Binge drinking among Dutch adolescents is among the highest in Europe. Few interventions so far have focused on adolescents aged 15 to 19 years. Because binge drinking increases significantly during those years, it is important to develop binge drinking prevention programs for this group. Web-based computer-tailored interventions can be an effective tool for reducing this behavior in adolescents. Embedding the computer-tailored intervention in a serious game may make it more attractive to adolescents.The aim was to assess whether a Web-based computer-tailored intervention is effective in reducing binge drinking in Dutch adolescents aged 15 to 19 years. Secondary outcomes were reduction in excessive drinking and overall consumption during the previous week. Personal characteristics associated with program adherence were also investigated.A cluster randomized controlled trial was conducted among 34 Dutch schools. Each school was randomized into either an experimental (n=1622) or a control (n=1027) condition. Baseline assessment took place in January and February 2014. At baseline, demographic variables and alcohol use were assessed. Follow-up assessment of alcohol use took place 4 months later (May and June 2014). After the baseline assessment, participants in the experimental condition started with the intervention consisting of a game about alcohol in which computer-tailored feedback regarding motivational characteristics was embedded. Participants in the control condition only received the baseline questionnaire. Both groups received the 4-month follow-up questionnaire. Effects of the intervention were assessed using logistic regression mixed models analyses for binge and excessive drinking and linear regression mixed models analyses for weekly consumption. Factors associated with intervention adherence in the experimental condition were explored by means of a linear regression model.P=.03) and those aged 16 years when they participated in at least 2 intervention sessions (P=.04). Interaction effects between excessive drinking and educational level (P=.08) and between weekly consumption and age (P=.09) were found; however, in-depth analyses revealed no significant subgroup effects for both interaction effects. Additional analyses revealed that prolonged use of the intervention was associated with stronger effects for binge drinking. Yet, overall adherence to the intervention was low. Analyses revealed that being Protestant, female, younger, a nonbinge drinker, and having a higher educational background were associated with adherence.In total, 2649 adolescents participated in the baseline assessment. At follow-up, 824 (31.11%) adolescents returned. The intervention was effective in reducing binge drinking among adolescents aged 15 years  Alcohol use in adolescents, especially dangerous drinking practices such as binge drinking  and excessive drinking  . Also, sIn the Netherlands in 2011, 57.4% of adolescents aged 16 years and 61.9% aged 17 to 18 years reported that they had engaged in binge drinking at least once in the previous 30 days , with siChanging alcohol use in adolescents could be achieved with the help of Web-based computer-tailored interventions . In the This is related to a general difficulty engaging adolescents in health interventions ,23. Yet,Furthermore, parents still play an important role in preventing adolescents from drinking too much alcohol. Studies have shown that setting clear rules ,29 and gThe aim of this study was to test the effectiveness of a Web-based computer-tailored intervention after 4 months to reduce binge drinking  in Dutch adolescents aged 15 to 19 years; as a secondary outcome, we also assessed the effects of the intervention on excessive alcohol use  and alcohol consumption during the previous week . Furthermore, we assessed differential intervention effects concerning age, gender, and educational level.As of January 1, 2014, the legal age to purchase alcohol in the Netherlands increased from 16 to 18 years , which hWe conducted a cluster randomized controlled trial (RCT) , randomizing Dutch schools of either lower secondary education and lower vocational training or higher secondary education into an experimental and a control condition. The experimental condition received the online intervention in the form of a game that contained computer-tailored feedback. The control condition only filled in the online baseline questionnaire. Both groups were given an online follow-up assessment after 4 months, responding to the same questionnaire as used in the baseline assessment. The study took place in the Netherlands between January and June 2014.Adolescents were recruited in schools. Information letters addressed to teachers and coordinators of the highest grades at secondary education schools (grades 4-6) and at vocational training schools were sent via postal mail. These information letters informed the teachers about the intervention and provided contact details and the address of the study website, so schools could obtain more information and subscribe to the study. All eligible schools in the Netherlands (approximately 600 schools) received an invitation. If schools did not respond, they were called 2 to 3 weeks later. Schools were randomly assigned to either the experimental or control condition after their consent to participate in the study. Schools were not blind to their condition because experimental schools had to plan 3 lessons for the intervention  and control schools had to plan 2 lessons (the baseline assessment and the 4-month follow-up).Approximately 3 weeks before the intervention started, teachers were provided with a letter containing more information about the procedure, privacy, and confidentiality. All adolescents in the classes were provided with a letter on the day of the intervention to avoid them starting the intervention prematurely. The letter informed the adolescents that all their answers in this study would never be shared with teachers, parents, or any other third person; would be used for research purposes only; would be analyzed anonymously; and that they could end participation at any point in time. Adolescents were also made aware that, at the end of the study, they would participate in a lottery for 300 gift vouchers worth €25 each. Furthermore, adolescents were provided with a letter for their parents. In this letter, the parents were informed that their child participated in an online alcohol intervention at school and the parents were invited to visit a separate website specifically for parents, where they could take part in the parental component of the intervention. When starting with the intervention, teachers asked the adolescents to visit the study website and create an account. They were routed to the according condition  based on the school they attended. Before starting with the baseline questionnaire, all adolescents had to check a box on the first page of the website that contained informed consent information confirming their informed consent. If they did not wish to participate or refused to provide informed consent, they could check an “I do not wish to participate in this study” box; they were thanked and could then close the intervention website  and older (19 years) adolescents because they are often in the same class. Schools had to provide the adolescents with individual access to a computer with Internet connection.The idea of a game instead of a purely text-based computer-tailored intervention was first brought up by adolescents during focus group interviews . During The intervention, Alcohol Alert, consisted of an online baseline questionnaire, after which the adolescents played 3 sessions of the game “What happened?!”. In these game sessions, the adolescent wakes up after a night of partying and does not remember what happened the night before. The goal of this 2-dimensional game was to find out what happened. Each of the game sessions depicted one of the most common drinking situations for adolescents . The sequence of the 3 game sessions was tailored and dependent on how many glasses of alcohol the adolescent indicated to typically drink in each of these situations. The adolescent started with the drinking situation in which he or she indicated drinking the most alcohol. Thus, if the adolescent indicated typically drinking 3 glasses at home, 5 glasses at a party, and 6 glasses in a bar, he or she would start with the bar scenario first, followed by the party scenario, and finally the home scenario. Each session started in the bedroom where the adolescent wakes up. The adolescent quickly discovers that something is wrong . The adolescent then navigates through different places in the game and talks to people he or she meets and gets clues about what happened the previous night .During the game sessions, the adolescent received questions and feedback on an in-game cell phone . These qThe content and methods used in the feedback messages varied depending on the message, but usually the answer of the respondent was repeated to enhance self-monitoring, correct assumptions were confirmed with positive feedback, and wrong assumptions were corrected with new information. All messages had a personal tone to show sympathy and to enhance commitment . For exaAfter 4 months, the adolescents in both conditions responded to the online follow-up questionnaire in school. If they did not finish the follow-up assessment at school, they received 2 reminders to do so at 1 and 2 weeks after the official deadline for the schools.A separate component was added to the intervention to involve parents. During the development, a convenience sample of 14 parents provided us with feedback on the layout, usability, and content of the parental component. At baseline, adolescents in the experimental condition were asked to enter the email address of one of their parents. Parents then received an email inviting them to a separate website, where parents responded to a short questionnaire and could also receive computer-tailored feedback on how to set appropriate rules concerning alcohol use and how to communicate with their child about alcohol use. If the adolescent did not know the email address of the parent or did not wish to send an email to the parent, they could refuse to do so. They were informed that the letter they received for their parents contained all the information about the parental component and instructions on how parents could participate. A detailed description of the parental component can be found in the study protocol .At baseline, we assessed gender , age (in years), educational level , religion , and ethnicity .We assessed different forms of alcohol use at baseline and at the 4-month follow-up. We assessed binge drinking, the primary outcome, with an open-ended question: “How often did you drink 4 (for girls) / 5 (for boys) or more glasses of alcohol on one occasion in the previous 30 days?” . Binge dFor a description on how these concepts were assessed, we refer to the study protocol . ReliabiAdherence was assessed by counting the number of intervention sessions (not the baseline assessment or follow-up assessment) in which the adolescent participated ranging from zero (did not participate in a single intervention session) to 5 .The primary outcome was the difference in number of binge drinking occasions in the preceding 30 days for the experimental group compared to the control group. Based on prevalence data from the time the study was designed, we aimed at reducing reported binge drinking occasions from 70% to 60% in the previous 30 days. We used the Optimal Design Plus Empirical Evidence (version 3.0) program . Becauset tests for continuous variables and chi-square tests for discrete variables. Chi-square tests and t tests were further used to describe differences between completers and participants who did not return to the follow-up assessment after 4 months.This study constituted a design with 3 levels: repeated measurements, nested within adolescents, nested within schools. The data were analyzed using SPSS version 20. Descriptive statistics were used to describe the characteristics of the baseline sample. Differences between the conditions in the baseline sample were assessed using To determine the effectiveness of the program, we analyzed the data with a logistic regression mixed models analysis for the outcomes binge drinking and excessive drinking and a linear regression mixed models analysis for the outcome weekly consumption. These models allow for dependencies among observations obtained for students within a school. These analysis models also allow for data missing at random, which is less strict than the requirement of data missing completely at random . The varThe associations between potential participant characteristics  and adherence  to the intervention were analyzed using a linear regression model.P≤.05. Interaction effects were considered significant if P≤.10.Main effects were considered significant if This trial was reviewed by the Medical Ethics Committee of Atrium Orbis Zuyd and was classified as research that does not fall under the Medical Research Involving Human Subjects Act and needed no further approval (METC number: 12-N-104).21=1.3, P=.25) on binge drinking , on excessive drinking , nor on weekly consumption . There was a significant interaction effect between condition and age (P=.08) (P=.03). Adolescents in the experimental group reported a significant decrease in binge drinking in the previous 30 days at 4 months after the intervention ended compared to adolescents in the control condition. Adolescents in the experimental group aged 16 years also engaged less in binge drinking after 4 months compared to the control group. This effect was not significant  (P=.04). A higher educational level (P<.001), a lower age (P<.001), and being Protestant (P=.03), Muslim (P<.001), or a member of another religion (P=.03)  were significant protective determinants of binge drinking  adolescents in the experimental and 585 of 1027 56.96%) adolescents in the control condition reported binge drinking in the previous 30 days. At the follow-up assessment, 194 of 456 (42.6%) adolescents in the experimental condition and 184 of 368 (50.0%) adolescents in the control condition reported binge drinking in the previous 30 days. The returning sample did not differ on baseline drinking characteristics. They did not differ on being a drinker  . Age gro, P=.07) , but cou.96% adol, P=.07) , when padrinking .P=.08). However, further analyses revealed no significant subgroup effects for either higher- or lower-educated adolescents (P<.001), a higher educational level (P=.01), and being younger (P<.001).At the baseline assessment, 116 of 1622 (7.15%) adolescents in the experimental condition and 129 of 1027 (12.56%) adolescents in the control condition engaged in excessive drinking. At the follow-up assessment, 28 of 456 (6.1%) adolescents in the experimental and 37 of 368 (10.2%) adolescents in the control condition reported excessive drinking. There was a significant interaction effect between condition and educational level (lescents . ProtectP<.001), having a higher educational level (P=.002), and being younger (P<.001)  were significant determinants with a protective effect on weekly consumption  standard glasses of alcohol in the previous week. Adolescents in the control condition drank a mean of 5.1 (SD 9.9) standard glasses of alcohol in the previous week. At the follow-up assessment, adolescents in the experimental condition reported a mean consumption of 3.3 (SD 7.7) and adolescents in the control condition reported a mean consumption of 4.6 (SD 8.9) standard glasses of alcohol during the previous week. Although the effects were in the expected direction, no significant effects of the intervention were found for weekly consumption. The analysis only revealed that being female  started with the first game session. Only 467 adolescents (28.79%) returned to the second and only 347 (21.39%) adolescents to the third game session. Just 27 (1.66%) adolescents returned to the fourth session at home, and zero participated in the fifth home session.Subsequently, to investigate the effects of adherence, we decided to rerun the analyses with the subsample of the group that completed the different game sessions. We made 3 groups: the first group consisted of all adolescents who participated in the first game session, the second group consisted of adolescents who also participated in the second game session, and the third group did all 3 game sessions. Descriptive analyses of prevalence of binge drinking per age group and per adherence group can be found in the P=.007 for adolescents that participated in at least 1 session; P<.001 for adolescents that participated in at least 2 sessions; P=.002 for adolescents that engaged in all 3 game sessions). When engaging in at least 1 session, only 15-year-old adolescents reported less binge drinking (P=.01). The effect sizes increased when 15-year-olds adhered longer to the intervention ; after 3 sessions: OR 0.22, 95% CI 0.09-0.54). A similar pattern was found for 16-year-old adolescents. There was a significant effect of the intervention after 2 sessions  which became stronger after 3 sessions . There was no significant effect for older adolescents. The analyses for excessive drinking revealed a significant interaction effect between condition and educational level  for adolescents that adhered to at least 1 session. However, the subgroup effects for higher  and lower  educated adolescents were both not significant. Weekly consumption revealed a similar result with a significant interaction effect with educational level  for adolescents that completed at least one session, but only small and nonsignificant subgroup effects for higher-  and lower-  educated adolescents. Furthermore, there was a significant interaction effect between condition and age on weekly consumption for adolescents that completed at least 2 sessions  and for those who completed at least 3 sessions ; however, although the effects were more positive for the younger age groups, no effect reached a significant level. Finally, significant predictors of adherence were being Protestant, being female, being younger, having a higher educational background, and being a nonbinge drinker , people who adhered more to the program were also adhering more to the national health guidelines . In otheIn our intervention, we tried to motivate adolescents to adhere to the intervention by designing a serious game that carried computer-tailored advice. Although we did not test the specific effect of the game on motivation , adherence rates were far from optimal. A possible explanation might be that alcohol use is very common among Dutch adolescents ,12,32 anAnother point was that whole schools dropped out before and during the intervention. The differences in characteristics of adolescents who did not return to the follow-up assessment compared to those who did return  can partly be explained by the dropout of the whole school. Furthermore, comparable characteristics of people who dropped out of the follow-up assessment have been reported in other studies as well ,19,42.High dropout rates in Web-based interventions are not uncommon ,65; therAlso important is our finding that parental participation in the parental component was associated with significantly lower rates of binge drinking among adolescents, which might be an indication that the parental component was an important addition to the intervention. However, due to methodological choices in parent recruitment , those data are observational rather than experimental and strong claims about the effect cannot be made. It is possible that other factors, such as family attachment, influenced the positive results. However, the low participation of parents is notable. On the one hand, just a small proportion of adolescents actually invited their parents to take part in the intervention. That could be an indication that adolescents do not feel the need or do not want to talk about the subject with their parents. On the other hand, of the 199 adolescents who invited their parents, which is likely a very selective group of adolescents already, only 91 parents actually visited the website. Other studies that focused on parent-child communication about risky sexual behavior also reported low attendance rates of parents ,69. GeneA strength of this study is that it is theory-based and was preceded by extensive qualitative and quantitative research. Furthermore, the target group was included and consulted during the whole development process . HoweverIn this study, only relatively short-term outcomes of the intervention were assessed. It is advisable to add more long-term assessments to evaluate what the true effects are after 12 or 24 months, or even after a longer time period.Another limitation is that all outcome measures were based on self-reports, which is more likely to result in greater underestimation of alcohol use compared to daily diaries . This unFinally, adolescents from the experimental and control conditions differed on alcohol use  as well as on several baseline characteristics  which was probably caused by the relatively high dropout of schools in the control condition after randomization (5 schools withdrew participation before the baseline assessment). There were no differences on baseline drinking measures for the returning sample, but they were added in the analyses as covariates to control for the baseline differences of the whole sample.Computer-tailored feedback can be an effective way to reduce binge drinking in adolescents aged 15 and 16 years. Also, participation of parents in those interventions may be beneficial and more research is needed to increase parental involvement. Further research is needed to increase adherence to eHealth interventions and to implement these interventions in practice; thereby, increasing their effectiveness and public health impact.


The uncommon headache related to a Valsalva maneuver (VM) is coded within the International Headache Society Classification (ICHD-3beta) among “Other primary headaches”, 4.1 “Primary cough headache” (PCH). This chapter deals with headaches precipitated by coughing or straining in the absence of any systemic or intracranial disorder. The clinical features of the pain are characterized by sudden onset, lasting from 1 s to 2 hours, and brought on by and occurring only in association with coughing, straining, and/or a VM. Neuroimaging plays an important role in differentiating secondary forms.A 71-year-old woman with obesity, high blood pressure, type 2 diabetes, hypothyroidism and glaucoma was admitted because for the past 18 months she had headache attacks with stabbing severe pain (NVR 10/10), on the right fronto-temporal side with parietal-occipital diffusion. The pain lasted from 30 to 360 minutes with and without intake of analgesic, respectively. For the first 6 months, the headache was triggered only when bending over. Subsequently, also other activities that required the execution of a Valsalva maneuver  caused the same headache attacks. Neurological examination and hematologic work up were normal. MRI of the brain, angiography and CSF circulation study were normal. The patient was treated with indomethacin 50 mg daily for 4 days and then 50 mg twice a day for two months. The headache gradually disappeared after 5 days of therapy. After 12 months of follow-up the patient is in good health.The pathophysiology of headache triggered by VM is unknown. The most reasonable hypothesis is a sudden increase in intracranial pressure secondary to high venous pressure, such as during coughing; other reported contributing factors are transient post-infective hypersensibility of pressure receptors localized in venous vessels, reduction of the posterior fossa volume with consequent crowding of its structures, incompetence of the valves of the internal jugular veins, venous stenosis, and intermittent intraocular pressure elevation. The initial history of our case and some cases reported in the literature suggest that the headache caused by maneuvers related to increased intrathoracic pressure  may not be triggered by coughing. In these cases, when structural lesions are excluded by MRI or similar tests, we propose the eponym, “primary Valsalva maneuver headache” . In these patients it is possible that the Valsalva maneuver provoked by the cough did not reach the pain threshold to cause headache.Written informed consent to publication was obtained from the patient(s).


In 2009, a worldwide supply constraint of imiglucerase led to treatment modifications or interruptions for patients with Gaucher disease (GD) type 1. In France, joint treatment recommendations were issued to protect the most vulnerable patients. This observational study evaluated the impact of imiglucerase treatment modifications on the clinical and biological course of GD.Retrospective data on patients’ characteristics, treatment, clinical and biological parameters from 01 June 2009 to 31 October 2010 were collected during a single visit.3/mm3/month) and an increase in chitotriosidase (+537 nmol/mL/h/month) and angiotensin-converting enzyme (+4 IU/L/month) in the subgroup of 61 patients who discontinued treatment for at least 3 months; this magnitude of change was not seen in the subgroup (32 patients) treated with reduced imiglucerase for at least 3 consecutive months. GD-related events were spontaneously reported by the study investigators for 39% of the whole study population, including asthenia/fatigue (8%), bone infarction and bone pain (4% each), and hepatomegaly (3%). A Kaplan-Meier estimate of the probability for a patient to present a bone, hematological or visceral event during the constraint was 37% for patients who discontinued the treatment and 10% for patients treated with a reduced imiglucerase dose.Ninety-nine GD1 patients, aged 7–84 years, were included (median age 47 years); 10 were children. Patients experienced a median of 4 different treatment modifications. Median change from pre-supply constraint dose (92 U/kg/4-weeks) was −69, −51, −29 and −60 U/kg/4-weeks at 3, 6, 9 and 12 months after first modification, respectively, with imiglucerase discontinuation reported for 70%, 47%, 29% and 55% of patients at these timepoints. Replacement with another ERT was reported for 35 patients. Results show a statistically significant decrease in hemoglobin (−0.8 g/L/month) and platelets  reported in some patients, emphasize the importance of maintaining appropriate individualized dosing. Gaucher Disease (GD) is an inherited lysosomal storage disease, attributable to glucocerebrosidase enzyme deficiency; in rare cases, the absence of saposin C, an activator of glucocerebrosidase, leads to a Gaucher-like disorder . GD is aTemporary manufacturing difficulties encountered at Genzyme’s manufacturing plant led to a worldwide significantly constrained imiglucerase supply between June 2009 and November 2010. Treatment recommendations were implemented with the European Medicines Agency (EMA); high-risk groups were identified and prioritized to receive imiglucerase and included infants, children, adolescents and adult patients at high risk for the development of severe, life-threatening disease progression ,20. In FThe goal of this study was to evaluate the clinical and biological impact of the imiglucerase supply constraint in France from 01 June 2009 to 31 October 2010 (17 months).This was an observational, retrospective, multicenter, national, non-comparative study.All patients with GD1 or GD3, treated with imiglucerase  for at least 6 months at the time of their therapeutic scheme modification, which was due to the imiglucerase supply constraint, could potentially be included in this study. To this aim, all French physicians treating at least one patient with GD at the time of the study implementation were proposed to participate as study investigators.The patient  was informed and agreed to participation. The study was approved by the French Healthcare Research Data Processing Advisory Board, the French National Data Protection Commission, and the Institutional Review Board of Paris North Hospitals. It was conducted in accordance with the French Good Epidemiological Practice guidelines.The study comprised a single visit for each patient that took place between May 2011 (first patient) and April 2012 (last patient). During this visit, the following data were collected: demographic data; information about GD history ; imiglucerase treatment status; biological and clinical characteristics (notably bone manifestations) in the 6 months preceding the first treatment modification; subsequent changes in the imiglucerase treatment regimen ; and evolution of clinical (weight) and biological parameters  during the course of the constraint period. GD-related events occurring after the first modification to the patient’s therapeutic scheme, i.e., clinical or biological events considered potentially related to GD (rather than treatment-related) were also spontaneously reported by investigators. Among those, bone events were of special interest; they were defined in the statistical analysis plan as symptomatic bone events (as per PNDS guidelines ) with a The absolute supply constraint period for the population was defined as starting on 01 June 2009 and ending on 31 October 2010. The start for each patient was defined as the date of the first imiglucerase treatment modification on or following 01 June 2009. For each patient, the constraint period extended from the time of first treatment modification to 31 October 2010.For each parameter, the pre-constraint value was defined as the most recent evaluation within 6 months prior to the start of treatment modification for the patient.All statistical analyses were computed with SAS software . Categorical variables were summarized using frequencies and percentages. Continuous variables were summarized by the number of non-missing observations, mean, standard deviation, median, minimum, and maximum (range). Analyses were mainly descriptive and statistical tests were performed for exploratory purposes. A two-sided type I error rate of 0.05 was used to define statistical significance.The primary population for all analyses was the full analysis set (FAS), which comprised all included patients who had experienced a treatment modification.whole constraint period, in order to isolate and assess the impact of imiglucerase treatment modification on the biological and clinical outcome of the patients, the analysis was performed on a constraint period limited to the period during which the treatment modification (discontinuation or reduced dose compared to pre-constraint dose) was stable for at least 3 consecutive months in a given patient (‘limited constraint period’). Two subgroups of patients were defined according to the first modification lasting at least 3 consecutive months:Subgroup 1: Discontinuation of imiglucerase without addition of another GD treatment  or another ERT).Subgroup 2: Treatment with a reduced imiglucerase dose (in U/kg/4-weeks) compared to pre-constraint dose. The changes in biological parameters over time during the constraint period were analysed using mixed-linear models for repeated-measures, with intercept and slope considered as random.Since the study patients had various treatment modifications in the course of the Analysis of GD-related events was performed on the FAS during the whole constraint period, and for each subgroup during the constraint period limited to stable modification. We described the number and nature of GD-related bone events before and after the supply constraint onset, i.e., during the whole study period (from the time of first treatment modification on or after 01 June 2009 to 31 October 2010) and during the preceding equivalent time period . Finally, time to occurrence and probability to present a bone, hematologic or visceral event during the limited constraint period was estimated with the Kaplan-Meier method.The characteristics of the 99 patients with GD 1 included in the study are described in Table The first treatment modification  took place at a mean time of 8 (±4) years after imiglucerase initiation. The doses of imiglucerase provided during the constraint period are presented in Table For the overall population of GD 1 patients included in this study, the mean duration of modification was 15 (±2) months. During this period, treatment modifications reached a median number of 4, with a median average duration of approximately 4 months for each patient. The treatment was modified once for 7 patients (7%), twice for 16 patients (16%), between three and six times for 59 patients (60%) and more than six times for 17 patients (17%). The types of modification over time  are presented in Figure Discontinuation of imiglucerase treatment without introduction of another treatment was reported for 32 patients at the first modification and for 63 patients 3 months after the first modification. Discontinuation of imiglucerase treatment progressively decreased to 15 patients by the last modification prior to 1 November 2010. At this last time point, replacement of imiglucerase by another ERT was reported for 35 patients .A dose reduction of 50% or more was reported for 30 patients (31%) at the first modification and 5 to 10 patients at subsequent timepoints. At 6 months after the first modification and at subsequent timepoints, 4% to 8% of the patients could return to the pre-constraint dose, and 14% to 18% of the patients were treated with higher doses compared to pre-constraint doses.The progression of the biological parameters was assessed on a period limited to the duration of the first stable modification. This period lasted 3 to 15 months depending on each individual, with a median of 5 months in the subgroup of 61 patients who discontinued imiglucerase, and a median of 6 months in the subgroup of 32 patients treated with a reduced dose .The results of mixed linear models used to assess the development of biological parameters are presented in Table 3/mm3/month. There was a statistically significant increase in chitotriosidase (p = 0.021) and in ACE (p = 0.012), but only 16 patients had available data for ACE.In the subgroup of 61 patients who discontinued imiglucerase, the models showed a statistically significant decrease in hemoglobin (p = 0.003) with a slope estimate of −0.8 g/L/month, and in platelets (p = 0.002) with a slope estimate of −5905.10Changes over time observed in the models for hemoglobin, platelets, ferritin, chitotriosidase and ACE in the subgroup of 32 patients treated with a reduced imiglucerase dose were not statistically significant.From the first modification for a given patient until the end of the constraint period (31 October 2010), 64 GD-related events were spontaneously reported by the investigators for 39 patients (39%) , but none were of severe intensity.GD-related events reported during the limited constraint period: comparison between the subgroup of patients who discontinued imiglucerase and the subgroup of patients treated with a reduced dose of imiglucerase.Apart from these events of special interest, the most frequently reported GD-related event was asthenia/fatigue (8%). Some biological changes were also spontaneously reported by the investigators, the most frequent being thrombocytopenia, increased serum ferritin (each reported in 5% of the whole study population) and increased chitotriosidase (4%). Overall, hematological events were reported for 11 patients (11%).As shown in Table According to Kaplan-Meier estimation, the probability that a patient would present with a bone, hematological, or visceral event during the constraint was 23%. This probability was 37% for patients who discontinued the treatment for at least 3 consecutive months and 10% for patients treated with a reduced dose compared to the pre-constraint dose for at least 3 months . The first treatment modification consisted of imiglucerase discontinuation for 34% of the whole study population, and a reduced imiglucerase dose without the introduction of another treatment for 66%. The dose reduction was over 50% compared to the pre-constrained dose for nearly half of these patients. Progressive re-supplying reduced the number of patients who had discontinued imiglucerase from 70% to 29% between 3 and 9 months after the first modification. A return to pre-constraint doses, or even higher doses, was possible for 18% to 26% of the patients 6 to 12 months after the first modification. However, the available imiglucerase supply decreased again in April 2010 and, at the last treatment modification prior to 01 November 2010, 58% of patients had discontinued imiglucerase treatment, including 37% who started treatment with another ERT, and 5% who started miglustat. These results were consistent with the treatment recommendations issued in September 2010 by the EMA, which dictated a progressive return to normal dose for patients who were treated with reduced doses, but no new initiation of treatment with imiglucerase or switch back to imiglucerase for patients who had discontinued.It was anticipated that the impact of the imiglucerase supply constraint on French Gaucher disease patients would be difficult to interpret overall because of the variability in local treatment management and the numerous consecutive dose changes according to supply availability. As a result, two subgroups of patients were defined for this analysis: a subgroup of 61 patients who discontinued imiglucerase, and a subgroup of 32 patients who were treated with a reduced imiglucerase dose for a period lasting a minimum of 3 consecutive months, without addition of another treatment for Gaucher disease. Results for these subgroups were analysed for the period of constraint limited to stable imiglucerase treatment regimen, relative to each patient. Six patients were not reported in the subgroups: 2 patients could not be classified (no stable modification for at least 3 consecutive months) and 4 patients took only miglustat for at least 3 consecutive months.This study has numerous methodological shortcomings that limit the extent of interpretation, e.g., retrospective data collection, an imbalance in statistical power between the two compared subgroups of patients due to disproportionate sample size, a small number of available data for some of the biological parameters studied, and a limited robustness of statistical models due to variability in the time of retrospective data collection. One should also mention that systematic quantitative bone and visceral follow-up measures were not available, which limited the outcome evaluation in the study population.Taking into account these limitations, the study results indicate that treatment discontinuation has a greater impact than imiglucerase dose reduction on the progression of biological parameters. Indeed, a statistically significant decrease in hemoglobin and platelet counts and an increase in chitotriosidase and ACE were observed in the subgroup of patients who discontinued the treatment for at least 3 consecutive months.The results observed in this French study are consistent with those reported on several smaller cohorts in different countries. The impact of the supply constraint has previously been described on 26 patients from Israel who discontinued treatment with imiglucerase , 34 ItalDuring the whole period analysed in this study, hematological, visceral and bone events were spontaneously reported as GD-related events in 11%, 3% and 8% of patients, respectively. It must be noted that, among the 8 patients who experienced bone events during the constraint period, all but one had reported a previous history of bone events, and 50% had undergone total splenectomy. Splenectomy and a history of bone events before treatment initiation have been shown to be risk factors for developing bone events, even under treatment with ERT . The ratFurthermore, GD-related events relying on imaging data must be analysed with caution , because these data were not collected systematically in participating centers and the assessments were likely heterogeneous across centers because of technical differences . Similarly, it is unlikely that bone pain, whether localized or diffuse, was homogenously assessed across centers. In addition to limiting the extent to which clinical outcome can be evaluated in this study, these observations highlight a need for improvement regarding the systematic assessment of splenic and hepatic volumes, and of bone lesion progression using standardized magnetic resonance imaging.As for the limited (to a stable modification) constraint period analysis, the percentage of patients who experienced at least one GD-related event was similar for patients who discontinued imiglucerase and those treated with a reduced dose . However, according to Kaplan-Meier estimation, the probability for a patient to present a bone, hematological or visceral event during the limited constraint period was higher for patients who discontinued the treatment compared to patients who were treated with a reduced dose: 37% and 10%, respectively. According to recommendations, patients who discontinued the treatment were the ones with lesser disease burden, so an increase in GD-related events in this population compared to patients treated with a reduced dose could be linked to treatment discontinuation.Taken altogether, these elements suggest that, in the context of a limited supply, it is preferable to maintain patients under treatment with reduced doses (or less frequent infusions) than to discontinue treatment with imiglucerase. These results are in line with the studies published before the supply constraint took place, which suggested that disease progression resumes following ERT interruption, and recommended avoiding this practice -33.This study concerned a limited period of observation, hence could not allow the evaluation of the long-term impact of dose reduction. Some events, particularly bone events, may arise even with treatment continuation  or yearsThese observations prove useful to depict how the health care community can respond to such circumstances. The convening of expert meetings at the European (EMA) and French level , as well as with patients’ associations and representatives of pharmaceutical companies allowed a timely issuing of treatment recommendations that, coupled with close case-by-case management at each physician’s level, limited the impact of the constraint on French Gaucher patients. The situation is now back to normal in France, allowing patients to return to their recommended imiglucerase dose with proven efficacy, as mentioned in the product Summary of Product Characteristics for imiglucerase . In the The imiglucerase supply constraint in France between June 2009 and November 2010 involved a large inter-individual variability in the therapeutic management of patients with GD, with numerous treatment modifications depending on supply availability. Overall, the joint recommendations issued by the French Medicine Agency, the National Committee for GD Treatment Evaluation, patient associations, and pharmaceutical companies allowed for satisfactory management of GD patients during the supply constraint in France while protecting the most vulnerable patients. Keeping in mind the methodological limitations of this observational retrospective study without long-term follow-up, imiglucerase dose decreases have shown a lower impact on the clinical and biological outcomes in this population compared to treatment discontinuation. However, general effects, such as fatigue and bone pain, reported in patients treated at a reduced dose or with interrupted imiglucerase therapy emphasize the importance of maintaining appropriate individualized doses for each patient.


Since fallen trees are a key factor in biodiversity and biogeochemical cycling, information about their spatial distribution is of use in determining species distribution and nutrient and carbon cycling in forest ecosystems. Ground-based surveys are both time consuming and labour intensive. Remote-sensing technology can reduce these costs. Here, we used high-spatial-resolution aerial photographs (0.5–1.0 cm per pixel) taken from an unmanned aerial vehicle (UAV) to survey fallen trees in a deciduous broadleaved forest in eastern Japan. In nine sub-plots we found a total of 44 fallen trees by ground survey. From the aerial photographs, we identified 80% to 90% of fallen trees that were >30 cm in diameter or >10 m in length, but missed many that were narrower or shorter. This failure may be due to the similarity of fallen trees to trunks and branches of standing trees or masking by standing trees. Views of the same point from different angles may improve the detection rate because they would provide more opportunity to detect fallen trees hidden by standing trees. Our results suggest that UAV surveys will make it possible to monitor the spatial and temporal variations in forest structure and function at lower cost. Fallen trees are an ecologically relevant indicator of forest biodiversity Recent advances in the technology of unmanned aerial vehicles (UAVs) have made UAVs ideal for remote sensing In this study, we photographed a deciduous broadleaved forest from a UAV, compared the positions of fallen trees identified in the images by eye with those recorded on the ground, and compared the number of the fallen trees detected between the original images and an orthorectified mosaic. The purpose of this study was to show the applicability and limits of this technique.Quercus serrata) and beech (Fagus japonica and F. crenata) The study was conducted in a 300-m × 200-m plot in the Ogawa Forest Reserve (OFR) in Kitaibaraki, Ibaraki, Japan  mounted beneath the UAV pointing straight down took images (5184 × 3456 pixels) every 5 s. The UAV was also equipped with a global positioning system (GPS) detector that recorded altitude, latitude, and longitude every 0.1 s. The GPS position with the timestamp closest to that of each photograph was used as the position of the UAV.On 29 November 2011, when the trees were bare, we flew a UAV , which assembled a 3D point cloud. We divided the plot (300 m × 200 m) into 1-m × 1-m cells, and the lowest elevation in each cell was used in the creation of a digital elevation model (DEM) of the site.The aerial photographs were orthorectified according to the DEM and the position (longitude and latitude) and attitude  of the UAV, and assembled into one mosaic image with the help of “tie points” in overlapping photographs.On 31 May 2012 in nine 10-m × 10-m sub-plots , ground Fallen trees were identified by eye in the original aerial photographs on a computer monitor. Positions were compared with those of fallen trees mapped in the ground survey and those identified by eye in the orthorectified mosaic.The OFR plot was covered by 211 aerial photographs  with a sIn the ground survey, we found a total of 44 fallen trees in the sub-plots . By eye,Because fallen trees are generally defined as being >2.5 cm in diameter Another factor contributing to the poor rate of visual identification of fallen trees might be ambiguity in colour. One of the clues we used in detecting fallen trees was the colour of mosses growing on them. Trees with mosses are easy to detect visually, but freshly fallen trees with no mosses might be confused with tree branches or fallen leaves.The orthorectification and mosaicking of aerial photographs according to the DEM require much labour and time, even for experts, and can also require specialized and expensive software. However, we identified fewer fallen trees from the orthorectified mosaic than from the original photographs. Thus, non-orthorectified photographs of the same point from different angles would allow better identification of fallen trees, at no additional cost, than orthorectified mosaics.We showed the applicability of aerial photographs captured from a UAV for the detection of large fallen trees in a deciduous broadleaved forest in eastern Japan. Because much tree death is episodic and irregular Table S1List of the diameters and lengths of fallen trees in the sub-plots.(DOC)Click here for additional data file.


Extended rural clerkships clearly increase the likelihood of rural practice post-graduation. What has not been determined is whether such rural interventions increase the likelihood of graduates practicing in more remote, versus inner regional, locations.The Australian Health Practitioner Regulation Agency database was used to identify the current workplace of every graduate of the Medical School of Western Australia, 1980 to 2011. There were 324 graduates working in a primary practice location defined by the Australian Standard Geographical Classification as inner regional to very remote. They were divided into 3 groups - 200 graduates who entered medical school before commencement of the Rural Clinical School of Western Australia (RCSWA), 63 who entered after the RCSWA had started, but not participated in RCSWA, and 61 who participated in the RCSWA. The RCSWA offers a longitudinal rural clinical clerkship throughout level 5 of the MBBS course.The two groups not participating in the RCSWA had 45.5% and 52.4% of subjects in outer regional/very remote locations, respectively. In comparison, 78.7% of those who had participated in the RCSWA were currently practicing in outer regional/very remote locations. When the 3 groups were compared, the significant predictors of working in a more remote practice compared to working in an inner regional area were being female  and participating in the RCSWA . In multivariate logistic regression that corrected for gender and remoteness of rural address before entry to medical school, participation in the RCSWA still predicted a more than 4-fold increase in the odds of practicing in a more remote area .Extended rural clinical clerkship during an undergraduate MBBS course is related to a much greater likelihood of practicing in more remote, under-serviced rural locations. Australia, like many other countries, suffers a chronic rural and remote doctor shortage  despite Retrospective studies have shown a consistently positive relationship between rural training  and the likelihood of rural practice -10. HoweThe relationship between rural training and remote practice is less clear. This is partly because the terms “rural” and “remote” are often ill-defined ,13. For Some degree of order to this discussion can be brought by using Australia’s national remoteness classification system . The AusVery little is known about the determinants of relatively remote practice (ASGC-RA 3–5) versus inner regional practice (ASGC-RA 2) among Australian rural doctors and whether it is influenced by rural training. The Rural Clinical School of Western Australia, a school in the University of Western Australia, offers a year of rural training in one of fourteen ASGC-RA 2–5 non-urban sites. This is an alternative to medical students obtaining the entire degree in an urban setting at the same university. In this paper we therefore explore the hypothesis that amongst graduates of the University of Western Australia who are currently working in rural practice, those who completed a longitudinal rural clerkship in the RCSWA are more likely to be practicing in more remote locations than graduates who completed all their training in urban areas.The study participants for this cohort study were drawn from all graduates of The University of Western Australia Medical School who entered from 1980 and had completed the course by 2011, ensuring that they were, at a minimum, in their third year after graduation. From February to May 2014, information was accessed from the Australian Health Practitioner Regulation Agency (AHPRA) database to identify each graduate’s current workplace location. Graduates were designated as working rurally if their primary practice location was in an area defined by the ASGC-RA as 2–5, and city/urban if ASGC-RA 1. Those identified as currently practicing rurally were the target population for this study. In terms of the reliability of the AHPRA database in identifying those currently practicing rurally, we have previously reported a more detailed comparison indicating at least 89% agreement against a corresponding RCSWA work location database [th MBBS year at one of 4 rural sites. In subsequent years, with the exception of international students, applications were invited from all students in the 4th year of the course to spend the entire 5th year of their course in the RCSWA. All applicants were subsequently ranked and 25% of each whole medical school cohort were then selected for participation, primarily on the basis of performance in a structured interview. From 2002 to 2010, the Rural Clinical School grew to 49 students over 12 separate rural sites. Figure In 2002, the RCSWA commenced as a pilot project, with 7 volunteer students spending the second half of their 5An active rural student recruitment process has been in place at the University of Western Australia since 2002 and by 2007 had resulted in the proportion of rural students increasing to a specified target of 25% of all students . Our defth year of the MBBS course entirely in urban locations, prior to commencement of the RCSWA programme. The second group comprised all those who completed the 5th year of the MBBS course after commencement of the RCSWA programme, but who likewise from 2002 until 2010 completed their 5th year in urban locations. The third group also completed the 5th year of the MBBS course from 2002 until 2010, but spent this year in the RCSWA. A comparison of current ASGC-RA practice location across these 3 groups permitted both an historical and a contemporaneous assessment of the impact of the RCSWA on the likelihood of more remote (ASGC-RA 3–5) versus inner regional practice (ASGC-RA 2) amongst those now practicing rurally.All international students, who were ineligible for entry to the RCSWA, were excluded from the study. The final study cohort was linked to both a database of all students recruited from a rural background and to a database of all students enrolled in the RCSWA since its inception. It was divided into 3 groups for subsequent comparisons. The first group comprised those who had entered the university from 1980 onwards and who had from 1984 until 2001 completed the 5Age, gender and type of school attended - publicly funded government or fee paying independent - were recorded at entry to medical school. Age at graduation from medical school exhibited marked kurtosis - deviation from normal distribution - and skew and it was dichotomised into those 23 years and younger vs those 24 years and older. As a socioeconomic indicator, the correspondence postcode at entry for each student was linked to the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) score from the Australian 2006 census Socio-Economic Indices for Areas (SEIFA) . The con2 test. Univariate analysis of current practice in an ASGC-RA 3–5 location vs an ASGC-RA 2 location utilised logistic regression. A final multivariate logistic regression model was constructed for the major outcome variable of current site of practice in 2014 (ASGC-RA 2 versus ASGC-RA 3–5), using those socio-demographic variables identified as having significant predictive value in the univariate analyses together with rural background and participation in the RCSWA.Data were analysed using IBM SPSS Statistics Release 20.0.0 (2011). All values are reported as Mean ± Standard Error of the Mean. Univariate comparisons of socio-demographic variables in each of the 3 study groups were made using the χThe project was approved by the University of Western Australia Human Research Ethics Committee, RA/4/1/1627.Of the 3282 graduates of the University of Western Australia Medical School who entered from 1980 and had completed the course by 2011, 3020 were able to be tracked on the AHPRA register of medical practitioners between February and April of 2014, 5 were known to have deceased, 257 (7.8%) could not be found. Of the 3020 currently on the register, 108 (3.6%) were either overseas or registered as non-practicing, 2579 (85.4%) were in a city/urban site of practice and 333 (11.0%) were in a regional/rural site. From these, 9 international students were excluded leaving 324 subjects currently in rural practice as the final study cohort.Of those currently working in a regional/rural site, there were 200 graduates who completed level 5 in medical school before 2002 and commencement of the RCSWA, 63 graduates who completed level 5 in medical school after commencement of the RCSWA but in urban locations and 61 graduates who also entered level 5 from 2002 but had participated in the RCSWA. Of the 61 participants in the RCSWA, 3 completed the RCSWA year at a site with an ASGC-RA index of 2 (4.9%), 24 at a site with an ASGC-RA index of 3 (39.3%), 32 at a site with an ASGC-RA index of 4 (52.5%) and 2 at a site with an ASGC-RA index of 5 (3.3%).A comparison of each of the 3 study groups by socio-demographic factors at entry or exit from the medical school is outlined in Table A breakdown of the ASGC Remoteness Area of current site of practice for each of these 3 groups is depicted in Figure Each of the socio-demographic factors were also assessed in univariate logistic regression to determine the extent to which they might predict the likelihood of rural practice in ASGC-RA 3–5 vs ASGC-RA 2 (Table In this study we have been able to compare the rural practice distributions of all 324 entrants to our medical school from 1980 who had graduated by 2011 and who were currently in rural practice in 2014. Rurally practicing graduates who had completed the RCSWA were greater than 4-fold more likely to be in practice in an outer regional, remote or very remote location relative to inner regional practice. This four-fold increase was the case relative to rurally practicing graduates who had entered medical school before 2002 when the RCSWA was not in place. It was also the case relative to graduates of all backgrounds who had completed traditional discipline specific clerkships in an urban location after the RCSWA had started. So although this entire group was practicing rurally, the odds of being in practice in an outer regional, remote or very remote location was significantly higher for those who completed a longitudinal rural clerkship in the RCSWA.It has been argued that the supply of doctors to remote locations is most likely to come from rural background students because rural background graduates enter rural work at higher rates ,17. HoweIt could be argued that the RCSWA association with an ultimate choice to be part of a more remote medical workforce could be due to specific selection of students into the RCSWA who already intended to work both rurally and remotely. Although this could be the case, in an earlier study we showed that urban background female students, who would otherwise be expected to work urban at high rates, instead were working rurally at high rates after graduation from RCSWA . This suThese data extend the results of a Canadian postgraduate study, which showed that graduates from regional and remote registrar training sites were more likely to be practicing both regionally and remotely relative to urban-trained graduates . But thaThe finding of a greater likelihood of more females in remote areas of practice after participation in the RCSWA was a surprising outcome given previous literature outlining the many barriers to rural practice for women . At leasWe have carefully considered whether differences in socio-demographic profiles might have confounded our results. With respect to the changes in socio-demographic profiles before and after the commencement of the RCSWA, those observed in these rurally working graduates were similar to those we have previously published for all school leaver entrants to our medical school , namely For graduates who choose to practice rurally, having been immersed in regional and remote locations for one academic year as medical students, is associated with practice in more remote locations. In comparison, graduates currently practicing rurally but whose undergraduate clinical training was predominantly in urban locations are more likely to be in an inner regional practice. For underserved communities, this is an outcome with significant implications for increasing the medical workforce in more remote rural locations.


Background: In clinical practice, the physician’s treatment decision making is influenced by many factors besides the patient’s clinical conditions and is the fundamental cause of healthcare inequity and discrimination in healthcare settings. Type 2 diabetes mellitus (T2DM) is a chronic disease with high prevalence, long average length of stay and high hospitalization rate. Although the treatment of T2DM is well guideline driven, there is a large body of evidence showing the existence of treatment disparities. More empirical studies from the provider side are needed to determine if non-clinical factors influence physician’s treatment choices.Objective: To determine the hospital and patient influencing factors of treatment schemes given to T2DM inpatients in Inner Mongolia, China.Methods: A cross-sectional, hospital-based survey using a cluster sampling technique was conducted in three tertiary hospitals and three county hospitals in Inner Mongolia, China. Treatment schemes were categorized as lifestyle management, oral therapy or insulin therapy according to the national guideline. Socio-demographic characteristics and variables related to severity of disease at the individual level and hospital level were collected. Weighted multinomial logistic regression models were used to determine influencing factors of treatment schemes.Results: Regardless of patients’ clinical conditions and health insurance types, both hospital and patient level variables were associated with treatment schemes. Males were more likely to be given oral therapy  and insulin therapy  compared to females who were given lifestyle management more frequently. Compared to the western region, hospitals in the central regions of Inner Mongolia were less likely to prescribe T2DM patients oral therapy  and insulin therapy  than lifestyle management. Compared with non-reformed tertiary hospitals, reformed tertiary hospitals and county hospitals were less likely to give T2DM patients oral therapy (RRR = 0.07 and 0.1 respectively) and insulin therapy (RRR = 0.11 and 0.17 respectively).Conclusion: Gender was the only socio-demographic factors associated with treatment scheme for T2DM patients. Hospitals from different regions have different T2DM treatment patterns. Implementation of reform was shown to be associated with controlling medication use for T2DM inpatients. Further studies are needed to investigate the causes of unreasonable treatment disparities so that policies can be generated accordingly. However, variations in medical practices are observed across and within countries6. More and more attention is now focused on health disparities that impair healthcare quality and overall health outcomes. It is estimated that $309 billion per year is lost due to the direct and indirect costs of health disparities in the United States of America7.The differences in healthcare among different population groups are defined as healthcare disparities10. Although the influencing factors differ among countries and regions, demographic and socio-economic factors are proposed in many studies12. Since the clinical conditions of the people are very difficult to evaluate from most population-based surveys by self-reported health status, there are biases when comparisons of treatments are made between different population groups. A hospital-based study may overcome this limitation and provide physicians defined clinical and non-clinical patient information, so that they have more confidence in comparing the healthcare services they receive. Yet evidence from the provider side is limited, especially in low- and middle-income counties13.Both clinical and non-clinical factors may lead to disparities in healthcare. From the view of healthcare equity, it is important to recognize the wide range of factors that contribute to disparities, especially non-clinical factors, such as socio-economic and healthcare system factors. Evidence from the population side suggests that a variety of factors are related to unequal health services received by peopleInner Mongolia is a self-governed province located in the northern part of China. Compared to other parts of China, healthcare accessibility is inferior in Inner Mongolia because of the low population density, limited health resources and underdeveloped social-economic status. All of these characteristics may promote healthcare disparities.14. Type 2 diabetes mellitus (T2DM) is one of the leading chronic diseases in Inner Mongolia. The prevalence of diabetes in Inner Mongolia was 2.6% in 2008, according to the fourth National Health Service survey, an increase of 160% from 200315. Besides having a high prevalence, diabetes is also associated with longer length of stay (LOS) in hospital and incurs a high medical expenditure. According to the data of Health Ministry of China in the year 2010 the average LOS of diabetes inpatients was 13.2 days, which was 3.2 days longer than the average LOS of all inpatients16. Healthcare disparities may exist in treatment of T2DM inpatients since the disease is chronic and more expensive than other diseases.Diabetes has become a large and rapidly-growing health problem. In 2011, it accounted for 8.2% of global all-cause mortality of people aged 20–7917. The International Diabetes Federation (IDF) and the American Diabetes Association (ADA) provide updated guidelines for T2DM treatment as well18. Treatment schemes in all the T2DM treatment guidelines consistently include three components: lifestyle management, oral therapy and insulin therapy19. Since type 2 diabetes is a progressive disease, patients who have had a longer duration of disease are likely to have reduced beta-cell function and require more intensive therapy compared to patients with a more recently diagnosed disease20.Treatment of T2DM is well guideline-driven. The Chinese Diabetes Society (CDS) issued the Chinese Guideline for Treatment of T2DM and has revised it every 3 to 4 yearsA hospital-based study was implemented aiming to determine the hospital and patient influencing factors on treatment schemes given to T2DM inpatients in Inner Mongolia of China. Both clinical and non-clinical factors from hospital and patient perspectives were considered. The potential influencing factors considered in this study were categorized as socio-demographic , disease characteristics  and hospital characteristics .A cross-sectional hospital-based study.The population of this study comprised T2DM inpatients in Inner Mongolia of China. Inner Mongolia has three-tier hospitals. Tertiary hospitals located in urban area serve both urban and rural people. County hospitals are secondary hospitals serving rural people mostly. Community health institutions and township hospitals provide primary healthcare in urban and rural areas respectively. Moreover, there are Mongolian hospitals included in the hospital system of Inner Mongolia that mainly serve minority people and use totally different techniques and drugs from western medicine. Tertiary and county hospitals, as major providers of T2DM hospitalization care in Inner Mongolia, were chosen for this study. A multistage cluster sampling method was used to select the study sample. Inner Mongolia was geographically classified into three regions and the largest tertiary hospital and county hospital in each region were purposively selected. The eligible hospitals should have facilities to provide standard T2DM inpatient services as required by clinical guidelines. Only hospitals with good quality medical records and those where hospital charge information could be extracted from hospital information system were selected. Three tertiary hospitals and three county hospitals were finally chosen. All consecutive inpatients with a principle diagnosis of T2DM (ICD-10 codes: E11.2–E11.9) admitted into the sampled hospitals and discharged during the data collection period were recruited into this study. Those who stayed in hospital for less than 24 hours or could not communicate by themselves were excluded. Finally, a total of 771 eligible participants were recruited into this study.Outcome variables. The outcome variable of this study was treatment schemes of T2DM inpatients, which were classified into three categories: lifestyle management, oral therapy and insulin therapy, according to China’s treatment guideline for T2DM.Explanatory variables. Socio-demographic variables , disease characteristics variables  score, diagnosis, participation in treatment planning), and institutional variables  were considered as explanatory variables for treatment schemes of T2DM inpatients.Patient interview data and medical records were collected and analyzed. Patient interviews were conducted one day before the patients were discharged using a questionnaire administered by well-trained research assistants. One week after the interview, the patients’ final medical records were reviewed by two researchers using a self-designed medical record review form. Both the patient interview questionnaire and the medical review forms were pre-tested in a pilot study for validation. A standard operating procedure was generated to standardize the data collection process.Socio-demographic variables and two clinical variables (duration of T2DM and participation in treatment planning) were collected by patient interview, the other variables were extracted from the medical records.21. Diagnosis was coded as T2DM, T2DM with complications, T2DM with comorbidities, and T2DM with complications and comorbidities. Patient participation in treatment planning was determined by asking patients: “Did the doctors discuss your treatment plan with you before they made a decision?” Hospital reform status was confirmed with the local government. Only the hospital which had implemented the reform policies  was defined as reformed hospital. Two of the surveyed county hospitals were assigned as pilot hospital of hospital reform under the framework of national medical reform, however, both of them were coded as non-reformed hospitals for having not started reform yet.Duration of T2DM was calculated by asking a patient the exact year when he/she was first diagnosed as T2DM by a clinician. ACCI scores were calculated automatically using an online calculator, with scores ranging from 0–37. The calculation was done by adding the weighted scores for 19 medical conditions. High scores are associated with a poorer prognosisData were presented as percentages for categorical variables or means for continuous variables. Multinomial logistic regression was used to explore the factors associated with treatment schemes. Weights were used to adjust the estimates due to cluster sampling. The strength of the association between factors and treatment scheme were presented as relative risk ratios (RRR) and 95% confidence intervals (95% CI). A P-value of less than 0.05 was considered as statistically significant. Data analysis was performed using the survey package of R software version 3.0.3 and Stata version 10.0.This study was approved by the Institutional Review Board of the Faculty of Medicine, Prince of Songkla University, Thailand. Permission was obtained from surveyed hospitals and written informed consent was obtained from each participant before enrollment in the study. No incentives or financial payments were provided for the interviewed patients. Personal identification was removed from the completed questionnaires and confidentiality was assured.Social-demographic characteristics of participants and their treatment schemes are shown inTreatment schemes significantly differed between genders. Females were more likely to be given lifestyle management and oral therapy, whereas males were more likely to be given insulin therapy. Lifestyle management and oral therapy were mostly given to those aged 60–69, those aged 50–59 were more likely to be given insulin therapy, however, the p-value was just on the cut point of statistical significance.Raw data of hospital and patient influencing factors on treatment schemes given for type 2 diabetes mellitus in patients in Inner MongoliaThe raw data of influencing factors on treatment schemes are provided.Click here for additional data file.Copyright: © 2016 Zhang N et al.2016Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).After controlling for clinical conditions such as duration of disease, ACCI score and diagnosis, the hospital level factor stood out of all the potential explanatory variables. Hospital location, reform status and hospital level were associated with treatment scheme for T2DM inpatients significantly, while gender was the only demographic variable related.22. However, the underlying reasons of the variations were not always the same23. There might be two possible explanations for regional variations in this study. First, the Western region in Inner Mongolia has a lower population density compared with the central region (23 person/km2 vs 174 person/km2). Since a general practice system has not been fully set up in China, especially in Inner Mongolia, inferior accessibility to healthcare may reduce the healthcare seeking behavior of T2DM patients, which will cause them to lose the opportunity for early treatment. Second, hospitals in the same region have more chance to have professional and academic exchanges and learn from each other under the circumstance of lacking clinical pathway management. More evidences are needed to get the precise information on the factors contributing to the variations so that policies could be designed accordingly.Compared with the Western region, T2DM patients treated in the central regions of Inner Mongolia were more likely to be given lifestyle management than medication. As one of the major causes for healthcare disparities, geographic variations in treatment pattern of T2DM have been reported in other studies24. In the first stage of the reform, enhancing internal management was carried out by many hospitals to improve the quality of care. Zero mark-up on part of essential medicines , and clinical pathway for T2DM were implemented in the reformed hospitals of this study. Although the hospitals had set out to implement the reform for less than three years when this survey was conducted, a series of policies was generalized and experimented by the hospitals to match the requirement of the government. Some studies report that the zero mark-up policy can decrease drug prescriptions and reduce total expense for both outpatient and inpatient services27. Clinical pathway has been shown to reduce the variability in clinical practices28. However, further studies are needed to confirm the causation between the reform and the change in physicians’ clinical practices.In this study we show that implementation of reform was associated with controlling medication use for T2DM patients. Reformed tertiary hospitals were less likely to give T2DM patients medication treatment compared to tertiary hospitals without any reform. The public hospital reform in China under the national healthcare reform framework started from tertiary hospitals29, and males have lower obedience to diet control and exercise30. However, gender differences in treatment protocols lead to unequal treatment and it should be avoided as much as possible. One way this can be done is by incorporating patient preferences into the treatment schemes. Systematic reviews done on the patient preferences for non-insulin diabetes medications during 2007–201232 have shown the importance of incorporating patient preferences into treatment decisions. These reviews showed that the key attributes of diabetes medication associated with patient preferences include treatment benefits (e.g. glycemic control and weight loss/control), treatment burden , and side effects 31. Therefore, gender differences in the treatment schemes can be allowed as long as they accommodate the patient’s preferences and treatment efficacy is not compromised.Among non-clinical characteristics, major gender differences in the treatment schemes given to T2DM patients were observed in this study. Males were more likely to be given oral therapy and insulin therapy than females who were mostly given lifestyle management. Many studies have revealed the fact that females have increased adherence to preventive practices34. However, ethnicity was not significantly associated with treatment schemes in this study. If we look at the distribution of ethnicity among T2DM inpatients, it was quite different from that of the whole population of Inner Mongolia. Our findings showed that minority groups with T2DM were rare (3.7%) across the six hospitals studied. This proportion was much lower than in the whole population of Inner Mongolia (21%). This could be because minorities prefer traditional medicine to Western medicine. However, further studies are needed to obtain information about accessibility and utilization of healthcare for minority groups with T2DM in Inner Mongolia. Where ethnic and racial disparities exist in the treatment of diabetes patients, it is evident that policy responses for addressing minority groups are needed.A number of studies have found evidence about health disparities in different ethnic groups35. However, other studies have put forward evidence that the educational level of patients had no association with untreated diabetes36 or with the prevalence of diabetes37. Although the possibilities for disparities in treatment types may exist by level of education, this study did not find any association between education level and the type of treatment schemes that was given to the patients.Education level was low among T2DM patients in this study. Only 6.5% of T2DM patients had attained a bachelor degree or above, which was lower than the whole population (10.3%). Education has been found to be associated with all aspects of T2DM treatment including prevention, outpatient care, inpatient care, and rehabilitation38. Physicians usually have different personal attitudes toward insured and uninsured patients. This was demonstrated in an analysis of patients who were insured which showed that they had a higher number of prescribed medications, and a higher total price of prescription than those who paid cash only39. It has been found that even insurers have major differences in attitude with regard to diabetes. Some patients who had declared their disease status to the insurers were refused acceptance for insurance and for some, their premiums were increased40. These evidences prove the importance of state mandated insurance programs, especially for diseases such as T2DM which has a long treatment period.This study also found that although the national health insurance system covered most (77.6%) of the participants, 21.2% of the participants had no insurance. In contrast, among all adults with diabetes in the USA, 92.0% had some form of health insuranceetc.) were not available, which would be a factor in determining treatment and adherence to the national guidelines.This was a hospital-based study using combined methods of patient interview and hospital record review to obtain clinical and non-clinical data, which can eliminate the recall bias on health service experience inherent in population based surveys. However, several limitations in this study should be acknowledged. First, it was a hospital-based study, therefore the findings cannot be generalized to the whole population of China, or T2DM patients. Second, due to the cross-sectional nature of the study, causality of certain risk factors and the study outcome cannot be established. Third, we did not measure all potential patient risk factors, such as hemoglobin A1C values, which were not available. As such, duration of T2DM, diagnosis and ACCI score were used to estimate severity of disease, which are known to be less precise. Fourth, physicians’ characteristics .10.5256/f1000research.9095.d12782541F1000Research: Dataset 1. Raw data of hospital and patient influencing factors on treatment schemes given for type 2 diabetes mellitus in patients in Inner Mongolia, In the limitation section, it would be better to explain if there any recall bias when using data from patient interview? If so, please state in limitation part.Give a few words to demonstrate “a series of policies was generalized and experimented by the hospitals” at the current health reform.This is a policy-relevant article to study hospital and patient factors influencing T2DM treatment in Mongolia. The rapid increasing of T2DM gives a pressure to the health system in Inner Mongolia. The authors are interested in exploring health care disparities by conducting a cross-section hospital survey in 6 hospitals in 3 regions. I would approve the article. However, there may be minor revisions if the authors accept the following comments.I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. The paper briefly sets out on page 3 the nature of equity issues in hospital health care and the problems of measuring health care disparities, especially from the clinical side. Using a transitional and developing region of China, Inner Mongolia, the paper focuses on the widely accepted practice of measuring disparities from the population side (socio-economic characteristics) factors. Importantly, the paper also focuses on different types of hospital and also measures clinical treatment differences for diabetes (T2DM) treatments. The choice of disease, T2DM, is justified as the research focus. The authors should be commended for their access to treatment records. On page 3, the authors might add a couple of sentences on tertiary versus county hospitals, especially given the differences in bed-size. Also, the choice of hospital depended on the quality of the records, and a sentence on differences (if any) in tertiary versus county hospital records would be useful. In terms of the explanatory variables (page 3), the authors might briefly define insurance scheme, hospital reform status and diagnosis in this section  covered in the section on ‘Data collection and measurement’). On page 8, the argument should make clear that type of insurance and ‘no insurance’ did not have an impact on treatment. The discussion contrasts the Inner Mongolia case of no differences in treat by insurance/’no insurance’ with other countries, but does not emphasize that there are no differences in the Inner Mongolia data between insurance/'no-insurance'. This requires only one sentence.I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.


Patients with overactive bladder (OAB) often have trouble perceiving urgency because of difficulties in distinguishing between urgency and desire to void. Empirical antimuscarinic treatment of patients with frequency only may be reasonable if conservative management has failed. We compared the efficacy of solifenacin in patients with frequency with or without urgency.This multicenter, 12-week, open-label, comparative, non-inferiority clinical trial assessed whether the solifenacin efficacy for frequency without urgency is non-inferior to its efficacy for frequency with urgency. All patients had micturition frequency ≥8 voids/day with or without urgency. Primary efficacy variable: daily frequency change at 12 weeks relative to baseline. Secondary efficacy variables: change at 12 weeks relative to baseline in Patients' Perception of Bladder Condition (PPBC), OAB Symptom Score (OABSS), and Benefit, Satisfaction, Willingness to continue (BSW) questionnaire.Of the 286 enrolled patients, 240 (83.9%) completed the study . Full dataset analysis revealed that the groups without and with urgency exhibited significant reductions in daily micturition frequency of −2.49±0.35 (mean ± standard error) and −2.63±0.37, respectively. The lower limit of the 95% two-sided CI of the comparison of the two group means was −1.14, which is smaller than the −0.8 margin of clinical equivalence. The two groups did not differ in improvement in PPBC, OABSS, or BSW scores. Both tolerated the treatment well.It was not possible to verify that the solifenacin efficacy for frequency alone was non-inferior to its efficacy for OAB. Nevertheless, solifenacin tended to be effective for frequency regardless of urgency.NCT00979472ClinicalTrials.gov  Overactive bladder (OAB) is defined by the International Continence Society (ICS) as urgency [with or without urgency urinary incontinence (UUI)] that is usually associated with frequency and nocturia The ICS defines urgency as “the complaint of a sudden compelling desire to pass urine which is difficult to defer” In clinical experience, it seems that many patients who present with urinary frequency complain of a desire to void without urgency as defined by ICS, yet it is not suited for the current ICS definition of OAB. Nevertheless, despite the fact that urgency is the key symptom in OAB, frequency is also regarded as one of the most bothersome OAB symptom We hypothesized that the some of the patients who complained of only frequency without urgency may be actually OAB patient who cannot perceive or express their urgency symptoms, and antimuscarinic drugs may be effective in patients who complained of only urinary frequency without urgency, as they are in patients with urgency. Thus, we compared the efficacy of solifenacin in patients with frequency only and frequency with urgency.The protocol for this trial and supporting CONSORT checklist are available as supporting information; see This multicenter, 12-week, open-label, comparative, non-inferiority study was based on the hypothesis, “The efficacy of solifenacin for frequency only is non-inferior to the efficacy of solifenacin for frequency with urgency”. It was conducted at nine sites between April 2009 and September 2011 in Korea. The study was conducted in accordance with the ethical principles in Korean Good Clinical Practice, the Declaration of Helsinki, and the International Conference of Harmonization Guidelines. This study was approved by the Institutional Review Board of Asan Medical Center (No. 2009-0014). Before enrollment in the study, all patients provided written informed consent.The study population consisted of men and women aged ≥18 years with symptoms of frequency for more than 3 months. All patients were assessed by a 3-day voiding diary and the urinary sensation scale (USS) The Patients were excluded if they had: significant stress urinary incontinence, an average total daily urine volume >3000 ml, serum liver enzymes or creatinine level >2 times the upper limit of normal, symptomatic urinary tract infection at screening, recurrent urinary tract infections (defined as receiving treatment for symptomatic urinary tract infections >4 times in the last year), interstitial cystitis, urothelial tumor, a post-void residual (PVR) urine volume >100 ml, clinically relevant bladder outlet obstruction, clinically significant pelvic organ prolapse, electrostimulation treatment, undergone bladder training in the preceding 2 weeks, received antimuscarinic medication in the preceding 2 weeks, and/or neurological conditions that can specifically affect bladder function.We classified the patients with average micturition frequency ≥8/24 hours without urgency as Group 1, and patients with average micturition frequency ≥8/24 hours with urgency (USS ≥3/3 days) as Group 2, based on a 3-day voiding diary. Patients received solifenacin 5 mg once daily. At the week 4 visit, the dose could be increased to 10 mg based on discussion between the subject and investigator regarding treatment efficacy and tolerability.To assess efficacy, the patients completed a 3-day voiding diary before the clinic visits at baseline and at weeks 4 and 12 . The primary efficacy variable was change in daily micturition frequency at 12 weeks relative to baseline. The secondary efficacy variables were change from baseline in Patients' Perception of Bladder Condition (PPBC) Sample size was calculated by using the Power Analysis and Sample Size (PASS) statistical software package . Sample sizes of 128 evaluable patients per treatment group were deemed to provide approximately 80% power to detect a non-inferiority margin of equivalence of −0.8  was used, namely, all patients who took the study medication and completed at least one efficacy evaluation. Per protocol (PP) analysis was performed for evaluation of changes in MFR and PVR relative to baseline. Categorical data were compared with chi-square statistics or Fisher's exact test and presented as frequencies. Continuous variables were analyzed using unpaired Student t- test and presented as mean ± standard error. All statistical tests had a two-sided significance level of 0.05 and were performed by using SPSS statistical software package .p = 0.408).A total of 286 patients were enrolled and 240 (83.9%) successfully completed the 12-week treatment period  . Twenty-p<0.001); At 12 weeks, Groups 1 and 2 both exhibited statistically significant reductions in average daily micturition frequency relative to baseline . The solifenacin escalators and non-escalators in Group 2 did not differ significant in terms of this variable.After 4 weeks of treatment, nine patients (7.8%) in Group 1 and four (3.2%) in Group 2 requested a dose escalation to 10 mg. This difference was not statistically significant. In Group 1, the solifenacin escalators had significantly more micturition episodes at baseline than the non-escalators .Adverse events were reported in 25.5% (36/141) in Group 1 and 39.3% (57/145), and the difference was not significant. However, these adverse events were generally mild . Dry mouTo the best of our knowledge, this is the first trial to evaluate the efficacy of an antimuscarinic agent for frequency without urgency. We demonstrated a reduction of approximately two frequency episodes per day in patients with frequency without urgency at week 12, which was similar to that in patients with frequency with urgency, as well as the mean change in daily micturition of antimuscarinic treatment in meta-analysis Urinary urgency is the cornerstone of the definition of OAB that is estimated to affect 10% of the worldwide population At present, the pathophysiology of frequency without urgency is poorly understood. The most common cause of frequency only would be that the vast majority of patients do not understand the subtle diagnostic nuances of urinary urgency. Indeed, a study on patient understanding of lower urinary tract symptoms showed that the term “urgency” was correctly defined by only 46% of the subjects The clinically significant efficacy of an antimuscarinic agent in our patients with frequency without urgency may be explained by an inhibitory effect of this agent on afferent bladder nerves. Antimuscarinic treatment is believed to repress the detrusor overactivity associated with OAB by blocking the muscarinic receptors in the detrusor muscle. However, several studies Overall, the 12-week solifenacin treatment was well tolerated in the patients with frequency with and without urgency.One limitation of this study was that we did not find that solifenacin had a non-inferior effect on frequency without urgency relative to its effect on frequency with urgency in terms of change in daily micturition frequency (the primary endpoint of this study). However, our study did show that solifenacin treatment significantly decreased the daily micturition frequency in patients with frequency regardless of urgency. Moreover, the difference between the urgency and non-urgency groups in terms of micturition frequency change did not achieve statistical significance. The inability of this study to detect non-inferiority may reflect the wide standard deviation (−2.56) associated with the mean number of micturitions per 24 hour that was reported by the study that was used to establish the margin of clinical equivalence for the present study It was not possible to verify that the solifenacin efficacy for frequency alone was non-inferior to its efficacy for OAB. Nevertheless, solifenacin tended to be effective for frequency regardless of urgency.Checklist S1CONSORT checklist.(DOC)Click here for additional data file.Protocol S1The original study protocol in Korean.(DOC)Click here for additional data file.Protocol S2English translation of the original study protocol.(DOC)Click here for additional data file.


A choroidal mass or granuloma is a feature of ocular tuberculosis (TB). Tubercles can arise in the early stages of progression of TB and indicate hematogenous dissemination before the development of symptomatic disease. Tubercular subretinal granuloma is responsive to treatment with anti-tuberculosis therapy, and prompt treatment helps resolve the lesion completely.Mycobacterium tuberculosis genome. Based on clinical history and investigations, treatment with four-drug regimen of anti-tubercular treatment with concomitant corticosteroids was started, and total healing of the lesion occurred in 3 months.We report a case of a solitary large active choroidal tuberculoma in one eye and multiple healed tubercles in the other. The patient was an immunocompetent girl with splenic and miliary TB and had a relatively asymptomatic systemic status. Aqueous humor analysis by polymerase chain reaction (PCR) and real-time PCR (RT-PCR) was negative for the This case highlights the fact that in some patients, analysis of the aqueous may not provide any clue to the confirmation of an active tubercular choroidal granuloma and an association between splenic tuberculosis and choroidal tubercles has never been reported in the past. The ocular involvement of tuberculosis is not uncommon but diverse. The ophthalmic presentation of ocular tuberculosis might be caused by direct infection or indirect immune-mediated hypersensitivity. There is an increasing incidence of tuberculosis even in the developed countries, due to migration from endemic areas and increase in the number of immunocompromised patients . Ocular A 13-year-old girl presented with complaints of diminution of vision in her left eye for 3 weeks. On examination, her best corrected visual acuity for distance and near was 6/6 with N6 in her right eye and 6/24 and N6 with effort in her left eye, respectively. Slit lamp examination of the anterior segment and intraocular pressure were normal. Vitreous was normal with no cells or haze. Dilated fundus examination of the right eye revealed multiple, well-defined, yellow subretinal, healed choroidal tuberculomas Figure . OCT in Mycobacterium tuberculosis (MTB) complex genome. DNA extraction from the aqueous humor was carried out using QIAMP DNA extraction kit  and RT-PCR for MTB was carried out using Genosen's MTB complex quantitative real-time PCR kit . Aqueous humor analysis revealed the absence of acid-fast bacilli, and both PCR and RT-PCR were negative for tuberculosis genome. On the basis of clinical, angiographic, and radiological evidence, multiple healed choroidal tuberculomas in the right eye and active military choroidal tuberculoma in the left eye were diagnosed. Management with anti-tubercular treatment in the form of four drugs with isoniazid, ethambutol, pyrazinamide, and rifampicin for 3 months and isoniazid and rifampicin for 6 months was done. This was supplemented with prednisolone tablet 30 mg a day for 1 week tapered to 5 mg weekly to help resolve the surrounding choroidal inflammation along with ranitidine tablet and oral calcium supplements. On review after 3 months, the patient showed an improvement in her best corrected visual acuity to 6/6 and N6 in the left eye. On examination, the choroidal tuberculoma was found to have completely resolved, the ocular status was stable, and the only evidence of the lesion was pigmentation , and by real-time polymerase chain reaction (RT-PCR) kit to detect n Figure .Figure 9Choroiditis is the most common ocular manifestation in patients with pulmonary and systemic tuberculosis . A histoA choroidal tuberculoma is one of the most common forms of ocular tuberculosis, and it is probably due to high blood supply of the choroid. This case highlights the fact that in some patients, analysis of the aqueous may not provide any clue to the confirmation of tubercular choroidal granuloma. An association between splenic tuberculosis and choroidal tubercles has not been reported till now. This patient was not very symptomatic despite chest and spleen involvement, thus proving that miliary tuberculosis has various forms of presentation. After the diagnosis of presumed or confirmed tuberculosis is established, surgical intervention should be avoided. Detection of choroidal inflammation can prevent visual loss as the ocular lesion resolves fully with timely management. Miliary tuberculosis was found as one of the most important independent factors linked to the development of ocular tuberculosis . Since d


In our study, we aimed to compare the application of benzalkonium chloride (BC) - a nanotechnology-based product - for 24-hour periods and didecyl dimethyl ammonium chloride (DDAC) for 12-hour periods regarding efficiency in application of surface antiseptics in the ICU.Two different areas with eight beds at both sides of a common corridor in the ICU were named as areas A and B. BC was applied in area A with 24-hour periods and DDCA was applied in area B with 12hour periods for surface cleaning. Samples were taken from a total of 20 different surfaces including nurse-station desks, phones, keyboards, beds, bedside monitors and ventilators by the same infection control nurse every 24 hours from area A and every 12 hours from area B for 7 days. Swab samples were cultured on 5% sheep bloody agar and McConkey agar in the laboratory. Then the cultured mediums were incubated at 35 to 37°C in an aerobic environment for 18 to 24 hours. NCSS  2007 and PASS 2008 Statistical Software  program were used for the statistical analysis.There were no statistical differences between two groups Table .The effect of a good surface disinfectant should begin immediately and it should have a long-lasting disinfecting effect on the surface. DDAC is an efficient disinfectant used in medicine and the food industry to protect the surfaces. However, it may cause severe skin itching. BC, which is a nanotechnology-based product, leaves its active metabolites on the surface; it is applied by constituting a spongy layer. Since the efficiency of BC lasts for 24 hours and it is applied to perform cleaning with 24-hour intervals, we think that it is preferable with regards to workforce gain and cost.