Search

During the COVID‐19 pandemic, one of the major changes that has occurred in emergency medicine is the evolution of telemedicine. With relaxation of regulatory and administrative barriers, the use of this already available technology has rapidly expanded. Telemedicine provides opportunity to markedly decrease personal protective equipment (PPE) and reduce healthcare worker exposures. Moreover, with the convenience and availability of access to medical care via telemedicine, a more fundamental change in healthcare delivery in the United States is likely. The implementation of telemedicine in the emergency department (ED) in particular has great potential to prevent the iatrogenic spread of COVID‐19 and protect health care workers. Challenges to widespread adoption of telemedicine include privacy concerns, limitation of physical examination, and concerns of patient experience. In this clinical review, we discuss ED telemedicine applications, logistics, and challenges in the COVID‐19 era as well as recent regulatory and legal changes. In addition, examples of telemedicine use are described from 2 institutions. Examples of future applications of telemedicine within the realm of emergency medicine are also discussed.

Background Comprehensive vision screening programmes for children are an important part of public health strategy, but do not exist in many countries, including Tonga. This project set out to assess: (1) the functional vision of children attending primary schools in Tonga and (2) how a new recognition acuity test (The Auckland Optotypes displayed on a tablet computer) compares to use of a standardised eye chart in this setting. Methods Children from three Tongan primary schools were invited to participate. Acuity testing was conducted using a standardised recognition acuity chart (Lea symbols) and the tablet test displaying two formats of The Auckland Optotypes. Measures of ocular alignment, stereo acuity and non-cycloplegic photorefraction were also taken. Results Parents of 249 children consented to participate. One child was untestable. Only 2.8 per cent of testable children achieved visual acuity worse than 0.3 logMAR in the weaker eye. Results from the Spot Photoscreener suggested that no children had myopia or hyperopia, but that some children had astigmatism. The tablet test was practical in a community setting, and showed ±0.2 logMAR limits of agreement with the Lea symbols chart. Conclusion The sample of children in Tongan primary schools had good functional vision. A modified version of the tablet acuity test is a promising option for vision screening in this context.

BACKGROUND: Screening for dementia in relevant healthcare settings may help in identifying low cognitive functioning for comprehensive cognitive assessments and subsequent dementia treatment after diagnosis. AIMS: This study sought to estimate the prevalence of no reported dementia-related diagnosis in a nationally-representative sample of older Americans with a cognitive impairment consistent with dementia (CICD) by healthcare utilization. METHODS: The unweighted analytical sample included 1514 Americans aged ≥ 65 years that were identified as having a CICD without history of stroke, cancers, neurological conditions, or brain damage who participated in at least one-wave of the 2010–2016 waves of the Health and Retirement Study. An adapted Telephone Interview of Cognitive Status assessed cognitive functioning. Those with scores ≤ 6 had a CICD. Dementia-related diagnosis was self-reported. Respondents indicated if they visited a physician, received home healthcare, or experienced an overnight nursing home stay in the previous two years. RESULTS: The prevalence of no reported dementia-related diagnosis in persons with a CICD who visited a physician was 89.9% (95% confidence interval (CI): 85.4%−93.1%). Likewise, the prevalence of no reported diagnosis in those with a CICD who received home healthcare was 84.3% (CI: 75.1–90.5%). For persons with a CICD that had an overnight nursing home stay, the prevalence of no reported dementia-related diagnosis was 83.0% (CI: 69.1–91.4%). DISCUSSION: Although the prevalence of no reported dementia-related diagnosis in individuals with a CICD differed across healthcare settings, the prevalence was generally high nonetheless. CONCLUSIONS: We recommend increased awareness and efforts be given to dementia screenings in various clinical settings.

Preeclampsia is a prevalent pregnancy complication characterized by new-onset maternal hypertension and inflammation, with placental ischemia as the initiating event. Studies of others have provided evidence for the importance of lymphocytes in placental ischemia-induced hypertension; however, the contributions of B1 versus B2 lymphocytes are unknown. We hypothesized that peritoneal B1 lymphocytes are important for placental ischemia-induced hypertension. As an initial test of this hypothesis, the effect of anti-CD20 depletion on both B-cell populations was determined in a reduced utero-placental perfusion pressure (RUPP) model of preeclampsia. Anti-murine CD20 monoclonal antibody (5 mg/kg, Clone 5D2) or corresponding mu IgG2a isotype control was administered intraperitoneally to timed pregnant Sprague-Dawley rats on gestation day (GD)10 and 13. RUPP or sham control surgeries were performed on GD14, and mean arterial pressure (MAP) was measured on GD19 from a carotid catheter. As anticipated, RUPP surgery increased MAP and heart rate and decreased mean fetal and placental weight. However, anti-CD20 treatment did not affect these responses. On GD19, B-cell populations were enumerated in the blood, peritoneal cavity, spleen, and placenta with flow cytometry. B1 and B2 cells were not significantly increased following RUPP. Anti-CD20 depleted B1 and B2 cells in peritoneum and circulation but depleted only B2 lymphocytes in spleen and placenta, with no effect on circulating or peritoneal IgM. Overall, these data do not exclude a role for antibodies produced by B cells before depletion but indicate the presence of B lymphocytes in the last trimester of pregnancy is not critical for placental ischemia-induced hypertension.NEW & NOTEWORTHY The adaptive and innate immune systems are implicated in hypertension, including the pregnancy-specific hypertensive condition preeclampsia. However, the mechanism of immune system dysfunction leading to pregnancy-induced hypertension is unresolved. In contrast to previous reports, this study reveals that the presence of classic B2 lymphocytes and peritoneal and circulating B1 lymphocytes is not required for development of hypertension following third trimester placental ischemia in a rat model of pregnancy-induced hypertension.

We investigated motivational regulation involving adjustment of recovery goals in post-stroke rehabilitation via standard in-clinic physiotherapy and in-home telerehabilitation (TR). We used a secondary dataset collected at 11 US sites as part of a clinical trial using video games and game control pads designed to induce certain arm movements required for recovery (n = 124; Mage = 61.44, SD = 13.30). Participants were randomly assigned to either the TR or in-clinic condition and underwent 36 therapy sessions, reporting on their activity-inherent enjoyment for 6-8 weeks. Compared with the in-clinic patients and TR patients with high game performance, TR patients with lower game performance reported lower activity-inherent enjoyment, which is an important motivational resource for successful recovery. The results suggest that these differences occur because TR patients become discouraged by low game score feedback, which may have signaled a poor prospect for recovery. However, the results also suggest that low game performers who successfully adjusted their recovery goals were resilient to the impact of low game score feedback on their motivational resources and satisfaction with therapy. The findings suggest that goal adjustment may be particularly beneficial when patients are discouraged by feedback indicating suboptimal recovery prospects.

IntroductionThe shape of the glucose curve during an oral glucose tolerance test (OGTT) reflects β-cell function in populations without diabetes but has not been as well studied in those with diabetes. A monophasic shape has been associated with higher risk of diabetes, while a biphasic pattern has been associated with lower risk. We sought to determine if phenotypic or metabolic characteristics were associated with glucose response curve shape in adults with type 2 diabetes treated with metformin alone.Research design and methodsThis is a cross-sectional analysis of 3108 metformin-treated adults with type 2 diabetes diagnosed ResultsThe monophasic profile was the most common (67.8% monophasic, 5.5% biphasic, 26.7% continuous rise). The monophasic subgroup was younger, more likely male and white, and had higher body mass index (BMI), while the continuous rise subgroup was more likely female and African American/black. HOMA2-S and fasting glucose did not differ among the subgroups. The biphasic subgroup had the highest early, late, and total insulin and C peptide responses (all pConclusionsBased on the large multiethnic GRADE cohort, sex, race, age, and BMI were found to be important determinants of the shape of the glucose response curve. A pattern of a continuously rising glucose at 2 hours reflected reduced β-cell function and may portend increased glycemic failure rates.Trial registration numberNCT01794143.

While the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood. The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, we show that BRN2 haplo-insufficiency is sufficient to promote melanoma initiation and metastasis, acting as a non-canonical tumor suppressor. Mechanistically, BRN2 directly modulates PTEN expression, and PI3K signaling, to drive tumor initiation and progression. Collectively our results reveal that somatic deletion of one BRN2 allele elicits melanoma initiation and progression.SIGNIFICANCEHere, we report frequent mono-allelic loss of the transcription factor BRN2 in human cutaneous melanoma metastases. We developed a mouse model for Brn2-deficient melanoma based on the most common alterations (BrafV600E and Pten loss) in human melanoma and established the role of Brn2 as a functional regulator of tumor initiation, tumor growth, and the formation of metastases in vivo. Mechanistically, BRN2 loss increases PI3K-signaling through PTEN repression, either via MITF induction or not. Overall, we describe a novel tumor suppressor of high prevalence in human melanoma that regulates several steps of in vivo melanomagenesis through two previously unknown molecular mechanisms.

In patients with anisometropic or strabismic amblyopia, interocular suppression can be minimized by presenting high contrast stimulus elements to the amblyopic eye and lower contrast elements to the fellow eye. This suggests a structurally intact binocular visual system that is functionally suppressed. We investigated whether suppression can also be overcome by contrast balancing in children with deprivation amblyopia due to childhood cataracts. To quantify interocular contrast balance, contrast interference thresholds were measured using an established dichoptic global motion technique for 21 children with deprivation amblyopia, 14 with anisometropic or mixed strabismic/anisometropic amblyopia and 10 visually normal children (mean age mean=9.9years, range 5-16years). We found that interocular suppression could be overcome by contrast balancing in most children with deprivation amblyopia, at least intermittently, and all children with anisometropic or mixed anisometropic/strabismic amblyopia. However, children with deprivation amblyopia due to early unilateral or bilateral cataracts could tolerate only very low contrast levels to the stronger eye indicating strong suppression. Our results suggest that treatment options reliant on contrast balanced dichoptic presentation could be attempted in a subset of children with deprivation amblyopia.

e14024 Background: Despite recommendations from premier institutions such as NCCN that all cancer patients should be entered on clinical trials, only 3 – 5 % of adult cancer patients are enrolled on clinical trials in North America. The reason for this is multi-factorial and includes poor trial design, inappropriate endpoints, inappropriate inclusion/exclusion factors, attitudes about trial participation held by patient and/or treating physician and lack of trial availability. Methods: To address issues of trial availability, in March 2019, we initiated a novel service to help Canadian patients find clinical trial options. The service compares patient demographic and health status information provided against potential opportunities sourced using clinicaltrials.gov and Canadian clinical trials websites. A report presenting outcomes of CTN review is developed for the requesting patient or physician. An interview is provided for the self-referring patient by supporting physicians. Results: To date 96 patients have used this service. Most (94%) were stage IV or refractory/ relapsed. Smaller disease sites represented 23% of our patient population (brain, sarcoma, pancreas). Our turn-around-time from request of services to delivery of report to patient or physician improved over time and is currently 24 hours during the working week. Of those eligible, 25% of patients died before referral, the median time from referral to the CTN to the patient’s death was 109 days (3 – 188 days). Conclusions: Significant interest from both physicians and patients for this service was identified. Strategies are being developed to encourage earlier referrals to clinical trials would improve number of patients entering clinical trials as 25% of our patients. [Table: see text]

Background Children with deprivation amblyopia due to childhood cataract have been excluded from much of the emerging research into amblyopia treatment. An investigation was conducted to determine whether contrast-balanced binocular treatment - a strategy currently being explored for children with anisometropic and strabismic amblyopia - may be effective in children with deprivation amblyopia. Methods An unmasked, case-series design intended to assess proof of principle was employed. Eighteen children with deprivation amblyopia due to childhood cataracts (early bilateral n = 7, early unilateral n = 7, developmental n = 4), as well as 10 children with anisometropic (n = 8) or mixed anisometropic and strabismic amblyopia (n = 2) were prescribed one hour a day of treatment over a six-week period. Supervised treatment was available. Visual acuity, contrast sensitivity, global motion perception and interocular suppression were measured pre- and post-treatment. Results Visual acuity improvements occurred in the anisometropic/strabismic group (0.15 ± 0.05 logMAR, p = 0.014), but contrast sensitivity did not change. As a group, children with deprivation amblyopia had a smaller but statistically significant improvement in weaker eye visual acuity (0.09 ± 0.03 logMAR, p = 0.004), as well a significant improvement in weaker eye contrast sensitivity (p = 0.004). Subgroup analysis suggested that the children with early bilateral deprivation had the largest improvements, while children with early unilateral cataract did not improve. Interestingly, binocular contrast sensitivity also improved in children with early bilateral deprivation. Global motion perception improved for both subgroups with early visual deprivation, as well as children with anisometropic or mixed anisometropic/strabismic amblyopia. Interocular suppression improved for all subgroups except children with early unilateral deprivation. Conclusion These data suggest that supervised contrast-balanced binocular treatment should be further investigated as a treatment option for children with deprivation amblyopia. However, for children with more severe deprivation amblyopia due to early unilateral cataracts, supplementary or alternative options should also be explored.

PurposeTo understand how we might improve the provision of medical care for children with cataracts.DesignA phenomenological design was employed. Semi-structured interviews were conducted to capture rich descriptions of the phenomena. Our goal in the interview and the analysis was to understand the sources of distress associated with treatment for cataract and deprivation amblyopia which (1) could be addressed by the medical community and (2) related to treatment adherence.SettingInterviews were conducted by a non-clinician researcher in New Zealand (NZ) in a location chosen by informants. In NZ, the red reflex screening test is performed shortly after birth, and surgery to remove paediatric cataracts is publicly funded.ParticipantsFamilies of children who had a history of cataract in Auckland, NZ were posted an invitation to participate. Twenty families were interviewed.ResultsOur analysis illustrated that informants described a wide range of experiences, from declined cataract surgery to full adherence to medical advice including years of patching for more than 4 hours a day. Across these experiences, we identified three relevant themes; timing of diagnosis, communication between the parent and clinician, and parental social support networks.ConclusionThe medical community may be better placed to support families dealing with childhood cataract by improving detection of childhood cataract, building appropriate communication pathways and promoting social support, with an emphasis on empathetic, individualised care.

Introduction Chronic lower back pain (CLBP) is a major healthcare problem with wide ranging effects. It is a priority for appropriate management of CLBP to get individuals back to work as early as possible. Interventions that identify biopsychosocial barriers to recovery have been observed to lead to successfully reduced pain-related work absences and increased return to work for individuals with CLBP. Modern conceptualisations of pain adopt a biopsychosocial approach, such as the flags approach. Biopsychosocial perspectives have been applied to judgements about future adjustment, recovery from pain and risk of long-term disability; and provide a helpful model for understanding the importance of contextual interactions between psychosocial and biological variables in the experience of pain. Medical students and general practitioner (GP) trainees are important groups to target with education about biopsychosocial conceptualisations of pain and related clinical implications. Aim The current study will compare the effects of an e-learning intervention that focuses on a biopsychosocial model of pain, on the clinical judgements of medical students and trainees. Methods and analysis Medical student and GP trainee participants will be randomised to 1 of 2 study conditions: (1) a 20 min e-learning intervention focused on the fundamentals of the flags approach to clinical judgement-making regarding risk of future pain-related disability; compared with a (2) wait-list control group on judgement accuracy and weighting (ie, primary outcomes); flags approach knowledge, attitudes and beliefs towards pain, judgement speed and empathy (ie, secondary outcomes). Participants will be assessed at preintervention and postintervention. Ethics and dissemination The study will be performed in agreement with the Declaration of Helsinki and is approved by the National University of Ireland Galway Research Ethics Committee. The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals. Trial registration number ISRCTN53670726; Pre-results.

The hyperexcitability of alpha-motoneurons and accompanying spasticity following spinal cord injury (SCI) have been attributed to enhanced persistent inward currents (PICs), including L-type calcium and persistent sodium currents. Factors controlling PICs may offer new therapies for managing spasticity. Such factors include calcium-activated potassium (KCa) currents, comprising in motoneurons an after-hyperpolarization-producing current (I KCaN) activated by N/P-type calcium currents, and a second current (I KCaL) activated by L-type calcium currents (Li and Bennett in J neurophysiol 97:767-783, 2007). We hypothesize that these two currents offer differential control of PICs and motoneuron excitability based on their probable somatic and dendritic locations, respectively. We reproduced SCI-induced PIC enhancement in a two-compartment motoneuron model that resulted in persistent dendritic plateau potentials. Removing dendritic I KCaL eliminated primary frequency range discharge and produced an abrupt transition into tertiary range firing without significant changes in the overall frequency gain. However, I KCaN removal mainly increased the gain. Steady-state analyses of dendritic membrane potential showed that I KCaL limits plateau potential magnitude and strongly modulates the somatic injected current thresholds for plateau onset and offset. In contrast, I KCaN had no effect on the plateau magnitude and thresholds. These results suggest that impaired function of I KCaL may be an important intrinsic mechanism underlying PIC-induced motoneuron hyperexcitability following SCI.

Background: Breast cancer is an important public health issue within the American Indian (AI) community in Oklahoma; however, there is limited information to explain the low screening mammography rates among AI women. Purpose: To identify the motivational factors affecting an AI woman's decision to obtain a mammogram. Methods: Through the use of the Theory of Planned Behavior, 24 elicitation interviews were conducted with eligible for mammography AI women obtaining services at an Oklahoma-based tribal clinic. Results: Most women had mixed attitudes toward screening mammography. Environmental-related factors also were cited as barriers in getting a screening mammogram and women recommended improved accessibility to mammography screening. Participants identified family members, friends and their personal physician as critical social referents. No specific culturally related beliefs or taboos were noted. Discussion: This study provides new theoretically guided insights into the motivation of AI wome...

Spasticity is commonly observed after chronic spinal cord injury (SCI) and many other central nervous system disorders (e.g., multiple sclerosis, stroke). SCI-induced spasticity has been associated with motoneuron hyperexcitability partly due to enhanced activation of intrinsic persistent inward currents (PICs). Disrupted spinal inhibitory mechanisms also have been implicated. Altered inhibition can result from complex changes in the strength, kinetics, and reversal potential ( ECl−) of γ-aminobutyric acid A (GABAA) and glycine receptor currents. Development of optimal therapeutic strategies requires an understanding of the impact of these interacting factors on motoneuron excitability. We employed computational methods to study the effects of conductance, kinetics, and ECl− of a dendritic inhibition on PIC activation and motoneuron discharge. A two-compartment motoneuron with enhanced PICs characteristic of SCI and receiving recurrent inhibition from Renshaw cells was utilized in these simulations. This dendritic inhibition regulated PIC onset and offset and exerted its strongest effects at motoneuron recruitment and in the secondary range of the current-frequency relationship during PIC activation. Increasing inhibitory conductance compensated for moderate depolarizing shifts in ECl− by limiting PIC activation and self-sustained firing. Furthermore, GABAA currents exerted greater control on PIC activation than glycinergic currents, an effect attributable to their slower kinetics. These results suggest that modulation of the strength and kinetics of GABAA currents could provide treatment strategies for uncontrollable spasms.

Background: NOD2 single nucleotide polymorphisms have been associated with increased risk of ileal Crohn's disease (CD). This exploratory study was conducted to compare ileal mucosal gene expression in CD patients with and without NOD2 risk alleles. Methods: Ileal samples were prospectively collected from 18 nonsmoking CD patients not treated with anti-TNF-α biologics and 9 nonsmoking control patients without inflammatory bowel disease undergoing initial resection and genotyped for the 3 major NOD2 risk alleles (Arg702Trp, Gly908Arg, Leu1007fs). Microarray analysis was performed in samples from 4 NOD2R (at least 1 risk allele) CD patients, 4 NOD2NR (no risk alleles) CD patients, and 4 NOD2NR controls. Candidate genes selected by significance analysis of microarrays (SAM) were confirmed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays of all the samples. Results: SAM detected upregulation of 18 genes in affected ileum in NOD2R compared to NOD2NR CD patients, including genes related to lymphocyte activation. SAM also detected altered ileal gene expression in unaffected NOD2NR ileal mucosal CD samples compared to NOD2NR control samples. qRT-PCR conducted on all the samples confirmed that increased CD3D expression in affected samples was associated with NOD2R status, and that increased MUC1, DUOX2, DMBT1 and decreased C4orf7 expression in unaffected samples was associated with CD, independent of NOD2 status. Conclusions: The results support the concept that NOD2 risk alleles contribute to impaired regulation of inflammation in the ileum. Furthermore, altered ileal gene expression, independent of NOD2 status, is detected in the unaffected proximal margin of resected ileum from CD patients. (Inflamm Bowel Dis 2010)

The aspartate-rich macromolecules found at nucleation sites of calcifying organisms are widely implicated in regulating biomineral formation. Anecdotal evidence suggests that their ability to influence the onset of nucleation and composition of calcified structures may arise from effects on ion hydration. This study investigates the interactions of acidic amino acids and dipeptides with hydrated cations using molecular dynamics. By monitoring the hydration states of Mg2+, Ca2+, and Sr2+ during their approach to negatively charged molecules, we show that carboxylate moieties of Asp promote dehydration of Ca2+ and Sr2+. A contact ion pair (CIP) is not required to disrupt cation hydration, and we demonstrate that reductions and rearrangements of first shell water can begin at ion-Asp separation distances as large as approximately 4.9 A for Ca2+ and approximately 5.1 A for Sr2+. CIP formation between Ca2+ and Sr2+ and carboxylate groups decreases the total first shell coordination number from an average of 8.0 and 8.4 in bulk water to 7.5 and 8.0, respectively. The energy barrier to physically replacing waters about Ca2+ with carboxylate oxygen atoms is small (approximately 2 kcal/mol) as compared to a somewhat larger barrier for Sr2+ (approximately 4 kcal/mol). This may be explained by differences in the strength of Coulombic interactions between the cations and the Asp, resulting in different paths of approach toward Asp for Ca2+ and Sr2+. In contrast, the primary solvation shell of Mg2+ remains largely unchanged during interactions with Asp until the abrupt physical replacement of water by carboxylate oxygen atoms, which comes at a high energetic cost. These insights support the claim that carboxylated biomolecules increase the growth rate of calcite by lowering the energy barrier to Ca2+ dehydration. The findings also suggest a physical basis for the idea that ion-specific behaviors of Ca2+ and Mg2+ in cellular systems arise from a critical balance between water binding in the ion hydration shells versus their interactions with ligands present in intracellular environments.

Background: Persistent infection with high-risk types of human papillomavirus (HPV) is associated with cervical and other anogenital cancers. Purpose: This paper reports results of awareness of an HPV diagnosis and HPV knowledge from a multi-site study of HPV knowledge, attitudes and behavior, and the impact of an HPV diagnosis on women and their partners. Methods: During September 2003 - November 2005, a survey containing shared and site-specific items was administered to 736 women who had received HPV DNA testing in conjunction with cytology for cervical cancer screening. Results: Overall, there was low knowledge about HPV transmissibility, curability and the effects of an HPV diagnosis across all sites regardless of a woman's racial/ethnic and/or socio-demographic background. Further, only about 50% of the women were aware of their HPV diagnosis even after receiving their results and counseling from a health care professional. Discussion: There is need for consistent and clear information abou...

Medical students encountering patients with unfamiliar, unconventional sexual practices may have attitudes that can affect open communication during sexual history-taking. We measured changes in first-year US medical student attitudes toward 22 non-traditional sexual behaviors before and after exposure to human sexuality instruction. An electronic, hand-held audience response system was used in a lecture hall to sample anonymous student attitudes toward this sensitive topic. Several attitudes were influenced by instruction, as shown by statistical comparisons before and after instruction. Students' attitudes shifted toward patterns favoring treatment for five out of 10 paraphilias that are not harmful of others. Most students favored imprisonment for pederasty before instruction, consistent with lessons about mandatory reporting of child sexual abuse, and this attitude increased non-significantly after instruction. Student attitudes were generally accepting of homosexuality, but were more accepting of fem...

The effect of polyparasite infections on cytokine and chemokine responses as well as the effect of antiparasite treatment was studied in children without parasite infection (the G0 group), in children singly infected with Schistosoma haematobium (the G1 group), and in children multiply infected with S. haematobium/Schistosoma mansoni, Entamoeba histolytica/Entamoeba dispar, and Necator americanus (the G3+ group). Linear regression analysis disclosed a significant risk for coinfection with hookworm and Schistosoma species. Polyparasite infections detected in 23% of children before treatment were present in 5% at 15 months after treatment. Chemokine responses to S. mansoni adult worm antigen (SmAg) diminished after treatment for macrophage inflammatory chemokine (MIP)-1alpha/chemokine (C-C motif) ligand (CCL)-3 (among G3+ children, by a factor of 200 [95% confidence interval {CI}, 33-1111]) and for MIP-1beta/CCL-4 (among G3+ children, by a factor of 26 [95% CI, 6-117]) but were enhanced for thymus- and activation-regulated chemokine/CCL-17 (among G3+ children, by a factor of 10 [95% CI, 3-32]) (P < .001 for all). In response to E. histolytica antigen, interleukin (IL)-13 levels increased after treatment among G1 children by a factor of 138 (95% CI, 12-1569) and among G3+ children by a factor of 21 (95% CI, 7-64) (P < .001 for both). Cellular production of interferon (IFN)-gamma in response to SmAg decreased 4 weeks after treatment among G3+ children, whereas T helper cell type 2 (Th2) IL-13 production was enhanced among G1 and G3+ children. In summary, polyparasite infections with S. haematobium/S. mansoni, E. histolytica/E. dispar, and N. americanus generated prominent proinflammatory cytokine and chemokine responses, and, after antihelminth treatment, the inflammatory chemokine response lessened as the Th2 responsiveness in coinfected children increased.

Objective To describe the prevalence of inadequately evaluated and treated psychopathology among insured workers making workers' compensation claims for psychiatric disability whose cases were reviewed by one forensic psychiatrist. To assess the relationship of inadequate evaluation and treatment to the outcomes of these workers' compensation claims. Methods Records of a series of 185 workers' compensation cases reviewed in 1998 and 1999 by a California forensic psychiatrist were abstracted. Patient factors (gender, Axis II pathology, psychosocial circumstances, substance abuse), case factors (psychiatric injury secondary to physical injury, or secondary to psychological stresses), type of provider (mental health, or other), adequacy of evaluation and treatment, forensic psychiatrist's recommendation, and claim outcome were categorized. The relationships between case characteristics, adequacy of care, and claim outcome were described. Results 22% of cases had adequate evaluation, 48% superficial, and 30% had no evaluation. 11% had adequate treatment, 67% superficial, and 22% had no treatment. Compared to claims for psychiatric disability related to a physical injury, claims related to psychosocial stresses more often had superficial diagnostic evaluations and treatments. Those with superficial treatment were less likely to have their claim granted (19.3%) than those with no treatment (47.5%) or those with adequate treatment (36.8%). Success of claim was not related to provider type. Conclusions The majority of the studied workers with employer-provided health insurance who sought workers' compensation for disability due to mental illness did so inappropriately, in that the workplace did not cause the psychopathology. Their seeking workers' compensation was plausibly due to the observed inadequate evaluation and treatment available through their employer-provided health insurance. The adequacy of their care influenced the likelihood their claim would be granted. The relations observed here merit further research to establish their generality and to determine their causes.

Summary The recommended control option against onchocerciasis is repeated ivermectin treatment, which will need to be implemented for decades, and it remains unknown how repeated ivermectin therapy might affect immunity against Onchocerca volvulus in the long term. O. volvulus-specific antibody reactivity and cellular cytokine production were investigated in onchocerciasis patients receiving ivermectin (150 µg/kg) annually for 16 years. In treated patients, the T helper type 2 (Th2) cytokine interleukin (IL)-5 and T regulatory IL-10 in response to O. volvulus antigen (OvAg) and bacteria-derived Streptolysin O (SL-O) diminished to levels found in infection-free endemic controls; also, cellular release of Th1-type interferon (IFN)-γ at 16 years post initial ivermectin treatment (p.i.t.) approached control levels. In ivermectin-treated onchocerciasis patients, IL-5 production in responses to the mitogen phytohaemagglutinin (PHA) decreased, but IL-10 in response PHA increased, and neither attained the cytokine production levels of endemic controls. At 16 years p.i.t., O. volvulus-specific IgG1 and IgG4 subclass reactivity still persisted at higher levels in onchocerciasis patients than in O. volvulus exposed but microfilariae-free endemic controls. In addition, cytokine responses remained depressed in onchocerciasis patients infected concurrently with Mansonella perstans and Necator americanus or Entamoeba histolytica/dispar. Thus, long-term ivermectin therapy of onchocerciasis may not suffice to re-establish fully a balanced Th1 and Th2 immune responsiveness in O. volvulus microfilariae-negative individuals. Such deficient reconstitution of immune competence may be due to an as yet continuing and uncontrolled reinfection with O. volvulus, but parasite co-infections can also bias and may prevent the development of such immunity.

This study assessed the extent to which older adults attribute a recent heart attack/stroke to “old age,” and examined consequences for subsequent lifestyle behavior and health-care service utilization. Community-dwelling adults ( N = 57, ages 73–98 years) were interviewed about their heart attack/stroke, and an objective health registry provided data on health-care utilization over a 3-year period. Endorsement of “old age” as a cause of heart attack/stroke negatively predicted lifestyle behavior change, and positively predicted frequency of physician visits and likelihood of hospitalization over the subsequent 3 years. Findings suggest the importance of considering “old age” attributions in the context of cardiovascular health events.

BACKGROUND Continuous intravenous infusion of prostacyclin is an effective treatment for primary pulmonary hypertension. This approach, however, requires the insertion of a permanent central venous catheter with the potential risk of serious complications. Recently, administration of aerosolized iloprost, a stable prostacyclin analogue, has been introduced as an alternative therapy for severe pulmonary hypertension. METHODS We evaluated the effects of treatment with aerosolized iloprost over a one-year period on exercise capacity and hemodynamic variables in patients with primary pulmonary hypertension. RESULTS Twenty-four patients with primary pulmonary hypertension received aerosolized iloprost at a cumulative daily dose of 100 to 150 micrograms for at least one year. The mean (+/- SD) walking distance in the 6-min-walk test increased from 278 +/- 96 meters at base line to 363 +/- 135 meters after 12 months (P < 0.0001). During the same period, the mean pulmonary artery pressure declined from 59 +/- 10 mmHg to 52 +/- 15 mmHg (P = 0.006), the cardiac output increased from 3.8 +/- 1.4 l/min to 4.4 +/- 1.3 l/min (P = 0.02), and the pulmonary vascular resistance declined from 1.205 +/- 467 dynes.s.cm-5 to 925 +/- 469 dynes.s.cm-5 (P = 0.0003). Treatment was generally well tolerated and except for mild coughing, minor headache and jaw pain in some patients, no side effects occurred. CONCLUSIONS Long-term treatment with aerosolized iloprost is safe and has sustained effects on exercise capacity and pulmonary hemodynamics in patients with primary pulmonary hypertension.

A case of malignant mesothelioma of the tunica vaginalis testis is reported in a 77-year-old male patient. There was no history of asbestos exposure. Recurrent right hydrocele with a papillar inguinal mass was the main clinical feature. An inguinal radical orchiectomy with en bloc resection of the surrounding tissue was performed. The therapeutic options for this rare, but aggressive neoplasm are discussed. Because of the disappointing results of antineoplastic chemotherapy or radiation therapy, the importance of initial radical surgical treatment with complete excision is emphasized.

We present our experiences with the approach of placing 2 parallel ureteral Double-J stents simultaneously in extrinsically obstructed ureters. In all 5 reported patients therapy with single ureteral stents had failed despite correct stent position. With the increased stiffness of 2 parallel ureteral silicon 7F Double-J stents ureteral kinking and luminal compression could be reduced leading to sufficient reduction of hydronephrosis. This approach with potential space between the stents preserves urinary flow through as well as around the stents which is considered to be the most important mechanism in stented ureters. In cases of extrinsic ureteral obstruction with failure of a single stent the simultaneous use of 2 parallel Double-J ureteral stents should be taken into account as a technically easy therapeutic option. It may obviate percutaneous nephrostomy tube placement or more invasive therapy.

The protective effect of ketotifen and disodium cromoglycate (DSCG) was evaluated by a randomised double blind cross-over study in 15 children with allergic bronchial asthma. 13 children were allergic to house dust mite (Dermatophagoides pteronyssinus), two to grass pollen. After a positive bronchial challenge test ketotifen or DSCG was given for 4 days followed by bronchial challenge with increasing allergen concentrations. Seven patients showed better allergen tolerance after ketotifen, 5 after DSCG. Protective action against late reactions was found only in 2 children after ketotifen and one child after DSCG.

We report the case of a 71-year-old man, who was transferred to our clinic with rapidly increasing dyspnea. On examination by flexible bronchoscopy the trachea was found to be almost completely obstructed by metastatic masses of a malignant melanoma. After endoscopic removal of the obstruction, we inserted a covered nitinol stent which led to instantaneous relief of symptoms. Chemotherapy and local radiotherapy were instituted. During the next 9 months there were no signs of recurrence of the tumour in regular pneumological control exams.

We report the case of a 71-year-old man, who was transferred to our clinic with rapidly increasing dyspnea. On examination by flexible bronchoscopy the trachea was found to be almost completely obstructed by metastatic masses of a malignant melanoma. After endoscopic removal of the obstruction, we inserted a covered nitinol stent which led to instantaneous relief of symptoms. Chemotherapy and local radiotherapy were instituted. During the next 9 months there were no signs of recurrence of the tumour in regular pneumological control exams.

We report a case of congenital retroperitoneal fibrosarcoma presenting in a 17-day-old male in which surgical tumor debulking was followed by chemotherapy. His clinical course was complicated. Intraoperatively, 80% of the tumor was removed and he experienced massive blood loss and significant cardiac arrhythmias. Following surgery he received chemotherapy and suffered life-threatening hepatic, hematological and gastrointestinal toxicity. The treatment resulted in clinical remission after 9 months of follow-up. A review of the current literature revealed the changing opinion of the optimal treatment of fibrosarcomas in children. Chemotherapy is playing an increasingly important role in the treatment of fibrosarcoma, both preoperatively and postoperatively.

PURPOSE: To determine whether the Xenopus laevis retina is capable of regenerating photoreceptor cells lost through apoptotic cell death in an inducible transgenic X. laevis model of retinitis pigmentosa (RP). METHODS: Acute rod photoreceptor apoptosis was induced in transgenic X. laevis expressing drug-inducible caspase 9. We subsequently monitored the ability of the retina to regenerate lost photoreceptors in the absence of drug, and in combination with physical injury or ectopic supplementation of basic fibroblast growth factor (FGF2). RESULTS: Direct activation of caspase 9 in rod photoreceptors resulted in the initiation of apoptosis and complete removal of rod photoreceptors within 4 days. Photoreceptors lost by apoptosis were not replaced over a 4-week recovery time frame. In contrast, physical disruption of rod-ablated retina was repaired by the end of a 3-week time frame, but did not result in rod photoreceptor regeneration other than at the site of injury. Furthermore, ectopic supplementation of FGF2 did not stimulate regeneration of photoreceptors lost by apoptosis. However, FGF2 supplementation increased the rate of regeneration of retina (including rod photoreceptors) in eyes from which retinal tissue was surgically removed. CONCLUSIONS: In the X. laevis retina, rod photoreceptors that undergo drug-induced caspase-9-mediated apoptosis are permanently lost and do not regenerate. In contrast, the neural retina (including rod photoreceptors) can regenerate in injured or retinectomized eyes, and this regeneration is promoted by supplementation with FGF2. However, FGF2 does not promote regeneration of rod photoreceptors that are selectively lost by apoptosis.

Many of the terms used in medical decision making are foreign to clinicians. This problem creates a barrier that can prevent physicians from acquiring these new clinical tools. This glossary contains definitions of the most common terms as well as examples of their usage by using Down syndrome as the illustrative condition.

OBJECTIVE: To determine current family physician beliefs concerning prostate cancer screening. DESIGN: Two hundred eighty-six Oklahoma family physicians were surveyed by mail. Fifty-three percent of physicians returned the questionnaire. Physicians were questioned on what tests they order for prostate screening, the reasons for ordering a serum prostate-specific antigen (PSA) test, what test results would cause a urologic referral for further evaluation of prostate cancer, and whether prostate cancer screening would decrease the patient's mortality or improve quality of life. RESULTS: Most physicians (74%) believed that both a digital rectal examination and a serum PSA determination are appropriate for prostate cancer screening. Physicians' primary reasons for ordering a PSA test were to decrease patient mortality and morbidity. Sixty-two percent of physicians believed that prostate cancer screening would decrease mortality and 69% agreed that screening would improve quality of life. Approximately 90% of physicians would refer patients with a PSA level greater than 12 micrograms/L or a PSA level of 5 micrograms/L and an indurated prostate. Significant variation was found between groups of physicians in their beliefs about prostate cancer screening. CONCLUSION: Although the literature has been inconclusive on the benefit of prostate cancer screening, the majority of Oklahoma family physicians would choose to screen their patients and believe that patients' mortality and morbidity are decreased by early identification of prostate cancer.

We tested the hypothesis that Crohn’s disease (CD)-related genetic polymorphisms involved in host innate immunity are associated with shifts in human ileum–associated microbial composition in a cross-sectional analysis of human ileal samples. Sanger sequencing of the bacterial 16S ribosomal RNA (rRNA) gene and 454 sequencing of 16S rRNA gene hypervariable regions (V1–V3 and V3–V5), were conducted on macroscopically disease-unaffected ileal biopsies collected from 52 ileal CD, 58 ulcerative colitis and 60 control patients without inflammatory bowel diseases (IBD) undergoing initial surgical resection. These subjects also were genotyped for the three major NOD2 risk alleles (Leu1007fs, R708W, G908R) and the ATG16L1 risk allele (T300A). The samples were linked to clinical metadata, including body mass index, smoking status and Clostridia difficile infection. The sequences were classified into seven phyla/subphyla categories using the Naive Bayesian Classifier of the Ribosome Database Project. Centered log ratio transformation of six predominant categories was included as the dependent variable in the permutation based MANCOVA for the overall composition with stepwise variable selection. Polymerase chain reaction (PCR) assays were conducted to measure the relative frequencies of the Clostridium coccoides – Eubacterium rectales group and the Faecalibacterium prausnitzii spp. Empiric logit transformations of the relative frequencies of these two microbial groups were included in permutation-based ANCOVA. Regardless of sequencing method, IBD phenotype, Clostridia difficile and NOD2 genotype were selected as associated (FDR ≤0.05) with shifts in overall microbial composition. IBD phenotype and NOD2 genotype were also selected as associated with shifts in the relative frequency of the C. coccoides – E. rectales group. IBD phenotype, smoking and IBD medications were selected as associated with shifts in the relative frequency of F. prausnitzii spp. These results indicate that the effects of genetic and environmental factors on IBD are mediated at least in part by the enteric microbiota.

Objective To determine whether the ratio of PSA and prostate volume provides additional useful information for the discrimination of benign prostatic hyperplasia from prostatic carcinoma. Patients and methods Since 1989, a prospective study has been in progress involving 229 patients (49 with locally confined prostatic carcinoma, 180 with benign prostatic hyperplasia) to establish whether the ratio of prostate-specific antigen (PSA) and prostate volume, determined by transrectal ultrasound (longitudinal × anterior-posterior × transverse diameter × 0.52), allows a better differentiation than the absolute PSA values. Results In this population of patients with prostatic disease, the positive predictive value for diagnosis of a prostatic carcinoma was 26% with an absolute PSA threshold value of 4.0 ng/ml, and 36% at a threshold value of 10 ng/ml. With a threshold value of the PSA/prostate volume ratio of 0.25 ng/(ml × cm3), the positive predictive value was 56% compared with 93% for a threshold value of 0.4 ng/(ml × cm3). Conclusion The ratio PSA/prostate volume is a superior method for the diagnosis of prostatic carcinoma both with regard to its sensitivity and its specificity in patients with absolute PSA values in excess of 4 ng/ml.

The serum half-life of prostate-specific antigen (PSA) was calculated in 66 patients subsequent to radical prostatectomy. Comparing serum half-life to disease outcome in 37 patients after a minimum follow-up of two years, it was found that PSA serum half-life identifies patients with residual disease earlier and more reliably than the presence or absence of detectable PSA levels postoperatively. It is suggested that residual tumor affects the half-life by contributing to the serum level of PSA. When PSA serum half-life was calculated solely in potentially cured patients, we found a half-life of 1.6 days, which is considerably shorter than in previous reports based on patient populations regardless of the outcome of disease in the follow-up. To elucidate the route of PSA elimination, serial urine PSA levels were determined before and after radical prostatectomy, revealing strong evidence for the assumption that PSA is not eliminated by the kidneys in its unchanged form.

Whole human genome (Agilent) expression profiling was conducted on disease-unaffected ileal RNA collected from the proximal margin of resected ileum from 47 ileal Crohn's disease (CD), 27 ulcerative colitis (UC) and 25 control patients without inflammatory bowel diseases (IBD). Cluster analysis combined with significance analysis of microarrays (SAM) and principal component analysis (PCA) and was used to reduce the data dimension to identify geneprobe clusters associated with early pathogenic changes in ileal CD and UC. Ingenuity Pathway Analysis (IPA) was used to identify the biological pathways associated with each cluster. We reduced the dimensions of the 26,765 gene probe set to 43 gene-probe clusters. Most of these clusters could be labeled as related to different biological pathways, such as Paneth cell antimicrobial peptides, the formation of organized lymphoid structures, or nuclear receptor signaling and xenobiotic metabolism. Molecular phylogenetic 16S rRNA sequence analysis was completed on 83 DNA samples from the same samples used to generate the gene expression profiles. We conducted an exploratory study to determine if the first principle component (PC1) of these clusters could be linked to specific phyla/subphyla taxa.

Biomolecules rich in aspartic acid (Asp) are known to play a role in biomineral morphology and polymorph selection, and have been shown to greatly enhance the growth kinetics of calcite. The mechanism by which these compounds favor calcification may be related to their effects upon cation solvation. Using molecular dynamics, we investigated the influence of small carboxylated molecules on the hydration states and water exchange rates of divalent cations. We show that the carboxylate moieties of Asp promote dehydration of Ca2+ and Sr2+ and that contact ion pair (CIP) formation is not required to disrupt the hydration of these cations. Ca2+- Asp and Sr2+ - Asp CIP formation decreases the total inner sphere coordination from an average of 8.0 and 8.4 in bulk water to 7.5 and 8.0, respectively. Water residence times estimated for Mg2+, Ca2+and Sr2+ follow the expected trend of decreasing residence time with increasing ionic radius. In the presence of Asp, both solvent-separated ion pair (SSIP) and CIP formation decrease the residence times of Ca2+and Sr2+ inner sphere water molecules. Comparable impacts on Mg2+ hydration are not observed. Mg2+ - Asp CIP formation is energetically unfavorable and Asp does not affect Mg2+ inner sphere water residence times.

The Institute for Tropical Medicine at University of Tubingen has established 30 years ago in Togo a Research Centre and Onchocerciasis Reference Laboratory (ORL). Onchocerca volvulus infection control and of other neglected tropical diseases has been the focus of activities, and those were performed together with the National Institute of Hygiene in Togo, the Medical Faculty at University of Lome, national disease control programs and district and regional hospitals. The ORL contributed significantly to the assessment of ivermectin as the prime choice for onchocerciasis treatment, and 24 years of repeated annual treatment with ivermectin has progressively reduced disease prevalence and notably the level of ocular and dermal manifestations of onchocerciasis in the endemic population. The ORL has shown that large parts of the rural population in Togo is concurrently infected with intestinal and intravascular protozoan and helminth parasites, notably school children. The application of repeated treatments with albendazole and praziquantel against Schistosoma spp. and instestinal helminthes for several years has reduced infection intensities by more than 80%. Longitudinal investigations of the cellular immune responses in adults and children have found that parasite co-infections will generate prominent pro-inflammatory responses, and a single or few interventions will not suffice to eliminate co-infections and not establish an appropriately balanced immunity.

Background: Abnormal host–microbe interactions are implicated in the pathogenesis of inflammatory bowel diseases. Previous 16S rRNA sequence analysis of intestinal tissues demonstrated that a subset of Crohn's disease (CD) and ulcerative colitis (UC) samples exhibited altered intestinal-associated microbial compositions characterized by depletion of Bacteroidetes and Firmicutes (particularly Clostridium taxa). We hypothesize that NOD2 and ATG16L1 risk alleles may be associated with these alterations. Methods: To test this hypothesis, we genotyped 178 specimens collected from 35 CD, 35 UC, and 54 control patients for the three major NOD2 risk alleles (Leu 1007fs, R702W, and G908R) and the ATG16L1T300A risk allele, that had undergone previous 16S rRNA sequence analysis. Our statistical models incorporated the following independent variables: 1) disease phenotype (CD, UC, non-IBD control); 2) NOD2 composite genotype (NOD2R = at least one risk allele, NOD2NR = no risk alleles); 3) ATG16L1T300A genotype (ATG16L1R/R, ATG16L1R/NR, ATG16L1NR/NR); 4) patient age at time of surgery and all first-order interactions. The dependent variable(s) were the relative frequencies of bacterial taxa classified by applying the RDP 2.1 classifier to previously reported 16S rRNA sequence data. Results: Disease phenotype, NOD2 composite genotype and ATG16L1 genotype were significantly associated with shifts in microbial compositions by nonparametric multivariate analysis of covariance (MANCOVA). Shifts in the relative frequencies of Faecalibacterium and Escherichia taxa were significantly associated with disease phenotype by nonparametric ANCOVA. Conclusions: These results support the concept that disease phenotype and genotype are associated with compositional changes in intestinal-associated microbiota. (Inflamm Bowel Dis 2011;)

Mrs. Jones is an 88-year-old demented nursing home resident who is admitted to the hospital one night with dehydration and a urinary tract infection that may have spread to her bloodstream. The resident on duty treats aggressively with IV fluids and also obtains a “do not resuscitate” (DNR) order. Mrs. Jones subsequently develops rales in her lungs that suggest heart failure. She also develops bradycardia down to about 45 beats per minute. Her systolic blood pressure drops to 60 mm Hg with the bradycardia. Mrs. Jones’s condition is likely terminal but the bradycardia can be corrected with a transvenous pacemaker. The family is equivocal, suggesting that the physician do whatever can help. After a family conference and an ethics consultation, the physician decides that Mrs. Jones deserves a pacemaker. She arrests in the recovery room after the procedure and cannot be resuscitated.

Dracunculiasis is a promising candidate for eradication, but transmission of Dracunculus medinensis and recrudescence of the disease have been observed repeatedly. In the present investigation, the D. medinensis-specific cellular cytokine response profiles and the parasite-specific antibody subclass reactivity were evaluated in dracunculiasis patients at distinct states of infection. Analysis of the cellular cytokine response in dracunculiasis patients disclosed a D. medinensis antigen-specific depression of IFN-gamma production with patent D. medinensis infection, while the T helper type 2 cytokine IL-10 was similar in patent, post-patent and control individuals, and IL-5 production was always the highest in controls. In parallel, diminished IFN-gamma and IL-12 responses to antigens from Ascaris lumbricoides, Entamoeba histolytica and mycobacteria were observed in patent and post-patent dracunculiasis cases. The parasite-specific IgG(1) and IgG(4) subclass reactivity profiles corresponded with the D. medinensis infection state, and a clear distinction between patent and post-patent patients and controls was found. Overall a depressed cytokine release was observed with patent D. medinensis, which extended beyond the parasite-specific immune responsiveness. The detection of D. medinensis-specific IgG(1) and IgG(4) isotypes may help to distinguish newly exposed, patent and post-patent D. medinensis infections.

SummaryIvermectin treatment will effectively diminish microfilariae (Mf) of Onchocerca volvulus in the skin of patients, but therapy is associated with adverse host inflammatory responses. To investigate the association of proinflammatory chemokines with the intensity of infection and clinical adverse reactions, chemokine serum levels were measured in patients following ivermectin treatment (100 µg/kg, 150 µg/kg or 200 µg/kg) or placebo. The density of O. volvulus Mf per mg skin decreased by 85%, 97%, 97% and 90% at day 3, at month 3, month 6 and at 1 year post-ivermectin. The cutaneous T cell-attracting chemokine (CTACK/CCL27) was found highly elevated in onchocerciasis patients compared to infection-free European controls (P = 0·0004) and it did not change following ivermectin or placebo to 1 year post-therapy. The chemokine RANTES/CCL5 (regulated on activated and normally T cell-expressed) was similarly high in onchocerciasis patients and infection-free European controls; the RANTES/CCL5 levels did not change following treatment until 6 months post-therapy but were slightly elevated at 1 year post-therapy (P

This study examined the impact of concurrent parasite infections (amoebiasis, filariasis, necatoriasis) and the effect of anti-parasite treatment on cytokine and chemokine responses in singly and poly-parasitized patients. Cellular reactivity and parasite-specific Th1- and Th2-type cytokine and chemokine profiles were investigated before and six weeks after treatment. In those patients infected with three parasite species, cellular secretion of interleukin 5 (IL-5) and IL-12p40 by PBMC was strongly diminished (p0.005) but IL-10 was elevated in parasite-infected patients (p0.0001) in response to protozoa- and helminth-specific as well as bacteria-specific antigens. Macrophage inflammatory chemokines (MIP-1alpha/CCL3 and MIP-1beta/CCL4), macrophage-derived chemokine (MDC/CCL22) and neutrophil activating chemokine (IL-8/CXCL8) were produced by PBMC in similar amounts in endemic controls and singly and poly-parasitized patients, but thymus and activation-regulated chemokine (TARC/CCL17) was produced the highest by PBMC from patients with triple parasite infections (p0.0001). Following anti-parasite therapy, secretion of IL-12p40 and IL-5 augmented significantly in treated patients while IL-10, MDC, MIP-1alpha, TARC and IL-8 substantially diminished (all p10(-5)) when their PBMC were activated with parasite- and bacteria-specific antigens. In summary, PBMC from poly-parasitized patients responded to protozoa- and helminth-specific antigens with a compromised IL-5 and IL-12p40 but high IL-10 and a substantial chemokine release. Chemokines may attract and activate effector cells in peri-parasitic tissues to limit parasite proliferation and dissemination, while depressed IL-5 and IL-12p40 but prominent IL-10 may prevent eosinophil and cytotoxic cell-mediated inflammatory processes and pathogenesis to the host. The changes in this profile following anti-parasite therapy disclosed the dynamics of an immune adaptation associated with parasite accumulation and also with clearance of parasite infections.

Objectives: Practice guidelines support informed or shared decision-making about prostate cancer screening. To compare beliefs across three racial/ethnic categories concerning prostate cancer etiology and risk, screening routines, and shared decision-making, we conducted 12 focus groups. Methods: Participants were recruited in primary care settings and included 33 African Americans, 35 Hispanics, and 22 non-Hispanic Whites. Of the 90 participants, 53% were male. Results: Groups identified heredity, age, race, sexual activity, and other lifestyle influences as risk factors. Few were aware that prostate cancer is asymptomatic in early stages. Confidence in knowledge of screening routines was high, but included misconceptions supporting initiation of screening at earlier ages and at shorter intervals than professional recommendations. Females encouraged screening of male relatives to protect their health. Discussion and conclusion: While racial/ethnic groups had similar views and knowledge about screening, African Americans wanted to organize to address the threat of prostate cancer in their communities. Hispanics had awakening awareness of the health risks of prostate cancer. Non-Hispanic Whites were aware of the health threat of prostate cancer, but their approach to health protection was more individual and less community focused than that of African Americans. Participants were not aware of controversy about screening. Practice implications: Developers of educational materials to support informed or shared decision-making should be aware that initial views of prostate cancer screening are positive. # 2005 Elsevier Ireland Ltd. All rights reserved.

Objective. Current reimbursement policies serve as potent disincentives for physicians who provide evaluation and management services exclusively. Such policies threaten nationwide availability of care for personnel-intensive services such as pediatric diabetes. This report describes an approach to improving reimbursement for highly specialized, comprehensive pediatric diabetes management through prospective contracting for services. The objective of this study was to determine whether pediatric diabetes intensive case management services are cost-effective to the payer, the patient, and a pediatric diabetes program. Methods. A contract with a third-party payer was created to reimburse for 3 key pediatric diabetes intensive case management components: specialty education, 24/7 telephone access to an educator (and board-certified pediatric endocrinologist as needed), and quarterly educator assessments of self-management skills. Data were collected and analyzed for 15 months after signing the contract. Within the first 15 months after the contract was signed, 22 hospital admissions for diabetic ketoacidosis (DKA) occurred in 16 different patients. After hospitalizations for DKA, all 16 patients were offered participation in the program. All were followed during the subsequent 1 to 15 months of observation. Ten patients elected to participate, and 6 refused participation. Frequency of rehospitalization, emergency department visits, and costs were compared between the 2 groups. Results. Among the 10 participating patients, there was only 1 subsequent DKA admission, whereas among the 6 who refused participation, 5 were rehospitalized for DKA on at least 1 occasion. The 10 patients who participated in the program had greater telephone contact with the team compared with those who did not (16 crisis-management calls vs 0). Costs (education, hospitalization, and emergency department visits) per participating patient were approximately $1350 less than those for nonparticipating patients. Differences between participating and nonparticipating groups included age (participants were of younger age), double-parent households (participants were more likely to be from double parent households), and number of medical visits kept (participants kept more follow-up visits). No differences in duration of diabetes, months followed in the program, sex, or ethnicity were observed. Conclusions. Contracting with third-party payers for pediatric diabetes intensive case management services reduces costs by reducing emergency department and inpatient hospital utilizations, likely a result of intensive education and immediate access to the diabetes health care team for crisis management. Such strategies may prove to be cost saving not only for diabetes management but also for managing other costly and personnel-intensive chronic diseases.

Background: Although the understanding of the health impact of hormone replacement therapy (HRT) is incomplete, even less is known about the attitudes, perceptions, and motivations of women faced with the decision to use HRT. The purpose of this study was to evaluate the relation between HRT use and women’s perceptions of the risk and benefits associated with HRT use. Methods: A written questionnaire was administered to 387 women, aged 45 years and older, responding to a health plan invitation for free bone mineral density screening. Women were asked to estimate the lifetime probability of developing breast cancer, uterine cancer, osteoporosis, and myocardial infarction when taking HRT and when not taking HRT. Women rated their quality of life in their current state of health, with breast cancer, with uterine cancer, with osteoporosis, and after myocardial infarction. Results: HRT users perceived a greater risk reduction using HRT compared with HRT nonusers for osteoporosis (34.9% vs 17.8%, P < .001) and myocardial infarction (20.7% vs 8.4%, P < .001). HRT nonusers perceived a greater risk increase using HRT compared with HRT nonusers for breast cancer (16.5% vs 3.3%, P < .001) and uterine cancer (9.2% vs 0.6%, P .004). HRT users estimated a greater quality-of-life reduction compared with HRT nonusers for osteoporosis (31.0 vs 24.5, P .006). Conclusions: Regardless of whether they used HRT, women in this study overestimated their risk for all four diseases. HRT users perceived greater benefit and less risk using HRT than nonusers. The results of our study show that continuing efforts are needed to help women understand the risks and benefits of HRT. (J Am Board Fam Pract 2003;16:270 –7.)