Video-laparoscopic assessment of the small bowel in Crohn's disease: a comparative study to evaluate surgeons' inter-observer variability.

BACKGROUND: Assessment of the entire small bowel is advocated during Crohn's disease (CD) surgery, as intraoperative detection of new lesions may lead to change in the planned procedure. The aim of this study was to evaluate the inter-observer variability in the assessment of extent and severity of CD at the small bowel laparoscopic "walkthrough". METHODS: A survey on laparoscopic assessment of the small bowel in patients with CD, including items adapted from the MREnterography or ultrasound in Crohn's disease (METRIC) study and from the classification of severity of mesenteric disease was developed by an invited committee of colorectal surgeons. Anonymous laparoscopic videos demonstrating the small bowel "walkthrough" in ileocolonic resection for primary and recurrent CD were distributed to the committee members together with the anonymous survey. The primary outcome was the rate of inter-observer variability on assessment of strictures, dilatations, complications and severity of mesenteric inflammation. RESULTS: 12 assessors completed the survey on 8 small bowel walkthrough videos. The evaluation of the small bowel thickening and of the mesenteric fat wrapping were the most reliable assessments with an overall agreement of 87.1% (k = 0.31; 95% CI - 0.22, 0.84) and 82.7% (k = 0.35; 95% CI - 0.04, 0.73), respectively. The presence of strictures and pre-stenotic dilatation demonstrated agreement of 75.2% (k = 0.06: 95% CI - 0.33, 0.45) and 71.2% (k = 0.33; 95% CI 0.15, 0.51), respectively. Evaluation of fistulae had an overall agreement of 75.3%, while there was a significant variation in the evaluation of mild, moderate and severe mesenteric disease with overall agreement ranging from 33.3 to 100%. CONCLUSION: Laparoscopic assessment of the small bowel thickening and of the presence of mesenteric fat wrapping is reliable for the intraoperative evaluation of CD with high inter-rater agreement. There is significant heterogeneity in the assessment of the severity of the mesenteric disease involvement.

Randomized Trial of Motivational Interviewing to Prevent Early Childhood Caries in American Indian Children.

INTRODUCTION: In a randomized controlled trial, the effectiveness of motivational interviewing (MI) combined with enhanced community services (MI + ECS) was compared with ECS alone for reducing dental caries in American Indian children on the Pine Ridge Reservation. The intervention was developed and delivered with extensive tribal collaboration. METHODS: A total 579 mother-newborn dyads were enrolled and randomized to the MI + ECS and ECS groups. They were followed for 36 mo. Four MI sessions were provided, the first shortly after childbirth and then 6, 12, and 18 mo later. Both groups were exposed to ECS, which included public service announcements through billboards and tribal radio, as well as broad distribution of brochures on behavioral risk factors for early childhood caries (ECC), toothbrushes, and toothpaste. MI impact was measured as decayed, missing, and filled tooth surfaces (dmfs). Secondary outcomes included decayed surfaces, caries prevalence, and maternal oral health knowledge and behaviors. Modified intention-to-treat analyses were conducted. Eighty-eight percent of mothers completed at least 3 of 4 MI sessions offered. RESULTS: After 3 y, dmfs was not significantly different for the 2 groups (MI + ECS = 10, ECS = 10.38, P = 0.68). In both groups, prevalence of caries experience was 7% to 9% after 1 y, 35% to 36% at 2 y, and 55% to 56% at 3 y. Mean knowledge scores increased by 5.0, 5.3, and 5.9 percentage points at years 1, 2, and 3 in the MI + ECS group and by 1.9, 3.3, and 5.0 percentage points in the ECS group (P = 0.03), respectively. Mean maternal oral health behavior scores were not statistically significantly different between the treatment arms. CONCLUSION: In summary, the MI intervention appeared to improve maternal knowledge but had no effect on oral health behaviors or on the progression of ECC (ClinicalTrials.gov NCT01116726). KNOWLEDGE TRANSFER STATEMENT: The findings of this study suggest that motivational interviewing focusing on parental behaviors may not be as effective as previously hoped for slowing the development of childhood caries in some high-risk groups. Furthermore, social factors may be even more salient determinants of oral health than what we previously supposed, perhaps interfering with the capacity to benefit from behavioral strategies that have been useful elsewhere. The improvement of children's oral health in high-risk populations characterized by poverty and multiple related life stresses may require more holistic approaches that address these formidable barriers.

A Cluster-Randomized, Community-Based, Tribally Delivered Oral Health Promotion Trial in Navajo Head Start Children.

The authors tested the effectiveness of a community-based, tribally delivered oral health promotion (OHP) intervention (INT) at reducing caries increment in Navajo children attending Head Start. In a 3-y cluster-randomized trial, we developed an OHP INT with Navajo input that was delivered by trained Navajo lay health workers to children attending 52 Navajo Head Start classrooms (26 INT, 26 usual care [UC]). The INT was designed as a highly personalized set of oral health-focused interactions (5 for children and 4 for parents), along with 4 fluoride varnish applications delivered in Head Start during academic years of 2011 to 2012 and 2012 to 2013. The authors evaluated INT impact on decayed, missing, and filled tooth surfaces (dmfs) increment compared with UC. Other outcomes included caries prevalence and caregiver oral health-related knowledge and behaviors. Modified intention-to-treat and per-protocol analyses were conducted. The authors enrolled 1,016 caregiver-child dyads. Baseline mean dmfs/caries prevalence equaled 19.9/86.5% for the INT group and 22.8/90.1% for the UC group, respectively. INT adherence was 53% (i.e., ≥3 child OHP events, ≥1 caregiver OHP events, and ≥3 fluoride varnish). After 3 y, dmfs increased in both groups (+12.9 INT vs. +10.8 UC; P = 0.216), as did caries prevalence (86.5% to 96.6% INT vs. 90.1% to 98.2% UC; P = 0.808) in a modified intention-to-treat analysis of 897 caregiver-child dyads receiving 1 y of INT. Caregiver oral health knowledge scores improved in both groups (75.1% to 81.2% INT vs. 73.6% to 79.5% UC; P = 0.369). Caregiver oral health behavior scores improved more rapidly in the INT group versus the UC group (P = 0.006). The dmfs increment was smaller among adherent INT children (+8.9) than among UC children (+10.8; P = 0.028) in a per-protocol analysis. In conclusion, the severity of dental disease in Navajo Head Start children is extreme and difficult to improve. The authors argue that successful approaches to prevention may require even more highly personalized approaches shaped by cultural perspectives and attentive to the social determinants of oral health (ClinicalTrials.gov NCT01116739).

Community Based Participatory Research to Reduce Oral Health Disparities in American Indian Children.

Community based participatory research is an approach aimed to equitably involve community members, representatives, and academic researchers in all aspects of the research process. Using this methodology can help integrate cultural knowledge into interventions, supporting researchers to effectively partner with communities in addressing health disparities. The Center for Native Oral Health Research (CNOHR) collaborates with two American Indian (AI) tribes to advance oral health knowledge and practice, including the conduct of randomized controlled clinical trials of culturally sensitive behavioral interventions for primary prevention of early childhood caries (ECC). This manuscript describes the development of researcher-community partnership, and the development and implementation of the two clinical trial in the community. It also gives a detailed account of the strategies developed through the community input in recruitment and retention of the study participants and finally the lessons learnt during the study implementation.

Making the most of Papua New Guinea's biodiversity: Establishment of an integrated set of programs that link botanical survey with pharmacological assessment in "The Land of the Unexpected"

An integrated and coordinated set of programs has been established to meet ICBG goals in Papua New Guinea (PNG). Here we give an overview of the PNG ICBG and focus on the key elements and major steps taken to establish a program necessary for the pharmacological assessment of botanicals and traditional medicines in PNG and, by extrapolation, in other developing countries.

Identifying the determinants of tuberculosis control in resource-poor countries: insights from a qualitative study in The Gambia.

Despite the availability of effective treatment, tuberculosis (TB) remains a major cause of death from an infectious disease in the world, particularly in resource-poor countries. Among the chief reasons for this are deficiencies in case tracing and in adherence to treatment. In order to investigate the contribution of non-biological factors to these deficiencies, we carried out a qualitative study in The Gambia, West Africa, from October 2000 to March 2001. The methods used were focus group discussions, interviews, participant and non-participant observation, and case histories. Four domains were distinctively investigated: the TB patients, the community, the health care providers (including programme staff), and the donors and policy makers. Analysis of the data from all these sources indicated the contribution of a wide range of socio-anthropological factors which influence the success or otherwise of the TB control programme in The Gambia, i.e. gender, urban/rural residence, recourse to traditional healers, adherence to national health policies, knowledge about TB, migration, and socio-economic factors. It is concluded that all these factors must be taken into account in formulating interventions to improve detection of TB cases and patient adherence to treatment within the framework of the national TB control programmes, and proposals have been made for targeted interventions.

Targeting the kinesin Eg5 to monitor siRNA transfection in mammalian cells.

RNA interference, the inhibition of gene expression by double-stranded RNA, provides a powerful tool for functional studies once the sequence of a gene is known. In most mammalian cells, only short molecules can be used because long ones induce the interferon pathway. With the identification of a proper target sequence, the penetration of the oligonucleotides constitutes the most serious limitation in the application of this technique. Here we show that a small interfering RNA (siRNA) targeting the mRNA of the kinesin Eg5 induces a rapid mitotic arrest and provides a convenient assay for the optimization of siRNA transfection. Thus, dose responses can be established for different transfection techniques, highlighting the great differences in response to transfection techniques of various cell types. We report that the calcium phosphate precipitation technique can be an efficient and cost-effective alternative to Oligofectamine in some adherent cells, while electroporation can be efficient for some cells growing in suspension such as hematopoietic cells and some adherent cells. Significantly, the optimal parameters for the electroporation of siRNA differ from those for plasmids, allowing the use of milder conditions that induce less cell toxicity. In summary, a single siRNA leading to an easily assayed phenotype can be used to monitor the transfection of siRNA into any type of proliferating cells of both human and murine origin.

Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial.

OBJECTIVE: To determine the minimum effective dose of folic acid required to appreciably increase serum folate and to produce a significant reduction in plasma total homocysteine (tHcy). DESIGN: Double-blind, randomised placebo-controlled intervention trial. SETTING: Community-based project in a New Zealand city. SUBJECTS: Seventy free living men and women with tHcy> or =10 micromol/l. Mean age (range) was 58 (29-90) y. INTERVENTIONS: Daily consumption over 4 weeks of 20 g breakfast cereal either unfortified (placebo) or fortified with 100, 200 or 300 microg folic acid. Dietary intake was determined by weighed diet records and consumption of commercially fortified products was avoided. MAIN OUTCOME MEASURES: Plasma tHcy and serum folate concentrations. RESULTS: Average serum folate concentrations (95% CI) increased significantly in the treatment groups relative to the control group by 28(9-51)%, 60(37-87)% and 79(51-114)% for supplementation with 100, 200 and 300 microg folic acid, respectively. A reduction in tHcy was observed, being 16(8-22)%, 12(4-18)% and 17(9-24)% in the three treatment groups, respectively. CONCLUSIONS: A regular intake of as little as 100 microg folic acid per day was sufficient to lower tHcy in persons at the upper end of the normal range for tHcy. Low-level fortification may also be appropriate for lowering the risk of neural tube defects given that, when aggregated from all sources, the total intake of folic acid may be sufficiently high to adequately improve the folate status of young women.

Opioid analgesics versus ketorolac in spine and joint procedures: impact on healthcare resources.

BACKGROUND: Ketorolac's efficacy as a postoperative analgesic has been shown to be comparable to that of narcotic analgesics, but with significantly fewer narcotic-related adverse events. OBJECTIVE: To assess whether the choice of postoperative analgesic, narcotic or ketorolac, has an impact on healthcare resource utilization and cost durng inpatients' recovery period. DESIGN: Retrospective, multicenter, controlled, parallel, cost-minimization analysis. SETTING: Six US teaching hospitals. PATIENTS: This study included 559 patients that underwent either a spine or joint procedure and received adequate doses of narcotic (n = 284 of either morphine or meperidine) or ketorolac (n = 275). MEASUREMENTS: Time to reach recovery milestones, average utilization of healthcare resources, and average per-case postoperative treatment cost. RESULTS: Several recovery milestones, including time to first bowel movement, first oral intake, and first unassisted ambulation, were reached sooner in the ketorolac group, with a resultant shorter mean length of postoperative stay (narcotic 3.78 d, ketorolac 2.80 d; p = 0.01). Total per-patient cost of treatment was 32% greater in the narcotic group, resulting primarily from higher costs associated with hospitalization. CONCLUSIONS: Despite the higher acquisition cost of medication, healthcare resource utilization and total per-patient cost of treatment were lower for patients in the ketorolac group compared with patients in the narcotic analgesic study group. The majority of patients in the ketorolac group were also given concurrent narcotic analgesics; therefore, the beneficial effects observed may be secondary to the combination of ketorolac and narcotic analgesics.

Management of febrile children in the age of the conjugate pneumococcal vaccine: a cost-effectiveness analysis.

OBJECTIVES: The optimal practice management of highly febrile 3- to 36-month-old children without a focal source has been controversial. The recent release of a conjugate pneumococcal vaccine may reduce the rate of occult bacteremia and alter the utility of empiric testing and treatment. The objective of this study was to determine the cost-effectiveness of 6 different management strategies of febrile 3- to 36-month-old children at current and declining rates of occult pneumococcal bacteremia. METHODS: A cost-effectiveness (CE) analysis was performed to compare the strategies of "no work-up," "clinical judgment," "blood culture," "blood culture + treatment," "complete blood count (CBC) + selective blood culture and treatment," and "CBC and blood culture + selective treatment." A hypothetical cohort of 100 000 children who were 3 to 36 months of age and had a fever of >/=39 degrees C and no source of infection was modeled for each strategy. Our main outcome measures were cases of meningitis prevented, life-years saved compared with "no work-up," total cost (1999 dollars), and incremental CE ratios. RESULTS: When compared with "no work-up," the strategy of "CBC + selective blood culture and treatment" using a white blood cell (WBC) cutoff of 15 x 10(9)/L prevents 48 cases of meningitis, saves 86 life-years per 100 000 patients, and is less costly at the current rate of bacteremia (1.5%). Using the strategy of "CBC + selective blood culture and treatment" with a lower WBC cutoff of 10 x 10(9)/L costs an additional $72 300 per life-year saved. If the rate of bacteremia declines to 0.5%, then the incremental CE ratio of "clinical judgment" compared with "no work-up" is $38 000 per life-year saved; however, strategies that include empiric testing or treatment result in CE ratios greater than $300 000 per life-year saved. CONCLUSIONS: "CBC + selective blood culture and treatment" using a WBC cutoff of 15 x 10(9)/L is cost-effective at the current rate of pneumococcal bacteremia. If the rate of occult bacteremia falls below 0.5% with widespread use of the conjugate pneumococcal vaccine, then strategies that use empiric testing and treatment should be eliminated.

Financial and clinical impact of false-positive blood culture results.

During a 4-year period, 9465 specimens for blood culture were obtained from 11,911 highly febrile, otherwise healthy young children. Of these specimens, 87 (0.9%) yielded nonpathogens and were considered to be false-positive blood culture results (FPBCRs). Seventy-two of the patients who provided these specimens were treated on an outpatient basis (resulting in $10,821 in treatment charges), and 7 were admitted to the hospital (resulting in $16,200 in charges) as a result of the FPBCRs. Studies performed during follow-up included a second blood culture (21 patients), complete blood cell count (11), urine analysis and culture (5), lumbar puncture (3), and chest radiography (3). Only a small minority of patients were hospitalized or underwent invasive procedures. The charges associated with FPBCRs are very small in comparison to the initial charges of culturing specimens obtained from children considered to be at risk. Concern about the consequences of FPBCRs should not deter clinicians from performing indicated cultures for children who potentially have bacteremia.

Development of a best-practice model at a university hospital to increase efficiency in the management of patients with community-acquired pneumonia.

An economic evaluation of drug acquisition, nursing care, pharmacy time, laboratory costs, supplies, and ancillary care was conducted as a first step toward developing a pneumonia management plan at the University of Kentucky Medical Center (UKMC). UKMC costs were compared with costs at other hospitals treating pneumonia patients on Medicare. Overall costs for pneumonia at the 25% of hospitals nationwide with the lowest costs for Medicare patients with this condition were determined and compared with costs at UKMC. Against nationwide benchmarks, efficiencies at UKMC for treating simple pneumonia ranged from 45% for pharmacy expenses to 81% for nursing costs. Efficiencies for complicated pneumonia ranged from 47% for laboratory costs to 67% for nursing costs. The most cost-efficient antimicrobial treatment options were promoted and integrated into a pneumonia management plan based on Infectious Diseases Society of America treatment guidelines. A comparison of pneumonia treatment costs at UKMC with those at the 25% of hospitals nationwide with the lowest treatment costs for Medicare patients with pneumonia revealed that UKMC pharmacy costs could be optimized. Strategies for standardizing the care of patients with community-acquired pneumonia (CAP) are being implemented.

Restriction of energy intake, energy expenditure, and aging.

Energy restriction (ER), without malnutrition, increases maximum life span and retards the development of a broad array of pathophysiological changes in laboratory rodents. The mechanism responsible for the retardation of aging by ER is, however, unknown. One proposed explanation is a reduction in energy expenditure (EE). Reduced EE may increase life span by decreasing the number of oxygen molecules interacting with mitochondria, thereby lowering reactive oxygen species (ROS) production. As a step toward testing this hypothesis, it is important to determine the effect of ER on EE. Several whole-body, organ, and cellular studies have measured the influence of ER on EE. In general, whole-body studies have reported an acute decrease in mass-adjusted EE that disappears with long-term ER. Organ-specific studies have shown that decreases in EE of liver and gastrointestinal tract are primarily responsible for initial reductions in EE with ER. These data, however, do not determine whether cellular EE is altered with ER. Three major processes contributing to resting EE at the cellular level are mitochondrial proton leak, Na(+)-K(+)-ATPase activity, and protein turnover. Studies suggest that proton leak and Na(+)-K(+)-ATPase activity are decreased with ER, whereas protein turnover is either unchanged or slightly increased with ER. Thus, two of the three major processes contributing to resting EE at the cellular level may be decreased with ER. Although additional cellular measurements are needed, the current results suggest that a lowering of EE could be a mechanism for the action of ER.

Mitochondrial uncoupling proteins in energy expenditure.

Four recently discovered homologues of the brown adipose tissue-specific mitochondrial uncoupling protein (UCP1) vary from 29% to 58% in their similarity to UCP1. Although these homologues share important structural features with UCP1 and like UCP1 can reduce the mitochondrial membrane potential when expressed in yeast, there is no clear evidence that they can function thermogenically in vivo. On the other hand, evidence continues to accumulate indicating that the up-regulation of Ucp1 reduces excessive adiposity.

Ten common estate planning mistakes to avoid.

While most Americans are aware of the importance of estate planning, many fail to make the proper arrangements for their heirs. Problems can arise from a number of mistake, such as underestimating assets, relying solely on a will, or not planning for estate tax payments.

Staying on track with your investment plan.

The key to successful investing is not to try to pick the "hot" stocks but rather to invest for the long run. The best approach is not trying to predict market trends but making financial goals and diversifying your investments to reach them.

The timing of do-not-resuscitate orders and hospital costs.

The relation between the timing of do-not-resuscitate (DNR) orders and the cost of medical care is not well understood. This prospective observational study compares hospital costs and length of stay of 265 terminally ill patients with admission DNR orders, delayed DNR orders (occurring after 24 hours), or no DNR orders (full code). Patients whose orders remained full code throughout a hospital stay had similar lengths of stay, total hospital costs, and daily costs as patients with admission DNR orders. Patients with delayed DNR orders, by contrast, had a greater mortality, longer length of stay, and higher total costs than full code or admission DNR patients, but similar daily costs. The causes of delay in DNR orders and the associated higher costs are a matter for future research.

The promise of public/private sector collaboration in the development of new contraceptives: the experience of CICCR.

The Consortium for Industrial Collaboration in Contraceptive Research (CICCR) was established in 1995 with funding from two philanthropic foundations. Now just over 3 years later, it is supported by five foundations and a United Nations agency. Work in three priority areas of male methods, vaginal methods and monthly methods for women is progressing well. Collaboration with 10 industrial entities has been established, and more than 60 contracts with investigators at not-for-profit institutions have been funded. It can be concluded that CICCR has provided an efficient and effective mechanism for promoting industrial collaboration in contraceptive R&D, and fills a need not covered by other agencies active in the field.