Obesity impedes functional improvement in youth with chronic pain: An initial investigation.

BACKGROUND: Youth with chronic pain are at higher risk for obesity than the general population. In youth with chronic pain, obesity exacerbates pain-specific activity limitations, and in adults with chronic pain, obesity perpetuates a cycle of disability. The current study examined whether weight status predicts functional disability outcomes over time in youth with chronic pain. METHODS: Data were obtained from a retrospective chart review of patients who consented to participate in a longitudinal outcomes study. The Child Activity Limitations Questionnaire was used to assess functional disability at intake, 1-, and 3-month follow-up. Height and weight were measured at intake. A linear mixed model was used to test whether weight status and time predicted functional disability. Trend analysis with polynomial contrasts was used to test whether improvements in functional disability showed a linear trend over time. RESULTS: The linear mixed model analysis showed a main effect of weight, suggesting that youth with higher BMI demonstrated less improvement in functional disability over time. The trend analysis suggested that improvements in functional disability were consistent with a linear trend for both healthy weight and overweight participants, but not for obese participants. CONCLUSION: These findings demonstrate that obesity impedes improvement in functioning for youth with chronic pain. Despite multidisciplinary pain treatment, youth with comorbid chronic pain and obesity demonstrate greater functional disability at follow-up and little improvement over time. These results support the need for interventions specifically tailored to the unique challenges faced by youth with comorbid chronic pain and obesity. SIGNIFICANCE: This study shows that obesity impedes improvement in functioning for youth with chronic pain. On the basis of these findings, interventions should be tailored to the unique challenges of this population.

Psoriasis disease severity measures: comparing efficacy of treatments for severe psoriasis.

Measurement of psoriasis disease severity and effectiveness of treatment involves both objective and subjective assessments.1 Comparing the efficacy of different treatments is complicated by the use of different metrics for measuring outcomes.2 Because these measures are not used routinely in clinical practice, interpreting these data, in particular assessing the degree of clinically meaningful improvement, is difficult. The drug approval process and product labeling reflect historical changes in standards of efficacy measurement.3 This paper reviews the metrics used to evaluate psoriasis treatment and compares available information on approved treatments for severe psoriasis. It further attempts to elucidate the value of these metrics and provide some guidance in properly evaluating the relative efficacy of current proven therapy with new treatments. While clinical trials are somewhat artificial, they provide proof that a drug is more effective than placebo. Efficacy in clinical practice, however, may be very different from the clinical trial setting. Comparison of efficacy under the current circumstances of varying evaluative metrics scales is possible with proper knowledge of the functionality of these methods.

Attrition from after school programs: characteristics of students who drop out.

A goal of many after-school programs is to provide supervision to youths who might potentially engage in delinquent activities during the afternoon hours. By comparing students who remained in a sample of Maryland after-school programs to students who withdrew prior to the end of the school year, this study provides evidence that after-school programs are serving a lower-risk population than intended. Findings indicate that prior to dropping out of the programs, dropouts scored in the more at-risk direction on 11 out of 12 indicators examined in this study and had significantly more peer drug models and days absent from school than students who stayed in the programs. Census data indicate that dropouts came from neighborhoods characterized by higher levels of social disorganization than students who stayed in the programs. Program attendance is also related to several of the risk-factors examined. The results suggest the need for improved communication with parents and further creativity in program planning as a means of retaining high-risk students.

Antibody responses to infections with strains of Plasmodium falciparum expressing diverse forms of merozoite surface protein 2.

Individuals living in areas where Plasmodium falciparum is endemic experience numerous episodes of infection. These episodes may or may not be symptomatic, with the outcome depending on a combination of parasite and host factors, several of which are poorly understood. One factor is believed to be the particular alleles of several parasite proteins to which the host is capable of mounting protective immune responses. We report a study examining antibody responses to MSP2 in 15 semi-immune teenagers and adults living in the Khanh-Hoa area of southern-central Vietnam, where P. falciparum is highly endemic; subjects were serially infected with multiple strains of P. falciparum. The MSP2 alleles infecting these subjects were determined by nucleotide sequencing. A total of 62 MSP2 genes belonging to both dimorphic families were identified, of which 33 contained distinct alleles, with 61% of the alleles being detected once. Clear changes in the repertoire occurred between infections. Most infections contained a mixture of parasites expressing MSP2 alleles from both dimorphic families. Two examples of reinfection with a strain expressing a previously encountered allele were detected. Significant changes in antibody levels to various regions of MSP2 were detected over the course of the experiment. There was no clear relation between the infecting form of MSP2 and the ensuing antibody response. This study highlights the complexity of host-parasite relationship for this important human pathogen.

Gabapentin in phantom limb pain management in children and young adults: report of seven cases.

Seven children and young adults with phantom limb pain (PLP) were treated with gabapentin. PLP resolved in six patients within two months. One patient still had symptoms to a lesser degree. Mean follow up time was 1.74 years. Gabapentin may be a useful adjunct to pain management in patients with PLP symptoms.

Complementary therapies for acute pediatric pain management.

A wide variety of tools to adequately treat pediatric pain is beneficial. The methods discussed herein typically involve the use of many areas of expertise to manage pain. Massage therapists, biofeedback technicians, physician-acupuncturists, child-life specialists, psychologists, and physical or occupational therapists can all be used as allies to battle acute pain in children. The incorporation of alternative forms of pain management, including education, relaxation techniques, hypnosis, guided imagery, biofeedback, and even acupuncture, to the standard methods may improve the management of children with acute pain. The management of children with pain does not have to be with an "either/or" approach using traditional pharmacologic methods or the cognitive and alternative therapies discussed here. Many areas need research to provide evidence that these therapies work well. What is known now suggests that the use of these adjunctive methods of pain management may complement pharmacologic pain management, thereby bringing physicians closer to optimal care of children with acute pain.

Social adaptability, cognitive abilities, and other predictors for children's reactions to surgery.

STUDY OBJECTIVE: To examine the relationship between social adaptability, cognitive abilities, and other personality characteristics to perioperative anxiety. STUDY DESIGN: Prospective cohort investigation. PATIENTS: 60 children ASA physical status I and II, age 3 to 10 years. SETTING: Tertiary care children's hospital. MEASUREMENTS: Temperament (EASI), cognitive abilities (KABC), and adaptive behavior (Vineland) were evaluated in a group of children undergoing surgery. Parental coping style (MBBS) and parental state (STAI-S) and trait (STAI-T) anxiety were assessed as well. On the day of surgery, anxiety of the child was measured at the preoperative holding area and during induction of anesthesia (m-YPAS). MAIN RESULTS: Univariate correlational analysis demonstrated that young age (r = -0.27), poor social adaptability (Vineland) (r = -0.38), shy and inhibited personality (EASI; temperament) (r = -0.33), higher intelligence (KABC) (r = 0.29), increased parental anxiety (r = 0.44), and parental high-monitoring coping style (r = -0.25) are all associated with higher levels of perioperative anxiety. Stepwise multivariate regression analysis has demonstrated that controlling for the variables above, parental anxiety (p = 0.004), child's social adaptive capabilities (p = 0.04), and child's temperament (sociability) (p = 0.04) are independent predictors for increased perioperative anxiety (R(2) = 0.38, F = 5.5, p = 0.003). CONCLUSIONS: Anesthesiologists need to pay close attention to the families of pediatric surgical children who are socially maladjusted, shy and inhibited, and have anxious parents.

Consequences of inadequate analgesia during painful procedures in children.

OBJECTIVE: To explore the effect of inadequate analgesia for painful procedures (bone marrow aspiration, lumbar puncture, or both) on the pain of subsequent procedures. DESIGN: A cohort of patients with cancer who had participated in a placebo-controlled, randomized study that documented the efficacy of oral transmucosal fentanyl citrate for painful procedures rated the pain associated with subsequent procedures performed with open-label oral transmucosal fentanyl. PARTICIPANTS: Twenty-one children undergoing diagnostic procedures who had been participants in previous study. INTERVENTION: All children were given oral transmucosal fentanyl, 15 to 20 microgram/kg, prior to the procedure; at its conclusion they were asked to rate the associated pain. RESULTS: In children younger than 8 years (n = 13), mean pain ratings during each subsequent procedure were consistently higher for those who had received placebo (n = 8) in the original study compared with those who had received the active drug (n = 5). A repeated-measures analysis of variance suggests that this difference is statistically significant (P = .04). Older children (n = 8) did not show this pattern. CONCLUSION: Inadequate analgesia for initial procedures in young children may diminish the effect of adequate analgesia in subsequent procedures.

Dual diagnosis subtypes in urban substance abuse and mental health clinics.

OBJECTIVES: This study sought to determine rates of dual disorders (psychiatric and substance use disorders) in a population of low-income inner-city outpatients, to compare the rates in outpatient mental health and substance abuse treatment settings, and to examine the clinical usefulness of classifying patients with dual disorders into three subtypes. METHODS: A total of 57 low-income urban residents receiving mental health treatment and 73 receiving substance abuse treatment were given semistructured clinical interviews to ascertain lifetime and concurrent DSM-III-R axis I disorders. Patients with dual disorders were classified into subtypes depending on whether their psychiatric or substance use disorder was caused by the comorbid disorder or whether both disorders existed independently. RESULTS: Eighty-three patients had a lifetime history of dual disorders: 34 patients (60 percent) in the mental health settings and 49 (67 percent) in substance abuse treatment. Among the 83 with dual disorders, more than half had experienced symptoms of both disorders within the past year. Each of the disorders was considered primary (that is, no indication was found that one was caused by the other) for 24 patients in the mental health settings (71 percent) and 31 in the substance abuse treatment settings (63 percent). CONCLUSIONS: In each type of treatment setting, nearly two-thirds of the patients met criteria for a lifetime diagnosis of a dual disorder. This high rate of comorbidity did not appear to be attributable to substance use causing psychiatric symptoms, or vice versa. The high rate suggests the need for greater integration of mental health and substance abuse treatment, regardless of setting.

Premedication in the United States: a status report.

We undertook a mailing survey study to assess the current practice of sedative premedication in anesthesia. A total of 5396 questionnaires were mailed to randomly selected physician members of the American Society of Anesthesiologists. Forty-six percent (n = 2421) of those sampled returned the questionnaire after two mailings. The reported rate of sedative premedication in the United States varied widely among age groups and geographical locations. Premedicant sedative drugs were least often used with children younger than age 3 years and most often used with adults less than 65 years of age (25% vs 75%, P = 0.001). Midazolam was the most frequently used premedicant both in adults and children (> 75%). When analyzed based on geographical locations, use of sedative premedicants among adults was least frequent in the Northeast region and most frequent in the Southeast region (50% vs 90%, P = 0.001). When the frequency of premedication was examined against health maintenance organization (HMO) penetration (i.e., HMO enrollment by total population) in the various geographical regions, correlation coefficients (r) ranged from -0.96 to -0.54. Multivariable analysis revealed that HMO penetration is an independent predictor for the use of premedication in adults and children. The marked variation among geographical areas in premedicant usage patterns underscores the lack of consensus among anesthesiologists about the need for premedication. The data suggest that HMO participation may affect delivery of this component of anesthetic care.

The use of oral transmucosal fentanyl citrate for painful procedures in children.

OBJECTIVE: To investigate the efficacy and safety of oral transmucosal fentanyl (OTFC) in providing analgesia and sedation for painful diagnostic procedures in children. DESIGN: Randomized, placebo-controlled clinical trial. METHOD: Forty-eight children referred to the University Connecticut Division of Pediatric Hematology/Oncology for bone marrow aspiration or lumbar puncture were randomized to receive either OTFC (15 to 20 micrograms/kg) or a placebo lollipop. Thirty minutes after administration, the procedure was begun. An anesthesiologist monitored the child's heart rate, blood pressure, and oxygen saturation every 10 minutes. At the conclusion of the procedure, the nurse, the child's parent, and all children over 8 years of age were asked to rate the pain associated with the procedure using a 1 to 10 visual analogue scale. Young children (less than 8) used a modified scale, the Oucher, yielding a 0 to 5 score. RESULTS: Significant differences in pain ratings between the OTFC and placebo groups were noted on the pain scores of the parents (P = .005), nurses (P = .001), younger children (P = .006), and older children (P = .013), and median pain scores in the OTFC group were reduced to tolerable levels. Vomiting (P = .003) and itching (P = .001) were more common in the OTFC group, but no clinically significant vital sign deviations occurred. CONCLUSION: OTFC is safe and effective for use in relieving the pain of pediatric procedures, but frequency of vomiting may restrict its clinical usefulness.

The glycoprotein Ib-IX complex-specific monoclonal antibody SZ1 binds to a conformation-sensitive epitope on glycoprotein IX: implications for the target antigen of quinine/quinidine-dependent autoantibodies.

The monoclonal antibody SZ1 is of interest for two reasons: it was used to define complex formation between glycoprotein (GP) Ib and GP IX, and its epitope is likely to be identical to that recognized by most quinine- and quinidine-dependent autoantibodies that cause thrombocytopenia. To determine the location of the epitope for SZ1 within the GP Ib-IX complex (which consists of three subunits: GP Ib alpha, GP Ib beta, and GP IX), we tested the ability of the antibody to bind transfected cells that expressed different combinations of complex subunits, and compared this binding to the binding of antibodies of known specificity. SZ1 bound to cells that expressed the entire GP Ib-IX complex in the same pattern as did AN51 (an antibody specific for GP Ib alpha). However, unlike AN51, SZ1 did not bind alpha beta cells (ie, cells that express GP Ib alpha and GP Ib beta, but not GP IX), but did bind to beta IX and alpha IX cells. We then compared the binding patterns of SZ1 and FMC25, an antibody specific for GP IX. Both bound virtually identically to cell lines that expressed every combination of two of the three GP Ib-IX complex subunits. However, the epitopes of the two antibodies were not identical, because fixation with 4% paraformaldehyde of cells that expressed GP IX destroyed the SZ1 epitope while maintaining the FMC25 epitope. Because of the ability of SZ1 to block the binding of many quinine- and quinidine-dependent antibodies, these data strongly suggest that GP IX is the component of the GP Ib-IX complex recognized by those antibodies.

Glycoprotein (GP) Ib beta is the critical subunit linking GP Ib alpha and GP IX in the GP Ib-IX complex. Analysis of partial complexes.

The glycoprotein (GP) Ib-IX complex is the receptor on platelet surfaces that mediates their adhesion to subendothelium. It comprises three polypeptides (GP Ib alpha, GP Ib beta, GP IX), each of which belongs to a superfamily of proteins containing conserved leucine-rich motifs. In this study, we used Chinese hamster ovary (CHO) cells expressing every combination of two GP Ib-IX complex subunits to demonstrate that GP Ib beta plays an essential role in the synthesis of the heterotrimer by associating with both of the other two subunits. Confocal microscopy demonstrated that GP Ib beta was present in the same cellular locations as GP Ib alpha in CHO alpha beta cells (cells expressing only GP Ib alpha and GP Ib beta) and as GP IX in CHO beta IX cells. The two polypeptides expressed in CHO alpha IX cells did not co-localize. Association between GP Ib alpha and GP Ib beta was demonstrated biochemically on immunoblots of detergent lysates of CHO alpha beta cells; electrophoresis under nonreducing conditions revealed the two subunits to be covalently linked through a disulfide bond. Association of GP Ib alpha and GP Ib beta was further demonstrated by the finding that immunoprecipitations with antibodies against either polypeptide precipitated both. Similarly, immunoprecipitations of lysates of CHO beta IX cells with antibodies against GP Ib beta or GP IX precipitated both polypeptides. In contrast, co-immunoprecipitation of the two polypeptides expressed in CHO alpha IX cells could not be demonstrated. Transient expression in CHO cells of GP Ib beta with GP IX yielded higher GP IX levels on the cell membrane than did expression of GP IX alone; supertransfection of CHO alpha IX cells with GP Ib beta also increased GP IX levels on the cell surface.

Association of GP Ib with actin-binding protein does not require GP IX.

GP IX is necessary for optimal expression of the GP Ib-IX complex on the surface of transfected cells, and presumably also on the surface of the platelet. The authors investigated whether increasing complex association with the cytoskeleton is one mechanism by which GP IX exerts its effect. CHO and L cell lines that express high levels of GP Ib were used to determine whether GP Ib (GPIb alpha and GPIb beta) associated with the cytoskeleton. GP Ib in these cells was found in the insoluble cytoskeletal fraction from Triton X-100 lysates in a proportion similar to that found in cells expressing the full complex. As in platelets and cells expressing the full complex, the association of GP Ib with the cytoskeleton was shown to be mediated by actin-binding protein (ABP). This was demonstrated by the observation that a monoclonal antibody against GPIb alpha precipitated ABP from GP Ib-expressing cells, and polyclonal anti-ABP antibodies specifically coprecipitated GP Ib. In addition, colocalization of the two components in intact cells was demonstrated by confocal microscopy. These data indicate that the association of GP Ib with the cytoskeleton is independent of GP IX, which therefore must increase surface expression of the complex by another mechanism.

Effects of tebufelone (NE-11740), a new anti-inflammatory drug, on arachidonic acid metabolism.

Tebufelone is a novel nonsteroidal anti-inflammatory drug (NSAID), of the di-tert-butylphenol (DTBP) class, which displays potent anti-inflammatory, analgesic and anti-pyretic properties in a variety of animal models. In this report, the effects of Tebufelone on arachidonic acid (AA) metabolism are reviewed. Tebufelone potently inhibits the formation of prostaglandins (PGE2) a key mediator of pain and inflammation, in isolated enzyme preparations (IC50 = 1.5 microM, KI = 0.35 microM), two in vitro cellular systems: rat peritoneal macrophages (IC50 = 0.02 microM) and human whole blood (IC50 = 0.08 microM), and ex vivo in man. In addition to PGE2 inhibition, which is common to all NSAIDs, higher concentrations of Tebufelone block the in vitro formation of products of the lipoxygenase pathway [leukotrienes (LTB4)] in rat macrophages (IC50 = 20 microM) and human whole blood (IC50 = 22 microM). Substrate incorporation studies (14C-AA) indicate that Tebufelone reversibly inhibits cyclooxygenase (CO) and 5-lipoxygenase (5-LO) enzymes rather than regulating the release of AA. Tebufelone was shown to be a more potent CO inhibitor than indomethacin and a less potent 5-LO inhibitor than RG-5901. Comparisons to structurally related compounds under development (E-5110, Esai; KME-4, Kanagafuchi), found Tebufelone to be the most potent CO inhibitor in vitro. All three DTBP compounds were equipotent 5-LO inhibitors. It is likely that Tebufelone's inhibitory effects on AA metabolism are, in part, responsible for its in vivo efficacy and enhanced safety profile.

Technetium 99m-MDP scintigraphy of patients undergoing implant prosthetic procedures: a follow-up study.

The clinical evaluation of peri-implant tissue is mainly based on x-rays. In recent years, radioisotope scintigraphy using Tc-99m-MDP (technetium-99m-methylene diphosphonate) proved to be a useful and reliable clinical method for measuring increased metabolic activity at specific sites of the skeletal tissue. Twenty-six (26) patients (26 to 75 years) who were diagnosed for implant prosthetic treatment modality were randomly chosen to participate in this study. Each patient was injected with 20 mCi of Tc-99m-MDP was scanned 2 hours later by gamma-camera for isotope uptake levels in the jaws. Each patient was scanned 1 to 4 times, starting 2 weeks after implant surgery and up to the 40th week postsurgery. Blade and screw type implants using the non-submerged, one-stage technique were placed. Therefore, the prosthetic reconstruction was initiated 2 weeks after implant surgery. In order to compare the different scans we formulated a relative "bone scan index" (BSI). The results of 62 scans were plotted as BSI against time after implant surgery. A mathematical regression analysis of the BSI was also performed. At the initial stage of 2 to 3 weeks after surgery the BSI is high and then gradually declines. While BSI of the implants in the mandible reaches baseline levels after 12 weeks, the BSI in the maxilla reaches baseline only after 20 weeks. On the other hand, there was no difference in BSI with regard to blade or screw type implant. Here we were able to demonstrate that the process is independent of implant modality and depends on the specific metabolic properties of the jaw.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopharmaceutical characterisation of a low-dose (75 mg) controlled-release aspirin formulation.

The release of aspirin from a 75 mg controlled-release formulation, designed to inhibit maximally thromboxane A2 production while sparing stimulated prostacyclin biosynthesis, was characterised in healthy subjects. The calculated in vivo release rate of aspirin matched the design goal of approximately 10 mg h(-1). The C(max) of aspirin associated with the controlled-release formulation was lowered 15-fold relative to a solution formulation of the same dose. The bioavailability of aspirin (based on salicylate concentrations) from the controlled-release formulation was approximately 90% relative to the solution, and drug release was not affected by co-administration of a standard breakfast.

Treatment of acne vulgaris with salicylic acid pads.

Most cases of acne vulgaris are either mild or moderate in severity and well-suited for treatment with nonprescription agents that are safe, effective, and convenient to use. A review of four clinical studies and a comedolytic assay attests to the efficacy and safety of 0.5% and 2% solutions of salicylic acid for the treatment of acne vulgaris. In three placebo-controlled studies and a comedolytic assay, salicylic acid pads reduced the number of primary lesions and thereby the number and severity of all lesions associated with acne. Comparative studies of salicylic acid have shown it to be superior to benzoyl peroxide in reducing the total number of acne lesions. Adverse reactions to salicylic acid are generally limited to mild, local irritation occurring in a minority of patients.