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Recent breakthroughs in computer vision offer an exciting avenue to develop new remote, and non-intrusive patient monitoring techniques. A very challenging topic to address is the automated recognition of breathing disorders during sleep. Due to its complexity, this task has rarely been explored in the literature on real patients using such marker-free approaches. Here, we propose an approach based on deep learning architectures capable of classifying breathing disorders. The classification is performed on depth maps recorded with 3D cameras from 76 patients referred to a sleep laboratory that present a range of breathing disorders. Our system is capable of classifying individual breathing events as normal or abnormal with an accuracy of 61.8%, hence our results show that computer vision and deep learning are viable tools for assessing locally or remotely breathing quality during sleep.

Methionine aminopeptidase 2 (MetAP2) inhibition is a promising approach to treating diabetes, obesity, and associated metabolic disorders. Beloranib, a MetAP2 inhibitor previously investigated for treatment of Prader-Willi syndrome, was associated with venous thrombotic adverse events likely resulting from drug effects on vascular endothelial cells (ECs). Here, we report the pharmacological characterization of ZGN-1061, a novel MetAP2 inhibitor being investigated for treatment of diabetes and obesity. Four weeks of subcutaneous administration of ZGN-1061 to diet-induced obese (DIO) insulin-resistant mice produced a 25% reduction in body weight, primarily due to reduced fat mass, that was comparable to beloranib. ZGN-1061 also produced improvements in metabolic parameters, including plasma glucose and insulin, and, in HepG2 cells, initiated gene changes similar to beloranib that support observed in vivo pharmacodynamics. In vitro studies in ECs demonstrated that ZGN-1061 effects on EC proliferation and coagulation proteins were greatly attenuated, or absent, relative to beloranib, due to lower intracellular drug concentrations, shorter half-life of inhibitor-bound MetAP2 complex, and reduced cellular enzyme inhibition. In dogs, ZGN-1061 was more rapidly absorbed and cleared, with a shorter half-life than beloranib. Unlike beloranib, ZGN-1061 did not increase coagulation markers in dogs, and ZGN-1061 had a greatly improved safety profile in rats relative to beloranib. In conclusion, ZGN-1061 and beloranib demonstrated similar efficacy in a mouse model of obesity, while ZGN-1061 had a markedly improved safety profile in multiple in vitro and in vivo models. The lower duration of exposure characteristic of ZGN-1061 is expected to provide a meaningfully enhanced clinical safety profile.

OBJECTIVES: The increasing prevalence of mobile devices in clinical settings has the potential to improve both patient care and education. The benefits are particularly promising in the context of family-centered rounds in inpatient pediatric settings. We aimed to increase mobile device usage by inpatient rounding teams by 50% in 6 months. We hoped to demonstrate that use of mobile devices would improve access to patient care and educational information and to determine if use would improve efficiency and perceptions of clinical teaching. METHODS: We designed a mixed-methods study involving pre- and post-implementation surveys to residents, families, and faculty as well as direct observations of family-centered rounds. We conducted rapid cycles of continual quality improvement by using the Plan-Do-Study-Act framework involving 3 interventions. RESULTS: Pre-intervention, the mobile computing cart was used for resident education on average 3.3 times per rounding session. After cycle 3, teaching through the use of mobile devices increased by ∼79% to 5.9 times per rounding session. On the basis of survey data, we determined there was a statistically significant increase in residents’ perception of feeling prepared for rounds, receiving teaching on clinical care, and ability to teach families. Additionally, average time spent per patient on rounds decreased after implementation of mobile devices. CONCLUSIONS: Integration of mobile devices into a pediatric hospital medicine teaching service can facilitate patient care and perception of resident teaching by extending the utility of electronic medical records in care decisions and by improving access to knowledge resources.

Stigma towards people with substance use disorders is a common phenomenon with far reaching effects. This study evaluated the long-term effect of using an educational intervention on the attitudes of physician assistant students.Physician assistant students received a one-week educational intervention focused on substance abuse. Changes in student attitudes were measured one year later using the Attitude to Mental Health Questionnaire (AMIQ).Significant and sustained improvement was noted in attitudes in the AMIQ score for the opiate use disorder vignette; no significant change was noted in the alcohol use disorder vignette.The persistence of improved attitudes (although they remained negative) in study participants towards people with opiate use disorders is a cautiously encouraging finding. Educational interventions can have a sustained effect on stigma reduction, but much more work on the etiology of these implicit and explicit beliefs is needed to inform robust future interventions.

Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats. HF/FG rats also exhibit changes in gut hormones linked to food intake, increased energy harvest by gut microbiota, and caloric spilling in the urine. Studies in gnotobiotic mice reveal that effects of fumagillin on energy expenditure but not feeding behavior may be mediated by the gut microbiota. In sum, fumagillin engages weight loss-inducing behavioral and physiologic circuits distinct from those activated by simple caloric restriction.

Aim: To assess the efficacy, safety and tolerability of beloranib treatment for obesity. Methods: This phase II, double-blind, randomized study investigated the effects of beloranib suspension (0.6, 1.2 and 2.4mg) or placebo, administered subcutaneously, for 12weeks in 147 participants (primarily white women) with obesity. No diet or exercise advice was administered. Results: At week 12, beloranib resulted in dose-dependent progressive weight loss of -5.5±0.5, -6.9±0.6 and -10.9±1.1kg for the 0.6, 1.2 and 2.4mg beloranib doses, respectively, compared with -0.4±0.4kg with placebo (all p

Previous publications suggested that the precision of the new Hologic Horizon densitometer might be better than that of the previous Discovery model, but these observations were confounded by not using the same participants and technologists on both densitometers. We sought to study this issue methodically by measuring in vivo precision in both densitometers using the same patients and technologists. Precision studies for the Horizon and Discovery models were done by acquiring spine, hip, and forearm bone mineral density twice on 30 participants. The set of 4 scans on each participant (2 on the Discovery, 2 on the Horizon) was acquired by the same technologist using the same scanning mode. The pairs of data were used to calculate the least significant change according to the International Society for Clinical Densitometry guidelines. The significance of the difference between least significant changes was assessed using a Wilcoxon signed-rank test of the difference between the mean square error of the absolute value of the differences between paired measurements on the Discovery (Δ-Discovery) and the mean square error of the absolute value of the differences between paired measurements on the Horizon (Δ-Horizon). At virtually all anatomic sites, there was a nonsignificant trend for the precision to be better for the Horizon than for the Discovery. As more vertebrae were excluded from analysis, the precision deteriorated on both densitometers. The precision between densitometers was almost identical when reporting only 1 vertebral body. (1) There was a nonsignificant trend for greater precision on the new Hologic Horizon compared with the older Discovery model. (2) The difference in precision of the spine bone mineral density between the Horizon and the Discovery models decreases as fewer vertebrae are included. (3) These findings are substantially similar to previously published results which had not controlled as well for confounding from using different subjects and technologists.

BACKGROUND AND OBJECTIVE: Patient safety events are underreported by physicians. Baseline data demonstrated that physicians submitted 3% of event reports at Our Lady of the Lake Children’s Hospital. Our aim was to increase the proportion of safety reports filed by residents and faculty to 6% of all reports within a 9-month period. METHODS: We used the Model for Improvement and serial Plan, Do, Study, Act cycles to test interventions we hypothesized would improve physician recognition and reporting of patient safety events. We tracked the percentage of Our Lady of the Lake Children’s Hospital event reports entered by residents or faculty over time as the primary outcome measure. Changes to teaching team processes included “patient safety rounds” prompted by text messages, an inpatient “superintendent” rotation with core patient safety responsibilities, and a “just-in-time” faculty development program called “QI on the Fly.” RESULTS: Physician-reported events increased to a monthly average of 24% of all events reported, an improvement that has been sustained over 17 months. Resident reporting accounted for most of the increase in physician reports. Increased physician reporting was temporally associated with implementation of the “superintendent” rotation. The total number of events reported increased as a result of increased physician reporting. CONCLUSIONS: Incorporating patient safety responsibilities into a teaching team’s workflow can increase physician safety event reporting. We plan additional Plan, Do, Study, Act cycles to spread this approach to other clinical settings and investigate the impact increased reporting might have on patient care.

A high throughput LC–MS/MS method for quantification of metformin substrate uptake enables conversion of radiometric transporter inhibition assays for multidrug and toxin extrusion transporters (MATE 1 and 2) and organic cation transporter 2 (OCT2) to a nonradioactive format. Such conversion greatly simplifies assay complexity and reduces assay costs. The development of a quantitative LC–MS/MS method for metformin in support of the high throughput transporter inhibition assays faced specific challenges of achieving both adequate chromatographic retention and rapid analytical turnaround. Here we report a method that circumvents both challenges. The utilization of a porous graphitic carbon column (Hypercarb) ensured adequate retention of highly polar metformin in biological samples. The combined employment of a ballistic gradient on a 3 mm × 30 mm, 5 μm Hypercarb column, and dual staggered chromatography coupled with multiple injection chromatography acquisition, yielded a fast injection-to-injection cycle time of 30 s. The method demonstrated good accuracy, precision and excellent robustness for high throughput applications, and has been successfully implemented in the development and validation of the nonradioactive transporter inhibition assays for MATEs and OCT2.

Stigma towards people with substance use disorders is pervasive and imbedded in our US culture. Prejudicial attitudes that are part of a health care practitioner’s value system are a barrier to people accessing health care and substance use treatment. This study aimed to reduce stigmatizing attitudes of graduate health care professional students by implementing an innovative curriculum combining multiple teaching methods. Physician assistant students received a 3-h educational intervention that consisted of lecture and discussion sessions, direct interaction with a recovering substance user, viewing a film portrayal of addiction and addiction treatment, and written self-reflection. Changes in student attitudes were measured using a subscale of the Attitudes to Mental Illness Questionnaire (AMIQ) instrument and analysis of coded written reflections. A follow-up focus group resulted in additional qualitative insight into attitudes. Post-intervention scores for the “heroin” AMIQ vignette significantly improved compared to pre-test scores (p

Medical professionals' negative attitudes toward patients with mental illness and substance abuse disorders can have negative consequences, and these attitudes are not rare. In surveys, patients have reported discrimination in mental health settings in the 16% to 44% range and 17% to 31% in physical health settings.1 More concerning than the perceived stigma experienced by patients is the potential for bias in medical decision making. For example, health care providers are less likely to refer people with mental illnesses for a mammogram, less likely to admit them for hospitalization after a diabetic crisis, and less likely to perform a cardiac catheterization.2 Stigmatizing beliefs also affect clinical decisions through diagnostic overshadowing, attributing physical symptoms to the mental condition and consequently not investigating or treating them.3 Although evidence suggests that patients with mental illnesses are no less likely to be adherent to treatment recommendations than others, health care professionals who endorsed more stigmatizing attitudes about mental illness were more likely to be pessimistic about the likelihood of patients adhering to treatment, and this contributed to impaired decision making.4

Persistent nasal carriage of Staphylococcus aureus is the primary reservoir for this pathogen and a risk factor for infection. The nares of 12 to 30% of healthy individuals are persistently colonized with staphylococci. Elucidating the yet enigmatic determinants of this phenomenon is of major public health interest. We hypothesized that differences in the levels of antimicrobial peptides (AMPs) that are found in human skin and have pronounced antistaphylococcal activity may contribute to this phenomenon. We compared constitutive and induced mRNA levels of RNase 7 and human β-defensin 3 (HBD-3) in healthy and experimentally wounded gluteal skin of 60 volunteers after ascertaining their carrier status through repeated nasal cultures. We found that levels of HBD-3 expression in skin of persistent nasal carriers of S. aureus were lower: induced levels in carriers were 63% (95% confidence interval, 43 to 94%; P = 0.02) and constitutive levels were 76% (95% confidence interval, 52 to 110%; P = 0.14) of those found in noncarriers. No such associations were present for RNase 7. In conjunction with existing knowledge, these findings suggest that healthy individuals with deficient HBD-3 expression in keratinocytes are more prone to persistent nasal colonization with S. aureus .

Background.—Puberty is assumed to influence the occurrence of headache, increasing the risk for recurrent episodes, especially in girls. The increase of headache, in particular recurrent headache, in girls from around the age of 12 on, is often ascribed to the occurrence of menarche as the most stringent indicator of completed puberty. Objectives.—We examined the hypothesis that the occurrence of menarche in girls is predictive of recurrent headache in reference to no or rare headache in the past 6 months. Furthermore, the assumption was tested that headache episodes increase after onset of menarche but remain unchanged in girls not having experienced their first menstruation. We also expected a higher probability of migraine type of headache after menarche. In a further analysis girls with and without menarche were compared with boys, and a difference between gender only for girls with menarche was predicted. Methods.—In an epidemiological study recruiting 8800 families with children 7-14 years in Southern Lower Saxony (Germany), we conducted 3 yearly panels based on postal questionnaires. Headache data are based on self-report of children from 9 years on. Parents were asked for information regarding the onset of menarche. Approximately 1100 girls and about the same number of boys constitute the sample for our analyses. Results.—The results of a logistic regression analysis demonstrate that in 11- to 16-year-old girls having experienced menarche in either the year of the assessment of headache or 2 years before that, the risk for recurrent headache is increased when compared with girls without menarche. Intraindividual longitudinal analyses, however, do not support our hypotheses that after the onset of menarche headaches become more frequent. The expected differences in headache between girls with menarche and boys were found. The risk for migraine-like headaches is not significantly higher after onset of menarche than before. Conclusions.—Thus, results do not consistently support the hypothesis that puberty is a moderator of headache frequency. Even in cases where the outcome of regression analyses is supportive of our expectations, explained variance is diminutive (maximum 2.2%). Thus, the influence of menarche on headache seems to be only marginal.

Background The objective of the present study was to assess the concordance between parent and child report regarding different domains of pediatric health, headache in particular. In addition, the influence of potential moderator variables on the agreement between parents and children was examined. Methodology In an epidemiologic study on a randomly drawn sample of households with at least 1 child in the family between 7 and 14 years of age (community registries), various pediatric health disturbances (headache, other pains, somatic symptoms, and depression/anxiety) were assessed via both child (from the age of 9 y on) and parent report (n=3461). Results A relatively high parent-child agreement (sigmaM=0.61) was found regarding the variable headache frequency, whereas consensus regarding other pains was, for the most part, markedly lower. The lowest agreement (sigmaM=0.27) was found for depression/anxiety symptoms. A moderator analysis (with age, sex, and parental headache) between child and parent failed to reveal significant differences regarding the degree of agreement between the 2 data sources. Children reported more frequent and more severe symptoms in all health domains. Conclusion The examined potential moderator variables did not elucidate processes underlying the differences in child and parent agreement. There is no convincing evidence that the children's appraisal is less valid than their parents'. In summary, parents' reports cannot be viewed as a substitute for children's reports in pediatric pain and health assessment. Instead, each perspective represents a unique subjective reality and as such, both are of importance for research on pediatric pain and other health variables.

In the last 15 years, reduction mammaplasty has been increasingly performed on an outpatient basis. Despite this evolution, few outcome studies have been published regarding outpatient breast reduction surgery.The authors documented clinical outcomes of reduction mammaplasty performed in an outpatient setting over an 11-year period and compared these results with published normative values in the plastic surgery literature.A retrospective review was undertaken of 884 reduction mammaplasties in 444 patients at a single outpatient surgical center performed by the senior author (W.G.S.) from 1995 through 2006. In all cases, a laser-assisted, inferior pedicle, Wise pattern, reduction mammaplasty was performed. In addition to demographic and surgical data, complication frequency and type were recorded. Complication data were further stratified into minor and major categories. Potential minor complications included seroma, hematoma, soft tissue infection, dog-ears requiring revision, and small incisional breakdowns or delayed healing of less than 2 cm. Potential major complications included large incisional breakdowns or delayed healing of greater than 2 cm, nipple/areolar necrosis, need for blood transfusion, deep vein thrombosis, pulmonary embolus, myocardial infarction, and death.The mean patient age was 38 years (range, 16 to 73 years). Mean body-mass index was 27 (range 17 to 47). The reported preoperative brassiere cup sizes ranged from a 34 C to a 38 K, with a DD being the most common size. The mean preoperative sternal notch-to-nipple distance was 29 cm (range 22 to 54 cm). Forty patients smoked (9%). Mean clinical follow-up was 13 months. Mean total resection weight of breast tissue was 1228 g (range 100 to 5295 g). Mean operative time for reduction mammaplasty was 115 minutes (range 50 to 195 minutes). Nineteen percent of patients underwent multiple procedures, including abdominoplasty, lipoplasty, and facial procedures, with a mean operative time of 132 minutes (range 75 to 345 minutes). The overall complication rate was 14%, with 70 minor complications occurring in 62 patients. Specific minor complications included one seroma, four hematomas, eight soft tissue infections, two of which required a short course of intravenous antibiotics, one patient with dog-ears requiring surgical revision, and 56 small incisional wound breakdowns (2 cm). The small incisional breakdowns, which represented the largest group of complications, were further subdivided into 44 minor T-zone wounds, 3 nipple-areolar complex wounds, and 9 wounds of the vertical and horizontal incisions. Three major complications (0.67%) were recorded. Two patients had development of partial nipple/areolar necrosis. A third patient required anticoagulation for a pulmonary embolus diagnosed 10 days after surgery. Statistical analysis of the complication data revealed one significant relationship. Patients with a body mass index above the mean had a 21% complication rate as compared with a 12% rate for those below the mean. Of note, there was no increase in complication rate in the context of multiple procedures.This retrospective series is the largest to date involving outpatient reduction mammaplasty. Complication data derived from this series are comparable to previously published studies and thus support the safety and efficacy of outpatient reduction mammaplasty performed in an accredited facility.

Human arylamine N-acetyltransferase 1 (NAT1) has been overexpressed in E. coli as a mutant dihydrofolic acid reductase (DHFR) fusion protein with a thrombin sensitive linker. An initial DEAE anion-exchange chromatography resulted in partial purification of the fusion protein. The fusion protein was cleaved with thrombin, and human rNAT1 was purified with a second DEAE column. A total of 8 mg of human rNAT1 from 2 1 of cell culture was purified to homogeneity with this methodology. Arylamine substrate specificities were determined for human rNATI and hamster rNAT2. With both NATs, the second order rate constants (k(cat)/ Kmb) for p-aminobenzoic acid (PABA) and 2-aminofluorene (2-AF) were several thousand-fold higher than those for procainamide (PA), consistent with the expected substrate specificities of the enzymes. However, p-aminosalicylic acid (PAS), previously reported to be a human NAT1 and hamster NAT2 selective substrate, exhibits 20-fold higher specificity for hamster rNAT2 (k(cat)/Kmb 3410 microM(-1) s(-1)) than for human rNAT1 (k(cat)/Kmb 169.4 microM(-1) s(-1)). p-aminobenzoyl-glutamic acid (pABglu) was acetylated 10-fold more efficiently by human rNAT1 than by hamster rNAT2. Inhibition studies of human rNAT1 and hamster rNAT2 revealed that folic acid and methotrexate (MTX) are competitive inhibitors of both the unacetylated and acetylated forms of the enzymes, with K(I) values in 50 - 300 micro range. Dihydrofolic acid (DHF) was a much poorer inhibitor of human rNAT1 than of hamster rNAT2. The combined results demonstrate that human rNAT1 and hamster rNAT2 have similar but distinct kinetic properties with certain substrates, and suggest that folic acid, at least in the non-polyglutamate form, may not have an effect on human NAT1 activity in vivo.

Chloroprocaine is being investigated as a possible replacement for spinal lidocaine. Adding fentanyl to lidocaine increases the quality of spinal anesthesia without prolongation of block. We report the characteristics of 2-chloroprocaine (2-CP) spinal anesthesia with or without fentanyl in 8 volunteers receiving 40 mg 2-CP with saline or 20 micro g fentanyl in a double-blinded, randomized, crossover manner. Spinal anesthesia was successful for all subjects with complete block regression, ambulation, and void by 110 min. Itching occurred in all subjects receiving fentanyl, though medication was not required. No subject reported signs of transient neurological symptoms. Peak block with fentanyl averaged T5 (T3-7) and without fentanyl T9 (L1-T4) (P = 0.005). Regression to L1 was 78 +/- 7 min with fentanyl and 53 +/- 19 min without fentanyl (P = 0.02). Tourniquet was tolerated for 51 +/- 8 min with fentanyl and for 34 +/- 14 min without fentanyl (P = 0.02). Complete regression of block occurred at 104 +/- 7 min with fentanyl and by 95 +/- 9 min without fentanyl (P = 0.02). We conclude that 2-CP spinal anesthesia provides rapid onset and adequate potency, giving it a positive profile for ambulatory surgery. The addition of fentanyl lengthens regression to L1 and tourniquet tolerance while minimally lengthening block duration.Spinal 2-chloroprocaine (40 mg) provides rapid onset and reliable blockade without signs of transient neurological symptoms, giving it a positive profile for ambulatory surgical settings. The addition of fentanyl appears to lengthen the regression to L1 dermatome and tourniquet time while minimally lengthening duration of block.

Chemokines are small secreted proteins that stimulate the directional migration of leukocytes and mediate inflammation. During screening of a murine choroid plexus complementary DNA library, we identified a new chemokine, designated neurotactin. Unlike other chemokines, neurotactin has a unique cysteine pattern, Cys-X-X-X-Cys, and is predicted to be a type 1 membrane protein. Full-length recombinant neurotactin is localized on the surface of transfected 293 cells. Recombinant neurotactin containing the chemokine domain is chemotactic for neutrophils both in vitro and in vivo. Neurotactin messenger RNA is predominantly expressed in normal murine brain and its protein expression in activated brain microglia is upregulated in mice with experimental autoimmune encephalomyelitis, as well as in mice treated with lipopolysaccharide. Distinct from all other chemokine genes, the neurotactin gene is localized to human chromosome 16q. Consequently we propose that neurotactin represents a new delta-chemokine family and that it may play a role in brain inflammation processes.

Multiplexed liquid chromatography (LC) coupled with multiple-injection-chromatogram acquisition has emerged as the method of choice for high-speed discovery bioanalysis, because it significantly reduces injection-to-injection cycle time while maintaining the chromatography quality. Historically, systems utilizing this approach had been custom built, and therefore relied on custom software tools to communicate with multiple vendor software for system control, which lacked transferability, flexibility and robustness.In this study, we refined a multiplexed bioanalytical system previously reported, by implementing open-deck auto-sampler manifold and multiple-injection-chromatogram acquisition, all on a commercially available system with single software control.As a result of these improvements, the developed LC/tandem mass spectrometry (MS/MS) method on the system was nearly three times faster than the previous method, while demonstrating comparable analytical accuracy, precision and robustness. This system has been evaluated for in vitro ADME screening assays including metabolic stability, CYP inhibition and Caco-2. The biological data generated on the developed system displayed good correlation with those from the previous LC/MS/MS approaches.The developed platform demonstrated applicability to the in vitro screening assays evaluated and has been successfully implemented to support the high-throughput metabolic stability assay, with a significantly improved bioanalytical throughput, capacity and data turnaround.

Evaluate the safety and tolerability of beloranib, a fumagillin-class methionine aminopetidase-2 (MetAP2) inhibitor, in obese women over 4 weeks.Thirty-one obese (mean BMI 38 kg/m2) women were randomized to intravenous 0.1, 0.3, or 0.9 mg/m2 beloranib or placebo twice weekly for 4 weeks (N = 7, 6, 9, and 9).The most frequent AEs were headache, infusion site injury, nausea, and diarrhea. Nausea and infusion site injury occurred more with beloranib than placebo. The most common reason for discontinuation was loss of venous access. There were no clinically significant abnormal laboratory findings. In subjects completing 4 weeks, median weight loss with 0.9 mg/m2 beloranib was -3.8 kg (95% CI -5.1, -0.9; N = 8) versus -0.6 kg with placebo (-4.5, -0.1; N = 6). Weight change for 0.1 and 0.3 mg/m2 beloranib was similar to placebo. Beloranib (0.9 mg/m2) was associated with a significant 42 and 18% reduction in triglycerides and LDL-cholesterol, as well as improvement in C-reactive protein and reduced sense of hunger. Changes in β-hydroxybutyrate, adiponectin, leptin, and fibroblast growth factor-21 were consistent with the putative mechanism of MetAP2 inhibition. Glucose and blood pressure were unchanged.Beloranib treatment was well tolerated and associated with rapid weight loss and improvements in lipids, C-reactive protein, and adiponectin.

Objective: The aim of the study was to ascertain the prevalence of multiple pains (MPs) and detect psychosocial risk factors assessed 1 year previously. Method: MPs were defined by the number of sites where pain was reported to occur at least "sometimes" in a general population sample of 2,219 German youths. Results: Two or more sites of recurrent pain were reported by 54% of the participants, whereas 27% reported no pains. Girls were much more prone to MPs than boys. Stability of MP was high in the two waves. Regression analysis revealed that prior MP, age, sex, internalizing/externalizing symptoms, and time spent with visual media explained 25% of the variance: the contribution of the psychosocial factors to the model was small. Separate analyses for boys and girls displayed different risk-factor profiles and a higher degree of predictability in girls. Conclusion: A supposedly biological disposition, namely pain vulnerability, being particularly high in girls, is assumed to build the basis of pains felt in various sites of the body. Further research is needed to corroborate and specify these assumptions.

Liquid chromatography/tandem mass spectrometry (LC/MS/MS) is the bioanalytical method of choice to support plate-based, in vitro early ADME (Absorption, Distribution, Metabolism and Excretion) screens such as metabolic stability (Metstab) assessment. MS/MS method optimization has historically been the bottleneck in this environment, where samples from thousands of discrete compounds are analyzed on a monthly basis, mainly due to the lack of a high-quality commercially available platform to handle the necessary MS/MS method optimization steps for sample analysis by selected reaction monitoring (SRM) on triple quadrupole mass spectrometers. To address this challenge, we recently developed a highly automated bioanalytical platform by successfully integrating QuickQuan 2.0, a unique high-throughput solution featuring MS/MS method optimization by automated infusion, with a customized in-house software tool in support of a Metstab screen. In this platform, a dual-column setup running parallel chromatography was also implemented to reduce the bioanalytical cycle time for LC/MS/MS sample analysis. A set of 45 validation compounds was used to demonstrate the speed, quality and reproducibility of MS/MS method optimization, sample analysis, and data processing using this automated platform. Metstab results for the validation compounds in microsomes from multiple species (human, rat, mouse) showed good consistency within each batch, and also between batches conducted on different days. We have achieved and maintained a monthly throughput of 1300 compound assays representing 500 discrete compounds per instrument per month on this platform, and it has been used to generate metabolic stability data for more than 25 000 compounds to date with an overall success rate of more than 95%.

Objective The study aimed at the assessment of disability in children with headache (n = 1585, 11–14 yrs) from a randomly drawn population based sample. We explored the suitability of the PedMIDAS in epidemiological research by various indicators of response quality. Furthermore, predictors of disability were examined, as well as its association with measures of health care behaviour. Methods The PedMIDAS measures functional interference in different domains of life by asking the children for the number of days that their headache partially or totally interfered with their activities. Results The examination of response behaviour revealed a marked attrition of responses (missing, invalid) in two items. As a consequence, the total score for disability could not be obtained for about 25% of the children. Analysis of homogeneity of the PedMIDAS items revealed low item/total correlations in two items. The grading of disability resulted in 81.2% of all children with headache showing no or low disability. Only 1.4% was “severely” disabled. Disability was predicted by frequency, type and intensity of headache. From all psychological variables only dysfunctional stress coping was significantly associated with disability. Disability itself was significantly associated with medical consultation. Conclusions Suitability of the PedMIDAS for epidemiological research was supported, however with a caveat and recommendations for item revision. Severe disability due to headache was rare in the studied unselected sample when defined by behavioural interference. It is suggested to explore the construct of disability by a multi-method approach, including further instruments assessing headache related distress, (respectively) quality of life.

Background: Combined cosmetic procedures have become increasingly popular. One of the most common combinations of cosmetic procedures includes abdominoplasty and cosmetic breast surgery. The shortened recovery and financial savings associated with combined surgery contribute to the increased demand for these combined surgeries. Objective: The goal of this study was to evaluate the safety and efficacy of combined abdominoplasty and breast surgery at a single plastic surgery practice that performs a large volume of these cases. This is an update to a study published in 2006. Methods: A retrospective review was performed for patients who underwent combined abdominoplasty and cosmetic breast surgery during the last 10 years at a single outpatient surgery center. Abdominoplasty inclusion criteria were defined as lower, mini, full, reverse, or circumferential abdominoplasty. Cosmetic breast surgery inclusion criteria were defined as augmentation, mastopexy, augmentation-mastopexy, reduction, or removal and replacement of implants. Pertinent preoperative and intraoperative data were recorded along with complications and revisions. Results: There were 268 patients during the 10-year period between 1997 and 2007. There were no cases of death, pulmonary embolism, deep venous thrombosis, or other life-threatening complications. The overall complication rate was 34%. Abdominoplasty seroma and scars requiring revision comprised 68% (n = 74) of the complications. The total revision rate was 13%. Conclusions: Combined abdominoplasty and cosmetic breast surgery was safe and effective in this large series of cases performed at a single plastic surgery practice. The complication and revision rates of the combined surgery were similar to those reported for individually staged procedures. (Aesthetic Surg J 2009;29:129–134.)

To describe footwear preferences of people with diabetes and a history of foot ulcer from two large western Washington State healthcare organizations.As part of a clinical trial of footwear, self-reported information on footwear preferences, use, and cost were obtained from persons with diabetes and a prior healed foot ulcer for the year before their study enrollment. All participants' shoes were allocated into optimal, adequate, and dangerous categories based on design, structural and safety features, and materials.The 309 males and 91 females in this study averaged 62 years of age. At baseline, men owned an average of 6 (+3) pairs of shoes, with an average purchase price of $56, while women owned an average of 8 (+5) pairs, with an average purchase price of $42. Women spent an average of 51% of their time in shoes in dangerous shoes compared to men who spent 27% of their time. Men and women spent nearly 30% of their time while out of bed in slippers, stockings, and barefoot.People with a history of diabetes and foot ulcers needed several styles of safe and attractive shoes for regular activities. Healthcare professionals can provide patients with information on good footwear choices to help them select adequate shoes while avoiding dangerous shoes. This approach is more realistic than trying to move all people with prior foot risk factors or ulcers into uniformly optimal footwear, since recent evidence does not support this practice.

Resident's case problem.An 18-year-old man presented to physical therapy 3 days after insidious onset of painless left shoulder girdle weakness.Decreased light touch sensation was noted on the lateral left shoulder. In addition, weakness was present with shoulder abduction, flexion, external rotation, and internal rotation. Results of magnetic resonance imaging and radiography of the cervical spine, brachial plexus, and left shoulder were normal, Electromyography and nerve conduction velocity study findings were consistent with axillary nerve palsy. The results of the physical examination and diagnostic studies were most consistent with axillary nerve mononeuropathy, probably caused by traction or pressure due to wearing a pack while hiking or firing a weapon.With sling protection, limitation of physical activity, and gradual return to progressive resistance exercises, the patient had full return of strength and function 2 1/2 months after onset of symptoms. The differential diagnosis for shoulder girdle weakness should be well understood by physical therapists. This knowledge will help the therapist promptly identify the cause of shoulder girdle weakness and initiate appropriate treatment. If the condition requires further evaluation or treatment by another healthcare provider, prompt identification of pathology will allow appropriate timely referral.

Cooperative health care clinics (CHCCs), or shared medical appointments, are a healthcare innovation that can improve access and expand physicians' capacity to manage common geriatric conditions. This report describes a pilot program and working model for extending CHCCs to patients with dementia. Three cooperative dementia care clinics (CDCCs) met monthly for up to 1 year, drawing participants from a dementia clinic roster of patients and caregivers who had required continued specialty care for at least 3 months. Twenty-six of 33 eligible patient-caregiver dyads expressed interest, and 21 enrolled; five whose clinical status changed during the year withdrew and were replaced with new members. Brief introductory socialization, individualized clinical management, and an educational focus selected from problems of patients and caregivers were common to all sessions. Most participants required several types of clinical intervention and educational support. One group ended after reaching a natural termination point, and two others are ongoing at the request of participants. CDCCs can be a viable approach to increasing dementia care capacity in health systems. Formal service intervention trials to evaluate the generalizability and comparative effectiveness and economic viability of this model versus usual care are an appropriate next step.

Feedforward activation processes are widely regarded as crucial for the automatic initiation of motor responses, whereas recurrent processes are often regarded as crucial for visual awareness. Here, we used a set of behavioral criteria to evaluate whether rapid processing in the human visuomotor system proceeds as would be expected of a feedforward system that works independent of visual awareness. We measured lateralized readiness potentials (LRPs) for key-press responses to color targets ("masks") preceded by masked color primes mapped onto the same or opposite response, and traced the time-course of motor activation as a function of different prime and mask characteristics. LRP time-courses showed that initial motor activation occurred in prime direction and was time-locked to prime onset. Response activation was then captured on-line by the mask signal, with motor activation now time-locked to the mask and proceeding in mask direction. Crucially, the time-course of early activation by the prime was independent of all mask characteristics. This invariance in early priming effects contrasted with large differences in visual awareness for the prime produced by different masks. Results suggest that primed responses to color stimuli are controlled by feedforward waves of activation sequentially elicited by prime and mask signals traveling rapidly enough to escape the recurrent processes leading to backward masking.

Background: This study was designed to evaluate and compare the complication rates of patients having abdominoplasty without breast surgery with the rates of those having abdominoplasty with various types of elective breast surgery, including breast augmentation, breast reduction, mastopexy, and mastopexy combined with simultaneous augmentation. Methods: The data collected represent a retrospective chart review of consecutive abdominoplasty procedures performed at a single outpatient facility by the senior surgeon(W.G.S.)overa15-yearperiod(1989to2004).Twogroupswerecompared: patients who underwent abdominoplasty without breast surgery and those who had abdominoplasty with breast surgery. The second group was subdivided by the various types of breast procedures noted above. The minor complications assessed included seromas, hematomas, infections, and small (5 cm) wound breakdowns. Major complications evaluated included large (5 cm) flap necrosis, need for blood transfusion, deep vein thrombosis, pulmonary embolus, myocardial infarction,anddeath.Additionaldatacompiledincludedage,sex,tobaccouse,bodymass index, past medical history, American Society of Anesthesiologists physical status level, and operative times. Results: Of the 415 abdominoplasty procedures, 264 (group 1) did not include simultaneous breast surgery. One hundred fifty-one procedures (group 2) involved simultaneous breast surgery, representing 36 percent of the total. Group 2 was further subdivided into those who had breast augmentation surgery (group 2A, n 50), those who had breast reduction surgery (group 2B, n 31), those who had mastopexy surgery (group 2C,n28), and those who had simultaneous mastopexy and breast augmentation surgery (group 2D, n 42). Removal and replacement of implants and capsulectomy/capsulotomy procedures were included in the augmentation group (group 2A). There were no major complications, including flap necrosis (open wound 5 cm), blood transfusions, deep vein thrombosis, pulmonary embolus, myocardial infarction, or death. No patients required hospitalization. No statistically significant associations with complications were noted between groups 1 and 2 (chi-square, 0.0045; p 0.95, not significant). Furthermore, when subdivided by type of breast surgery, no statistically significant associations were noted among subgroups: group 1 versus 2A (chi-square, 0.96; p 0.05, not significant), group 1 versus 2B (chi-square, 0.032; p 0.9, not significant), group 1 versus 2C (chi-square, 0.003; p 0.975, not significant), and group 1 versus 2D (chi-square, 0.83; p 0.5, not significant). Conclusion: The results of this retrospective review indicate that combining electivebreastsurgerywithabdominoplastydoesnotappeartosignificantlyincreasethe number of major or minor complications. (Plast. Reconstr. Surg. 118: 207, 2006.)

Arylamine N-acetyltransferases (NAT; EC 2.3.1.5) catalyse the transfer of acetyl groups from acetylCoA to xenobiotics, including drugs and carcinogens. The enzyme is found extensively in both eukaryotes and prokaryotes, yet the endogenous roles of NATs are still unclear. In order to study the properties of eukaryotic NATs, high-throughput substrate and inhibitor screens have been developed using pure soluble recombinant Syrian hamster NAT2 (shNAT2) protein. The assay can be used with a wide range of compounds and was used to determine substrate specificity of shNAT2. We describe the expression and characterisation of shNAT2 and also purified recombinant human NAT1 and NAT2, including the use of the assay to explore the substrate specificities of each of the enzymes. Hamster NAT2 has similar substrate specificity to human NAT1, acetylating para-aminobenzoate but not arylhydrazine and hydralazine compounds. The overlapping but distinct substrate-specific activity profiles of human NAT1 and NAT2 were clearly observed from the screen. Naturally occurring compounds were tested as substrates or inhibitors of shNAT2 and succinylCoA was found to be a potent inhibitor of shNAT2.

Over a period of 12 years, 24 burns have been treated by a Cambodgian and French team (Doctors of the World). This experience has revealed some characteristics of this population: (1) a majority of young women (2/3), (2) victims of assault (20 cases). These notions are found in the medical literature particularly South East Asia. All cases are of a third degree. Every surgeon, every anesthetist should apply emergency measures which are recalled here. The aims is to close all the burns surface through a skin graft within a month. However the patients are treated 6 months to 2 years after the burn and have, at this stage, terrible sequella (22 patients). Treating them requires the coordinated efforts of a multidisciplinary specialized team. The challenge is to save the eyes, the mouth, the nose and give back a "human" face to these young burns who are often rejected because of their handicap. Enabling them to smile again is a strong commitment from the surgeon and from the patient who has to undergo multiple operations and a long treatment over the years.

Plants containing aloin A, aloe emodin, and structurally related anthraquinones have long been used as traditional medicines and in the formulation of retail products such as laxatives, dietary supplements, and cosmetics. Since a recent study indicated that topically applied aloe emodin increases the sensitivity of skin to UV light, we examined the events following photoexcitation of aloin A and aloe emodin. We determined that incubation of human skin fibroblasts with 20 microM aloe emodin for 18 h followed by irradiation with UV or visible light resulted in significant photocytotoxicity. This photocytotoxicity was accompanied by oxidative damage in both cellular DNA and RNA. In contrast, no photocytotoxicity was observed following incubation with up to 500 microM aloin A and irradiation with UVA light. In an attempt to explain the different photobiological properties of aloin A and aloe emodin, laser flash photolysis experiments were performed. We determined that the triplet state of aloe emodin was readily formed following photoexcitation. However, no transient intermediates were formed following photoexcitation of aloin A. Therefore, generation of reactive oxygen species and oxidative damage after irradiation of aloin A is unlikely. Although aloin A was not directly photocytotoxic, we found that human skin fibroblasts can metabolize aloin A to aloe emodin.

This study determined the incidence, pivotal events, etiology, and levels of amputation in a prospectively followed cohort of 400 people with diabetes and a prior healed foot ulcer who participated in a randomized footwear trial. Participants were seen every 17 weeks for 2 years. Subjects with foot lesions were referred to their healthcare provider for treatment. In this cohort, 11 participants required lower limb amputation (rate 13.8 per 1000 person-years). Pivotal event analysis revealed that only one amputation was related to footwear, six amputations were due to non-footwear-related minor environmental trauma, two were due to progression of vascular disease (dry gangrene from critical ischemia), one was due to a self-care injury while cutting the toenails, and one was due to a decubitus ulcer. Previously proposed strategies to reduce the amputation rates in individuals with diabetes have focused heavily on footwear and education. However, even with this emphasis, amputation rates in the United States are still high. This study suggests that the prevention of minor environmental trauma, including household accidents, merits additional attention. We believe that further efforts to reduce amputation rates for individuals with diabetes will need to emphasize the prevention of minor trauma, especially in those already compromised with neuropathy and vascular disease.

This study presents a least mean squares (LMS) algorithm for the ensemble modeling of a multivariate ARMA process. Generally, an LMS algorithm makes possible the tracking of parameters for nonstationary time series. Our estimation incorporates multiple process observations that improve the accuracy of the parameter estimation. As a consequence, the estimation sequences come close to the true model parameters with a fast adaptation speed. This advantage also holds true of spectral quantities (e.g., the momentary coherence), which are derived from the model parameters. Thus the extension of the ARMA fitting from one to multiple trajectories allows the investigation of nonstationary biological signals with an increased time resolution. The applicability of the algorithm is demonstrated for event-related EEG coherence analysis of the Sternberg task. The changing interaction between posterior association cortex and anterior brain area was shown for verbal and nonverbal stimuli by means of the time-variant theta coherence.

Because of the importance of oscillations as a general phenomenon of neuronal activity the use of EEG spectral analysis is among the most important approaches for studying human information processing. Usually, oscillations at different frequencies occur simultaneously during information processing. Thus, the question for synchronisation of different frequencies by phase coupling and its possible functional significance is of primary importance. An answer may be given by bispectral analysis. Estimation of the (cross-) bispectrum allows to identify synchronised frequencies and possibly, the existence of non-linear phase coupling of different oscillators. Previous studies have demonstrated the simultaneous occurrence of slow (4-7 Hz) and fast (20-30 Hz) oscillations at frontal and prefrontal electrode positions during memory processing. However, interrelations between these rhythms have not been investigated up to now. In order to test short-term memory, the Sternberg task with random figures and number words was carried out on 10 female subjects. During the task EEG was recorded. Power and bispectral analyses from frontal, prefrontal and frontopolar regions were performed off-line. Increased power was found in both the theta and the gamma bands. Strong phase-coupling between theta at Fz and gamma at F3 and at Fp1, respectively, was shown for memorising number words by means of cross-bicoherence. A possible reason for this is an amplitude modulation of gamma frequencies by slow oscillations. The correspondent coherence analysis between the envelope of gamma frequencies at Fp1 and the raw EEG at Fz supports this presumption. This finding is interpreted as an EEG aspect of the functional linking between the prefrontal areas and the G.cinguli (as part of the limbic system), which are both extremely important for memory functions.

Medical schools have long relied on volunteer clinical faculty to assist in teaching medical students.1 Community physician preceptors are often recruited to help teach basic physical examination and history-taking skills to medical students and to provide early exposure to clinical practice for students in their preclinical years. As medical education continues to move from the tertiary care teaching hospital to the ambulatory care setting,2,3 such preceptors will be called on even more to provide educational experiences. However, even as medical schools are becoming more dependent on volunteer clinical faculty, these faculty are experiencing increasing demand for their skills and time.4,5,6,7 Many fear that the current trend in medicine for increased productivity and the growing pressure of nonclinical responsibilities may begin to hinder community physician involvement in medical education. Skeff and colleagues8 theorized that if current pressures for clinical productivity continue, academic institutions will survive financially, but the educational experience may suffer. They described a possible “national tragedy” in which physicians are no longer able to continue the medical tradition of passing on what they have learned. The University of Washington School of Medicine, Seattle, depends heavily on volunteer physician faculty and shares this concern. Although an accurate historical dropout rate is not known, the staff coordinators of the preclinical programs included in this study noted that the dropout rate among our volunteer faculty has been increasing, particularly among physicians in staff-model health maintenance organizations (HMOs). For example, during the past year, 7 (25%) of 26 small-group tutors had dropped out of the first-year Introduction to Clinical Medicine course, and 10 (23%) of 42 physicians had dropped out of the second-year course. In addition, 10 physicians dropped out of the half-day-a-week continuity preceptorship in the winter quarter compared with a usual turnover of 3 to 4 per course per quarter. In this study, we surveyed physicians who volunteer their time to teach first- and second-year medical students. The instrument assessed 3 factors that may affect future clinical faculty involvement in teaching: current motivation and rewards, current or potential barriers, and the effect of increasing clinical and nonclinical demands on the willingness of the clinical faculty to volunteer their time. With the survey, we attempted to go beyond the question of how teaching affects productivity and to explore to what extent the drive for productivity and the increased workload in general is affecting volunteer physician educators. More specifically, is there a trend to decrease volunteer teaching activities? If so, what area of medical practice is most likely to be affected? Documenting this information is essential to enable medical schools to proactively address the problem if it exists, to initiate collaboration with professional societies to identify physicians who are willing to teach, and to find creative ways to reward those who do.

To determine whether televised public service announcements (PSAs) demonstrating the fundamentals of CPR were effective in increasing the rate of layperson bystander-initiated CPR.Two 30-second PSAs were shown 597 times from September 8, 1996, through April 12, 1997. In each, CPR was given to one member of an older couple by the other in the home. The authors measured rates of bystander CPR in communities that were exposed to the PSA and in communities that were not exposed in two time periods, a before-airing period, January 1, 1993, through September 7, 1996, and a during-airing period, September 8, 1996, through April 12, 1997. A case was defined as a patient with a nontraumatic cardiac arrest that occurred before arrival of EMS personnel, and for whom CPR was initiated by EMS personnel or lay bystanders.There were 1,786 cardiac arrests in the "before" period and 289 in the "during" period. The rate of bystander CPR increased from 43% to 55% (p0.05) in the intervention community and remained the same in the comparison community (33%).Airing of the PSA was accompanied by an increase in the rate of bystander CPR, though the increase may be attributable to a secular trend.

Certain strains of Staphylococcus aureus express one or both of two related, but immunologically distinct, exfoliative toxins (ETA and ETB). These toxins induce the symptoms associated with staphylococcal scalded skin syndrome. Both ETs have been shown to stimulate T cell proliferation. Recently, it was reported that ETA is a superantigen that stimulates T cells bearing human Vbeta2 or several murine Vbetas. However, other investigators have proposed that the superantigenicity reported for ETA resulted from contaminants in commercial preparations. This present study addresses those conflicting reports by assessing the biological and immunologic activities of highly purified rETs. ETA and ETB required APCs to induce selective polyclonal expansion of several human Vbetas (huVbetas), although, neither toxin expanded huVbeta2. ETB induced expansion of murine T cells bearing Vbetas 7 and 8, those that have the highest homology to the huVbetas expanded by ETA and ETB. Although flow cytometry of ETB-stimulated T cells matched PCR results, stimulation by ETA reduced percentages of T cells positive for several huVbetas that had been shown to have increased levels of mRNA transcripts. ETA and ETB induced contrasting reactions in vivo. In rabbits, ETB was moderately pyrogenic and enhanced susceptibility to lethal shock, while ETA lacked both activities. Predictions based on comparisons with other superantigens suggest molecular regions potentially involved in receptor binding in the ETA crystal structure and a modeled ETB three-dimensional structure. These results show that ETs are superantigens with unique properties that could account for the discrepancies reported.

A method for the analysis of high-mannose glycoproteins based on capillary electrophoresis and electrospray mass spectrometry (CE−ESI MS) was developed. The combination of UV and MS data allowed for the determination of the identities of glycoform peaks separated by CE, using molecular weight information obtained by ESI MS. The method does not require oligosaccharide release or derivatization, and is applicable for neutral glycans such as high-mannose structures. Two high mannose-containing proteins, ribonuclease B (RNase B) and recombinant human bone morphogenetic protein-2 (rhBMP-2), were used as examples to demonstrate the utility of this technique. Microheterogeneity observed in the CE−UV separation of glycoforms was accounted for by the reconstructed ion chromatograms in ESI MS. Carbohydrate-specific reporter ions generated by in-source fragmentation of the intact proteins during ESI was compared to the chromatographic UV results. This analysis may prove to be a useful qualitative or semiquantitative...

The utility of matrix-assisted laser desorption time-of-flight (MALD-TOF) mass spectrometry for the analysis of recombinant glycopeptides is discussed and compared to information which may be obtained by fast atom bombardment mass spectrometry (FABMS) and tandem mass spectrometry (MS/MS). MALD-TOF appears to be 10-100 times more sensitive than FAB MS for the analysis of underivatized glycopeptides, providing qualitative site-specific information regarding the carbohydrate microheterogeneity without the extensive isolation and derivatization procedures required to obtain similar information by FAB MS. Analysis of a digest mixture in the positive and negative ion mode of MALD-TOF indicated that, in mixtures, sialylated glycopeptides are preferentially detected in the negative ion mode. The determination of the molecular masses of a glycopeptide with MALD-TOF prior to and after treatment with a variety of specific glycosidases, often without removal of the buffers, coupled to a comparison of molecular mass information available from a carbohydrate database facilitates the assignment of a carbohydrate composition. The vast majority of the molecular ion signal observed in the linear mode for sialylated glycopeptides are metastable ions. Reflector mass spectra reveal a shift to lower mass consistent with the loss of most of the neuraminic acid residues. The loss of Hex and HexNAc residues is also observed. Sequential lowering of the reflector potential reveals structurally significant fragment ions representing the carbohydrate and peptide portions of the molecule.

ContextMany people with diabetes experience lower-limb ulcers. Footwear has been implicated as a primary cause of foot ulcers, yet research is limited on the efficacy of shoe and insert combinations to prevent reulceration.ObjectiveTo determine whether extra-depth and -width therapeutic shoes used with 2 types of inserts reduce reulceration in diabetic individuals with a history of foot ulcer.Design, Setting, and ParticipantsRandomized clinical trial of 400 diabetes patients with history of foot ulcer in 2 Washington State health care organizations who did not require custom shoes for foot deformity and were enrolled between August 1997 and December 1998 and followed up for 2 years. Data collected at regular intervals documented physical, foot, and diabetes characteristics; footwear use; foot lesions; and ulcers.InterventionsParticipants were randomly assigned to receive 3 pairs of therapeutic shoes and 3 pairs of customized medium-density cork inserts with a neoprene closed-cell cover (n = 121); to receive 3 pairs of therapeutic shoes and 3 pairs of prefabricated, tapered polyurethane inserts with a brushed nylon cover (n = 119); or to wear their usual footwear (controls; n = 160).Main Outcome MeasureFoot reulceration, compared among the 3 groups.ResultsTwo-year cumulative reulceration incidence across the 3 groups was low: 15% in the cork-insert group, 14% in the prefabricated-insert group, and 17% in controls. In the intent-to-treat analysis, patients assigned to therapeutic shoes did not have a significantly lower risk of reulceration compared with controls (risk ratio [RR] for the cork-insert group, 0.88; 95% confidence interval [CI], 0.51-1.52 and RR the for prefabricated-insert group, 0.85; 95% CI, 0.48-1.48). All ulcer episodes in patients assigned to therapeutic shoes and 88% wearing nonstudy shoes occurred in patients with foot insensitivity.ConclusionsThis study of persons without severe foot deformity does not provide evidence to support widespread dispensing of therapeutic shoes and inserts to diabetic patients with a history of foot ulcer. Study shoes and custom cork or preformed polyurethane inserts conferred no significant ulcer reduction compared with control footwear. This study suggests that careful attention to foot care by health care professionals may be more important than therapeutic footwear but does not negate the possibility that special footwear is beneficial in persons with diabetes who do not receive such close attention to foot care by their health care providers or in individuals with severe foot deformities.

Limited aspects of Blinder's pragmatically derived classification of depressives based on syndrome characteristics were assessed. Blinder's syndrome descriptions were cast into items for an observer-rated interview and into a parallel, patient-rated schedule. Interobserver ratings were statistically reliable (γ′ = .78, p < .001). Patients' self-ratings were positively related to observer ratings (γ′ = .69, p = 01), but observers rated patients as more depressed than patients rated themselves ( t = 2.93, p = .01). Observer ratings only were factor analyzed. The unrotated factors obtained accorded better with previous factor analytic studies than with the syndrome aspect of Blinder's pragmatic classification.