the current science and practice of ergonomics in agriculture.

We investigate the psychometric validity and reliability of three-item screening measures for emotional exhaustion, depersonalization, and personal achievement comprising an abbreviated version of the Maslach Burnout Inventory®. Despite its utilization in multiple studies, the shortened instrument has not been sufficiently validated in diverse settings, populations, and organizational contexts. We examine its ability to assess burnout accruing from patient care practice in a rural, underserved area. Utilizing data from a cross-sectional survey of 308 rural-based medical professionals, we investigate how the three short-form subscales of the nine-item abbreviated inventory compare with their gold-standard parent subscales from the original 22-item human services scale in measuring corresponding dimensions of burnout. The findings provide significant evidence that the three-item measures are valid and reliable proxies for the long-form subscales. The short-form measures are highly correlated with the original subscales and display high convergent and discriminant validity. Each of the abbreviated subscales manifests the kind of high sensitivity with adequate specificity that one would expect to see in a good screening instrument. We conclude that the short-form measures can be utilized to rapidly screen human service professionals such as rural health care practitioners for symptoms of each of the three dimensions of burnout.

BACKGROUND: Current recommendations call for most Americans, 2 years of age and over, to ent more fruits and vegetables. OBJECTIVE: To determine, in a sample of healthy children, the extent to which young children's diets include the recommended numbers of fruit and vegetable servings per day. DESIGN: Cross-sectional study. SETTING: A general primary care health center in upstate New York. PARTICIPANTS: One-hundred-sixteen 2-year-old children and 107 5-year-old children, who were scheduled for a non-acute visit, and their parent/primary caretaker (PPC) were recruited between 1992 and 1993. MEASUREMENTS: For 168 children (94 2-year-old children and 74 5-year-old children), mean dietary intakes were calculated from 7 days of written dietary records, entered and analyzed using the Minnesota Nutrition Data System. The numbers of fruit and vegetable servings/day were calculated according to USDA definitions of serving sizes. RESULTS: The 2-year-old children consumed the same amounts of fruits, 100% fruit juice, and total fruits and vegetables as the 5-year-old children (0.8 and 0.7 fruit servings/day, 1.0 and 0.8 juice servings/day, and 2.2 and 2.1 total fruit and vegetable servings/day, respectively). Fruit juice accounted for 54% of all fruit servings consumed and 42% of all fruit and vegetable servings consumed. Total fruit consumption (fruits plus juice) was correlated with carbohydrate intake (R = 0.46), and inversely correlated with total fat and saturated fat intakes (R = -0.48 and R = -0.36, respectively, both p < 0.0001) and with cholesterol intake (R = -0.21, p < 0.01). Citrus fruit and juice consumption was strongly correlated with vitamin C intake (R = 0.56, p < 0.0001). Total vegetable consumption was strongly correlated with beta-carotene and vitamin A intakes (R = 0.63 and R = 0.32, respectively, both p < 0.0001). Total fruit and vegetable consumption correlated with intakes of beta-carotene, vitamin A, vitamin C, fiber, and potassium (R = 0.55, R = 0.31, R = 0.56, R = 0.58, and R = 0.66, respectively, all p < 0.0001). Forty percent of 2-year-old children and 50% of 5-year-old children consumed < 2 servings/day of fruits and vegetables. Ninety-five percent of children consuming > or = 2 servings/day of fruits and vegetables met the RDA for vitamin C vs. 50% of those consuming < 2 servings/day (p < 0.001). CONCLUSIONS: In this study, preschool-aged children consumed, on average, about 80% of the recommended fruit servings/day, but only 25% of the recommended vegetable servings/day. Low intakes of fruits and vegetables were associated with inadequate intakes of vitamin A, vitamin C, and dietary fiber, in addition to high intakes of total fat and saturated fat.

OBJECTIVE: We examined child and parent outcomes of training providers to engage families efficiently and to reduce common symptoms of a range of mental health problems and disorders. METHODS: Training involved three 1-hour discussions structured around video examples of family/provider communication skills, each followed by practice with standardized patients and self-evaluation. Skills targeted eliciting parent and child concerns, partnering with families, and increasing expectations that treatment would be helpful. We tested the training with providers at 13 sites in rural New York, urban Maryland, and Washington, DC. Children (5-16 years of age) making routine visits were enrolled if they screened "possible" or "probable" for mental disorders with the Strengths and Difficulties Questionnaire or if their provider said they were likely to have an emotional or behavioral problem. Children and their parents were then monitored for 6 months, to assess changes in parent-rated symptoms and impairment and parent symptoms. RESULTS: Fifty-eight providers (31 trained and 27 control) and 418 children (248 patients of trained providers and 170 patients of control providers) participated. Among the children, 72% were in the possible or probable categories. Approximately one half (54%) were white, 30% black, 12% Latino, and 4% other ethnicities. Eighty-eight percent (367 children) completed follow-up monitoring. At 6 months, minority children cared for by trained providers had greater reduction in impairment (-0.91 points) than did those cared for by control providers but no greater reduction in symptoms. Seeing a trained provider did not have an impact on symptoms or impairment among white children. Parents of children cared for by trained providers experienced greater reduction in symptoms (-1.7 points) than did those cared for by control providers. CONCLUSION: Brief provider communication training had a positive impact on parent mental health symptoms and reduced minority children's impairment across a range of problems.

Previously, we have validated a 4-drug phenotyping cocktail, the "Cooperstown cocktail," using caffeine (cytochrome p450 [CYP] 1A2, N-acetyltransferase-2 [NAT2], and xanthine oxidase [XO]), dextromethorphan (CYP2D6), omeprazole (CYP2C19), and intravenous midazolam (hepatic CYP3A). Data suggest that warfarin can be used as a safe and accurate biomarker for CYP2C9, and if warfarin is administered with vitamin K, the pharmacodynamic effect is ablated. Twelve subjects received the Cooperstown cocktail, warfarin plus vitamin K, and both sets of biomarkers (Cooperstown 5+1 cocktail) in a randomized crossover fashion. On the basis of log-transformed data and a paired t test, no significant difference was seen for S-warfarin area under the serum concentration-time curve from time 0 to infinity (P =.09), omeprazole metabolic ratio (P =.374), caffeine metabolic ratio (P =.169 for CYP1A2 activity), midazolam plasma clearance (P =.573), or dextromethorphan metabolic ratio (P =.747) with the Cooperstown cocktail, warfarin plus vitamin K alone, or the Cooperstown 5+1 cocktail. During drug administration, the only side effect was mild and short-lived sedation after intravenous midazolam administration. Phenotypic measurements were in concordance with the subject's CYP2C9, CYP2C19, and CYP2D6 genotypes. The Cooperstown 5+1 cocktail may be used to simultaneously assess the activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A, NAT2, and XO.

BACKGROUND: Simultaneous administration of several probes enhances the utility of phenotyping, but poor specificity, side effects, and use of drugs not approved by the Food and Drug Administration limit the usefulness of prior phenotyping cocktails. OBJECTIVES: To evaluate potential drug-drug interactions associated with use of a cocktail of caffeine, omeprazole, dextromethorphan, and midazolam for simultaneous phenotyping of CYP1A2, CYP2C19, CYP2D6, CYP3A, N-acetyltransferase-2, and xanthine oxidase. METHODS: Twelve subjects received caffeine + dextromethorphan, omeprazole, and midazolam (each alone), and a cocktail of caffeine + dextromethorphan + omeprazole + midazolam. Blood samples were collected at 120 minutes for omeprazole and 5/-hydroxyomeprazole, and at 0, 5, 30, 60, 120, 240, 300, and 360 minutes for midazolam. Twelve-hour urine samples were collected for analysis of dextromethorphan, caffeine, and metabolites. RESULTS: The median CYP1A2 metabolic ratio after administration of caffeine + dextromethorphan was not significantly different from that obtained with the cocktail (P = .84). Likewise, the median N-acetyltransferase-2, xanthine oxidase, and CYP2D6 metabolic ratios were not significantly different after cocktail administration (P = .977 for each N-acetyltransferase-2; P = .795 for xanthine oxidase; P = .75 for CYP2D6). The median CYP2C19 metabolic ratio after cocktail administration was not significantly different from that obtained after omeprazole administered alone (P = 1.000). Also, midazolam plasma clearance was not significantly different after cocktail administration compared with that after administration of midazolam alone (P = .708). The only side effect was sedation, which was associated with intravenous midazolam and occurred to a similar extent after both individual and cocktail phenotyping. CONCLUSIONS: These results indicate no pharmacokinetic or pharmacodynamic interactions that would limit the utility of this phenotyping cocktail for simultaneous measurement of the activity of multiple drug-metabolizing enzymes.