P < 0.001). However, the RECIST 1.1 showed high concordance with the RECIST 1.0 in the assessment of best tumor responses (k = 0.908). Seventeen patients (5.6%) showed discrepancy in the best tumor response between the RECIST 1.0 and RECIST 1.1. This pooled study demonstrates that the RECIST 1.1 shows the highly concordant response assessment with the RECIST 1.0 in patients treated with targeted agents.Patients treated with targeted agents were not included in the data warehouse when the RECIST 1.1 was revised in 2009. We conducted this pooled analysis to investigate the impact of the RECIST 1.1 on the assessment of tumor response in cancer patients treated with targeted agents. We surveyed MEDLINE, EMBASE and PubMed for articles with terms of the RECIST 1.0 or RECIST 1.1. We searched for all the references of relevant articles and reviews using the ‘related articles’ feature in the PubMed. There were six articles in the literature comparing the clinical impacts of the RECIST 1.0 and RECIST 1.1 in patients treated with targeted agents for advanced or metastatic cancer. A total of 322 patients were recruited from the six trials; 217 with non-small cell lung cancer, 23 with thyroid cancer, 20 with gastrointestinal stromal tumor, and 62 with renal cell carcinoma. Because of new lymph node criteria, eight patients (2.5%) had no target lesions when adopting the RECIST 1.1. The number of target lesions by the RECIST 1.1 was significantly lower than that by the RECIST 1.0 ( The decision on subsequent cancer treatments usually depends on radiologic changes in the tumor burden. Thus, the accurate assessment of objective therapeutic response is essential for routine anti-cancer treatment as well as clinical trials using new drugs. Since the early 1980s, the World Health Organization (WHO) criteria were used as the standard method for evaluating tumor response , 3.18F) fluorodeoxyglucose-positron emission tomography (FDG-PET), requested an update of the RECIST 1.0 [In 2000, the Response Evaluation Criteria in Solid Tumors (RECIST) Working Group proposed the new response evaluating criteria, the RECIST guidelines version 1.0 (RECIST 1.0) . The impCIST 1.0 .In 2009, the revised RECIST guidelines version 1.1 (RECIST 1.1) was presented to overcome the limitations of the original RECIST guidelines . The RECWhen the RECIST 1.1 was revised, patients treated with targeted agents were not included in the data warehouse . Since tThere were eleven articles , 18–23 aet al. [et al. [A total of 322 patients treated with targeted agents for metastatic cancer were collected from the six trials; 217 with NSCLC –20, 23 wet al.  and Nish [et al.  had limiPatients with metastatic NSCLC were treated with epidermal growth factor receptor TKIs (EGFR-TKIs) such as gefitinib and elrotinib –20. All P < 0.001, paired Student's t-test). The median number of target lesions was 3  by the RECIST 1.0 and 2  by the RECIST 1.1, respectively. Among 188 patients who had at least one target lesion from the 4 studies, 104 (55.3%) showed a decrease in the number of target lesions when the RECIST 1.1 was used . The ORRs, which were estimated in total regardless of the primary tumor site, were not significantly different between the two criteria .We compared the best tumor responses between the two criteria in 304 patients who had at least one target lesion by the RECIST 1.1 (Table Seventeen patients (5.6%) showed discrepancy in the assessment of tumor responses between the RECIST 1.0 and RECIST 1.1. The details of the patients showing disagreement between the two criteria was described in Table The RECIST 1.1 has shown high concordance with the RECIST 1.0 in the assessment of tumor responses in several studies with a small number of patients treated with targeted agents –23. In tAs expected, the RECIST 1.1 significantly decreased the number of target lesions. Among 188 patients who had at least one target lesion from the 4 studies in which the number of target lesions were described –21, 23, at al. reported that 66 (38%) out of 172 LNs regarded as target lesions by the RECIST 1.0 were defined as target lesions based on the RECIST 1.1 in patients with metastatic GC [et al., only 38 (40%) out of 95 LNs considered to be target lesions according to the RECIST 1.0 were classified as target lesions by the RECIST 1.1 in patients with metastatic CRC [The RECIST 1.1 recommends that LNs should be measured along its short axis, regarding LNs of at least 15 mm as target lesions. LNs with at least 10 mm but less than 15 mm in its short axis, even though it may be pathological, are regarded as non-target lesion, and LNs with a short axis of less than 10 mm are recorded as normal. This new LN criteria were the most common cause of the reduction of target lesions in this pooled analysis, which led to the reduction of target lesions in 67 patients (35.6%), including 14 (7.4%) in whom the reduction was resulted from both the new LN criteria and the reduction in the maximum number of target lesions. In this pooled study with 312 patients who had target lesions according to the RECIST 1.0, 8 (2.6%) had no target lesions when adopting the RECIST 1.1. In these patients, all the target lesions according to the RECIST 1.0 were LNs smaller than 15 mm along the short axis, which was no longer met the RECIST 1.1 criteria for target lesions. Similar findings have been shown in patients with GC . Fuse atatic CRC . These fP = 0.212). Of note, however, the best tumor response tends to be upgraded in some patients when adopting the RECIST 1.1. Thirteen (76.5%) of 17 patients with the disagreement between the two criteria showed the better response classification according to the RECIST 1.1: from PR to CR in 2, from SD to PR in 9, and from PD to SD in 2. This finding may be mainly resulted from the more stringent LN criteria in the RECIST 1.1. In the study by Sun et al. [When the updated RECIST 1.1 was presented in 2009, patients treated with targeted agents were not included in the data warehouse . Recentln et al. , two NSCThe RECIST working group recently reported the results of a survey in oncology communities assessing satisfaction with the current RECIST 1.1, areas of concern, and suggestions for a new version of the RECIST . Of 65 rThis pooled study has several limitations needed to be noted. First, a single radiologic method, CT, was mainly used for tumor measurements and PET was not routinely performed in all six studies. New lesions detected on PET scans change the tumor response from PR or SD to PD according to the RECIST 1.1. In this study, the best tumor response in two NSCLC patients was changed from SD to PD by the new lesions on PET scans. Second, the best tumor responses between the two criteria were compared only in patients with target lesions based on the RECIST 1.1. According to the RECIST 1.1, patients with SD or PR based on target lesion response are classified as PD, only when substantial progression of non-target lesions is observed. Based on the RECIST 1.0, however, the increase in size of only one or a few non-target lesions was also regarded as PD, although target lesions were stable or responding. Therefore, if the studies had included patients with non-target lesion, the new criteria for non-target lesions would have affected the concordance between the RECIST 1.0 and RECIST 1.1. Third, the data in this study were quite heterogeneous with relatively small number of patients with different tumor types and different targeted agents used (EGFR–TKI or VEGF–TKI). Therefore, it is necessary to verify the results in studies with larger homogeneous patients' cohort. Fourth, monoclonal antibodies such as cetuximab, bevacizumab or trastuzumab are frequently used to treat a variety of cancers. However, this study only included patients treated with TKIs. Finally, as I mentioned above, four articles –21 incluIn conclusion, this pooled analysis demonstrates that the RECIST 1.1 provides highly concordant response assessment with the RECIST 1.0 in patients treated with targeted agents for advanced or metastatic cancer. With the increasing use of novel targeted agents, however, the RECIST 1.1 still needs to be verified if it can also applicable in patients receiving those agents.We thoroughly looked into all potentially eligible studies through the following searching strategy. We surveyed the Cochrane Central Register of Controlled Trials , MEDLINE (from 2009 to September 2015) and EMBASE  for articles including the following terms in their titles, abstracts, or keywords; ‘RECIST 1.0 or RECIST 1.1’, ‘target lesion’ and ‘tumor response’. In addition, we searched for all the references of relevant articles and reviews. We used the ‘related articles’ feature in the PubMed to identify the related articles. We also investigated all abstracts presented in the conferences of the American Society of Clinical Oncology and European Society for Medical Oncology held between 2009 and 2015.t test. Chi-square test was used to compare the overall response rates (ORRs) between two groups. P-values less than 0.05 were considered significant. The level of concordance of the best tumor responses between the two criteria was calculated using linear weighted ĸappa statistics. Agreement between the two criteria was interpreted as poor (k < 0), slight (k = 0–0.20), fair (k = 0.21–0.40), moderate (k = 0.41–0.60), substantial (k = 0.61–0.80), and almost perfect (k > 0.80) [The statistical significance of changes in the number of target lesions between the RECIST 1.0 and RECIST 1.1 was assessed using the paired Student's  > 0.80) .


Acute infectious diarrhea is one of the most important causes of morbidity and mortality worldwide.The objective of this study was to characterize antimicrobial resistant diarrheagenic Escherichia coli strains isolated from diarrheic children in Tehran, IR Iran.In total, 550 stool samples from diarrheic pediatric patients, aged less than 60 months, were collected and immediately transferred to the laboratory. Isolation and identification of E. coli strains was done using bacteriological methods. Antimicrobial susceptibility testing was performed using the disk diffusion technique. Multiplex PCR was used to detect aadA1, tetA, tetB, dfrA1, qnr, aac (3)-IV, sul1, blaSHV, CITM, cat1, and cmlA antibiotic resistance genes.From the total of 550 fecal samples examined, 154 samples (28%) were positive for diarraheagenic E. coli. High rates of antibiotic resistance were seen against penicillin ﴾100%), ampicillin ﴾89.6%﴿ and tetracycline ﴾83.1%﴿. Resistance against ciprofloxacin was low ﴾28.6%﴿. The prevalence of different resistance genes in the studied strains varied from 96.10% for aadA1 gene to 40.25% for sul1 gene. The frequencies of aadA1, tetA, tetB, dfrA1, qnr, aac(3)-IV, sul1, blaSHV, CITM, cat1, and cmlA genes were 96.10%, 85.06%, 84.41%, 51.94%, 72.07%, 54.54%, 40.25%, 57.79%, 90.25%, 59.74% and 60.38%, respectively.Our results indicated that antibiotic resistance is increasing in diarraheagenic E. coli strains in Iran. It is imperative to develop strategies for prevention and control of resistant organisms. Changes in patterns of resistance against commonly used antibiotics in Iran indicate that an applied surveillance system and introduction of guidelines for appropriate antibiotic prescription are necessary. Acute infectious diarrhea (AID) is one of the most important causes of morbidity and mortality worldwide. This disease remains a major public health challenge, particularly in developing countries where it is a leading cause of death -3. A varE. coli. Knowledge on antimicrobial resistance of diarrheagenic pathogens is important for selecting the appropriate therapy and necessary for physicians in order to treat infections using appropriate antibiotics . Information on some clinical and epidemiological features was obtained through questionnaires. These patients presented different types of symptoms including nausea, fever and dysentery. Stool specimens were collected using sterile swabs, and transported to the laboratory at 4°C using a cooler with iced-packs. Sample collection was performed with the consent of the children’s parent or guardian, and the study was approved by the local bioethical committee of Shahrekord Islamic Azad University. Control subjects included healthy children with no history of diarrhea for at least one month.Three milliliters of each sample was blended with 225 mL of nutrient broth  for two minutes at normal speed, using a Stomacher lab blender and incubated at 37°C for 24 hours. A 1 mL sample of the nutrient broth culture was mixed with 9 mL of MacConkey broth  and further incubated at 37°C for 24 hours. One loop of each tube was streaked on MacConkey agar . A typical purple colony of E. coli from each sample was streaked on a separate eosin methylene blue agar (EMB agar) plate  and incubated at 37°C for 24 hours. A metallic green colony from each plate with a typical E. coli morphology was selected and examined by biochemical tests, including hydrogen sulfide, citrate, urease and indol based on the API test system  .Escherichia coli ATCC 25922 was used as a quality control organism for antimicrobial susceptibility determination.All E. coli isolates were tested for susceptibility to penicillin (10 u/disk); tetracycline (30 µg/disk); streptomycin (10 µg/disk); chloramphenicol (30 µg/disk); sulphonamides (100 µg/disk), sulfamethoxazol 25 µg/disk); gentamycin (10 µg/disk); lincomycin (2 µg/disk); cephalothin (30 µg/disk); trimethoprim (5 µg/disk); enrofloxacin (5 µg/disk); ciprofloxacin (5 µg/disk); ampicillin (10 u/disk); by the Kirby-Bauer disk diffusion method  . Resista µg/disk;DNA extraction was carried out using the boiling method. Briefly, the culture of each isolate was inoculated in Tryptose soy broth  and incubated at 37°C for 24 hours. Bacteria were harvested from an overnight broth culture and suspended in sterile water (DDW), after which the bacterial suspension was boiled for 10 minutes and chilled on ice and finally the debris were separated by centrifugation. The supernatant was taken as the DNA template for PCR.Multiplex PCR amplification was used to identify 11 antibiotic resistant genes including aadA1 for streptomycin ; tetA, aThe data were analyzed using the SPSS  software and P values were calculated using Chi-square and Fisher's exact tests to determine significant relationships between various criteria and distribution of antibiotic resistance properties of STEC strains isolated from diarrheic pediatric patients. A P value less than 0.05 was considered statistically significant.The present study was accepted by the ethical committee of the Baqyiatallah and Peyambar-Azam Hospitals of Tehran, Iran and Microbiology and Infectious Diseases Center of the Islamic Azad University of Shahrekord, Iran. Written informed consent was obtained from all of the studied patients or their parents. The agreement between the Islamic Azad University of Shahrekord and the two mentioned hospitals had been signed before sampling (on 10th of April and 15th of April 2013).E. coli strains isolated from children between the ages of one month to five years. Totally, 154 samples (28%) were positive for diarrheagenic E. coli. The greatest rates for isolates recovery were from the 13-24 month age group (38.3%), followed by the 1-12 month age group (23.38%)  and 80 (51.9%) were isolated from female and male patients, respectively  . Incidenectively . In totaAll of the isolates had resistance to more than one antibiotic. There was a significant statistical difference for incidence of bacteria between 13-24 month old and 37-48 month old pediatrics (P < 0.05). Also, differences were significant (P < 0.05) for bacterial resistance between ampicillin and penicillin with ciprofloxacin and enrofloxacin (P < 0.05). However, there were no significant statistical differences between the sex of the patients and rates of antibiotic resistance. There were no significant differences for incidence of bacteria between the male and females. The results obtained from analysis of the antimicrobial resistance genes showed that 11 resistance genes were identified in all E. coli strains. The distribution of resistance genes among E. coli isolates is summarized in E. coli have been often used as useful indicators for survey of the selective pressure of antimicrobial agents and distribution of acquired resistance genes  was observed. This finding is comparable to previously reported studies on children from Peru and Bolivia, Vietnam, Tanzania, Mexico, Argentina and Mozambique that reported a prevalence of ampicillin resistance of more than 70% in DEC isolates . In anot9.6% was E. coli strains, could be a potential source for antibiotics resistance genes  was observed in 90.25% of ampicillin resistant isolates. However, this speculation does not apply to streptomycin, which has had limited clinical use for many years; nevertheless, the high rate of resistance (78.2%) to this drug has persisted . Possiblce genes .E. coli isolated from slaughtered commercial chickens by multiplex PCR. They reported the distribution of studied genes as: tetA and tetB ﴾52.63%﴿, dfrA1, qnrA, catA1 and cmlA ﴾36.84%) and sul1 and ereA ﴾47.36%). Ahmed et al. (In the recent years, molecular methods have been reported as rapid and sensitive techniques. Multiplex PCR is a rapid and specific diagnostic method for simultaneous detection of several virulence and antimicrobial resistance genes in one PCR reaction -41. Studd et al.  studied According to the progressive increase in antibiotic resistance among enteric pathogens, particularly in developing countries, it is imperative to implement strategies to prevent and control the emergence and spread of resistant organisms by inexpensive, sensitive, and simple methods. Practitioners should pay more attention to antibiotic prescription especially that related to diarrhea in children.


P. falciparum candidate artemisinin resistance biomarkers L263E, E431K, A623E, and S769N in the pfatpase6 gene in a high transmission area in Tanzania in a retrospective cross sectional study using 154 archived samples collected from three previous malaria studies in 2010, 2011 and 2013. Mutations in pfatpase6 gene were detected in parasite DNA isolated from Dried Blood Spots by using PCR-RFLP. We observed overall allelic frequencies for L263E, E431K, A623E, and S769N to be 5.8% (9/154), 16.2% (25/154), 0.0% (0/154), and 3.9% (6/154). The L263E mutation was not detected in 2010 but occurred at 3.9% and 2.6% in 2011 and 2013 respectively. The L263E mutation showed a significant change of frequency between 2010 and 2011, but not between 2011 and 2013 (P < 0.05). Frequency of E431K was highest of all without any clear trend whereas S769N increased from 2.2% in 2010 to 3.6% in 2011 and 5.1% in 2013. A623E mutation was not detected. The worrisome detection and the increase in the frequency of S769N and other mutations calls for urgent assessment of temporal changes of known artemisinin biomarkers in association with in vivo ACT efficacy.We aimed to determine the current prevalence of four  P. falciparum resistance to conventional antimalarial medicines such as chloroquine and sulphadoxine-pyrimethamine (SP) led to a change in malaria treatment policy in endemic countries [ P. falciparum resistance to ACTs in Senegal, in French Guiana, and on the Thai-Cambodia border have recently been reported [2+-ATPase- (SERCA-) type protein, encoded by the pfatpase6 gene, is an important chemotherapeutic target of artemisinins [ pfatpase6 gene affect in vitro sensitivity to artemisinins [50 with pfatpase6 SNPs , particularly, the pfatpase6 S769N mutation [ pfatpase6 SNPs, E431K and A623E, have been shown to affect inhibition of PfSERCA by artemisinin [ pfatpase6 gene at codons 263, 431, 623, and 769 in four high malaria transmission villages in Bondo ward in Handeni in North Eastern Tanzania, for changes in their frequencies over time between 2010 and 2013.Resistance to antimalarial drugs is a major public health problem, which hinders the control of malaria. Widespreadountries . ACTs haountries . Despitereported , 4 whichreported . This coreported , 6. Howemisinins –11. Moremisinins –10. In amutation . The L26emisinin , 14. Manemisinin , 16, limemisinin , 17, 18.The study was retrospective cross-sectional study whereby samples collected from three different cross-sectional malaria studies in 2010, 2011, and 2013 in Bondo Village were used. Bondo village is located in Handeni District in the coastal region of Tanga, North-Eastern Tanzania. The region is endemic to malaria with a perennial transmission. It is known to be a focal area for malaria drug resistance due to the drug selection pressure . The stu pfatpase6 gene was carried out in a final volume of 25 μL containing 2 μL of extracted DNA, 250 nM primers, Taq buffer, 2 mM MgCl2, 125 μM each of the four deoxyribonucleotide triphosphates (dNTPs), and 0.4 U High Fidelity Platinum Taq polymerase. Secondary PCR reactions were carried out in similar conditions as the primary PCR except that 1 uL of primary PCR product was used as template. Conditions for restriction digestion, amplicon sizes and enzymes, are shown in  ApoI, MBoII, Cac8I, and DdeI for detection of mutations at positions L263E, E431K, A623E, and S769N, respectively. Restriction digestion was carried out as described by manufacturer. Restriction products were resolved on 1.5–3% agarose gel containing ethidium bromide and visualized under UV florescent illuminator, as a way of quality assurance.DNA was extracted from DBS using chelex100-saponin method as previously described earlier . PCR reaEthical approval for this study was granted by the Kilimanjaro Christian Medical University College Ethics and Research Committee (CRERC) with a certificate number 554.Pfatpase6 gene was successfully amplified and genotyped in all 154 P.  falciparum field isolates. Detection of pfatpase6 SNPs within positions L263E, E431K, A623E, and S769N indicated 5.8% (9/154), 16.2% (25/154), 0.0% (0/154), and 3.9% (6/154) overall prevalence of pfatpase6 mutant genotypes (both heterozygous and homozygous mutant combined), respectively. The homozygous allelic frequency was distributed such that, for L263E, E431K, A623E, and S769N, frequencies were 8 (1.4%), 17 (11.0%), 0 (0.0%), and 5 (3.2%), respectively. Majority of parasites had the wild type allele: L263E, 145 (94.2%); E431K, 125 (81.2%); A623E, 0 (100%); and S769N, 148 (96.4%).We analyse data to determine allelic frequency changes in the period from 2010 to 2013. Results for analyses that combined heterozygous and homozygous allelic distribution are presented in χ2 = 5.7239, P = 0.05716). Pairwise comparisons of frequencies by Fisher's exact test revealed a significant change of L263E frequency only between 2010 and 2011, but not between 2011 and 2013 (P < 0.05).We explored data for all four SNPs to determine if there was a significant change in frequency between the years 2010 and 2013 using Fisher's test. To accomplish this analysis, we combined heterozygous and homozygous mutants for the analyses and data are presented in  in vivo efficacy studies are conducted. Many previous studies have reported molecular markers for ACT partner drugs resistance .parasite , 14, 28. pfatpase6 gene  [The E431K mutation occurred at the highest frequency compared to other studied mutations. This is similar to what was reported in previous studies done in Cameroon and Iran , 31, 32.lsewhere , 14 althlsewhere . The E43Our data show a sudden increase of L263E and S769N SNPs from 2010 to 2013. The relatively fast increase of the two SNPs within a short period of time from 2010 to 2013 may have a number of different explanations. For many years, the study area had experienced perennial and holoendemic malaria transmission. However, in recent years, malaria transmission has declined substantially and entomological inoculation rate has declined from 148 infectious bites per person per year in 2000  to 39 in P. falciparum infections to ACTs three years after they were introduced [Based on the low transmission theory, the rapidly declining transmission patterns in the study area and neighboring areas may partly explain the rapid increase in the frequencies of two of the studied SNPs which are more closely associated with antimalaria resistance. The renewed and sustained reinforcement of malaria control programs in Tanzania based on both ACT chemotherapy and integrated vector control may have contributed greatly to the decline in malaria transmission and hence favor the increase of resistant strain frequencies. This argument is supported by findings from a recent study conducted in Kenya that reported a significant decline of early response rates oftroduced .Many factors could commonly contribute to the key mechanisms of emergence of resistant parasite strains in the study area, in common with other relatively underdeveloped malaria endemic regions. Most important is the poor reinforcement of the concept of rational therapy. Improper use of antimalaria drugs is based on presumptive, clinical diagnosis alone or on misdiagnosis due to poor technical expertise on interpretation of laboratory results , 37, 38.The prevalence of counterfeit or clinically substandard ACTs that contain small quantities of the artemisinin derivatives threatens to subvert ACT efficacy as it provides an ideal mechanism for the selection of resistance. Recent estimates show that 33%–53% of all ACT tablets in mainland Southeast Asia region are counterfeit . A previAlthough our observations are based on molecular detection of resistance biomarkers only, more studies that associate biomarkers with ACT clinical efficacy should be conducted to ascertain the current status of ACT effectiveness. Regular monitoring of ACT resistance biomarkers should continue in order to detect the earliest signs of possible emergency of ACT resistance.


Despite a substantial increase in use of SMS text messages for collecting smoking-related data, there is limited knowledge on the parameters of response. This study assessed response rates, response speed, impact of reminders and predictors of response to text message assessments among smokers.n = 198) and general smokers (n = 293) sent text message assessments during 3-month cessation programs. Response rates were calculated using data from the host web-server. Changes in response over time, impact of reminders and potential demographic  and smoking  predictors of response were analyzed.Data were from two SMS cessation intervention trials using clinical samples of pregnant (P = .003) for general smokers only. Text message reminders had a significant effect on response (Ps < .001), with observed mean increases of 13.8% (pregnant) and 17.7% . Age  and deprivation  weakly predicted response among pregnant smokers and nonsmoking status at 4 weeks follow-up  predicted response among general smokers.Mean response rates were 61.9% (pregnant) and 67.8%  with aggregated median response times of 0.35 (pregnant) and 0.64  hours. Response rate reduced over time (Text message assessments within trial-based cessation programs yield rapid responses from a sizable proportion of smokers, which can be increased using text reminders. While few sources of nonresponse bias were identified for general smokers, older and more deprived pregnant women were less likely to respond.This study demonstrates that most pregnant and general smokers enrolled in a cessation trial will respond to a small number of questions about their smoking sent by text message, mostly within 1 hour of being sent the assessment text message. For those who do not initially respond, our findings suggest that 24- and 48-hour text message reminders are likely to increase response a small but meaningful amount. However, older age and higher deprivation among pregnant smokers and relapse among general smokers is likely to reduce the chance of response. For example, estimating the speed of response profile and the impact of reminders would help optimize the use and timing of reminders and help inform interventions contingent on data input during delivery such as tailored interventions.This study uses data from two text message smoking cessation intervention trials. In addition to a general sample, a pregnant sample is included given this group’s distinct quitting motivations and public health priority status. Three research questions are addressed: (1) What are the response rates and speed of response to text message assessments sent to smokers participating in intervention studies? (2) What impact do text message assessment reminders have on response? (3) Which characteristics are associated with response?n = 198) of a trial of pregnant smokers (MiQuit) and the intervention arm participants only (n = 293) of a trial of general  smokers (iQuit in Practice). Inclusion was restricted to trial participants sent an initial text message assessment enquiring about smoking status (3 weeks post-enrolment).Data from two randomized controlled trials evaluating smoking cessation SMS text message interventions were used. Only participants in these trials who were sent text message assessments were included in the present study; participants from both control and intervention arms  Trusts. Trial inclusion criteria were 16 years of age or over, under 21 weeks pregnant, smoked seven or more cigarettes per week, had regular use of a mobile phone and could understand written English.Participants were patients receiving smoking cessation support at one of 32 UK General Practices. Trial inclusion criteria were aged 18–75 years, smoked at least one cigarette a day, had regular use of a mobile phone, willing to set a quit date within 14 days, and not using smoking cessation medications at randomization.9 Trial withdrawals were excluded from analysis . NHS ethical approval was obtained for both trials .Participants received a £5 (iQuit) or £10 (MiQuit) shopping voucher for trial participation. Further details are reported elsewhere, including descriptions of the interventions, behavior change techniques used and support delivery schedules.Intervention arm participants in both trials received a 3-month program of automated smoking cessation support text messages plus a tailored advice leaflet/report. Intervention participants in both trials and control participants in the pregnant smokers trial (who received assessment texts only) were sent text message based assessments at multiple timepoints; 3, 5, and 7 weeks (MiQuit) and 3 and 7 weeks (iQuit) post-enrolment. The week 3 and 7 messages invited a reply to confirm whether participants had smoked within 7 days: (MiQuit) “Hi [name], have you been smoking in the last 7 days (even a puff)? Reply with YES if you have smoked or NO if you haven’t smoked”; (iQuit) “Hi [name], How’s it going? Have u smoked at all (even a puff) in the last week? If u have smoked reply YES now, otherwise text NO. Thanks.” The week 5 message (MiQuit only) assessed confidence in quitting on a 5-point scale: “Hi [name], how confident do you feel in quitting for the remainder of your pregnancy? Reply with a number from 1 to 5 .” A participant reply triggered a response text. Assessment messages were sent at randomly selected times between 10.05–13.05 (MiQuit) and 10.05–15.05 (iQuit) on the day the message was scheduled to be sent. Reminders were sent if no reply was received within 24 hours, apart from the MiQuit 5- and 7-week assessments where reminders were sent after 48 hours. Reminder texts highlighted that a response had not yet been received and repeated the assessment question. Responses to these assessment text messages and reminders form the focus of the current study. No other text messages sent during the programmes requested a response.10 smoking status , determination to quit, age, ethnicity, Index of Multiple Deprivation ,11 gender , previous prenatal smoking history and parity (pregnant sample only).Response and time to response to text assessments were recorded by a University of Cambridge webserver. Response rates are defined as the proportion of participants who text a reply for each assessment text sent . Potential predictors of response were: nicotine dependence using an adapted Heaviness of Smoking Index (excluding “≤5 minutes” category for time to first cigarette on waking),Response rates (%) with 95% confidence intervals (CIs) for the text assessments were computed and presented on graphs generated by Kaplan-Meier (KM) curve analyses. Repeated measure logistic regression for binary response within the framework of generalized estimating equation (GEE) was used to assess whether response rates changed significantly from the 3-week assessment to the subsequent assessments. GEE with the assumption of Poisson distribution and log link was used to assess whether the response time changed significantly from the 3-week assessment to the subsequent assessments.Increases in response rate for each assessment after reminders were estimated with 95% CIs. The effect of the reminder on response time and ultimately response rate was assessed using the accelerated failure time model with the assumption of Weibull distribution. We bounded the maximum response time as 7 days after the original assessment message was sent.Predictors of response to at least one smoking assessment text (excluding the self-efficacy assessment text) versus nonresponse were explored using bivariate logistic regression. Variables reaching a 5% significance level were entered simultaneously into a logistic regression model.For the pregnant and general samples respectively, 99.0% and 98.0% had a white ethnic background, with median ages of 26 and 41, and 26.3% and 60.8% had high nicotine dependence .2(2) = 3.22, P = .200). Among general smokers, 73.5% (95% CI 68.1%–78.5%) and 62.1% (95% CI 56.2%–67.8%) replied to the 3- and 7-week assessments, respectively. The response rate significantly declined from weeks 3 to 7 by 15.5%  = 8.56 P = .003).Among pregnant smokers, response rates to the assessments at 3, 5, and 7 weeks were 66.8% (95% CI 59.8–73.4), 60.7% (95% CI 53.4%–67.7%), and 58.2% (95% CI 50.8%–65.3%), respectively  with no 2(2) = 4.32, P = .115; general: GEE Wald test: χ2(1) = 1.65, P = .199).Median response time in hours (interquartile range) for the pregnant sample was 0.31 (0.03–23.19), 0.33 (0.02–9.55), and 0.40 (0.02–26.37) at 3, 5, and 7 weeks, respectively with no significant differences between trial arms. For the general sample, it was 0.40 (0.04–7.68) and 0.88 (0.04–24.45) hours for the 3- and 7-week assessments. Increases in response times from the 3-week assessment to subsequent assessments were not statistically significant  and general smokers .For pregnant smokers, after the reminders were sent, increases in response rate were 16.3% (95% CI 11.4%–22.3%), 12.0% (95% CI 7.8%–17.5%), and 13.2% (95% CI 8.7%–18.9%) at weeks 3, 5, and 7, respectively. Equivalent increases in response for general smokers were 17.2% (95% CI 13.0%–22.0%) and 18.2 % (95% CI 13.9%–23.2%) at weeks 3 and 7, respectively. The accelerated failure time model revealed a significant effect of the reminder on the response times for pregnant smokers  and lower IMD deprivation score  were associated with response to a smoking assessment message. The strength of the associations changed little when these variables were entered into a multivariate model, although age no longer reached statistical significance . Together these characteristics accounted for 7.6% of the variance in response. Among general smokers, only nonsmoking status at 4 weeks follow-up was associated with response , accounting for 13.3% of variance.Among pregnant smokers, lower age  grant number C1345/A5809. The iQuit in Practice trial was funded by the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR).The MiQuit feasibility trial was funded by None declared.


Noroviruses are an important cause of gastroenteritis but little is known about disease and re-infection rates in community settings in Asia.Disease, re-infection rates, strain prevalence and genetic susceptibility to noroviruses were investigated in a birth cohort of 373 Indian children followed up for three years. Stool samples from 1856 diarrheal episodes and 147 vomiting only episodes were screened for norovirus by RT-PCR. Norovirus positivity was correlated with clinical data, secretor status and ABO blood group.FUT2 enzyme (se428se428) were at a significantly lower risk (48/190) of infection with norovirus (p = 0.01).Of 1856 diarrheal episodes, 207 (11.2%) were associated with norovirus, of which 49(2.6%) were norovirus GI, 150(8.1%) norovirus GII, and 8 (0.4%) were mixed infections with both norovirus GI and GII. Of the 147 vomiting only episodes, 30 (20.4%) were positive for norovirus in stool, of which 7 (4.8%) were norovirus GI and 23 (15.6%) GII. At least a third of the children developed norovirus associated diarrhea, with the first episode at a median age of 5 and 8 months for norovirus GI and GII, respectively. Norovirus GI.3 and GII.4 were the predominant genotypes (40.3% and 53.0%) with strain diversity and change in the predominant sub-cluster over time observed among GII viruses. A second episode of norovirus gastroenteritis was documented in 44/174 (25.3%) ever-infected children. Children with the G428A homozygous mutation for inactivation of the This is the first report of norovirus documenting disease, re-infection and genetic susceptibility in an Asian birth cohort. The high incidence and apparent lack of genogroupII specific immunity indicate the need for careful studies on further characterization of strains, asymptomatic infection and shedding and immune response to further our understanding of norovirus infection and disease. Caliciviridae. The viral genome consists of three open reading frames (ORFs), with ORF 1 encoding six non-structural proteins including the RNA dependent RNA polymerase (RdRp). ORF 2 encodes for the major capsid protein (VP1) and ORF 3 encodes a minor capsid protein (VP2)  Vesikari score = 5 [p = 0.111). No difference in associated vomiting or fever between episodes occurring below and above the age of 1 year was observed among the two viral genogroups.A total of 50 87.7%) and 98 62%) episodes of diarrhea in children ≤1 year of age were associated with norovirus GI and GII respectively. The median age of norovirus diarrhea was 7 4.5–12) months. Median age (IQR) of diarrhea with norovirus GI and GII were 5 (3–7) months and 8.8(5.7–15.3) months respectively. The median (IQR) duration in infants was similar between the two genogroups of the virus . Diarrhe.5–12 mon.7% and 92% episodThe overall incidence of norovirus diarrhea was 0.14 (0.12–0.16) per child-year which is lower than the incidence of rotavirus diarrhea in the same population, 0.25 (0.22–0.29) per child-year . The incidence of norovirus diarrhea was highest during the first year of life, 0.26 (0.22–0.32) per child-year and decreased to 0.09 (0.07–0.13) and 0.07 (0.05–0.10) per child-year during the second and third year, respectively.p = 0.753. There was no difference in the severity of diarrheal episodes, vomiting or febrile symptoms pre- and post-weaning in children with either genogroup.Eight 8/57, 14%) GI and 11  GII associated diarrheal episodes occurred before the introduction of supplementary feeding or weaning . No sign4% GI andp = 0.500). When the household hygiene scores were compared between children with single . Similarly, children with only GI infections  infections.The median (IQR) household hygiene score among the norovirus infected and uninfected children was 11 8–14) and 11 9–13.5), respectively  norop = 0.027) and wasted  at 12 and 24 months of age, respectively (Complete anthropometry data was available for 362 (97.1%) of the 373 children under observation. The proportion (with 95% CI) of stunted, wasted and underweight children at 12, 24, and 36months of age among those with and without norovirus infection is presented in ectively . The proA total of 215 samples were genotyped by sequencing of the amplicons. Three GI and 26 GII samples failed in sequencing reactions, but are included in the overall analysis because all PCRs were repeated at least twice, and band sizes re-confirmed with absence of non-specific bands.Sequence analysis of the GI genogroups showed a predominance of GI.3 genotype in 23/57 (40.3%) of the samples, followed by GI.1 , GI.2  and GI.6 . Phylogenetic analysis of norovirus GII genogroup of either the capsid or the RdRp region  showed tThe GII.4 strains were placed in 3 sub-clusters when analyzed with reference sequences. Of the 35 samples identified as GII.4 at the ORF 1–2 capsid junctions, 17 strains with 96% nucleotide identity clustered in the Hunter sub-cluster, 6 with 93% nucleotide identity with the Farmington sub-cluster and 12 with 98% nucleotide identity with the Sakai sub-cluster. Fifteen children between the ages of 2.5–8.3 months were infected with the Hunter sub-cluster, with 2 children having two episodes of infection 17 and 159 days apart, respectively. Six children between the ages of 4.2–8.6 months were infected with the Farmington sub-cluster. The Hunter and Farmington sub-cluster infections were seen in children between the years 2002–2003, indicating the circulation of this sub-cluster in the community. However, there was a predominance of the Sakai sub-cluster in 12 children who were infected between 2004–2005. Nine samples were genotyped as GII.3 and clustered with 94% nucleotide identity to the Toronto strain. Ten samples were genotyped as GII.2 with 98% nucleotide identity to the Snow Mountain strain.Nucleotide sequences of positive samples from the study have been deposited in the GenBank and the accession numbers are JN654720-JN654766.ABO blood group and secretor status were determined for 293 children from whom appropriate samples were available. The most common ABO blood group was O (39.3%), followed by B (32.5%), A (20.9%) and AB (7.2%). One hundred eighty-six children  were secretor positive.p = 0.167). For the 115 children with GII infection, 75% of those with GII.4 (n = 56) were secretor positives, whereas only 57.8% of children with non GII.4 infection (n = 57) were secretor positives (p = 0.054). Moreover, genotyping for the FUT2 SNP showed that children with the G428A homozygous mutation for inactivation of the FUT2 enzyme (se428se428) are significantly at a lower risk of infection with norovirus  in stool compared to the proportion of diarrheal stools positive for norovirus . Earlier studies on children have reported a higher percentage of vomiting episodes than diarrheal episodes in norovirus associated outbreaks of gastroenteritis, described as 'winter vomiting disease'.A study The median Vesikari score for norovirus GI and GII diarrhea was 5, similar to studies from other developing countries , 42, andThe severity and frequency of vomiting and fever associated with norovirus was higher among the GII infected children ; this fiSymptomatic norovirus associated diarrhea was detected in children during the first 6 months of age suggesting that breast feeding did not confer protection, unlike the absence of symptomatic infection among younger children in the Peruvian study . Re-infeA high degree of genetic diversity was seen among circulating noroviruses, with four GI genotypes and nine genotypes of norovirus GII detected. These data are similar to other studies where a higher diversity of norovirus has been documented in gastroenteritis in the community when compared to outbreaks, generally in the adult and/or elderly population , 49–53. in vitro binding studies that have shown that carbohydrate binding is essential for GI infection [FUT2 gene and susceptibility to norovirus infection was examined by checking for two common mutations in Asian populations, which showed that children with a nonsense mutation at G428A were significantly at a lower risk of infection with norovirus, as has been previously shown by other studies [The link between the Histo-Blood Group Antigen (HBGA) binding and secretor status is well documented for the prototype GI virus, Norwalk virus. In this study, there was no significant association between blood groups and norovirus GI infection, but higher infection rates were seen among secretors compared to non-secretors, which is similar to previous studies of volunteer challenge and nfection , 55–57. nfection –60. Expr studies , 62.In summary, this report shows that norovirus infections are a common cause of pediatric gastroenteritis in southern India. A previous report from the same region found 15% of hospitalized gastroenteritis cases in children <5 years of age to be positive for norovirus . In the S1 Dataset(XLSX)Click here for additional data file.


Salmonella from dogs in Maiduguri Metropolis were determined using standard bacteriological methods to assess the risk of possible transmission of Salmonella infection from dogs to humans. Of 119 samples, Salmonella was isolated from 52 (43.7%). Males had higher prevalence of 50.0% compared with 34.7% in females (P < 0.05). Dogs older than 24 months had higher prevalence of 61.0% and the lowest was seen in dogs aged 13–24 months (P < 0.05). The prevalence of 31.8%, 41.2%, and 58.8% was observed in dogs aged 3–6, 10–12, and 7–9 months, respectively. High prevalence of 49.5% was observed in Mongrels, while Terrier and Alsatian breeds had 30.0% and 8.3%, respectively. Salmonella isolates from Alsatian and Terrier breeds showed about 100% susceptibility to all the tested antimicrobials. Higher percentage of the Salmonella isolates from Mongrels also showed susceptibility to ciprofloxacin (89.7%), amoxicillin (87.6%), vancomycin (86.6%), and chloramphenicol (84.5%). However about 50% of these isolates showed resistance to ofloxacin. The carrier status of Salmonella is high among dogs especially Mongrels. Therefore good environmental hygiene, discouraging straying coupled with feeding of dogs with properly cooked and uncontaminated feeds was recommended to mitigate risk of human salmonellosis.The prevalence and antimicrobial sensitivity of  Salmonella, belonging to the family Enterobacteriaceae [ Salmonella enterica, the causative agent of salmonellosis, is known to be a primary inhabitant of the gastrointestinal tract of numerous animal species including humans and mostly affects a wide host range with the exception of a few Salmonella serovars that are host-specific: Salmonella Typhi in humans, S. Gallinarum and S. Pullorum in poultry, and S. Dublin in cattle [ Salmonella infection to humans and even to other animals [ Salmonella spp. from healthy dogs and subsequent transmission of the infection to humans [ Salmonella by dogs as a possible source of infection for dog owners and their communities [ Salmonella infections and infected ones may remain carriers and feacal shedding therefore may serve as sources of infection to man and other animals [ Salmonella infection to humans. There is paucity of information regarding the role of dogs as sources of Salmonella infection to humans in Maiduguri Metropolis and therefore this study aims to determine the carrier status of Salmonella in dogs and their role as potential sources of infection to humans.Salmonellosis is a broad term applied to enteric infections caused by a group of gram-negative bacteria of the genuseriaceae . Salmonen cattle . They arn cattle . Consequn cattle . Feaces  animals . Severalo humans –7. Othermunities , 9. Dogs animals . Due to I–11.83° North Latitude and 13°09I–13.15° East Longitude. It shares an extensive border with Niger to the North, Chad to the Northeast, and Cameroon to the East. Its altitude is about 350 metres above sea level and has an area of 75,540.9 km2. Its population is about 4,171,104 with a population density of 60 people per km2 (2006 census figures). The climate is favourable, with a mean annual rainfall and temperature of about 650 mm and 32°C, respectively. The months of March and April are the hottest periods of the year with temperatures ranging between 30°C and 40°C. It is usually cold and dry during the harmattan, November to January being the coldest months (http://en.wikipedia.org/wiki/Maiduguri).Maiduguri is located in the Sahel Savannah region of Northeastern Nigeria at 11°50n = 20), University of Maiduguri staff quarters (n = 11), Mairi village (n = 23), Gwange ward (n = 15), Bulunkutu Polo (n = 18), Custom area (n = 10), Gommari (n = 13), and Ummalari (n = 9) wards. A total of 119 feacal samples, comprising 70 males and 49 females, were collected from three breeds of dogs . The age of the dogs was determined by dental eruption at the time of sample collection. Only one dog was sampled per household visited. Most of the household visited had 3 to 4 dogs. A total of 97 Nigerian local breed Mongrel and 12 Alsatian and 10 Terrier breeds were sampled. All the ages of the sampled dogs ranged from <3 months to older than 2 years. All the dogs were apparently healthy dogs with only 5 (4.2%) having diarrhoea as at the time of sample collection.The dogs investigated in this study were from Maiduguri Metropolis and its environs. Samples were obtained only from dogs kept at home for security/guard or other purposes and from dogs at the Veterinary Teaching Hospital  (Oxoid), and Xylose Lysine deoxycholate (XLD) agar (Oxoid). The cultured plates were incubated at 37°C for 24–48 hours [ Salmonella based on cultural and morphological characteristics: presumptive Salmonella colonies appearing colourless and nonlactose fermenting on McConkey agar, dome-shaped colonies with central black spot on XLD agar, transparent colonies with black centre on SSA, and pink colonies surrounded by a red medium were selected as presumptive Salmonella colonies and subjected to further biochemical tests and gram staining as described by Barrow and Feltham [Rectal swabs were collected aseptically using sterile swab sticks (Oxoid) and placed in tubes containing Carry-Blair transport medium . The samples were immediately transported ice cooled within 8 hours of collection to the Microbiology Laboratory, Faculty of Veterinary Medicine, University of Maiduguri, for further processing and analysis. All the samples collected were then inoculated into 2 mL of Selenite-Feaces-broth  for enrichment and incubated aerobically at 37°C for 24 hours. Subcultures were then made from each broth culture by streaking onto Brilliant Green Agar (BGA) (Oxoid), McConkey agar (Oxoid),48 hours . The cul Feltham .μg), gentamycin (30 μg), chloramphenicol (30 μg), ciprofloxacin (10 μg), ofloxacin (5 μg), streptomycin (10 μg), ampicillin (30 μg), amoxicillin-clavulanic acid (AMC) (5 μg), vancomycin (30 μg), neomycin (25 μg), trimethoprim (25 μg), and erythromycin (15 μg).Antibiotic susceptibility pattern of isolates to various routine antibiotics was carried out using the Kirby-Bauer disk diffusion method  on Muell Salmonella infection was expressed in percentages and proportions in Microsoft Excel version 2010 before finally importing the data into Statistical Package for Social Sciences (SPSS) software version 16.0 to determine the statistical association between dependent and independent variables. The association between infection and other risk factors was determined using Chi-square test at 5% significance level [Prevalence ofce level .Of the 119 sampled dogs, 70 (58.8%) and 49 (41.2%) were males and females, respectively; 97 (81.5%), 12 (10.1%), and 10 (8.4%) were Nigerian local breed Mongrel, Alsatian, and Terrier, respectively; 2 (1.2%), 22 (18.5%), 17 (14.3%), 17 (14.3%), 20 (16.8%), and 40 (34.5%) were from dogs aged < 3, 3–6, 7–9, 10–12, 13–24, and older than 24 months, respectively . Salmonella. Of these (52), 50.0% and 34.7% were the male and female infection rates, respectively (P < 0.05) in the prevalence of Salmonella infection in either sex. Highest prevalence was observed in dogs aged older than 24 months with 61.0% (25/41) and except for dogs < 3 months, the lowest was seen in dogs 13–24 months with 15.0% (3/20). While the prevalence of 31.8%, 41.2%, and 58.8% was observed in dogs aged 3–6, 10–12, and 7–9 months in this order of infection rates (P < 0.05) in the prevalence of Salmonella infection across the age groups. Highest prevalence of 49.5% (48/97) was observed in the Nigerian local breed Mongrel, while Terrier and Alsatian breeds had 30.0% (3/10) and 8.3% (1/12), respectively (P < 0.05).Of the 119 dogs examined, 52 (43.7%) were positive forectively . There won rates . There wectively . This wa Salmonella isolates reveals that Salmonella isolates from the Terrier and Alsatian breeds had high susceptibility to all the antimicrobials used, with small pockets of resistance , amoxicillin (87.6%), vancomycin (86.6%), chloramphenicol (84.5%), trimethoprim (81.4%), ampicillin (80.4%), neomycin (77.3%), and gentamycin (71.1%)  , however Salmonella spp. worldwide have been incriminated as the potential sources of Salmonella infection to humans especially children due to close contact and interaction that exists between them [ Salmonella transmission from dogs to humans resulting into severe infection in humans have been documented [ Salmonella by dogs is more common than the prevalence of clinical disease [ Salmonella spp. from clinically healthy dogs was reported to be between 0.0% and 43.0% [ Salmonella in feacal samples from clinically healthy or hospitalized dogs to range from 1% to 36% [ Salmonella was isolated from 52 (43.7%) of the dogs examined. This prevalence is within the reported 0.0% and 43.0% range of prevalence of Salmonella isolated from clinically healthy dogs [ Salmonella serotypes. Another study by Khan [ Salmonella. The differences in the sample sizes, period of study, type of feacal samples, geographical areas, and isolation methods employed in the various studies above may account for the differences in the prevalence and may all affect the prevalence [ Salmonella contaminated food materials in the environment . This could be due to the differing number of samples in each sex , amoxicillin-clavulanic acid (AMC) (87.6%), vancomycin (86.6%), and chloramphenicol (84.5%). However, about 50% of these isolates were resistant to ofloxacin ( Salmonella has become a major public health concern. Mongrels are more likely to harbor Salmonella serovars due to their scavenging nature and therefore are more likely to be treated with antibiotics than the exotic breeds in the study area. Alsatian and Terrier breeds are mostly restricted and fed at home and are not allowed to scavenge or stray in the environment. This makes them less likely to acquire Salmonella infection and therefore not likely to be treated with antibiotics. Indiscriminate use of antibiotics in animals could be responsible for the emergence of antimicrobial resistant strains of bacteria [ Salmonella isolates from the study area.The antimicrobial sensitivity testing results reveal that high percentages of thefloxacin . In the bacteria . Therefo Salmonella carrier status in dogs kept in households in Maiduguri Metropolis, Nigeria. Mongrels had high Salmonella carrier status compared with the other breeds in the study area. Most of the households visited keep Mongrels, where they are left to wander and scavenge for food in the environment and only return back home in the evening. This has public health significance as dogs may pose a risk to humans where close contact between dogs and their owners occurs in households and children and immunosuppressed individuals may be particularly at risk [In conclusion, this study revealed a high at risk . As the


The contact LD50 for phosmet of 0.22 ug/bee and oral LD50 for phosmet of 0.37 ug/bee from Agritox were used for calculations in all succeeding tables. Please see the correct In Table 1, there should be two lines of LD


Absenteeism, or missing scheduled appointments is a serious problem to the healthcare system, affecting healthcare institutions that cannot maximize their staff appointments, thus increasing their costs, and also to patients, who face difficulties in accessing the system.The aim of this study was to assess whether sending scheduled appointment date reminders through Short Message Service (SMS) for attendance at a healthcare unit would reduce the absenteeism in our institution.The study enrolled patients who scheduled appointments with an interdisciplinary team (up to 5 scheduled appointments per shift), from January-December 2012, before the SMS reminders, and compared to January-December of 2013 and 2014. Absenteeism was analyzed by the total number of patients scheduled appointments (TSA), compared to the absentees at the appointed date and also the number of health care providers scheduled appointments (NSA) compared to the team's idle time during the study period. The SMS was sent a week before the appointment date.In 2012, before the SMS intervention, TSA absenteeism was 20.0±3.3% (7736 scheduled patients/1524 no-show patients), in 2013 was 15.9±2.1% (7509/1199) and in 2014 was 15.4±1.8% (7285/1118). A TSA absenteeism reduction of 20.5% (p=0.0024) was observed in the first year of the intervention and of 23.0% (0.0004) in the second year. The NSA absenteeism in 2012 was 14.9±1.9% (17196 scheduled appointments/2510 idle time), in 2013 was 11.9±1.9% (16674/1988) and in 2014 was 11.5±1.7% (17867 /2024). During the study period, there was an idleness reduction of TSA  and NSA .The use of phone reminders with scheduled appointment dates through SMS was effective in reducing healthcare absenteeism, being an important tool to optimize the services offered by the institution.


Aim. Many studies demonstrated that alopecia areata (AA) and vitiligo are commonly associated with autoimmune thyroid diseases. We aimed to investigate the frequency of thyroid dysfunctions and autoimmunity related with vitiligo and AA. Material and Methods. 200 patients, 92 AA and 108 vitiligo diagnosed, were surveyed retrospectively. The control population was in reference range and from Konya, central Anatolian region of Turkey. Thyroid function tests  and serum thyroid autoantibody  levels were evaluated in all patients. Results. In vitiligo patients, 9 (8.3%) had elevated anti-TG levels and 16 (14.8%) had elevated anti-TPO, and in 17 patients (15.7%) TSH levels were elevated and 3 (2.8%) patients had elevated fT4 levels and 5 (4.6%) had elevated fT3 levels. Within AA patients, 2 (2.2%) had anti-TG elevation and 13 (14.1%) had anti-TPO elevation, in 7 patients (7.6%) TSH were elevated, and in 1 patient (1.1%) fT4 were elevated and 5 (5.4%) patients had elevated fT3 levels. Conclusion. In our study, impaired thyroid functions and thyroid autoantibodies in vitiligo and AA patients were identified at lower rates than the previous studies. According to results of this study there is no need for detailed examination in alopecia areata and vitiligo patients without clinical history. Alopecia areata (AA) is an inflammatory disease characterized by scarless alopecia of the scalp and/or whole body hair. It affects 1% of the general population and this complaint takes up to 0.7–4% of all patients presented to the dermatology clinics [Vitiligo is an acquired, idiopathic disease with no clear etiology and characterized by destruction of melanocyte, which results in development of depigmented macules . Even th3, free T4, and thyroid stimulating hormone) and serum thyroid autoantibody (anti-thyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO)) levels of 200 patients were also examined in the study. The AA and vitiligo patient's laboratory data was compared with the reference controls for all the parameters. The normal ranges were according to the laboratory standards of Konya Research and Training Hospital, a reference hospital in Turkey. fT3, fT4, insulin, and TSH were measured by Advia Cetaur XP with chemiluminescence method . Anti-TG and anti-TPO levels were measured by Immulite 2000 with chemiluminescence method . The results obtained from the patients were evaluated based on the reference value set by the manufacturer.After local ethical committee approval for our study, the records of 92 AA and 108 vitiligo patients who presented to our dermatology clinic between January 2010 and January 2014 were, respectively, reviewed. Thyroid function tests  and 50.9% were females (n = 55). Mean age of the patients with alopecia areata was 26.25 ± 12.37 years; 59.8% of the patients were males (n = 55); 40.2% of patients were females (n = 37). Mean free T3 (fT3) levels were 3.63 ± 0.65 pg/mL in the patients with vitiligo and were 3.67 ± 0.61 pg/mL in the patients with alopecia. Mean free T4 (fT4) levels were 1.25 ± 0.31 ng/dL in the patients with vitiligo and were 1.32 ± 0.28 ng/dL in the patients with alopecia. While geometric mean of TSH levels was 2.06 (0.01–150.00) micro-IU/mL in vitiligo patients, it was measured as 1.94 (0.45–4.91) micro-IU/mL in alopecia patients. In the patients with vitiligo, geometric mean of anti-TPO levels was 18.52 (7.94–1000.00) IU/mL and in alopecia patient the mean was found as 18.70 (7.38–1000.00) IU/mL. Geometric mean of anti-TG levels was 23.90 (10.00–3000.00) IU/mL in vitiligo patients and the geometric mean was calculated as 21.07 (10.00–3000.00) IU/mL in the patients with alopecia.A total of 108 vitiligo patients and 92 AA patients were included in the study. Mean age of vitiligo patients was 30.15 ± 17.07 years and 49.1% of patients were males  of vitiligo patients, TSH levels were within normal limits, and in 15.7% (n = 17) of vitiligo patients the level was higher than normal values. While TSH measurements were evaluated as within the normal limits in 92.4% (n = 85) of alopecia patients, it increased in 7.8% (n = 7) of the patients diagnosed with alopecia. On the other hand, normal fT3 levels were shown in 95.4% (n = 103) of the vitiligo patients and in 4.6% (n = 5) of these patients the level was high. The levels of fT3 were evaluated as normal in 94.6% (n = 87), while it was increased in 5.4% (n = 5) of the patients with alopecia. fT4 levels were within normal limits in 98.2% (n = 105) of the patients with vitiligo and were high in 2.8% (n = 3). fT4 measurement was normal in 98.9% (n = 91) of the patients with alopecia and it was high in 1.1% (n = 1) (p > 0.05)  . EvaluatAA is a disease with unknown etiology characterized by oval or round scarless hair loss. The lesion can be single and self-limiting or may be widespread, and recurrence can be seen in the course of the disease. Its etiology is not fully understood, although genetic susceptibility, autoimmunity, and stress are suggested as some of the causative factors. Some researchers claimed that cell-mediated immunity plays a role on lymphocytic infiltration surrounding anagen hair follicles. Humoral immunity has been also suggested to have an important role in the development of AA. Specific IgG antibody to the hair follicles was found in higher concentration in peripheral blood of the patients with AA compared to control subjects –5.Vitiligo is considered as an autoimmune disease characterized by wide spread white patches which result from loss of melanocytes. Autoimmune diseases, genetic factors, autotoxic metabolites which occurred during melanin synthesis, accumulation of neurochemical substances, free radicals, deficiency of melanocytes growth factors, and deterioration in function or structure of melanocytes are believed to be responsible factors in the pathogenesis of vitiligo .AA and vitiligo are often observed with other autoimmune diseases. Among these diseases, vitiligo, lichen planus, lichen sclerosus et atrophicus, pernicious anemia, atopic dermatitis, Hashimoto's thyroiditis, hypothyroidism, endemic goiter, diabetes mellitus, lupus erythematosus, and Graves' disease can be included. However, the chance of coexistence with autoimmune thyroid diseases is higher than the others –12.Previous studies which investigated frequency of autoimmune thyroid disease in vitiligo patients revealed very different results. Positive anti-TG titers were found in 30%, and thyroid dysfunction was found in 10–20% of the patients with AA. Likewise, positive thyroid autoantibodies were shown in 2–50% of vitiligo patients. These variable results were believed to stem from possible presence of methodological mistakes and the differences in strength level of the studies .Bakry et al. reported that subclinical hypothyroidism was found in 16% of 50 AA patients and anti-TG antibodies were positive in 23 (46%) of these patients. They also demonstrated positive TPO-Ab titers in 24 (48%) patients . In our Abnormalities in thyroid function were demonstrated in 8 (11.4%) out of 70 AA patients in a retrospective study. Significantly high thyroid autoantibody level was present in 18 (25.7%) patients with AA compared to the controls. No significant correlation between presence of antibodies and disease severity was demonstrated .A study regarding 87 vitiligo patients demonstrated positive anti-TG titers in 23% (20/87) of the patients and TPO-Ab were positive in 24.1% (21/87) of the patients, and the results were found significantly higher when compared to healthy controls. Same researchers demonstrated that presence of antibodies was more frequent in female patients between the ages of 11 and 20 .Study of Kasumagic-Halilovic et al. found high levels of anti-TPO in 11 (27%) out of 40 vitiligo patients and they demonstrated significantly elevated levels of anti-TPO compared to the control group . ElevateUncu et al. did not demonstrate hypo- or hyperthyroidism in the assessment of 50 children with vitiligo; however they reported significantly higher frequency of autoimmune thyroiditis in girls and in the patients with long duration of generalized vitiligo . In our p = 0.015) [The study of Ağırgöl et al. regarding thyroid autoimmunity in 112 AA patients and 62 control subjects revealed the presence of autoimmune thyroid disease in 19 (17%) patients and in 3 (5%) control subjects, and the difference between the groups was considered as significant  patients and the presence of thyroid autoantibody in 16 out of 109 (14.7%) patients. They demonstrated significant correlation between the duration of AA and the level of autoantibodies . These rn = 24) of the patients had thyroid function test (TFT) abnormalities. Of these abnormalities, 24.7% (n = 22) were considered as clinically insignificant. Anti-thyroid peroxidase antibody (anti-TPO) was found positive in 9% (n = 8) of the patients. High levels of anti-TG were present in 3.3% (n = 3) of the patients, and these patients have been evaluated as euthyroid. Therefore, they concluded that, regardless of TFT and basal level of thyroid autoantibodies, regular monitoring might be meaningful in children with AA [In a retrospective study regarding 89 patients with AA, Doğan et al. found Hashimoto's thyroiditis in 5 (5.6%) patients who have been considered as euthyroid; 27% ( with AA . AutoantIn our study, thyroid dysfunction and the level of autoantibodies were lower compared to previous studies. Contrary to some studies, no significant correlation could be observed between the gender and anti-TPO level in our study.In our study, thyroid dysfunction and autoantibody level were lower than previous studies. In the lights of present data, we concluded that because of high cost and time consuming nature of the tests detailed thyroid autoimmunity tests are not required for all of the patients with vitiligo and AA who presented to the clinics; we think it is more suitable that further evaluation should be done in the patients with positive family history, if suspicious findings are obtained during the examination.


Scientific Reports5: Article number: 1360310.1038/srep13603; published online: 09092015; updated: 10282015.This Article contains an error in the order of the Figures. Figures 8 and 10 were published as Figures 10 and 8 respectively. The correct Figures 8 and 10 appear below as


Obstructive Sleep Apnea (OSA) describes intermittent collapse of the airway during sleep, for which continuous positive airway pressure (CPAP) is often prescribed for treatment. Prior studies suggest that discontinuation of CPAP leads to a gradual, rather than immediate return of baseline severity of OSA. The objective of this study was to determine the extent of OSA recurrence during short intervals of CPAP depressurization during sleep.20) or atmospheric pressure, in alternating fashion for 1-hour periods during the night. We compared sleep architecture and metrics of OSA during CPAP-on and CPAP-off periods.Nine obese (BMI = 40.4 ± 3.5) subjects with severe OSA (AHI = 88.9 ± 6.8) adherent to CPAP were studied during one night in the sleep laboratory. Nasal CPAP was delivered at therapeutic . The average 3% ODI during CPAP-on and CPAP-off was 4.7 ± 2 and 20.4 ± 4.7 respectively (p<0.05). CPAP depressurization also induced more awake (p<0.05) and stage N1 (p<0.01) sleep, and less stage REM (p<0.05) with a trend towards decreased stage N3 (p = 0.064).Acute intermittent depressurization of CPAP during sleep led to deterioration of sleep architecture but only partial re-emergence of OSA. These observations suggest carryover effects of CPAP. Obstructive Sleep Apnea (OSA) is a common breathing disorder characterized by intermittent collapse of the airway during sleep, for which continuous positive airway pressure (CPAP) is the principal treatment. CPAP increases the intra-luminal pressure of the airway, overcoming the collapsing pressures of the surrounding tissues. OSA is Patients often use CPAP irregularly, including sporadic usage within a single night. It is nPatients were recruited from the sleep clinics at the Johns Hopkins and Johns Hopkins Bayview Sleep Disorders Center. This study was approved by Johns Hopkins IRB NA_00086830. All participants gave written consent for participation. Patients were recruited with severe sleep apnea and a good history of CPAP adherence. Specifically, Inclusion criteria included adults of all races ages 20–65 years old with a history of severe OSA (AHI>40 events/hour) documented within the preceding 4 years. They also needed clinical documentation of good adherence characterized by CPAP use for >70% of nights exceeding 4 hours in the previous month, or a clinic visit within the preceding year where the patient exhibited ≥3 months of equivalent adherence. A total of 9 subjects  were recruited for the study. 1 subject was not able to tolerate the CPAP depressurizations and left after approximately 1 hour of sleep. Remaining subjects completed the protocol without difficulty and their results were included in the analysis. Exclusion criteria included uncontrolled hypertension with blood pressure > 160/100; history of congestive heart failure; insulin dependent diabetes; pregnancy; or commercial driver or pilot unable to refrain from duties the day following study. Some of the exclusions above were related to metabolic outcomes that are planned in separate analyses. The study was approved by the institutional review board of Johns Hopkins. All subjects gave informed consent prior to participation.3-A2, C3-O1, F3-A2), bilateral electro-oculograms, submental electromyogram, 3-lead electrocardiogram, and oxyhemoglobin saturation. Respiratory effort was measured by thoraco-abdominal movement assessed by mercury strain gauges. Leg movements were monitored by electrodes placed on the anterior tibialis muscles. Signals were recorded on a computer with RemLogic software. Transcutaneous CO2 monitoring  was used to confirm that no hypoventilation during sleep occurred when CPAP pressure was lowered to atmosphere. Airflow was measured using a pneumotachograph . Nasal pressure was measured using a pressure transducer  from a side port in the nasal mask. Pressure was delivered to the nasal mask using a customized CPAP device  capable of rapid remote controlled pressure adjustments.After informed consent, subjects reported to the clinical research unit at the Johns Hopkins Bayview Medical Center. Standard polysomnographic recording techniques were used with a full montage that included electroencephalograms . The nasal mask was equipped with an anti-asphyxia valve which prevented CO20 increments every 3 breaths to avoid sudden shifts in pressure or noise from rapid closure of the anti-asphyxia valve.The CPAP setup is shown in Sleep was staged and respiratory events scored according to American Academy of Sleep Medicine guidelines . Apneas 2 nadir, arousal index (AI) and respiratory arousal index (RAI). All indices were calculated based on time asleep during each hour. We combined the data from the 4 CPAP-on hours and the 4 CPAP off-hours to and compared the two groups using a Wilcoxon matched-pair signed rank test. A similar comparison was made for CPAP-on and CPAP-off periods  In all figures, the mean and standard error of the mean are depicted. Additional analyses were performed to examine effects of time, CPAP state, or their interaction on AHI and sleep architecture parameters. A two-way analysis of variance (ANOVA) with repeated measures was used for this analysis. Calculations were performed in GraphPad Prism 6.0 . Comparisons were considered significant at the p<0.05 level.Each study was divided into 8 hour-long blocks, each with its own sleep staging and tabulation of respiratory events including the apnea hypopnea index (AHI), 3% oxygen desaturation index (ODI), average SpO Most of the study subjects were middle aged (48.1 ± 3.3 years) morbidly obese (BMI = 40.4 ± 3.5) men. At the time of study entry, 2.5 ± 0.4 years had elapsed since the initial clinical PSG when OSA was diagnosed. Subjects gained 5.3 ± 3.6 kg during this time interval. Baseline clinical PSG results are shown in Table 2. Subjects BA and DR underwent split-night studies while the remaining subjects underwent full night PSG.Demographics of study subjects are shown in Tables 2 nadir during respiratory events was 87.5% and the mean of the lowest SpO2 nadir was 81.9%. All subjects were accustomed to nasal CPAP masks at home. The mean therapeutic CPAP pressure used by subjects was 11.1 ± 0.6 cm H20. Objective adherence monitoring demonstrated that subjects used CPAP on 97.0 ± 1.5% of nights. Four hours of CPAP use/night was exceeded on 86.5 ± 6.1% of nights. In 7/8 subjects, residual AHI data were available from their CPAP adherence card, with an average of 1.5 ± 0.8 events/hour.As a group, based on the data available, there was neither an effect of REM sleep nor body position on the severity of OSA. However, no periods of non-supine sleep were captured in 3 subjects, and no periods of REM were captured in 3 others. The average SpO2 during transitions between CPAP pressure Click here for additional data file.S2 Fig(TIF)Click here for additional data file.


In the pre-cART era, anemia was a frequent complication observed in HIV patients. But, recent studies showed a persistent high prevalence of anemia, integrating anemia in the premature aging observed in HIV patients. The aim of the study was to estimate the prevalence of anemia in our patient’s cohort.All patients, except pregnant women, seen in our unit after 2007 were included in this analysis. For each patient, last hemoglobin’s concentration was collected. Incidence of anemia was calculated according WHO’s definition.544 patients  with a median age of 45.9 years (18.9-80.8) were included. 513 patients were on ART (94.3%). Median CD4 was 546.5 (14-2707), viral load (VL) < 50 in 75.9% of patients.Anemia was present in 141 patients (25.9%): mild 18.9%, moderate 6.8%, severe 0.2%. No correlation with VL was seen: mean Hb for patients with CV>50 versus <50 was respectively 13.3 and 13.4. No correlation with CD4 was seen: mean CD4 for anemic and non-anemic patients was respectively 502 and 544 (NS). However, a correlation with age was seen with an incidence of anemia of 24.5% for patients under 60 y and 36.4% for patients ≥60 y (p<0.001). These impact on age was only seen in men with an incidence of anemia of 12.6% for age under 60 y vs 33.3% for age ≥60 y (p<0.001). For women, age has no impact on prevalence of anemia.In the era of c-ART, incidence of anemia remains high especially in patients above 60 years. Given the growing age of HIV patients, physicians should be attentive to this problem in the oldest patients. Further prospective studies are needed to better characterize the mechanisms of anemia observed in this population.


Sporadic HFMD  cases and outbreaks caused by etiologic agents other than EV71 and CA16 have increased globally. We conducted this study to investigate the prevalence and genetic characteristics of enteroviruses, especially the non-EV71 and non-CA16 enteroviruses, causing HFMD in Shanghai. Clinical specimens were collected from patients with a diagnosis of HFMD. A partial length of VP1 was amplified with RT-PCR and subjected to direct sequencing. Phylogenetic analyses were performed using MEGA 5.0. The ages of the HFMD cases ranged from 3 to 96 months, and the male/female ratio was 1.41. The median hospital stay was 2.96 days. Up to 18.0% of patients had neurologic system complications such as encephalitis, meningoencephalitis or meningitis. Of the 480 samples, 417 were positive for enterovirus (86.9%) with RT-PCR. A total of 13 enterovirus genotypes were identified. The most frequent genotypes were CA6 (31.9%), EV71 (30.6%), CA16 (8.8%) and CA10 (7.5%). Infections with CA6, EV71, CA16 and CA10 were prevalent throughout the years of study, while the proportion of CA6 notably increased from Sep. 2012 to Dec. 2013. Phylogenetic analyses showed that EV71 strains belonged to the C4a subgenogroup and CA16 was identified as B1b subgenogroup. The CA6 strains were assigned to genogroup F, whereas the CA10 strains were assigned to genogroup D. Patients infected with CA6 were typically younger, had a shorter hospital stay and had a lower incidence of neurologic system complications when compared to patients infected with EV71. Our study demonstrates that the enterovirus genotypes causing HFMD were diversified, and there was an increasing prevalence of the non-EV71 and non-CA16 enteroviruses from 2012 to 2013. CA6 was the most predominant pathogen causing HFMD from Sep. 2012 to Dec. 2013, and it often caused relatively mild HFMD symptoms. Most severe HFMD cases were associated with EV71 infection. Hand foot and mouth disease (HFMD), characterized by fever, and vesicular exanthema on the hands, feet, oral mucosa and buttocks, is a global and common disease in children, particularly in those less than 5 years old. Although HFMD is classically a mild disease and most infections resolve spontaneously, severe HFMD with fatal cardiopulmonary and neurologic complications have increasingly occurred in the Asian-Pacific region since 1997 and have attracted attention from many countries .HFMD is caused by enteroviruses belonging to the genus of the Picornavirus family. Typically, enterovirus 71 (EV71) and coxsackievirus A16 (CA16) of the enterovirus A species have been the most common causative agents, and EV71 has become the dominant pathogen causing severe HFMD –8. From In China, large outbreaks of HFMD have occurred every year in different provinces in the past few years, and EV71 and CA16 are still the most frequent pathogens in co-circulation –8. From http://www.nhfpc.gov.cn/yzygj/s3593g/201306/6d935c0f43cd4a1fb46f8f71acf8e245.shtml) at Children’s Hospital of Fudan University, Shanghai, China. The complications involving neurologic, respiratory or circulatory system diseases as a result of HFMD were defined in “A Guide to Clinical Management and Public Health Response for Hand Foot and Mouth Disease (HFMD)” .From 1 Jan 2012 to 31 Dec 2013, a total of 480 stool specimens were collected from patients hospitalized with HFMD who were diagnosed according to the Ministry of Health’s diagnostic criteria  stool specimens by TRIzol  and dissolved in 20 μl DEPC (Diethypyrocarbonate) water. The cDNA sample was synthesized by using PrimeScript TM RT kit  in a total volume with 4 μl of RNA, 100 μmol random primers, and 2.5 U reverse transcriptase.The detection and genotyping were performed by nested-PCR using the VP1 junction region of the enterovirus, as described . For theThe genetic identity of each PCR product was first determined by comparison with the standard strains in GenBank . All the sequences obtained in this study were then deposited to GenBank with the given accession numbers KP717564-KP717665 for CA6, KP717666-KP717683 for CA10, KP717684-KP717686 for CA16 and KP717687-KP717759 for EV71. Multiple sequence alignment was conducted using ClustalW. Phylogenetic trees based on partial VP1 genes were built using the neighbor-joining method in the Molecular Evolutionary Genetics Analysis program, version 5.0 (MEGA 5.0). Gaps were treated as a complete deletion. Statistical support for each clade was assessed using bootstrap analysis with 1000 replicates. Genetic distances were calculated with the P-distance model. All the reference strains used were retrieved from Genbank database, which shared the highest identity with our sequences.x2 tests and/or Fisher’s exact tests were used, and Student’s t tests were used for continuous variables. P values were two-tailed, and they were considered significant if P≤0.05. Data analysis was performed with SPSS, version 18.0.For categorical variables, From Jan. 2012 to Dec. 2013, a total of 480 HFMD patients were recruited in the study with ages ranging from 3 months to 96 months (29.12±17.41 M). The vast majority, 94.2% of the patients, were less than 5 years of age, and the male/female ratio was 1.41. The median hospital stay was 2.96 days. Up to 18.0% of these patients had neurologic system complications such as encephalitis, meningitis and meningoencephalitis.Among 480 samples, 417 (86.9%) were positive for enterovirus. A total of 13 genotypes were detected by sequencing. The most prevalent genotype was CA6 , followed by EV71 , CA16 , CA10  and Echo 3 , CA2 , CA4 , CA9 , CA5 , CA8 , CA12 , CA14 , and CB4  . In 2012Genotypes CA6, EV71, CA16 and CA10 were detected throughout the years of 2012 to 2013. The proportion of CA6 notably increased from Sep. 2012 to Dec. 2013, while the detection ratio of EV71 showed a decreasing trend .Nucleotide sequence alignment of the partial VP1 gene was performed using 102 Shanghai CA6 strains isolated from the HFMD patients in this study. The partial VP1 genes of CA6 strains in our study showed 92.7%-99.7% similarity, and the pairwise distances among them ranged from 0.000 to 0.073. According to the criteria established for genogrouping EV71 and CA16 by calculating genetic distance, the CA6 strains could be classified into A-F genogroups by the selected genetic distance threshold as 0.09  17,18].,18.17,18All of the CA6 strains identified in our study were categorized into genogroup F, which could be further divided into four clusters. The majority of our CA6 strains displayed a close genetic relationship with the Chinese strains identified from other provinces in China and Taiwan, during 2010 and 2013, and these strains were also similar to strains from Thailand in 2012, Finland and Spain in 2008, Japan in 2011 and Cuba in 2012, which were associated with onychomadesis subsequent to HFMD.The CA10 strains in our study showed 90.8%-99.1% similarity, and the pairwise distance among them ranged from 0.001 to 0.091. According to the criteria established for genogrouping EV71 and CA16 by calculating genetic distance, the CA10 strains could be assigned to 4 genogroups (A-D) by the selected genetic distance threshold as 0.09  17,18].,18.17,18Both phylogenetic trees were also constructed with EV71 and CA16. The results revealed that the two viruses circulated continuously in 2012 and 2013. All the EV71 strains identified in this study belonged to subgenogroup C4a, with a high similarity of 93.9%-99.8% between the sequences . PhylogeP<0.05) (P<0.05). An elevated serum C-reactive protein (CRP) level >40 mg/L was noted in a substantial proportion of the patients in the CA6 and CA10 infection groups. The CA16 infection group had a higher incidence of abnormality of cardiac troponin I (cTnI) when compared to the EV71 infection group (P<0.05)  . EV71-in(P<0.05) . Furtherhttp://www.chinacdc.cn/tjsj/).HFMD, first reported in New Zealand in 1957 as a common infectious disease, has since become a serious threat to public health in China. Multiple, large-scale outbreaks have occurred in the past few decades and have caused numerous deaths every year  replaced EV71 and CA16 as the most causative agent of HFMD in Shanghai, while the detection rate of CA10 was as high as 7.5%. To clarify the genetic characteristics, phylogenetic trees based on partial VP1 sequences from CA6 and CA10 strains were constructed. The representative sequences used in this study, that available from Genbank, still formed an independent cluster in the same genogroup as that in the other studies ,27. All The genogroup of EV71 in Shanghai during 2012 and 2013 was C4a, which is most closely related to the strains isolated in different provinces in China. In China, except for one C3 genogroup strain isolated in 1997 and five A genogroup strains isolated in 2008, all the EV71 strains have been classified into the C4a genogroup in outbreaks after 2004 –31. CA16Most HFMD infections are self-limited and do not require hospitalization. Previous studies have demonstrated that EV71 more frequently causes severe complications in young children than other enteroviruses and often leads to acute flaccid paralysis and brainstem encephalitis associated with poor outcomes –37. In tRecent studies in Finland, Taiwan, France, American and China have shown that patients infected with CA6 express clinical symptoms such as onychomadesis and extensive skin ulcerations that are different from those infected with other enterovirus genotypes –14,24,38In summary, this study strongly indicated that CA6 was the predominant HFMD pathogen from late 2012 to 2013, which emphasized the necessity of surveillance of all the enterovirus genotypes causing HFMD in China. While the HFMD vaccine was developed for EV71, these changes in pathogenic compositions of an HFMD outbreak should affect future vaccine development and clinical management.


Mortality in children under five years has been widely studied, whereas mortality at 5–9 years has received little attention. Using unique data from national registers in three Nordic countries, we aimed to characterize mortality directionality in children aged 0 to 9 years.The cohort study included all children born in Denmark from 1973 to 2008 , Sweden from 1973 to 2006 , and a random sample of 89.3% of children born in Finland from 1987 to 2007 . Children were followed from 0 to 9 years, and cumulative mortality and mortality rates were compared by age, gender, cause of death, and calendar periods. Among the 7,105,962 children, there were 48,299 deaths during study period. From 1981–1985 to 2001–2005, all-cause mortality rates were reduced by between 34% and 62% at different ages. Overall mortality rate ratio between boys and girls decreased from 1.25 to 1.21 with the most prominent reduction in children aged 5–9 years (from 1.59 to 1.19). Neoplasms, diseases of the nervous system and transport accidents were the most frequent cause of death after the first year of life. These three leading causes of death declined by 42% , 43% (from 3.7 to 2.1) and 62% (from 3.9 to 1.5) in boys, and 25% (from 4.1 to 3.1 per 100000 person years), 42% (from 3.4 to 1.9) and 63% (from 3.0 to 1.1) in girls, respectively. Mortality from neoplasms was the highest in each age except infants when comparing cause-specific mortality, and half of deaths from diseases of the nervous system occurred in infancy. Mortality rate due to transport accidents increased with age and was highest in boys aged 5–9 years.Mortality rate in children aged 0–9 years has been decreasing with diminished difference between genders over the past decades. Our results suggest the importance of further research on mortality by causes of neoplasms, and causes of transport accidents—especially in children aged 5–9 years. However, statistically significant gender differences were only observed in children under 1 year with RRm/f of 1.21 (95% CI: 1.09–1.35) in 1981–1985 and 1.22 (95% CI: 1.04–1.43) in 2001–2005  before 1 year of age. After 1 year of age, boys had higher mortality rate than girls with the RRm/f from 1.04 to 1.60. We found no obvious change in patterns of mortality rate among age-groups. When taking length of time into consideration, mortality rate decreased by 42% in boys and 25% in girls. Mortality rate showed an overall downward directionality with calendar periods in aggregated age-groups with obvious fluctuations among calendar periods (m/f in children less than 10 years decreased from 1.49 (95%CI: 1.22–1.83) to 1.15 (95%CI: 0.94–1.41) with a reduction in children aged 5–9 years from 1.71 (95%CI: 1.27–2.27) to 1.24 (95%CI: 0.91–1.69)  per 100,000, with boys of 42 (95%CI: 40–45) per 100,000 and girls of 35 (95%CI: 33–37) per 100,000. Both genders had higher mortality at 0–27 days than in other ages . Boys ha periods . Particu91–1.69) . Leukemim/f: 1.18, 95%CI: 1.07–1.29), but a pronounced gender difference was not observed in separated age groups. When taking length of follow-up time into account, mortality in children less than 1 year had declined remarkably. In contrast, the decline in mortality rate after 1 year of age was modest. At 5–9 years of age, mortality rate remained quite stable around 1.00 per 100,000 person years across the entire follow-up period.Disease of the nervous system was the most frequent cause of death in children of both 1 year and 1–9 years of age and cumulative mortality before 10 years was 27 (95%CI: 25–28) per 100,000, with boys of 29 (95%CI: 27–31) per 100,000 and girls of 25 (95%CI: 23–26) per 100,000. The highest risk was obtained among children younger than 1 year and 52% of deaths occurred before 1 year of age. Mortality rates decreased with age in the early ages and kept relatively stable after 3 years of age . Boys ham/f of 1.10(95%CI: 0.87–1.40). Infant mortality rate (<1 year) decreased dramatically over calendar periods, and from 1 year of age mortality rate was relatively stable across calendar periods (m/f of 1.09(95%CI: 0.84–1.42).In most calendar periods, mortality rates in boys were slightly higher than that in girls . During  periods . During  periods . MortaliAmong the diseases of the nervous system, meningitis is the first leading cause of death (28.5%), followed by cerebral palsy (12.7%) in children before 10 years. More than 64% of deaths by meningitis and 44% of deaths by cerebral palsy occurred in infancy. Mortality rate due to meningitis and cerebral palsy in children under 10 years decreased by 65% , and 68%  from 1981–1985 to 2001–2005.m/f in children less than 10 years increased from 1.29 (95%CI: 1.01–1.65) to 1.34 (95%CI: 0.96–1.87) with a large increase in age group of 5–9 years from 1.50 (95%CI: 1.08–2.09) to 1.75 (95%CI: 1.08–2.85). Compared with the other three groups , boys aged 5–9 years had higher mortality rate in all calendar period. Because of the very small number of deaths before 1 year of age in both genders, mortality rate in infancy was not compared with those in other age groups.Transport accidents was the most frequent cause of death after 1 year of age and cumulative mortality before 10 years was 22 (95% CI: 21–23) per 100,000, with boys of 26 (95% CI: 24–28) per 100,000 and girls of 18 (95% CI: 17–20) per 100,000. Mortality rate in boys increased with age while those in girls differed slightly between ages . Boys haThis study presents an overview of mortality directionality in children aged 0–9 years in combined data of three Nordic countries. In this study, which to our knowledge is the first study examining mortality over age at 1-year interval, we found that overall mortality rates decreased with age before 5 years and were relatively stable between 5 and 9 years. Mortality rate in boys was higher than that in girls at each age and the gender differences were more pronounced in children between the ages of 5–9 years. From 1981–1985 to 2001–2005, all-cause mortality rates were reduced by between 34% and 62% at different ages. Mortality rate ratio between boys and girls aged 0–9 years decreased with a pronounced decline in aged 5–9 years. Mortality in infancy (<1 year) making up 70% of the total deaths, still greatly exceeded that of all other ages in the recent years of 2006–2010. Most of death in infancy was caused by certain conditions originating in the prenatal periods, congenital malformations, sudden infant death syndrome, and unknown or unspecified causes. After 1 year of year, neoplasms were the most frequent cause of death, followed by diseases of the nervous system and transport accidents. These three most important causes of death declined over time, both in boys and girls. Mortality from neoplasms was the highest in each age group except for infants among the three leading causes of death, and half of deaths from diseases of the nervous system occurred in infancy. Mortality due to transport accidents increased with age and boys aged 5–9 years had higher risk compared to boys and girls in any other age groups.Our finding of a reduction in mortality in children aged 0–9 years in the past decades is consistent with previous studies from high-income countries , 9–12. UInfant mortality rate has decreased by more than 50% from 1981–1985 to 2001–2005. Preterm birth complications are the leading cause of death in neonates and the second common cause of death in children younger than 5 years. SurviviOur data showed that boys had higher mortality than girls in the total study period, which was in line with the results from the studies in Nordic countries and from the UK , 22, 23.Mortality rate due to neoplasms in both genders decreased dramatically with time. The ACCIS project in Europe  reportedOur study showed that half of death due to diseases of the nervous system occurred in infancy (<1 year). Over calendar period, mortality rates were decreased by 43% in boys and 42% in girls. Holt et al  previousWe observed that mortality due to transport accident was higher in boys than in girls at each age. In boys, mortality rates increased with age, reaching a relatively high level at 7 to 9 years. In contrast, mortality rates in girls remained quite stable. A study from 50 countries  identifiOur study has a number of strengths. We combined nationwide data from three Nordic countries in which have complete individual level register data on population and their deaths. The individual level data over two decades permitted us to examine mortality directionality across a different time periods as well as major groups of cause of death. Even with the small number of death in children aged from 1 to 9 years, especially from 5 to 9 years, the combined data from the three countries still provides the possibility to examine the mortality over age in 1- year interval.Our findings should also be interpreted in the light of limitations. First, we cannot rule out the possibility that changes in long-term directionality in cause-specific mortality are related to coding changes between and within ICD revisions . Second,We observed decreased mortality in children at 0–9 years in the three Nordic countries during the past decades. Mortality rates showed overall downward directionality with age and calendar time, and suggests further possibilities for improving survival in children. Infants, particularly in neonates, have much higher mortality than children aged 1–9 years. Mortality rate in boys was higher than in girls and gender difference on mortality declined with calendar time. Although advances in treatment have improved the survival rate of children with cancer, neoplasms is still the most frequent cause of death in children aged 1–9 years in the three Nordic countries and mortality was the highest in each age group except for infants. Mortality due to transport accidents, one of the most common causes of death in children, increased with age and was highest in boys aged 5–9 years. Our results suggest the importance of further study on mortality by causes of neoplasms, and causes of transport accidents—especially in children aged 5–9 years.The data collection was approved by the Data Protection Agency and Research Ethics Committee of the Central Region in Denmark, the Research Ethics Committee (EPN) at Karolinska Institute in Sweden, the National Institute for Health and Welfare (THL) in Finland and Statistics Finland. No informed consent from participants is required as the register-based study is based on secondary data for which participants’ information was anonymized and de-identified.S1 Table(XLSX)Click here for additional data file.S2 Table(XLSX)Click here for additional data file.S3 Table(XLSX)Click here for additional data file.S4 Table(XLSX)Click here for additional data file.S5 Table(XLSX)Click here for additional data file.S6 Table(XLSX)Click here for additional data file.S7 Table(XLSX)Click here for additional data file.


The use of ultrasound scan (USS) in Malaysian Emergency Departments (ED) began ten years ago but has increased exponentially over the last four years. The aim of our study is to determine the current training and usage of emergency ultrasound.A questionnaire was distributed to 47 hospitals with Emergency Physicians (EP) in Malaysia. Questions included patient load, background on USS courses attended and frequency of ultrasound usage in clinical management.29 hospitals responded including 15 general hospitals, 11 district hospitals and 3 university hospitals. All ED has at least 1 ultrasound machine.In general hospitals, patient load ranged between 60,000 – 320,000 per year. Mean number of EPs is 4. Mean percentage of EPs who had attended any course is 79% (SD 27.8). In 7 hospitals, 100% had attended a course. In 1 hospital, the sole EP has not attended an USS course. The average percentage of Medical Officers (MO) who had attended an USS course is 41% (SD 17.7). In terms of frequency of USS usage, 80% cited usage of ‘very often’ and 20% cited ‘often’.In district hospitals, patient load varied between 45,000 -130,000 per year. Most EDs had at least 1 EP. Except for one EP, all had attended an USS course. 35% of MOs had attended an USS course (SD 32.9). The frequency of use cited was 30% as ‘very often’ and 70% as ‘often’.Whilst in university hospitals, patient load was between 65,000 – 100,000 patients per year. The mean number of EPs was 11. An average of 53% of EPs had attended an USS course, but only 26% of MOs had attended a similar course. In terms of frequency of use, 67% cited ‘very often’ and 33% cited ‘often’.All agreed that USS changed their clinical management significantly.Across the different hospital settings in Malaysia, all cited that USS is used ‘often’ and ‘very often’. However, there are more EPs and MOs in general hospital that has been trained in USS compared to university setting. This is in contrast with the study in California (2009) where most ED do not use ultrasound and academic EDs used it more than community EDs. The issue now is the credentialing process is not fully determined.