It is not currently known what is the patient's viewpoint of a "good" physician. We set out to define patient's priorities regarding different physician's attributes in 3 domains important in medical care.Patients hospitalized or attending clinics at a large teaching hospital selected the 4 attributes that they considered most important out of 21 listed arbitrarily in a questionnaire. The questionnaire included 7 items each in the domains of patient autonomy, professional expertise and humanism.Participating patients  selected professional expertise (50%), physician's patience and attentiveness , and informing the patient, representing the patient's interests, being truthful and respecting patient's preferences (25–36% each) as the most essential attributes. Patient's selections were not significantly influenced by different demographic or clinical background. Selections of attributes in the domain of patient's autonomy were significantly more frequent and this was the preferred domain for 31% and as important as another domain for 16% – significantly more than the domain of professional expertise (P = 0.008), and much more than the domain of humanism and support (P < 0.0005).Patients studied want their physicians to be highly professional and expert clinicians and show humaneness and support, but their first priority is for the physician to respect their autonomy. That can be seen as a prototype or role model of a first class physician. However, these laudable qualities, discussed in many texts -3, were most important and would like the best in their own physician. No grading was required. The questionnaire aimed at the patient's image of an excellent physician in general, and did not specify whether the physician was hospital-based or in primary care. The 21 attributes included 7 characteristics in each one of three domains: reflecting professional expertise and high-quality care; reflecting a humanitarian, patient-centered approach; and reflecting patient's autonomy and attentiveness to the patient's preferences and rights. Then patients supplied basic demographic data and the questionnaire was collected about 20 minutes later. The selection of the 21 different physician characteristics or behaviors started from collecting pertinent articles on patient autonomy; physician's humanism and patient support; and on physicians' expertise and professionalism using the author's (AS) collection and a Medline search. Some of the articles were based on patient-derived data. The next stage involved a series of meetings and discussions at the Department of Ambulatory Care and Prevention, Harvard Medical School, Boston. Three senior researchers  – RH Fletcher, T Peters and AS, selected and categorized the 21 items based on the literature and on personal experience. The third stage was a validation study among thirty residents in various stages of their training. They were presented with a mixed list of the 21 items and requested to categorize each one into one of the 3 domains. To rule out that patients categorized these characteristics differently, we performed an additional post-study validation on 30 outpatients that were representative of our study population. Results were similar to those obtained from the residents and confirmed that the vast majority of participants view each of the items as representative of the corresponding domain (Appendix 1) [see Patients hospitalized at our 600-bed teaching medical center or attending one of its day clinics were randomly approached and asked to fill in a one-page questionnaire. Over a period of one month, patients were approached by one of the authors (DR) and invited to participate. Every third patient on the specific day's ambulatory clinic lists and every fifth patient on the list of patients hospitalized at the Department of Medicine were approached. If the fifth patient was found to be too ill to participate  the next name on the list was selected. These numbers were arbitrarily chosen. Following a brief explanation they were handed the questionnaire. The questionnaire listed 21 physicians' characteristics or behaviors regarding the care of patients, presented in a varying order (different order for different patients) to prevent bias due to an item's position on the list. Patients were asked to select 4 attributes that they considered the x 1) see . No chanA total of 450 patients received the questionnaire and all but 5 consented to participate and returned the filled questionnaires (n = 445). Patient's ages varied from 18 to 89 years (mean 57.5 ± 16) and two thirds were aged 50–80 years. Other patient's characteristics are summarized in Table Our study population of 445 patients was heterogeneous Table , yet no at all by almost 30% of participating patients. An overview of the results reveals that patients studied want their physicians to show professional expertise and provide humane personal care  . Not surprisingly, patients want their physicians to be experienced and highly professional. This was the physician's characteristic that was chosen by 50% of the patients Table , Top. HoOn the other hand, 'humane' qualities that are traditionally considered important, such as showing empathy or being friendly with the patient were surprisingly found to be among the least selected attributes , headed the list.None declared.AS initiated, designed and supervised the study, analyzed the results and wrote the manuscript. DR performed the actual study. NJ provided statistical advice and analysis. All authors read, discussed, contributed to and approved the final manuscript.The pre-publication history for this paper can be accessed here:The patient's questionnaire including the 21 attributes in the three domains.Click here for file


Competition experiments demonstrate that while hMutSα predictably binds the G:T mismatch to a much greater extent than G:A, hMutSα demonstrates a surprisingly equal ratio of competitive inhibition for both G:T and G:A mismatch binding reactions at the H-ras hot spot of mutation. Further, mismatch repair assays reveal almost 2-fold higher efficiency of overall G:A repair (5'-nick directed correct MMR to G:C and incorrect repair to T:A), as compared to G:T overall repair. Conversely, correct MMR of G:T → G:C is significantly higher (96%) than that of G:A → G:C (60%).Electrophoretic mobility shift (gel shift) experiments demonstrate that DNA containing mismatched bases are recognized and bound equally efficiently by hMutSα in both MMR proficient and MMR deficient  may contribute to the observed increased frequency of incorrect repair of G:A, resulting in the predominant GGC → GTC  ras-activating mutation found in a high percentage of human tumors.Combined, these results suggest that initiation of  Factors contributing to these and other hot spots of mutation are still largely unknown, despite much investigation, but now appear to have several different contributions, such as type of DNA damage, genomic location, surrounding sequence, cell cycle position, efficiency of the optimal DNA repair pathway, and involvement of alternate repair and other cellular pathways.Several different DNA repair systems have evolved within all living cells to correct mispaired or damaged nucleotide residues generated either by endogenous events or by exposure to exogenous mutagenic agents ,2. The fras-activating mutations, have been reported as frequent occurrences in HNPCC and other MSI tumors -G:T oligos incubated with nuclear extracts from these MMR proficient cells. In confirmation of hMutSα binding to a G:T mismatch at this oncogenic site, the hMutSα :DNA complex was efficiently interrupted by goat anti-hMSH6 and with rabbit anti-hMSH2  by incubation with unlabeled G:A-oligo, to determine if equal ratios of competitive binding might occur for G:T and G:A, despite the very different avidities of hMutSα for each mismatch. This would provide an indication of equal recognition of each type of mismatch by hMutSα, despite unequal binding avidity for these two mismatches. For these experiments, it was necessary to extend incubation periods from 30 min. to 2.5 hr, as sufficient concentrations of gel shifted bands can be detected with the G:A oligo only after extended incubation (unpublished observations). As expected, binding of hMutSα to [32P]-G:A-oligo is approximately 100 fold weaker in intensity than for [32P]-G:T-oligo after the extended incubation , as determined by comparison of the densitometric intensity of each band. All of the above experiments have been repeated with similar results.An alternate approach to more precisely define the extent of this phenomenon was to measure competitive inhibition of radioactively labeled G:A-oligo ; G:T → G:C = 95%, G:A → G:C = 78%, in agreement with our previously published results using a different plasmid vector , 5 mg/ml BSA, 6% glycerol, in a final volume of 15 – 20 μl. In addition, each reaction contained 100-fold molar excess (100X) unlabeled homoduplex 69 mer, unless otherwise noted. Incubations were for 30 min. at 37°C, unless otherwise noted. Gel shifts of each reaction were electrophoresed at 20 mA within a 4.8% nondenaturing acrylamide gel in 0.5 × TBE buffer, at room temperature. Radioactively labeled oligomers were visualized by autoradiography of the dried gel.Gel shift assays were performed using nuclear extracts from either HCT116 or HCT116 + Ch. 3 cells and ).Correct repair efficiency = 100 × {(fraction of correctly repaired incubated with human nuclear extract) - [(fraction of correct repair by NR9161 direct transformation) × ]}.Incorrect repair efficiency = Total repair efficiency - Correct repair efficiency.Statistical comparisons of G:T and G:A results were conducted by a non-parametric equivalent to the Student's t-test for differences between proportions. Statistical significance was indicated for those comparisons with a P < 0.05 assuming a 2-tailed distribution .ME designed and carried out the MMR assay studies and helped draft the manuscript. HH designed and carried out all other experiments. AS performed all densitometry measurements and helped draft the manuscript. MF and SB helped carry out the MMR assays. KW conceived of the study, participated in its design and coordination and wrote the final manuscript.


TT virus is prevalent worldwide, but its prevalence and genotype distribution in Central and East-Europe has not been determined. The high prevalence of TTV in multiply-transfused patients points to the importance of a parenteral mode of transmission, but since more than half of the general population is infected other possible routes of transmission must be considered.In our study, we investigated the epidemiology, transmission and phylogeny of TTV in the Czech Republic. The following groups were selected: a control group of 196 blood donors, 20 patients with hemophilia, 49 intravenous drug users, 100 sex workers, 50 penitentiary prisoners, 208 healthy children aged 1 to 14 years, 54 cord blood samples, 52 patients with non-A-E hepatitis, 74 patients with hepatitis C, and 51 blood donors with increased ALT levels. Primers specific for the non-coding region were used. The genotype distribution was studied in 70 TTV-positive samples.The prevalence rate of TTV among the Czech population was 52.6%. We have shown that TTV is not transmitted prenatally. Children were infected after birth with two peaks: one at the age of two years and the other after the beginning of primary school. Adults have shown a further increase in the TTV prevalence with age. The highest TTV prevalence was found in the group of patients who had received multiple blood transfusions. The TTV prevalence rate in subjects at an increased risk of sexual transmission was not significantly higher than in the general population. Genotypes G2 and G1 were most prevalent among the Czech population, followed by G8 and G3. The subjects positive for markers of HBV and/or HCV infection tested significantly more often TTV DNA positive, which is suggestive of a common route of transmission of these three infections.This study on TTV prevalence, mode of transmission and age-specific prevalence is the most extensive study performed in Central and Eastern Europe. It showed insights into the epidemiology of TTV infection, but failed to associate TTV infection with clinical manifestations. TTV, a non-enveloped small circular single-stranded DNA virus, was recently placed in a novel virus family named Circinoviridae . In spitTTV has a worldwide distribution. The prevalence of the most common TTV genotypes G1 and G2 is similar all over the world, while the reports on the distribution of other genotypes are scarce and not conclusive. The rate of TTV DNA detection is influenced by the selection of the primer annealing sites. PCR using primers which target the ORF1 region can detect only TTV genotypes 1–6 of group 1, but PCR primers designed for the NCR can detect nearly all genotypes or genetic groups known so far [The prevalence of TT virus in the general population has ranged between 1.9 and 98%, with the highest rates detected in the African and South American countries ,6. The TThe mechanisms of TTV transmission have not yet been elucidated. Even though numerous studies have suggested that the parenteral transmission via transfusion of contaminated blood and blood products is the most common route of TTV infection , the detTTV was originally isolated from a blood-transfused patients in which increased alanine aminotransferase (ALT) levels were detected . TherefoTo investigate the possible routes of TTV transmission, age-specific prevalence and genotype distribution in the population of the Czech Republic, we analyzed sera of 854 subjects divided into 5 groups based on the type of risk of TTV transmission. The age-specific distribution of TTV and correlation with the anti-HBV and/or anti-HCV status were determined. TTV genotypes were determined in 70 patients selected from the different groups.The Human Subjects Committee of the Institutional Review Boards approved all experimental protocols, and all subjects enrolled in the study signed an informed consent form. Additional samples were obtained from the collection of the national reference laboratory for viral hepatitis (NRL-VH). Five groups of subjects were analyzed:Group 1  was selected from 778 healthy blood donors . All donors had normal ALT levels, and were negative for anti-HCV, anti-HIV and HBsAg. Since the TTV DNA prevalence in the first 100 subjects tested was very high we decided to randomly select sera  to incluGroup 2  consisted of 20 hemophiliacs  were collected from 10 patients)  and 49 IVDUs. Patients with hemophilia were screened for anti-HCV, anti-HIV, anti-HBc and HBsAg, IVDUs were tested for anti-HBc and anti-HCV.Group 3  included 85 sex workers and 15 promiscuous men . All of them were screened for anti-HCV, anti-HBc, HbsAg and HIV.Fifty penitentiary prisoners  were tested for a potential increased risk of parenteral and/or sexual transmission of the virus. They were screened for anti-HCV and HBsAg.Group 4 (at risk of transuterine and mother to child virus transmission) consisted of 54 cord blood samples and 208 sera of children selected by age .Group 5  included 52 patients with non-A-E hepatitis , 51 blood donors with elevated ALT levels  and 74 patients with hepatitis C . All blood donors with elevated ALT levels and all patients with non-A-E hepatitis tested negative for anti-HCV and HBsAg. All blood donors were also negative for anti-HIV. All patients with hepatitis C were HBsAg negative.DNA was extracted from 200 μL of serum using the QIAamp Blood kit  and dissolved in 100 μL of elution buffer . Extracted DNA was stored at -20°C.PBMCs were separated by centrifugation from the whole blood on a Ficoll-Paque gradient  according to the manufacturer's protocol. PBMCs were digested with proteinase K (100 μg/ml)  in 1 ml of lysis buffer . Thereafter, proteinase K was inactivated for 10 min at 95°C and samples were stored at -20°C.Five microlitres of total DNA were analyzed in a PCR thermocycler PTC 200 . TTV DNA detection was performed with two sets of primers. A 271 bp long fragment of the ORF1 was amplified in a semi-nested PCR with a modified primer set designed by Okamoto . By nestFor the PCR with NCR specific primers the same conditions as for ORF1 specific PCR were used. In the first PCR we used 50 pmol of primer NG133 (3'GTAAGTGCACTTCCGAATGGCTGAG 5') and NG147 (3'GCCAGTCCCGAGCCCG AATTGCC 5'), for the second PCR 50 pmol of primers NG134 (3'AGTTTTCCA CGCCCGTCCGCAGC 5') and NG132 (3'AGCCCGAATTGCCCCTTG AC 5'). Each of the 35 cycles of the first PCR and 25 cycles of the second PCR consisted of 30 s of denaturation at 94°C, 30 s of annealing at 58°C and 45 s of elongation at 72°C, with a final extension for 7 min at 72°C. Ten microlitres of the PCR product were separated electrophoretically on a 3% agarose gel .N) testing positive was used as a relative titer for determining the viral titer per 1 ml of TTV DNA in serum and PBMCs.DNA extracted from sera and PBMCs of 4 patients with hemophilia was serially diluted (in 10-fold steps) in distilled water and TTV DNA was determined by PCR with NCR primers. The highest dilution , which revealed a clear band on the agarose gel, was determined. PCR products were excised from a 3% agarose gel and purified with MinElute Gel Extraction kit  according to the manufacturer's protocol. Both strands of the 271 bp long products generated by PCR with ORF1-specific primers were sequenced directly with the NG061 and NG063mod primers using the ABI Big Dye Sequencing kit . The sequencing was performed on an ABI PRISM 310 automated DNA sequencer .DNA sequences  were aligned using the CLUSTAL X program  with theHBsAg (V2) AxSYM, CORE AxSYM, AUSAB AxSYM, HCV3.0 AxSYM  tests were used for the detection of HBsAg, anti-HBc, anti-HBs and anti-HCV markers. HBsAg reactive samples were confirmed with the HBsAg Confirmatory AxSYM test.The statistical analysis was performed using the Fisher exact test. Odds ratios (OR) with 95% confidence intervals (CI) and two-tailed P values were calculated in 2 – 2 tables using the EPI INFO statistical package (version 2002) and GraphPad InStat (version 3.05) . In all tests, the basic significance level was P = 0.05.In total, 854 samples were screened for the presence of TTV DNA using a NCR-PCR. The TTV genotype was determined by sequencing part of the ORF1 region from 70 TTV isolates.The prevalence rates of TTV DNA in different groups are shown in Table As indicated in Figure As indicated in Table The results of our sequencing and phylogenetic analysis are summarized in Table Tree of four patients positive in both serum and PBMCs by the ORF1 PCR system yielded a PCR product adequate for sequencing analysis. Genotypes and sequence homologies are shown in Table Four groups of subjects were compared for correlation of past HBV and/or HCV infection with TTV DNA prevalence. We compared subjects at a higher risk of sexual transmission, IVDUs, patients with hemophilia and penitentiary prisoners. There was no evidence of present or past HCV or present HBV infection in blood donors. The prevalence of anti-HBc in blood donors in the Czech Republic is very low . These data imply that our control group was at a low risk of sexually and parenterally acquired infections. Also all children were anti-HBc and anti-HCV negative. Both the groups of hemophiliacs and IVDUs presented evidence of frequent past or current HBV (50% and 22%) and HCV (82% and 72%) infection. Thirteen percent of sex workers and promiscuous men showed past or current HBV exposure. The study subjects positive for HBV and/or HCV markers had a significantly higher prevalence of TTV DNA regardless of the primer set used Table .The present study on TTV prevalence, mode of transmission and age-specific prevalence is the largest study performed in Central and East Europe. This study showed that TTV infection is quite common among the Czech population. The prevalence rates of TTV in blood donors (52.6%) were similar to those found in other developed countries (for review see ).The most interesting result was the lack of TTV DNA in 54 cord blood samples, suggestive of the absence of transuterine transmission of TTV. Furthermore, we have shown that the prevalence of TTV DNA was age dependent. In children, we observed a dramatic increase of TTV prevalence within the first two years of age. The prevalence of TTV further gradually increased in children aged 8 to 14 years. Similarly, Ohto et al. reported that the TTV prevalence in children at the age of 2 years was comparable with that in mothers, while children younger than 3 months of age were infected only exceptionally . In the In adults, we have shown the increase of TTV prevalence with age irrespective of study group. Similar results have been reported by others ,30-33.We observed an increased prevalence of TTV in various groups of hepatitis patients. Since many hepatitis viruses share the same modes of transmission, multiple viral infections may occur in one patient . Our resIn agreement with other studies we detected the highest prevalence of TTV in hemophiliacs and IVDUs, which supports the importance of the parenteral route of transmission of TTV ,35-38. NAs for TTV sexual transmission, the results of our study suggest that if TTV is sexually transmitted, this mode of transmission is likely to be less important. Even though 13% subjects of the group at risk for sexual transmission of TTV showed past or current HBV exposure, indicative of high promiscuity, the prevalence of TTV was not significantly different from that of the control group (62% and 52.6%). To the best of our knowledge, so far only one study found a significant difference in the TTV prevalence in sex workers , while oIn the group of penitentiary prisoners the significantly higher prevalence of TTV seems to be most probably a consequence of intravenous drug abuse rather than sexual promiscuity since the prevalence of HCV was four-times higher than in the group at risk for sexual transmission (20% versus 5%).An increased prevalence of TTV in non-A-E hepatitis patients was observed in the present study in agreement with many previous studies. Additionally, our data showed an increased TTV prevalence in blood donors with increased ALT levels. Several studies have shown a correlation between TTV-titer and elevation of serum ALT levels ,30 but tThe heterogeneity of TTV is extreme. Because the NCR region is too conserved for evolutionary analyses, the ORF1 region of the TTV genome is most often used for genotyping. Out of the 70 sequenced isolates, G2 followed by G1 were the most frequent genotypes among the Czech population. The phylogeny analysis showed no evidence of association of particular TTV genotypes with any of the risk groups.Our results demonstrated a high prevalence of TTV in the Czech population. Our data show the absence of transuterine transmission of TTV, but postnatal route of transmission from mother to child and infection via frequent social contacts seem to be very important modes of transmision in children. The sexual mode of transmission is most likely to be low effective. No convincing evidence was found to support the involvement of TTV in the pathogenesis of hepatitis.Our data, as well as the results of other studies, show that optimization of the primer set for more standard TTV detection and genotyping is still needed. Improved serological approach to TTV detection could be of value. It is evident that more data are still needed for a better understanding of the natural history of TTV infection.The author(s) declare that they have no competing interests.RT and VN conceived of the study and participated in its design and coordination. MS carried out most of the experimental work and participated on the preparation of the initial draft of the manuscript. Part of the experimental work was done by JK. RT did all the statistical analysis and evaluation of the results and writing of the final version of the manuscript. All authors contributed to the preparation of the final manuscript.The pre-publication history for this paper can be accessed here:


Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration, thus enhancing innate immunity. We tested the safety and tolerability of aerosolized iso-osmotic xylitol in mice and human volunteers.This was a prospective cohort study of C57Bl/6 mice in an animal laboratory and healthy human volunteers at the clinical research center of a university hospital. Mice underwent a baseline methacholine challenge, exposure to either aerosolized saline or xylitol (5% solution) for 150 minutes and then a follow-up methacholine challenge. The saline and xylitol exposures were repeated after eosinophilic airway inflammation was induced by sensitization and inhalational challenge to ovalbumin. Normal human volunteers underwent exposures to aerosolized saline (10 ml) and xylitol, with spirometry performed at baseline and after inhalation of 1, 5, and 10 ml. Serum osmolarity and electrolytes were measured at baseline and after the last exposure. A respiratory symptom questionnaire was administered at baseline, after the last exposure, and five days after exposure. In another group of normal volunteers, bronchoalveolar lavage (BAL) was done 20 minutes and 3 hours after aerosolized xylitol exposure for levels of inflammatory markers.In naïve mice, methacholine responsiveness was unchanged after exposures to xylitol compared to inhaled saline (p = 0.49). There was no significant increase in Penh in antigen-challenged mice after xylitol exposure (p = 0.38). There was no change in airway cellular response after xylitol exposure in naïve and antigen-challenged mice. In normal volunteers, there was no change in FEV1 after xylitol exposures compared with baseline as well as normal saline exposure (p = 0.19). Safety laboratory values were also unchanged. The only adverse effect reported was stuffy nose by half of the subjects during the 10 ml xylitol exposure, which promptly resolved after exposure completion. BAL cytokine levels were below the detection limits after xylitol exposure in normal volunteers.Inhalation of aerosolized iso-osmotic xylitol was well-tolerated by naïve and atopic mice, and by healthy human volunteers. Human airway surface is covered by a thin layer of liquid (airway surface liquid [ASL]) that contains many antimicrobial substances including lysozyme, lactoferrin, human β defensins, and the cathelicidin LL-37 -4. The ain vitro  - 1) × [2Pef/3Pif ], where Penh equals enhanced pause, Te equals expiratory time (in seconds), Tr equals relaxation time (in seconds), Pef equals peak expiratory flow (in milliliters per second), and Pif equals peak inspiratory flow (in milliliters per second).All experiments were reviewed and approved by the animal care and use committee of the University of Iowa. Except during exposures and evaluation, mice were allowed access to food and water ad libitum. C57bl/6 mice  underwent baseline methacholine challenge test using a whole-body plethysmograph  as previously described . RespiraMice (6/group) were exposed to aerosolized saline (0.9 % NaCl) or aerosolized xylitol  for 150 minutes in an exposure chamber; all mice were evaluated for bronchial hyperreactivity to inhaled methacholine (using the Buxco whole body plethysmography system) before and after the exposures; other mice were monitored periodically during exposure by whole body plethysmography. All mice underwent whole lung lavage the next day for cell count and differential. After euthanasia, the trachea was cannulated, and the lungs were lavaged with 3.0 mL of sterile normal saline (0.9% NaCl). The lavage samples were immediately processed for total and differential  cell counts. In a separate group of naïve mice, whole body plethysmography was used to monitor Penh, respiratory rate, and tidal volume periodically during exposure to xylitol and saline for 10, 20, 40, and 80 minutes for a cumulative total dose of 150 minutes.We repeated the saline and xylitol exposure protocol to 2 more groups of six mice each after they were sensitized to and challenged with an antigen . Mice weGiven the concerns that have been raised about the reliability of airway resistance measurement by Buxco equipment, in a select number of mice we confirmed airway hyperresponsiveness using invasive measurement. Airway responsiveness was measured 24 hours after xylitol exposure in ova-challenged mice and compared to measurements made on naïve mice and ova-challenged mice without any exposure. Mice were anesthetized with Ketamine at 90 mg/kg and Pentobarbital at 50 mg/kg and attached to a small-animal ventilator . Animals were ventilated at 150 breaths/min. Positive end-expiratory pressure (PEEP) was maintained between 2–3 cmH2O, with the computer setting the tidal volume from the entered weight of each animal. Central airway resistance (R) was measured at baseline and after 10 sec. of nebulized methacholine at doses of 12.5, 25 and 50 mg/ml.The study was approved by the University of Iowa Institutional Review Board as well as the Food and Drug Administration. Since this is a pilot study and would be the first time xylitol is being used as aerosol, there was no information available on expected complications. Ten subjects aged 18 or greater were studied. Pregnancy or any chronic medical conditions such asthma, atopy, and diabetes were grounds for exclusion. After giving written informed consent subjects underwent a screening spirometry . Baseline measurements of serum electrolytes, and serum and urine osmolarity were carried out. Baseline oxygen saturation was measured using a pulse oximeter. A brief questionnaire of respiratory symptoms that was developed using a visual analog scale (VAS) was administered at baseline ,32.Subjects received 10 ml of aerosolized saline  . The parThirty minutes after the exposures, subjects completed a follow-up questionnaire, and underwent spirometry and O2 saturation measurement. The procedure was repeated after exposure to 1, 5, and 10 ml of 5% xylitol . Xylitol was prepared by adding 5 gm of crystal sugar to every 100 ml of sterile water . The solution was sterilized using FDA approved techniques and osmolarity confirmed to be 292 mOsm using a 5500 vapor pressure osmometer . After completing the exposures, repeat blood and urine tests for electrolytes and osmolarity were carried out. Finally, subjects repeated the symptom questionnaire five days after the first visit, over the telephone. The pre-established criterion for discontinuing study participation was a decline in FEV1 by greater than 20% from baseline.Spirometry was performed using a Vmax V6200 Autobox , according to guidelines published by the American Thoracic Society . The spiThe amount of symptoms was assessed at baseline and after each exposure. Subjects scored chest tightness, shortness of breath, cough, headache, chills, muscle soreness, phlegm, nausea, stuffy nose, sneezing, and fatigue on a visual analog scale from 0–10 cm (0 being symptom-free and 10 being extreme amount) ,32.++ and Mg++ and suspended in complete medium, Roswell Park Memorial Institute (RPMI) tissue culture medium . Differential cell counts were determined with cytospin  slide preparations by using Wright-Giemsa stain. The cell-free fluid was frozen at -70°C until required for cytokine assay.We also examined the effect of aerosolized xylitol on markers of inflammation in the airways. A separate group of subjects underwent bronchoscopy and bronchoalveolar lavage (BAL) according to American Thoracic Society standards at 30 minutes (n = 6), and 3 hours (n = 5) after exposure to 10 ml of aerosolized iso-osmolar xylitol . BAL wasCytokine measurements were performed using enzyme linked immunosorbent assays for IL-6 and LTC-4. IL-6 levels were determined by a Quantikine Human IL-6 ELISA kit . The limit of detection of IL-6 is 0.70 pg/ml. LTC-4 (leukotriene) levels were determined by a leukotriene C4 EIA kit . The limit of detection of LTC4 is 10 pg/ml. LTC4 of BALs were extracted and concentrated with Cysteinyl-Leukotriene Affinity Sorbent .We studied ten subjects with a gradual increase in exposure dose in the pilot safety study. Differences were analyzed using t-test, Wilcoxon signed rank test, and one way and two-way repeated measures analysis of variance (ANOVA) as indicated. Ninety-five percent confidence intervals were calculated where appropriate. All analyses were performed using SAS version 8.2  and at a 5% significance level.Mice tolerated the exposures well without any visible distress. The corresponding volume of the 150-minute exposure was approximately 45 ml. Among naïve mice, exposure to xylitol resulted in no significant change in bronchial hyperresponsiveness compared to saline Figure . We carrWhole lung lavage showed no significant differences in lavage fluid cell count and differential due to xylitol exposure. Naïve mice exposed to saline or xylitol demonstrated, as expected, a macrophage-predominant response. In contrast, OVA-sensitized/-challenged mice were characterized by airway eosinophilia in both saline- and xylitol-exposed groups Table . In summTable As shown in Table An additional 11 subjects underwent bronchoscopy and bronchoalveolar lavage following xylitol inhalation. The mean cell count in the BAL fluid at 20 minutes (n = 6) and 3 hours (n = 5) after xylitol exposure was 1.2 ± 0.07 million cells/ml and 2.94 ± 1.48 million cells/ml respectively. All cell preparations had between 95–100% alveolar macrophages. BAL IL-6 and LTC-4 levels after xylitol exposure were below 0.70 pg/ml and 10 pg/ml respectively at all time points.Lower respiratory tract colonization is an important step in the pathogenesis of pulmonary manifestations of chronic diseases such as CF and dyskinetic cilia syndrome and certain acute clinical entities such as ventilator-associated pneumonia. There is a continuing need for simple, cost-effective, and safe intervention to decrease colonization of lower airways. Studies have shown that lowering the salt concentration of airway surface liquid can enhance innate immunity by increasing the potency of the natural antimicrobial peptides. In addition to increasing the activity of individual ASL factors, lowering the NaCl concentration also independently enhances synergistic interactions . Thus, lXylitol, when applied to airways as an iso-osmolar agent, can potentially lower airway salt concentration and therefore lower bacterial colonization in chronic infections. In addition to having low transepithelial permeability, it has the added advantage of being poorly metabolized by bacteria. In recent years, many osmotic agents have been aerosolized into human airways for mucus clearance. However, there are reports of bronchospasm associated with their use. This is the first study to our knowledge to use xylitol in an aerosolized form.The main adverse effect reported from oral xylitol use was diarrhea when the dose exceeded 40–50 gm/day . Intraveet al. [2. The depth of ASL may vary from the trachea to the small bronchioles; if an average depth of 10 μm is estimated, the total ASL volume would be ~2.5 mL. Thus, if we assume a uniform aerosol distribution, administration of a total volume of 2.5 mL of 300 mM xylitol to the airways would be expected to lower the salt concentration in half simply by a dilutional effect. If the mean ASL depth were 20 μm, then 5 mL of delivered solution would be required. Because the solution is iso-osmotic, immediate, major osmotic shifts of water across the epithelium should not occur, which leads to dilution of the salt concentration. Moreover, with time, the volume and salt concentration may decrease due to Na+-dependent salt absorption, the osmotic effects of which are counterbalanced by xylitol in the ASL [We made calculations of the amount of xylitol to be delivered to the airway surface of an adult. Mercer, et al.  measured the ASL .et al. [Our preliminary calculations for dosing for mice experiments were derived as follows; Mercer, et al.  also estet al. . Assuminet al. , which wThis study shows that aerosolization of iso-osmotic xylitol is likely to be safe and well tolerated by human volunteers. There was no change in spirometry, laboratory test results as well as BAL cytokine levels after xylitol exposure. Earlier studies have reported bronchial hyperresponsiveness with aerosolization of hypotonic and hypertonic solutions. Thus, aerosolization of iso-osmotic xylitol could be tested for prevention and treatment of airway colonization.There are several potential limitations with this study. The validity of body plethysmography as a measure of respiratory physiology in mice has been recently questioned ,49. HoweIn summary, our data indicate that iso-osmotic xylitol can be safely delivered by aerosol to normal volunteers. Studies of safety with long-term exposure to animals are required before human use can be attempted. This could lead to exciting interventions to enhance the innate immunity of airway epithelia.ANOVA Analysis of VarianceASL Airway Surface LiquidCF Cystic FibrosisFEV1 Forced Expiratory Volume in 1 secondGSD Geometric Standard DeviationPenh Enhanced PauseVAS Visual Analog ScaleBAL Bronchoalveolar Lavage


There is little information on the effectiveness of modern compared to traditional malaria treatment from the rural areas of Africa.Follow-up of 402 episodes of clinical malaria among pre-school children in Nouna Health District, northwestern Burkina Faso. The exposure of interest was the type of treatment ; the outcome was clinical response to treatment.Out of the 402 observed malaria episodes, 87% were treated with chloroquine and 13% with traditional remedies. Overall, community effectiveness was 67% with chloroquine and 54% with traditional treatment. Chloroquine effectiveness was associated with age and ethnicity. An additional interview survey demonstrated wide variations in the dosages of chloroquine given to young children in this community.The effectiveness of chloroquine, when used within the community, was significantly lower in this study than its known efficacy in the study area. This concerns, in particular, the very young children. These findings demonstrate the need for better education of parents about correct dosage of first-line malaria drugs, and for particular attention in the treatment of very young children. It has been estimated that at least one million annual malaria deaths occur among young children in rural sub-Saharan Africa (SSA). Most of these deaths are in areas with little access to health services -4. UnderThe situation is now complicated by the increasing resistance of Plasmodium falciparum to chloroquine in most SSA countries . MoreoveTraditional treatment for malaria is very common, particularly in the rural areas of SSA, but only few data exist regarding the efficacy of such treatments ,12. In rThis paper reports on the community effectiveness of chloroquine compared to traditional remedies in the treatment of uncomplicated falciparum malaria in young children of rural Burkina Faso.The study was conducted in the rural part of the research zone of the Centre de Recherche en Santé de Nouna (CRSN), in Nouna Health District, north-western Burkina Faso. The CRSN study zone comprises 41 villages and Nouna town, with a total population of 55,000. The Nouna area is a dry orchard savanna, populated by subsistance farmers of different ethnic groups. There is a short rainy season which usually lasts from June until October. Malaria is holoendemic but highly seasonal in the study area . Formal This is an observational study at the community level. Data for this study were extracted from the database of a trial on the effects of zinc supplementation on malaria morbidity conducted in the Nouna area in 1999 . During Field methods for data collection have already been described . In brieAll relevant signs and symptoms manifested by the children were recorded on a standard questionnaire during regular visits of field staff. Moreover, a comprehensive questionnaire was filled in for each disease episode which included information on specific signs and symptoms as well as place, time and type of treatment received. No specific information was recorded on the dosage of chloroquine and on the type of traditional remedies given to the study group.For this study, only children with a diagnosis of falciparum malaria, defined as an axillary temperature of ≥37.5°C together with a density of ≥5,000 P. falciparum parasites per μl of blood were considered. Inclusion criteria were falciparum malaria treated with chloroquine (with or without antipyretics) but without traditional remedies (group CQ), or with traditional remedies only (group TRAD). Exclusion criteria were a history of febrile illness during the previous four weeks, malaria treatment during the previous four weeks, any treatment with another antimalarial drug during follow up, and missing temperature measurements during the two-weeks follow up period. Multiple episodes of malaria in individual children were considered to be independent with regard to treatment choice .To evaluate treatment outcome, a modified definition of the WHO protocol for assessment of therapeutic efficacy of antimalarial drugs in areas with intense transmission was used . TreatmeTo retrospectively estimate the chloroquine dosages usually given to febrile young children in the study area, 55 individual interviews with randomly selected mothers of young children from three villages in the study area were conducted during a malaria survey at the end of the 2001 rainy season. The villages were purposely selected to represent the rural study population in its socio-cultural, demographic and geographical diversity. Questions concerned the kind of treatment  and the dosages of western drugs used during treatment of the last febrile episode of survey children, the current availability of chloroquine in the household and the origin of chloroquine drugs. The weight of children was measured with a Salter hanging spring scale.Blood films were kept in closed slide boxes until they were transported to Nouna (two to three times per week). They were Giemsa-stained at the Nouna hospital laboratory and transported afterwards to the Centre National de Recherche et de Formation sur le Paludisme (CNRFP) in Ouagadougou for reading. All films were examined by two experienced laboratory technicians using a ×100 oil immersion lens and ×10 eyepieces. In case of significant discrepancy between the results of the two technicians, blood slides were read by a third investigator. Blood films were analysed for the species-specific parasite density per μl by counting against 500 white blood cells and multiplying by sixteen . Slides were declared negative if no parasites were seen in 400 fields on the thick film.Data were entered at the data management department of the CRSN into a data bank . All questionnaires were checked by supervisors before computer entry. Parasitological data were entered into EpiInfo (version 6.0) at the CNRFP, and the data were transferred to the CRSN. All data were checked for range and consistency before data entry.The outcome of malaria episodes (AR vs. TF) was assessed dependent on the treatment given by the caretakers. Episodes in which the child had received at least one dose of chloroquine were grouped in the treatment group CQ, and episodes in which caretakers had given only traditional treatment in the treatment group TRAD. The hypothesis was tested that the samples in the CQ and the TRAD treatment groups were from populations with the same distribution of baseline variables using the Wilcoxon ranksum test for continuous variables and the chi-squared test for categorical variables. Community effectiveness of treatment with chloroquine was assessed both by intention to treat (i.e. adherence to advice by the field workers to give chloroquine) and considering only those cases who actually complied. A stratified analysis by age bands was started, assuming that age would be an important determinant of treatment outcome. Logistic regression modelling was then used to control for differences in the distribution of baseline characteristics such as age, sex and parasite density in the two treatment groups. Stata 7.0 statistical software was used for all calculations.Approval for the RCT from which the data used were drawn was granted by the Ethical Committee of the Heidelberg University Medical School and the Ministry of Health in Burkina Faso.A total of 330 children (175 boys and 155 girls), who contributed 402 episodes of falciparum malaria, were followed up. Most of the episodes (65.7%) occurred between August and October (Table In 350 (87.1%) of the episodes, the child had received at least one dose of chloroquine (treatment group CQ); in 52 episodes (12.9%), the caretakers had given only traditional treatment (treatment group TRAD). Table The caretakers had been advised to give chloroquine to all children participating in this study. Compliance with this advice, stratified by age group, is shown in Table The crude odds ratio for TF in the CQ group vs. the TRAD group was 0.59 with a 95% confidence interval that included unity . During the most recent fever episodes of respective children, home treatment with chloroquine was reported in 32/55 (58%) , treatment at the local health centre in 15/55 (27%), traditional treatment in 6/55 (11%), and only paracetamol treatment in 2/55 (4%). The mean weight of chloroquine-treated children was 8.5 kg (range 3.2 – 12.0 kg). The mean (median) total dose of chloroquine used was 34 mg/kg and 25 mg/kg respectively (range 5–110 mg/kg) (figure 1). Only 9/55 (13%) mothers reported current availability of chloroquine tablets in their household . Most chloroquine drugs were purchased from local shops and drug sellers.The main finding of this study is a rather low community effectiveness of chloroquine in the treatment of malaria episodes among young children in rural Burkina Faso. Overall, a failure rate of 35% was observed which declined only marginally to 33% when malaria episodes in which caretakers did not comply with the advice to give chloroquine were excluded. This is considerably higher than the 10% treatment failure rate observed in a study on chloroquine efficacy in young children of the area . These fThe effectiveness of treatment with chloroquine increased significantly and almost linearly with age, even after controlling for parasite density. The most likely explanation is a rapid development of immunity within the age range of our study children, as has been observed in other studies ,17,18. TOnly a small number of episodes were treated solely with traditional treatment, possibly a consequence of the view of the local population that western malaria treatment is more effective than traditional treatment . This maThis study has two limitations. First, information on the dosage of chloroquine and on the nature of traditional remedies given to children in the study was lacking. However, data from the interview survey provide a good estimate of chloroquine dosages used. Although these data demonstrate a wide variation of chloroquine dosages, it is reassuring that the reported median dosage complies with the national recommendations of a total dose of 25 mg/kg chloroquine for uncomplicated malaria. So why is there such a difference between efficacy and effectiveness? The reason may well be a combination of partly chloroquine underdosing, poor quality of drugs purchased from local shops and drug sellers and high frequency of vomiting in febrile young children -23. MoreIn conclusion, this study provides clear evidence for a rather low and age-dependant community effectiveness of chloroquine in the treatment of P. falciparum malaria in an area of rural Burkina Faso where the efficacy of chloroquine is still sufficiently high in use as first-line treatment. The observed discrepancy between efficacy and community effectiveness implies that many children received insufficient doses of chloroquine. Our findings thus point to the importance of (1) better education of parents on correct dosage of first-line malaria drugs, as well as on danger signs requiring a visit at a health centre, (2) quality-control of all malaria drugs used in the community, and (3) particular care in the treatment of immunologically naïve very young children. Finally, more studies on the types and effects of traditional treatments used in different population groups are needed.


Brugia malayi is endemic in several Asian countries with the highest prevalence in Indonesia. Determination of prevalence of lymphatic filariasis by serology has been performed by various investigators using different kinds of antigen (either soluble worm antigen preparations or recombinant antigens). This investigation compared the data obtained from IgG4 assays using two different kinds of antigen in a study on prevalence of antibodies to B. malayi.Serum samples from a transmigrant population and life long residents previously tested with IgG4 assay using soluble worm antigen (SWA-ELISA), were retested with an IgG4 assay that employs BmR1 recombinant antigen (BmR1 dipstick [Brugia Rapid™]). The results obtained with the two antigens were compared, using Pearson chi-square and McNemar test.There were similarities and differences in the results obtained using the two kinds of antigen (SWA and BmR1). Similarities included the observation that assays using both antigens demonstrated an increasing prevalence of IgG4 antibodies in the transmigrant population with increasing exposure to the infection, and by six years living in the area, antibody prevalence was similar to that of life-long residents. With regards to differences, of significance is the demonstration of similar antibody prevalence in adults and children by BmR1 dipstick whereas by SWA-ELISA the antibody prevalence in adults was higher than in children.Results and conclusions made from investigations of prevalence of anti-filarial IgG4 antibody in a population would be affected by the assay employed in the study. Brugia malayi and Brugia timori ) and detection of IgG4 antibodies were evaluated using the same set of serum samples. The BmR1 dipstick test has previously been shown to be highly specific and sensitive for the detection of brugian filariasis. In a study involving four international laboratories, the BmR1 dipstick was found to be 93% sensitive and 100% specific when tested with 535 serum samples from patients with various infections and healthy controls . The BmR1 recombinant antigen was expressed from The results obtained with BmR1 dipstick were compared to the results obtained previously with SWA-ELISA. The similarities and differences in the results were analyzed by comparing proportion of related samples using McNemar test; and comparing proportions of unrelated samples by using Pearson Chi-square (if indicated Fischer exact test was used instead).B. malayi, as determined by BmR1 dipstick assay and SWA-ELISA, in the transmigrant population who had resided for various lengths of time in the endemic area and the antibody prevalence in the LLR population. The first detection of IgG4 antibody by the BmR1 dipstick was recorded at 3 years post-exposure, the antibody prevalence increased from 0% in the new arrivals (≤ 1 month and 2–4 months) to 7.4%, 11.1%, 39.1% and 42 % in populations exposed to the infection for 3, 4, 5 and 6 years respectively. Comparison of IgG4 assays using the two kinds of antigen demonstrated similarities in three areas. First, using both SWA-ELISA and BmR1 dipstick, the total prevalence of specific IgG4 in the transmigrant population was found to increase with increasing length of residence in the endemic area. Thus the BmR1 dipstick test confirmed the previously reported finding which demonstrated that the development of anti-filarial IgG4 correlated with the duration of exposure in previously unexposed population [Figure pulation . Second,pulation . Thus thpulation . Third, Differences between the two kinds of antigen were also observed Figure . First, Figure Strongyloides antibody responses was found to be associated with higher antifilarial IgG4 responses in assay that uses crude filaria extract as compared to assay that uses B. malayi Bm14 recombinant antigen [Thus the BmR1 dipstick test demonstrated that the establishment of anti-filarial IgG4 in the children and adults of the transmigrant population occur at comparable rates; this is not in agreement with the previous finding, using SWA-ELISA, that demonstrated IgG4 was established more rapidly in the adult population than in children . The abo antigen .The discrepancy between the results of SWA-ELISA and BmR1 dipstick may also be partly due to the greater sensitivity of the former as compared to the latter. Out of 120 of 381) discrepant results, 111 were positive by SWA-ELISA but negative by BmR1 dipstick. Out of these 111 samples, 38 had low ELISA titers . If the stringency of the cut-off value of the SWA-ELISA is increased from 4.02 to 4.5, then the discrepancy can be considerably reduced to 88 (of 381), with 73 positive by SWA-ELISA but negative by BmR1 dipstick. On the other hand, since BmR1 dipstick test has been reported to be highly specific 1 discrep, it is ualbeit equally specific) than BmR1 dipstick test [B. malayi infection. Thus in this study if the ELISA format had been used to determine prevalence of IgG4 antibodies to BmR1 instead of the dipstick format, the SWA-ELISA would still be detecting significantly more positives than the BmR1-ELISA.Due to the problem of maintaining the antigenicity of the BmR1 antigen when shipped from Malaysia to Netherlands, the dipstick (immunochromatography) assay, which can be transported at room temperature, was employed to test the BmR1 antigen. However the difference in the assay formats is unlikely to be the reason for the lower overall antibody prevalence levels seen with the latter. This is because we have previously shown that ELISA using BmR1 was less sensitive . In the adult population, except for the earlier initial detection, a similar pattern was observed with the results of the BmR1 dipstick i.e. increasing rate of antibody prevalence in the transmigrants with exposure; and the IgG4 prevalence at year 6 is not significantly different (p = 0.430) than the antibody prevalence in the LLR adult population.This study highlights that assays using both BmR1 and SWA antigens demonstrate an increasing prevalence of specific IgG4 antibodies in the transmigrant population with increasing length of residence in an area endemic for brugian filariasis, and, by six years residency that the antibody prevalence was similar to that observed in the LLR population. This study also documented three main differences in results derived from assays using two antigens i.e.1. Earlier detection and higher rate of antibody prevalence by SWA-ELISA as compared to the results demonstrated by BmR1 dipstick;2. Similar rate of acquisition of antibody prevalence in children and adults by BmR1 dipstick; whereas by SWA-ELISA adults were found to become antibody positive faster than in children;3. By BmR1 dipstick the increasing total prevalence of IgG4 with exposure was primarily due to the adult population, whereas by SWA-ELISA this was attributed to both children and adult populations.Brugia malayi infection may vary with the kind of antigen used in the assay. Thus comparison of results of different studies must take into account the kind of antigen employed, especially if one study uses native antigen and another uses recombinant antigen. It would be interesting to compare seroepidemiological data of IgG4 assays using two different recombinant antigens on the same population.This study demonstrates that some aspects of seroepidemiology of Rahmah Noordin is the inventor of the commercialized BmR1 dipstick test (Brugia Rapid™)RN drafted the paper and supplied the BmR1 dipstick test; SW & AM supplied the sera and edited the paper; LBH performed most of the statistical analysis; ES and MY conceived the study and contributed significantly in editing of the paper: In addition ES performed the BmR1 dipstick test and some statistical analysis. All authors read and approved the final manuscript.


Osteoid osteoma is a benign bone neoplasm which is seen in the long bones of appendicular skeleton. It is rarely seen in the cranium. Skull base osteoid osteoma is extremely rare and has been anecdotally reported.The authors report a case of a large osteoid osteoma of the ethmoid with intraorbital and intracranial extension in a 33 year old male patient. He presented with loss of vision in the left eye. The intra-cranial extension was excised through a single burr-hole fronto-orbitotomy. The ethmoid and orbital portions were approached and excised through a Weber-Ferguson incision and inferior orbitotomy. Radical excision of the tumor could thus be achieved through a craniofacial approach.Although benign and rare, skull base osteoid osteoma can present with neurological deficit due to its mass effect and involvement of vital structures. A multispeciality team approach is advisable in such cases if radical excision is to be achieved. A craniofacial approach made radical single stage excision of this multicompartmental osteoid osteoma possible with an uneventful postoperative period. Osteoid osteoma is a rare benign osteoblastic lesion usually involving the long bones of the lower limbs. Cranial involvement has been mainly localised to the skull vault. Osteoid osteoma of the skull base is a rare entity . SurgicaA 33 year old male presented with decreased vision in the left eye and left sided headache of 3 months duration. Examination revealed left eye blindness with primary optic atrophy and no other neurological deficit. Imaging revealed a bony tumor in the left ethmoid sinus invading the left orbit and compressing the left optic nerve. Intracranial extension into the anterior cranial fossa on the left side was noted Figure . Core biA multispeciality team approach was devised to achieve radical excision of the tumor. Bicoronal scalp flap and pericranial flaps were raised separately. A single burr hole left fronto orbital bone flap was raised including the orbital roof and left zygomaticofrontal process Figure . Dura waPost-operatively patient had a frozen left eye  with no improvement in the left eye vision in the immediate postoperative period. His postoperative period was otherwise uneventful. Histopathological examination revealed an osteoid osteoma Figure . On follOsteoid osteoma is a benign osteoblastic lesion and constitutes 1% of all bone tumors and 11% of benign bone lesions . CranialThe radiological diagnosis rests on Computerised Tomography and isotope bone scan . RadiogrThe treatment generally consists of en bloc resection or curettage of the tumor. Recurrence rate after incomplete resection may be upto 10% . Our patHistologically the nidus is sharply delineated from the surrounding variably thick layer of dense bone. The nidus is composed of more or less calcified osteoid lined by plump osteoblasts within a highly vascularised connective tissue stroma  Figure . It doesOsteoid osteoma of the skull base is rare and anecdotally reported. Radical excision is difficult especially if the tumor involves major blood vessels and cranial nerves. The surgical team constituted the neurosurgeon, surgical oncologist and plastic surgeon. A craniofacial approach made radical single stage excision of this multicompartmental osteoid osteoma possible with an uneventful postoperative period.All the authors of the article "ETHMOIDAL OSTEOID OSTEOMA WITH ORBITAL AND INTRACRANIAL EXTENSION -CASE REPORT" hereby declare that there are no competing interests – financial and non financial.SBP performed the craniotomy, excised the intracranial extension of the tumor, assisted in excising the orbital portion, drilled the ethmoidal portion and drafted the manuscript.KH excised the orbital portion and helped draft the manuscript.MSV and US performed the orbitotomy, helped in tumor excision and closure.DJ did the histopathological examination and helped in drafting the manuscript.All authors have read and approved of the manuscript.The pre-publication history for this paper can be accessed here:


The degree of volume depletion in severe malaria is currently unknown, although knowledge of fluid compartment volumes can guide therapy. To assist management of severely ill children, and to test the hypothesis that volume changes in fluid compartments reflect disease severity, we measured body compartment volumes in Gabonese children with malaria.Total body water volume (TBW) and extracellular water volume (ECW) were estimated in children with severe or moderate malaria and in convalescence by tracer dilution with heavy water and bromide, respectively. Intracellular water volume (ICW) was derived from these parameters. Bioelectrical impedance analysis estimates of TBW and ECW were calibrated against dilution methods, and bioelectrical impedance analysis measurements were taken daily until discharge. Sixteen children had severe and 19 moderate malaria. Severe childhood malaria was associated with depletion of TBW (mean [SD] of 37  ml/kg, oSignificant hypovolaemia does not exacerbate complications of severe or moderate malaria. As rapid rehydration of children with malaria may have risks, we suggest that fluid replacement regimens should aim to correct fluid losses over 12–24 h. Some investigators have suggested that children with malaria need a lot of fluids. But this paper casts doubt on this assumption, and assesses a novel way to assess fluid balance ICW is calculated by subtraction of the ECW from the TBW.Malaria claims one million lives annually, with more than 90% of these being those of children in sub-Saharan Africa . Most deTracer dilution methods are expensive and invasive and cannot be repeated at short intervals. Therefore, we simultaneously calibrated a noninvasive technique of bioelectrical impedance analysis (BIA)  to estimWe hypothesised that volume changes in fluid compartments would reflect disease severity in malaria and that these changes would be related to established markers of disease severity . We alsoThe study was conducted at the Albert Schweitzer Hospital, Lambaréné, Gabon, and Centre Hospitalier de Libreville, Gabon. It was approved by the ethics committees of the International Foundation of the Albert Schweitzer Hospital, the Gabonese Ministry of Health, and the University of Tübingen.Plasmodium falciparum in thick or thin blood films. Severe malaria was malaria with one or more of the following features: blood lactate ≥ 5 mmol/l, blood glucose ≤ 2.2 mmol/l, Blantyre coma score ≤ 2, or repeated, observed seizures  is plasma sodium concentration (millimoles/litre), [glucose] is plasma glucose concentration (millimoles/litre), [urea] is plasma urea concentration (millimoles/litre), 1.86 is a correction factor as sodium chloride is only 93% dissociated, and 0.93 is the assumed proportion of water in plasma.where OG is osmol gap, MO is measured osmolality, ) time from admission to administration of tracers was 54 (37–84) min, during which complications such as convulsions or hypoglycaemia were treated. The baseline characteristics of children are given in p > 0.5). There was rapid correction of vital signs in all children (2O with no significant rise in the first 24 h.The volume of fluid (including blood) given in the first 4 h of the study was similar in children with severe  and moderate  malaria  but not for moderate cases (p = 0.109). The mean (SD) TBW was lower in severe than moderate malaria at admission: 524 (44) ml/kg versus 555 (50) ml/kg (p = 0.052). The mean (SD) change in TBW between admission and follow up was 48 (42) ml/kg and 12 (37) ml/kg for severe and moderate cases, respectively. Individual data from the children with severe malaria are shown in Volume determinations using isotope dilution were available at baseline in all but one of the children with severe malaria. The values for the TBW, ECW, and ICW are given in p = 0.045). Admission ICW measurements were significantly lower in children with severe malaria than in those with moderate malaria (p < 0.001).Bromide space (ECW) measurements were available in all but two children with severe malaria and in all but one of the children with moderate malaria. At baseline, the mean (SD) ECW was significantly lower in children with moderate than in those with severe malaria (2 divided by impedance at 50 kHz (H2/Z50) and measured TBW. The ‘best fit' regression equation to predict TBW from BIA was derived using the variables age, weight, and H2/Z50 :As predicted by theory , there wA is age (months), H is height (centimetres), W is weight (kilograms), and Z50 is impedance at 50 KHz frequency. Disease severity and gender did not contribute significantly to this model, allowing data from admission to be pooled in this prediction equation. Repeating the analysis using impedances measured at other frequencies (4–1012 kHz) did not show a clear advantage, so all data for TBW prediction are given for measurement at 50 kHz.where H2/R0 emerged as the strongest predictive term :By contrast, ECW was not significantly associated with age or weight, and in agreement with previous studies in babies  H2/R0 H is height (centimetres), and 0R is resistance at zero frequency. Again, disease severity and gender did not contribute significantly to this model. Prediction equations based on segmental BIA data for ECW and TBW were inferior to whole body BIA models and are therefore not shown here.where Errors in BIA estimates of TBW and ECW compared to values measured by isotope dilution are displayed with 95% limits of agreement in Fluid volume estimates were available from BIA in 14 children with moderate and 11 with severe malaria on admission and 16 with moderate and 12 with severe malaria at discharge. Values for the TBW, ECW, and ICW are shown in p = 0.034). TBW increased from admission to discharge in children with severe malaria by 37 (33) ml/kg or 6.7% (6.0%) , but there were no significant changes in TBW for children with moderate malaria between admission and discharge.BIA-determined TBW was significantly lower in those with severe compared with moderate malaria (mean [SD] of 539  versus 5p = 0.002). ICW remained unchanged between admission and discharge in children with moderate malaria. In the severe malaria group mean (SD) of ICW at admission was 40 (22) ml/kg, or 11.7% (11.0%) lower at admission than at discharge (p = 0.002). There were no differences in the fluid volume measurements of the four children with adverse and those with good outcomes.ECW did not differ between the severe and moderate groups on admission and did not change significantly between admission and discharge. Serial measurements of ECW did not show any rise during the first 4 d after admission, at discharge, or at day 28 in children with severe or moderate malaria (data not shown). ICW at admission was significantly lower in the severe malaria group than in the moderate malaria group, with a mean (SD) of 293 (17) ml/kg versus 325 (28) ml/kg . For those with moderate malaria the deficit was not significant: −0.3% (4.6%) /−0.9%  (p = 0.41). As predicted, the deficits in weight and TBW were correlated .Admission weight relative to the weight at discharge showed a mean (SD)/median  percentage deficit of −4.3% (4.4%)/−4.0%  for the children with severe malaria on admission (p = 0.036). Plasma potassium concentration and osmolality were higher in children with severe than in those with moderate malaria . Plasma urea and creatinine were significantly higher in those with severe malaria. Osmol gap was significantly higher in children with severe than in those with moderate malaria (p < 0.001), with 15/16 children in the severe group having an osmol gap greater than 8.2 mOsm (considered high in United States children [The concentrations of plasma electrolytes are shown in children ).We have shown that severe childhood malaria is associated with mild dehydration in most cases, with a mean (SD) depletion of TBW of 37 (33) ml/kg, or 6.7% (6.0%). Only 3/16 children 19%) in our study had moderate volume depletion (> 60–90 ml/kg), and none were severely dehydrated (> 100 ml/kg) . Moderat% in our Our findings suggest that the degree of dehydration in children with severe malaria is unlikely to be a primary pathological process in the evolution of the disease. These findings are also consistent with our previous suggestion that hyperlactataemia arises from tissue hypoxia resulting from microvascular obstruction by infected erythrocytes ,22 ratheOur estimates of fluid compartment volumes in children after recovery from malaria are entirely consistent with previous work in children  , althougIn sepsis, ECW increases by up to 50% of TBW because capillary permeability increases by up to 300% of normal. There are no significant increases in ECW in children with severe malaria, confirming earlier studies that indicate that sepsis and malaria syndromes result from different pathophysiological processes ,28. StudHyponatraemia  has beenWhat are the implications of our findings for optimal fluid replacement therapy in malaria? We cannot answer precisely on the basis of measuring fluid compartment volumes because regimens are sometimes designed not only to correct existing fluid deficits and to provide maintenance requirements, but also to rehydrate more vigorously to maintain circulating volume. Such approaches are advocated by others for different populations of children with severe malaria, for example, in a series of studies published from Kilifi, Kenya ,5,34. HoThere are risks to over-vigorous fluid administration just as there are with inadequate fluid replacement, particularly in hospitals where measuring plasma electrolyte concentrations and providing assisted ventilation are difficult. These risks include pulmonary  and cereA correlation between capillary refill time and blood lactate concentrations but none with fluid volume status suggests that prolongation of capillary refill time may be due to the common underlying process of microvascular obstruction.Our findings do not support the widespread use of aggressive fluid volume replacement in children with severe malaria. Clearly, volume depletion indicated by hypotension or by CVP measurements requires more aggressive therapy, but wherever possible plasma electrolyte concentrations should be closely monitored. Because of elevated requirements for glucose in childhood severe malaria (3–6 mg/kg/min) , there iThe tracer dilution techniques that we have used are expensive and time-consuming and consequently not amenable to large-scale deployment. We took this opportunity to calibrate a much simpler methodology (BIA) to derive TBW and ECW and validated BIA estimations in this population. We are now using BIA measurements to assess much larger numbers of patients . BIA is an excellent noninvasive screening tool that should detect subgroups of children with severe malaria who may be severely volume depleted.Although we have known for many years what causes malaria, how it is passed from person to person by mosquito, and how to treat the infection, more than a million people still die of malaria every year, mostly children under five years living in Africa. Children are affected most because they have not had the chance to develop the resistance to malaria that normally builds up over a lifetime when living in places with malaria. As well as being given specific drug treatments against the malaria, children are also often given fluids into their veins, as they appear dehydrated.The researchers studied children who were sick with malaria and measured how dehydrated the children were. To do the measurements, they used an accepted technique that required injections into the vein, and also a newer, simpler method that used electrodes. Neither technique suggested that any of the children were severely dehydrated.The study suggests that severe dehydration isn't a big problem in children with severe malaria. So it may not be necessary to give lots of fluids into the vein. The new technique for measuring dehydration will need to be assessed in larger studies: this study is small, so the results may not be entirely accurate.http://www.who.int/topics/malaria/en/).The World Health Organization is coordinating many of the initiatives to combat malaria (http://www.mmv.org/pages/page_main.htm).Medicines for Malaria Venture is trying to develop new affordable antimalarial drugs (


Influenza vaccination has been shown to reduce morbidity and mortality in the older adult population. In Canada, vaccination rates remain suboptimal. We identified factors predictive of influenza vaccination, in order to determine which segments of the older adult population might be targeted to increase coverage in influenza vaccination programs.The Canadian Study of Health and Aging (CSHA) is a population-based national cohort study of 10263 older adults (≥ 65) conducted in 1991. We used data from the 5007 community-dwelling participants in the CSHA without dementia for whom self-reported influenza vaccination status is known.Of 5007 respondents, 2763 (55.2%) reported having received an influenza vaccination within the previous 2 years. The largest predictive factors for flu vaccination included: being married , having attained a higher education , smoking , more alcohol use , poorer self-rated health , regular exercise , and urban living .While many other differences were statistically significant, most were small , higher comorbidity .Residents of Ontario were more likely (64.6%) to report vaccination (p < 0.0001), while those living in Quebec were less likely to do so . Factors retaining significance in a multivariate analysis included older age, higher education, married status, drinking alcohol, smoking, engaging in regular exercise, and having higher comorbidity.The vaccination rate in this sample, in whom influenza vaccination is indicated, was low (55.2%). Even in a publicly administered health care setting, influenza vaccination did not reach an important proportion of the elderly population. Whether these differences reflect patient preference or access remains to be determined. Influenza has the potential to cause serious complications , especially in the older adult >= 65) population and in those with comorbid illness -3. Influ5 populatDespite current evidence and recommendations, influenza vaccination rates remain suboptimal. Estimates of vaccine coverage in high-risk groups (including older adults) range from 10–40% in the UK , and 45–To our knowledge, no previous studies have examined predictors of vaccination in community-dwelling older Canadians. The objectives of our study were to determine the vaccination rate in this community-dwelling population of older Canadians and to identify factors predictive of influenza vaccination, in order to determine which segments of the older adult population should be targeted to achieve better coverage in influenza vaccination programs.The Canadian Study of Health and Aging (CSHA) is a population-based representative sample drawn from Canadians over the age of 65, designed to study the prevalence, incidence, and risk factors for development of dementia . A technvs. rural residence. As a second step, a multivariate analysis done by stepwise selection of parameters found to be significant in the univariate analysis was then conducted. Analyses comparing responders vs. non-responders to the relevant SARFQ questions as well as comparing respondents who reported first-time vs. regular influenza vaccination were also undertaken. The possibility of interaction between variables was considered. We included in the multivariable model interaction terms of pairs of variables where interaction was plausible .Respondents were designated vaccinated if they reported having had an influenza vaccine within the 2 years preceding completion of the SARFQ. As the data were collected over a two-year period, whereas the question about the last vaccination asked for a date, we designated as unvaccinated those who did not report receiving a vaccination within the previous 2 years. Vaccinated and unvaccinated respondents were compared; as a first step crude analyses were done taking each variable individually (not adjusted for any others). Chi-squared test or Fisher's exact test was used for categorical variables and one-way ANOVA was used for continuous variables. Characteristics analyzed included age, gender, education, region of residence, marital status, smoking status, alcohol intake, self-assessed health status, exercise, diagnosis of dementia, Modified Mini-Mental State Examination (3MS) score, nInfluenza vaccination status could be determined for 5007 (76.8%) of the 6521 non-demented, community-dwelling participants in the CSHA who completed the SARFQ. Of these, 2763 (55.2%) reported having received at least one influenza vaccination within the previous two years.The univariate analysis, in which each variable was examined individually without adjusting for the effects of others, showed several differences between the demographics, region of residence, lifestyle, and health status of the two groups Table . ImmunizOf note, smokers were significantly more likely than non-smokers to have received the influenza vaccination. The same was true of individuals who consumed alcohol regularly when compared with those who drank rarely or not at all. Regular exercise was found to be a predictive factor for vaccination. Those who had received the vaccination had significantly more health problems, as did those who saw themselves as being in poorer health.In the multivariate analysis Table  predictivs. 74.1 years, p < 0.0001), had more comorbid illness , and poorer self-rated health . Residents of Atlantic Canada  and those living in rural areas  were less likely to be regular users.To investigate the impact of response bias, we compared those who had answered the influenza vaccination question and the 23.2% of the original sample who had not Table . Repeat Our data were collected in the early 1990s and may therefore not reflect current practice patterns. Although the Canadian Study of Health and Aging was not designed to study influenza vaccination, it does provide a large and unique data set of primarily community-dwelling older Canadians, and is therefore potentially useful in the examination of health-related risk factors and demographics that may influence decisions to vaccinate. Given the importance of influenza vaccination in the prevention of significant morbidity and mortality in populations at risk, the vaccination rate of 55.2% in our community-dwelling sample of older adults is concerning. People who were not vaccinated tended to be younger, non-smokers and to have fewer co-morbid illnesses. They were also found to have a lower level of education, not to be married and not to engage in regular exercise. These were the factors that retained statistical significance in the multivariable analysis, suggesting that these associations are unlikely to have arisen due to confounding by any of the variables investigated.Vaccination has previously been studied in the CSHA, but only in relation to its status as a potentially protective factor with respect to cognitive impairment . The weiAnother important source of potential error is our reliance on self-reported immunization status. However, self-report of influenza vaccination status in elderly outpatients has been found to be highly sensitive and moderately specific when checked against medical record documentation .Other studies have identified predictive factors for vaccination in other countries ,12. An AOur data suggest that there appears to be an important degree of targeting of vaccination resources within the older adult population to people who are less healthy. Even within these higher risk groups, however, immunization is incomplete. Perhaps such people are perceived by their health care providers as being at higher risk from influenza infection, and are thus more likely to be immunized. Similar explanations may account for the higher vaccination rates among smokers and those who consumed more alcohol. However, according to the current Canadian guidelines , influenRegular exercise was shown to be a factor predictive of influenza vaccination. Interestingly, this association may have been confounded by generally health-protective behaviour , given that individuals exhibiting healthy lifestyle choices (such as exercise) may have been more likely to have sought preventative health care and to have visited their health care providers more regularly, thus providing more opportunity to be vaccinated. Regular exercise did, however, retain significance in our multivariate analysis.vs. urban residence did not retain statistical significance in the multivariable regression model suggests that this crude association may be due to confounding by other factors.The regional differences identified in our study may point to geographic differences in access to influenza vaccination, although the general milieu and level of awareness in both the medical community and society at large may also be significant. These regional differences suggest that certain areas may benefit from targeting of vaccination efforts. However, over and above questions of health policy and public health education, the question of access to vaccination is of vital importance if we are to achieve acceptable rates of coverage in this target population. The finding that rural residence is a negative predictor of vaccination is particularly concerning, and points to the larger equity issue of how uptake of influenza vaccination can be improved outside of major urban centers. However, our finding that rural Our analysis comparing non-responders with those for whom influenza vaccination status was known on the basis of the SARFQ showed that response bias was indeed likely. Non-responders were more likely to drink more alcohol, a factor which was associated with being immunized. However, several factors which were associated with not being immunized, including younger age, good self-rated health, having fewer comorbidities, and residence in a rural area, were more prevalent among non-responders. This over-representation of a number of factors predictive of non-immunization among non-responders suggests that our results may well have been influenced by response bias. For example, we may have over-estimated the prevalence of vaccination in this population.The analysis comparing regular users of the influenza vaccine with those who reported first-time immunization in the SARFQ demonstrated a number of factors that differed between the two groups. The finding that younger age is associated with first time vaccination may be at least partially explained by those at the younger end of the > = 65 age group having spent less time in this "target group" for vaccination. As such, they would be more likely to be receiving the vaccination for the first time. The effect of age may also play a role in the finding that those with better self-assessed health and fewer comorbidities were more likely to be first-time users . However, being in better health was also a predictive factor for non-vaccination within the previous two years, as was rural residence, suggesting that these factors may influence decisions to initiate as well as to sustain influenza vaccination over subsequent years.Despite current recommendations and proven benefit, influenza vaccination rates in our Canadian sample were suboptimal; only 55.2% of older adults in our representative sample reported being vaccinated within the past two years. The predictive factors identified in this analysis may facilitate the study of targeting of older adults in future vaccination programs.SM and HM have been involved in trials of Influenza vaccines funded by ID Biomedical. Neither has received any personal financial compensation for their involvement. MKA and KR have no competing interests.MKA wrote the first draft, and reviewed each of the analyses. SM & KR reviewed the analyses and revised the manuscript. KR is a co-Principal Investigator of the CSHA. HM did the statistical analyses. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


A readmission is classified as a patient necessitating readmission to hospital due to a post-operative complication following discharge. An overstay however, is classified as a patient having to stay longer than the planned duration in hospital (not having been discharged in the interim) due to a post-operative complication. This study aims to investigate patient-related factors that predispose to readmission or overstay and thus make recommendations to decrease the likelihood of readmission or overstay.In this retrospective study 312 'day-case nasal procedures', were selected from a total cohort of 4274 ENT patients over a 17-month period. This sub-group was investigated for a range of demographic factors including, age, gender and ethnicity with regards to their relationship to readmission rates and overstay frequency and duration.The rates were 2.88% and 9.62% for readmission and overstay respectively. The total number of days spent in hospital as a result of readmission was 27. Epistaxis was the leading cause for readmission/overstay (28.9%) followed by high levels of post-operative pain preventing them from being discharged (23.7%). All procedures in this study had readmission rates that were below those recommended in the guidelines set by the Royal College of Surgeons of England. Women overstayed significantly longer  than men.Suitable candidates for day-case ENT surgery highlighted by this study include healthy individuals between the ages of 20 and 60. Operating in the morning would increase the immediate post-operative recovery time, which may reduce the numbers of patients who complain of high levels of pain at the time of discharge. Procedures such as septorhinoplasty being performed routinely in the ambulatory setting require additional research into more effective methods of pain control. Standards need to be improved so that the causes of overstay and readmission are clearly identifiable in patient records. Day-case surgery has rapidly expanded as a cost-effective and resource-conserving surgical intervention to the point that well in excess of two million operations are performed in a day-case/ambulatory setting in the United Kingdom alone each year . Day-casA King's College Hospital Study commissioned by the Department of Health has suggested that day-case surgery may not be saving the NHS money . HoweverStudies have shown that day-case septorhinoplasty is associated with a low complication rate and is a safe and acceptable procedure provided that stringent patient selection criteria are adhered to . A speciThere have been no studies performed, which have directly investigated the 'patient demographic factors' which predict the likelihood readmission or overstaying the electively planned period in hospital following day-case ENT operations. This is of importance as it would be beneficial to know if certain groups of patients require more rigorous screening pre-operatively in an attempt to reduce readmission and 'overstay' rates. By identifying this cohort of patients, the NHS could save substantial amounts of acute and primary care expenditure in the backdrop of ever-rising day-case ENT procedure numbers. Many studies have suggested that ENT procedures currently performed as overnight cases could be performed as day-cases provided strict criteria are applied in the selection of patients ,11. HowePrevious data fails to distinguish between readmissions and overstays following nasal day-case surgery . They alThis study investigates departmental day-case nasal surgery at Guy's hospital and aims to determine:a) If it has readmission rates below that of the accepted standard for day-case surgery stipulated by the Royal College of Surgeons of England.b) If readmission rate and unplanned overnight stay are related to epidemiological characteristics of the sample such as age, gender, and ethnicity.and to report results in the context of clinical management by making recommendations to improve the readmission rates in each category proposed.rd January 2002 and 28th June 2003 were investigated. All ENT patients operated on during this period were selected from the Guy's & St. Thomas' NHS Trust database. The hospital database has a limited range of broad categories and this can limit interpretation of results thus all available patient notes were also reviewed.This is a retrospective study in which the total number of ENT operations performed between the period of 3All planned day-case procedures were selected from the total cohort of elective ENT operative procedures. The day-case procedures were then further narrowed down to 'nasal day-case procedures'.Firstly the total number of readmission episodes, overstay frequency and duration in the 'day-case nasal procedures' were calculated. A readmission is classified as a patient necessitating readmission to hospital due to a post-operative complication following discharge. An overstay however, is classified as a patient having to stay longer than the planned duration in hospital (not having been discharged in the interim) due to a post-operative complication. The groups of nasal operations of interest in this study in the light of previous studies are (septo)rhinoplasty, excision of lesion, polypectomy, sinus operation and other .A range of demographic factors including, age, gender and ethnicity were investigated with regards to their relationship to readmission rates and overstay frequency and duration. Statistical analysis including Chi-square tests, t-tests and ANOVA were performed on the above variables.rd January 2002 and 28th June 2003 were 4274. From this cohort 501 operations (11.72%) were planned as elective ENT day-case procedures. This selected sub-sample of 501 day-cases was further narrowed down to those, which pertained to 'nasal procedures' and this group numbered 312 (62.28%). There were a total of 9 readmission episodes following 'day-case nasal procedures' during the 17-month period, which equates to a readmission rate of 2.88%. The total number of days spent in hospital as a result of readmission was 27. All patients readmitted following day-case nasal procedures were male . The nasal operations were grouped into (septo)rhinoplasty, excision of lesion, polypectomy, sinus operation and other.The total number of ENT operations performed between the period of 3Those patients that were required to stay longer than electively planned i.e. one day, are termed by the Guy's & St. Thomas' NHS Trust and indeed in this study as 'over-stays'. The minimum duration of overstay in our sample was one day and the maximum was 2 days. The total incidence of patients overstaying was 30 (overstay rate = 9.62%) during the timeframe studied and this equates to a total of 48 overstayed days.n = 11/38 (28.9%) followed by levels of post-operative pain unacceptable to the patient and thus preventing them from being discharged (23.7%).Epistaxis was the leading cause for readmission/overstay The readmission rate for (septo)rhinoplasty is 1.38% and the overstay rate is 9.22%. From the analysis of days overstayed expressed as a fraction of the number of procedures performed, polypectomy and sinus operations have the highest number of days overstayed per procedure. Although the (septo)rhinoplasty overstay rate is 9.22% the number of days overstayed expressed in the context of the number of actual (septo)rhinoplaties performed is equal to the average  than men.The frequency of readmission is highest in those patients aged <20 followed by those in the 60–70 year age category. Although the patients aged above 70 years have the lowest readmission frequency, the sample size is low (n = 5) and thus the 30–40 year age category is more reliable a sample representative of a low readmission frequency. Analysis of the age of patients and frequency of day-case procedures revealed that the group containing those patients aged between 30–40 underwent the greatest number of nasal day-case procedures. However, when considering the number of overstays in terms of the numbers of procedures performed, the 30–40 age category has the lowest overstay duration as opposed to the >70 which has the highest.Analysis of variance (ANOVA) shows that the difference in overstay rates between ethnic groups did not reach statistical significance .In July 2000, the Department of Health published that 75% of surgical procedures carried out by the NHS should be performed in a day-case setting by 2010. This initiative was supported by the both The Royal College of Surgeons of England and The Royal College of Physicians of England.Within the period of the current study there were a total of 4274 ENT operations performed at Guy's during the time-frame of investigation. Of this group 501 (11.72%) were planned as elective ambulatory procedures with the intention of same day discharge. Primarily the government target was ambiguous with regard to the types of procedure for which it aimed to conduct on a routine day-case basis. Whilst it is conceivable that some ENT procedures such as myringotomy could be performed safely as a day-case procedure, more complex and involved procedures such as deep exploration of the neck and tumour excision would be unsuitable for such rapid discharge. With no clear guidelines as to which procedures are suitable for the day-case setting, the responsibility of advancing the boundaries of ambulatory surgery rests on the clinicians, with the patients' wellbeing being at the forefront of interest.The readmission in this study is 2.88%. These readmission rates are lower than those reported in the contemporary literature ,8,11. ThEpistaxis was the leading cause for readmission/overstay (28.9%) followed by levels of post-operative pain unacceptable to the patient and thus preventing them from being discharged (23.7%). The cause of epistaxis was not recorded in the notes nor was the reason behind why some patients experience more pain than others. These results are in contrast to previous subjective patient based studies, which show that septorhinoplasty is generally acceptable to the patient in terms of pain and overall satisfaction parameters . Women oAge is not a contraindication for ENT day-case surgery. The low readmission rate of patients over 70 years of age could be attributed to a number of factors including, heightened caution of the clinician in patient discharge, a low sample number and age-related variation of procedure type are dominant.There have been no previous studies, which have investigated the effects of ethnicity on readmission rates or overstay duration. The current study shows that mixed race patients followed by black patients have the highest number of days overstayed per procedure. Analysis of variance (ANOVA) shows that there is no significant difference between ethnic groups and the length of overstay .Day-case procedures should be performed on suitable candidates on a sound clinical basis. This includes meticulous patient selection, both on the part of the surgeon and the health care professionals in the preoperative assessment. Suitable candidates for day-case ENT surgery highlighted by this study include healthy individuals between the ages of 20 and 60. A protocol for day-case surgery does exist and this may need revision.In the clinical setting however, epistaxis needs to be made a clinical priority by ensuring that all levels of healthcare professionals are aware of its causes and its effective immediate management. We suggest from experience that operating in the morning would increase the immediate post-operative recovery time, which may reduce the numbers of patients who complain of high levels of pain at the time of discharge. Procedures such as septorhinoplasty being performed routinely in the ambulatory setting require additional research into more effective methods of pain control. Clinical administration standards need to be improved so that the causes of overstay and readmission are clearly identifiable in patient records.The authors declare that they have no competing interests.Mr. Gurminder Singh (first and corresponding author) performed the data collection and wrote the paper with assistance from Mr. David McCormack (second author). Mr. David Roberts supervised the study and reviewed the completed manuscript.The pre-publication history for this paper can be accessed here: