New concept: "TARN friendly trauma reporting" (what radiologists say really does matter).

AIM: To establish if detailed review of trauma reports with reference to coding manual improved accuracy of ISS and to establish if demonstrated changes in coding affected performance and tariff payment. MATERIALS AND METHODS: A study was undertaken which gathered data from 6 months across the five trusts with information on imaging undertaken, mechanism of injury (MOI), Injury Severity Score (ISS), and injury descriptors was included. Patients with ISS near to a best practice tariff boundary of 9 and 16 (5-8 and 11-15) then had their imaging reviewed by the Radiology Department with direct reference to the ISS coding manual. Injuries were then re-coded and ISS recalculated. RESULTS: Over the 6-month period, 1,693 patients were admitted to the database from the five hospitals. One hundred and sixty-nine (9.9%) patients met the inclusion criteria for review. Thirty-five (20.7%) had a change in abbreviated (region specific) injury code, with 30 a change in the resultant ISS. Three had a decrease in ISS and 27 increased ISS with all 27 moving across an ISS best practice tariff and three moving across two payment tariff boundaries. With re-coding, there was a potential £15,000 of lost revenue from the major trauma centre (MTC) alone. CONCLUSION: Reporting with reference to ISS description improves the accuracy of ISS significantly. Radiologists improving the descriptions of specific injury patterns and adopting 'Trauma Audit and Research Network friendly' reporting strategies may improve data accuracy, performance, and payment of best practice tariffs to hospitals.

Alopecia areata: a review of disease pathogenesis.

BACKGROUND: Alopecia areata is a disorder that results in nonscarring hair loss. The psychological impact can be significant, leading to feelings of depression and social isolation. Objectives In this article, we seek to review the pathophysiological mechanisms proposed in recent years in a narrative fashion. METHODS: We searched MEDLINE and Scopus for articles related to alopecia areata, with a particular emphasis on its pathogenesis. RESULTS: The main theory of alopecia areata pathogenesis is that it is an autoimmune phenomenon resulting from a disruption in hair follicle immune privilege. What causes this breakdown is an issue of debate. Some believe that a stressed hair follicle environment triggers antigen presentation, while others blame a dysregulation in the central immune system entangling the follicles. Evidence for the latter theory is provided by animal studies, as well investigations around the AIRE gene. Different immune-cell lines including plasmacytoid dendritic cells, natural killer cells and T cells, along with key molecules such as interferon-γ, interleukin-15, MICA and NKG2D, have been identified as contributing to the autoimmune process. CONCLUSIONS: Alopecia areata remains incurable, although it has been studied for years. Available treatment options at best are beneficial for milder cases, and the rate of relapse is high. Understanding the exact mechanisms of hair loss in alopecia areata is therefore of utmost importance to help identify potential therapeutic targets.

Protocol guided bleeding management improves cardiac surgery patient outcomes.

BACKGROUND AND OBJECTIVES: Excessive bleeding is a risk associated with cardiac surgery. Treatment invariably requires transfusion of blood products; however, the transfusion itself may contribute to postoperative sequelae. Our objective was to analyse a quality initiative designed to provide an evidenced-based approach to bleeding management. MATERIALS AND METHODS: A retrospective analysis compared blood product transfusion and patient outcomes 15 months before and after implementation of a bleeding management protocol. The protocol incorporated point-of-care coagulation testing (POCCT) with ROTEM and Multiplate to diagnose the cause of bleeding and monitor treatment. RESULTS: Use of the protocol led to decreases in the incidence of transfusion of PRBCs (47·3% vs. 32·4%; P < 0·0001), FFP (26·9% vs. 7·3%; P < 0·0001) and platelets (36·1% vs. 13·5%; P < 0·0001). During the intra-operative period, the percentage of patients receiving cryoprecipitate increased (2·7% vs. 5·1%; P = 0·002), as did the number of units transfused (248 vs. 692; P < 0·0001). The proportion of patients who received tranexamic acid increased (13·7% to 68·2%; P < 0·0001). There were reductions in re-exploration for bleeding (5·6% vs. 3·4; P = 0·01), superficial chest wound (3·3% vs. 1·4%; P = 0·002), leg wound infection (4·6% vs. 2·0%; P < 0·0001) and a 12% reduction in mean length of stay from operation to discharge (95%: 9-16%, P < 0·0001). Acquisition cost of blood products decreased by $1 029 118 in the 15-month period with the protocol. CONCLUSIONS: The implementation of a bleeding management protocol supported by POCCT in a cardiac surgery programme was associated with significant reductions in the transfusion of allogeneic blood products, improved outcomes and reduced cost.

Group 2 innate lymphoid cells and CD4+ T cells cooperate to mediate type 2 immune response in mice.

BACKGROUND: Innate lymphoid cells (ILCs) play important roles in innate immunity and tissue remodeling via production of various cytokines and growth factors. Group 2 ILCs (ILC2s) were recently shown to mediate the immune pathology of asthma even without adaptive immunity. However, little is known about possible interactions between ILC2s and other immune cells. We sought to investigate the capacity of ILC2s to regulate effector functions of T cells. METHODS: We isolated ILC2s from the lungs of naïve mice. We cultured CD4(+) T cells with ILC2s in vitro and examined the functions of these cell types. The mechanisms were investigated using blocking antibodies and cells isolated from cytokine-deficient mice. For the in vivo study, we adoptively transferred ILC2s and CD4(+) T cells into Il7ra(-/-) mice and subsequently exposed the mice to ovalbumin and a cysteine protease. RESULTS: Lung ILC2s enhanced CD4(+) T-cell proliferation and promoted production of type 2 cytokines in vitro. The interaction between ILC2s and CD4(+) T cells involved costimulatory molecule OX40L and cytokine IL-4, which was mainly derived from ILC2s. Adoptive transfer of both ILC2 and CD4(+) T-cell populations, but not each population alone, into Il7ra(-/-) mice resulted in induction of a robust antigen-specific type 2 cytokine response and airway inflammation. CONCLUSION: Lung ILC2s function to promote adaptive immunity in addition to their established roles in innate immunity. This novel function of ILC2s needs to be taken into account when considering the pathophysiology of asthma and other allergic airway diseases.

Immuno-epidemiology of Ascaris lumbricoides infection in a high transmission community: antibody responses and their impact on current and future infection intensity.

The role of the humoral immune system in human infection with Ascaris lumbricoides remains unclear. This study documents an epidemiological investigation in a highly endemic community in Vietnam, whereby serum antibody levels were assessed before treatment and after a 6-month reinfection period. These data were examined by correlation with infection status using an age-structured approach in an attempt to help shed light on the role of the humoral immune response. The first part of this study characterized levels of all serum antibody isotypes from the community in response to antigens of both adult and larval A. lumbricoides. Data were assessed in terms of their relation to host age and infection intensity with the aim to provide a broadly detailed account of immune responses to the parasite. In the second part, antibody responses to both life-stages of A. lumbricoides in serum samples collected before anthelmintic chemotherapy were analysed in relation to intensity of re-infection with the parasite 6 months following treatment. The results suggest that antibody responses may not confer protection from current infection or re-infection with A. lumbricoides and may not serve as reliable indicators of future infection intensity. Our results thereby lend support to the theory that immunity to A. lumbricoides may not be based on the humoral immune system.

Hematopoietic stem cell mobilization with intravenous melphalan and G-CSF in patients with chemoresponsive multiple myeloma: report of a phase II trial.

Multiple myeloma (MM) is an incurable hematologic malignancy for which autologous hematopoietic stem cell transplantation (HCT) is a standard therapy. The optimal method of stem cell mobilization is not defined. We evaluated intravenous melphalan (60 mg/m2), the most effective agent for MM, and G-CSF (10 microg/kg/day) for mobilization. End points were safety, adequacy of CD34+ collections, MM response, and contamination of stem cell components (SCC). In total, 32 patients were mobilized. There were no deaths or significant bleeding episodes; 14 patients (44%) required hospitalization for neutropenic fever. Median days of grade 3 or 4 neutropenia or thrombocytopenia were 7 (2-20) and 8 (3-17). Median mobilization days, CD34+ cells/kg and total leukaphereses were 16 (12-30), 12.1 million (2.6-52.8), and 2 (1-5) respectively. Four patients (12.5 %) failed to achieve the target of 4 million CD34+ cells/kg in five leukaphereses. Reduction in myeloma was seen in 11 patients (34%) with 3 (9%) achieving complete response; 15 (47%) maintained prior responses. Estimated MM contamination per SCC (N=48) was 0.0009% (range 0-0.1) and 0.21 x 10(4) cells per kg (range 0-41.2). Increased contamination was associated with increased patient age. This strategy for mobilization is feasible, frequently requires hospitalization and transfusion, and controls disease in most patients.

Multiplex PCR allows simultaneous detection of pathogens in ships' ballast water.

There is enormous potential for global transfer of microorganisms, including pathogens, in ships' ballast water. We contend that a major advancement in the study of ballast-water microorganisms in particular, and of aquatic pathogens in general, will be expedited sample analysis, such as provided by the elegant technology of DNA microarrays. In order to use DNA microarrays, however, one must establish the appropriate conditions to bind target sequences in samples to multiple probes on the microarrays. We conducted proof-of-concept experiments to optimize simultaneous detection of multiple microorganisms using polymerase chain reaction (PCR) and Southern hybridization. We chose three target organisms, all potentially found in ballast water: a calicivirus, the bacterium Vibrio cholerae, and the photosynthetic protist Aureococcus anophagefferens. Here, we show simultaneous detection of multiple pathogens is possible, a result supporting the promising future use of microarrays for simultaneous detection of pathogens in ballast water.

Community perception of school-based delivery of anthelmintics in Ghana and Tanzania.

This paper presents the results of an evaluation of community perception of two large-scale, government-run, school-based health programmes delivering anthelmintic drugs to primary school children, in Ghana (80 442 children in 577 schools) and Tanzania (110 000 children in 352 schools). Most teachers (96% in Ghana and 98% in Tanzania) were positive about their role in the programme, including administration of anthelmintic drugs, and parents and children fully accepted their taking on this role. The benefits of the programme were apparent to teachers, parents and children in terms of improved health and well-being of the children. Over 90% of parents in both Ghana and Tanzania indicated a willingness to pay for the continuation of drug treatment. The evaluation also highlighted areas that are critical to programme effectiveness, such as communication between schools and parents, the issue of collaboration between the health and education sectors, parents' perception of the importance of helminth infection as a serious and chronic health problem (compared with more acute and life threatening illnesses such as malaria), and who should pay for treatment of side-effects.

Consensus conference: acitretin in combination with UVB or PUVA in the treatment of psoriasis.

Although adjunctive treatment with retinoids in concert with either psoralen-ultraviolet A (PUVA) or ultraviolet B (UVB) phototherapy has been a treatment option for chronic, moderate to severe plaque psoriasis for nearly two decades, acitretin-UV therapy is an underutilized therapeutic modality. According to a recent member survey by the National Psoriasis Foundation, many psoriasis patients are frustrated with available treatment options, which they perceive as ineffective, inconvenient, and/or excessively conservative. Treatment of psoriasis with acitretin in concert with UVB or PUVA is emerging as a viable clinical strategy. Compared with either acitretin or UV light monotherapy alone, the combination regimen enhances efficacy and limits treatment frequency, duration, and cumulative doses. These effects translate into care that is more effective, better tolerated, more convenient, less costly, and, perhaps, safer during long-term treatment than phototherapy alone. Drawing from an extensive literature search and the expertise of its participants, this consensus conference advances clinical recommendations as well as "clinical pearls" for health providers who treat patients with chronic, moderate to severe plaque psoriasis and suggests avenues for future research.

Multiple helminth infections in children: impact and control.

Parasitic worm infections are amongst the most widespread of all chronic human infections. It is estimated that there are more than 3 billion infections in the world today. In many low income countries it is often more common to be infected than not to be. Indeed, a child growing up in an endemic community can expect be infected soon after weaning, and to be infected and constantly reinfected for the rest of her or his life. Infection is most common amongst the poorest and most disadvantaged communities, and is typically most intense in children of school going age. As the risk of morbidity is directly related to intensity of infection, it follows that children are the most at risk from the morbid effects of disease. Multiparasite infections are also common in such communities and there is evidence that individuals harbouring such infections may suffer exacerbated morbidity, making children even more vulnerable. Thus, these infections pose a serious threat to the health and development of children in low income countries. For many years, the need to control these infections has lain uncontested, and with the advent of broad-spectrum anthelminthic drugs that are cheap, safe and simple to deliver, control has at last become a viable option for many communities. Furthermore, there is now increased emphasis being placed on a multispecies approach as a cost-effective mechanism to control the morbidity of virtually all the major helminthic infections of humans.

A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne.

BACKGROUND: Isotretinoin is very frequently the drug of choice for the management of severe recalcitrant nodular acne. Recently, a new micronized and more bioavailable formulation of isotretinoin has been developed that permits once-daily administration in lower doses than usually used with standard isotretinoin (Accutane), regardless of whether it is taken with or without food. OBJECTIVE: Our purpose was to determine whether micronized isotretinoin and standard isotretinoin are clinically equivalent. METHODS: In this multicenter, double-blind, double-dummy study, 600 patients with severe recalcitrant nodular acne were treated with either 0.4 mg/kg of micronized isotretinoin once daily without food (n = 300) or 1.0 mg/kg per day of standard isotretinoin in two divided doses with food (n = 300). Lesion counts were monitored over 20 weeks. RESULTS: Both treatment groups in this well-controlled clinical trial experienced an equivalent reduction in the number of total nodules (facial plus truncal). In addition, an equivalent proportion of patients achieved 90% clearance of the total number of nodules. Both formulations had similar results for other efficacy variables. CONCLUSION: Once-daily use of the micronized and more bioavailable formulation of isotretinoin under fasted conditions is clinically equivalent to the standard twice-daily formulation under fed conditions in the treatment of severe recalcitrant nodular acne.

Safety of a new micronized formulation of isotretinoin in patients with severe recalcitrant nodular acne: A randomized trial comparing micronized isotretinoin with standard isotretinoin.

BACKGROUND: Isotretinoin is a very effective drug for treating severe recalcitrant nodular acne. A new micronized formulation of isotretinoin has been shown to be clinically equivalent to standard isotretinoin with improved bioavailability and minimal food effect. The safety profile of the micronized formulation has not been described previously. OBJECTIVE: The objective of this article is to report the incidence and intensity of adverse events found in a comparative, double-blind efficacy study that showed clinical equivalence of the new micronized formulation of isotretinoin and the standard isotretinoin formulation (Accutane). METHODS: Six hundred patients with severe recalcitrant nodular acne were treated with micronized isotretinoin (n = 300) under fasted conditions or standard isotretinoin (n = 300) under fed conditions. One cohort received single daily doses of 0.4 mg/kg of micronized isotretinoin without food and the other cohort received 1.0 mg/kg per day of standard isotretinoin in two divided doses with food. Adverse events were monitored during 20 weeks of drug therapy. RESULTS: The proportion of adverse events in most body systems was generally lower in patients receiving micronized isotretinoin than in those receiving standard isotretinoin. CONCLUSION: Micronized isotretinoin appears to have a safety profile similar to that of standard isotretinoin and to carry a lower risk of mucocutaneous events and hypertriglyceridemia.

The impact of tacrolimus ointment on health-related quality of life of adult and pediatric patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis can have detrimental effects on health-related quality of life (QOL). OBJECTIVE: Our purpose was to examine the QOL impact of tacrolimus ointment in patients with atopic dermatitis. METHODS: The Dermatology Life Quality Index (DLQI), Children's DLQI (CDLQI), and Toddler QOL Survey were used to assess QOL in adults (16 years or older), children (5-15 years), and toddlers (2-4 years) enrolled in 12-week, randomized, double-blind studies comparing two concentrations of tacrolimus ointment (0.03% and 0.1%) versus vehicle ointment for treatment of atopic dermatitis. QOL was assessed at baseline, week 3, and week 12/early discontinuation. RESULTS: Of the 985 patients enrolled, 91.5% had evaluable QOL data. Among adults, both tacrolimus ointment groups experienced improved QOL relative to the vehicle control group for all QOL scales (P<.001). Among children and toddlers, both tacrolimus ointment groups demonstrated significant QOL improvements relative to the vehicle control group (P<.05) for all but the Personal Relationships scale in the 0.03% tacrolimus ointment group among children. CONCLUSION: Tacrolimus ointment is associated with significant QOL benefits in adults, children, and toddlers with atopic dermatitis.

Chemopreventive effects of green tea polyphenols correlate with reversible induction of p57 expression.

Green tea polyphenols are known to induce apoptosis in certain types of tumor cells. However, the mechanism(s) that enables normal cells to evade the apoptotic effect is still not understood. In this study, Western blot analysis combined with cycloheximide treatment was used to examine the effects of green tea polyphenols on the expression levels of p57, a cyclin-dependent kinase and apoptosis inhibitor, in normal human keratinocytes and in the oral carcinoma cell lines SCC25 and OSC2. The results showed that the most potent green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), induced p57 in normal keratinocytes in a dosage- and time-dependent manner, while the levels of p57 protein in oral carcinoma cells were unaltered. The differential response in p57 induction was consistent with the apoptosis status detected by annexin V assay. The data suggest that the chemopreventive effects of green tea polyphenols may involve p57-mediated cell cycle regulation in normal epithelial cells.

The implications and management of drug interactions with itraconazole, fluconazole and terbinafine.

The efficacy and safety of many pharmacological agents can be adversely affected by drug interactions. However, an appreciation of the mechanisms and incidence of these interactions, together with a knowledge of the patient's medical history, means that the majority are predictable and can be managed successfully. Drug interactions involving oral antifungal agents such as itraconazole, fluconazole and terbinafine have been studied extensively and are well understood. When problems are known to arise, they can often be overcome or minimised by varying the dosage regimens, or by drug monitoring. Where certain drugs are definitely contraindicated with antifungal agents, suitable alternatives can usually be found. Clinical trials and surveillance monitoring have demonstrated that when viewed in a wider context, drug interactions do not represent a particular safety problem for the newer oral antifungal agents. An improved understanding of the drug interaction processes and appropriate control measures mean that the high benefit-to-risk ratio of these medications can be maintained.

Food stamps are associated with food security and dietary intake of inner-city preschoolers from Hartford, Connecticut.

The goal of the present study was to examine the association of the Food Stamp Program with the food security and dietary intake of low-income children from Hartford, CT, who were enrolled in the Supplemental Food Program for Women, Infants, and Children (WIC). We compared the food and nutrition situation of low-income preschoolers who received food stamps (FS, n = 59) with that of those who did not receive food stamps (NFS, n = 40). Children were an average age of 2.7 +/- 0.6 y, and 95% were receiving WIC benefits at the time of the study. Groups were comparable in demographic characteristics, but the socioeconomic status of the FS group was lower than that of the NFS group (P < 0.05). Food security was assessed with the Radimer/Cornell hunger scale, and dietary intake was assessed with a single 24-h recall and a 14-item food frequency questionnaire. Multivariate analyses within the FS group indicated that a monthly duration of food stamps of <4 wk was a predictor of household food security (odds ratio 0.10, 95% confidence interval 0.02-0.56). Food stamp use was associated with above-median energy-adjusted intakes of vitamin B-6 (3.13, 1.16-8.45), folate (2.92, 1.09-7.81) and iron (3.72, 1.31-10.54). The NFS children were more likely to consume <8 mg iron/d (3.73, 1.09-12.80). These results suggest that the Food Stamp Program is associated with food security and preschoolers' micronutrient intake.