The aim of this study was to evaluate the benefits of the use of ultrasonic dissector (UAS) From June 2009 to May 2010 we evaluated 321 consecutive patients electively admitted to undergo total thyroidectomy for thyroid carcinoma. The first 201 patients  presenting to our Department underwent thyroidectomy with the use of UAS while the following 120 patients  underwent thyroidectomy performed with a conventional technique (CT): vessel clamp and tie.vs. 113 min in CT, range: 54 to 120 min in UAS vs. 68 to 173 min in CT) was much shorter in the group of thyroidectomies performed with UAS. The incidence of transient laryngeal nerve palsy (UAS 3/201 patients (1.49%); CT 1/120 patients (0.83%)) was higher in the group of UAS; the incidence of permanent laryngeal nerve palsy was similar in the two groups (UAS 2/201 patients (0.99%) vs. CT 2/120 patients (1.66%)). The incidence of transient hypocalcaemia (UAS 17/201 patients (8.4%) vs. CT 9/120 patients (7.5%)) was higher in the UAS group; no relevant differences were reported in the incidence of permanent hypocalcaemia in the two groups (UAS 5/201 patients (2.48%) vs. 2/120 patients (1.66%)). Also the average postoperative length of stay was similar in two groups (2 days).The operative time (mean: 75 min in UAS vs. 0.83% in CT) and transient hypocalcaemia (8.4% in UAS vs. 7.5%in CT). No significant differences in the incidence of permanent laryngeal nerve palsy (0.8% in UAS vs. 1.04% in CT) and permanent hypocalcaemia (2.6% in UAS vs. 2.04% in CT) were demonstrated. The level of surgeons’ expertise is a central factor, which can influence the complications rate; the use of UAS can only help surgical action but cannot replace the experience of the operator.The only significant advantage proved by this study is represented by the cost-effectiveness (reduction of the usage of operating room) for patients treated with UAS, secondary to the significant reduction of the operative time. The analysis failed to show any advantages in terms of postoperative transient complications in the group of patients treated with ultrasonic dissector: transient laryngeal nerve palsy (1.49% in UAS  The definitive histopathology examination confirmed the diagnosis of thyroid carcinoma in all of the patients (251 papillary and 70 follicular). Considering the TNM staging system we observed 199 patients with T1 tumors, 65 patients with T2 tumors, 43 patients with T3 tumors, and 14 patients with T4 tumors.vs. the CT: operative time (minutes from the skin incision to skin closure); intraoperative blood loss (mL in the aspirator column); transient laryngeal nerve palsy ; permanent laryngeal nerve palsy ; transient hypocalcaemia ; permanent hypocalcaemia ; average postoperative length of stay; and wound infection rate.The following outcomes were used to compare the thyroidectomies performed using the UAS On every patient, preoperative fibrolaryngoscopy was used to evaluate pre-existing conditions affecting the vocal cords functionality. Transient RILN palsy was assumed on patient with symptoms persisting for more than one week after surgery but resolving in less than six months. Permanent palsy was proved with laryngoscopy on patients with symptoms persisting for more than six months.Wound infections were clinically detected on the basis of purulent discharge from the scar.vs. CT are shown in Table The studies in literature comparing thyroidectomy with UAS vs. 113 min in CT, range: 54 to 120 min in UAS vs. 68 to 173 min in CT) was considerably shorter in the group of thyroidectomies performed with UAS. The incidence of transient laryngeal nerve palsy (UAS 3/201 patients (1.49%) vs. CT 1/120 patients (0.83%)) was higher in the UAS group; the incidence of permanent laryngeal nerve palsy was similar in the two groups (UAS 2/201 patients (0.99%) vs. CT 2/120 patients (1.66%)). The incidence of transient hypocalcaemia (UAS 17/201 patients (8.4%) vs. CT 9/120 patients (7.5%)) was lower in the thyroidectomy conventionally performed; no statistically significant differences in the incidence of permanent hypocalcaemia (UAS 5/201 patients (2.48%) vs. 2/120 patients (1.66%)) were demonstrated between the two groups. There was a statistically significant reduction in the amount of blood loss (weighted mean difference (WMD), -60.10 mL; 95% confidence interval (CI), -117.04 to 3.16 mL) (P = 0.04) and of the overall volume of fluid collected in the surgical drains  (P = 0.00001) in the group of patients treated using the UAS. Data regarding the wound infection rate did not demonstrate any significant differences between the two groups. The average postoperative length of stay also was similar in two groups (2 days).Perioperative outcomes are summarized in Table Our study highlights that the main advantage brought by the use of UAS in thyroidectomies for malignant disease, is the shorter operating time (OT). This significant reduction in the OT was a result of the simultaneous coagulation and dissection exerted by the UAS; this technique resulted quicker compared to the repetitive ‘clip, cut and tie’ technique . The samvs. CT 1/120 patients (0.83%); transient hypocalcaemia: UAS 17/201 patients (8.4%) vs. CT 9/120 patients (7.5%)) and it is similar in permanent complications  vs. CT 2/120 patients (1.66%); permanent hypocalcaemia: UAS 5/201 patients (2.48%) vs. 2/120 patients (1.66%). Hypocalcaemia represents the most common postoperative complication after thyroidectomy [et al., permanent recurrent laryngeal nerve palsy was observed in 1.4% and permanent hypocalcaemia in 3.5% in the TT group [P = 0.001); but there is no statistically significant difference in the incidence of postoperative hypocalcaemia (P = 0.55) [et al. encountered a variable IRLN palsy rate according to the method of examining the larynx and ranging from 2.3% to 26% [The incidence of both transient and permanent postoperative complications were higher in the UAS group  % vs. CT TT group . Re-inte = 0.55) . A syste% to 26% . While n% to 26% -17 the e% to 26% -17, we bKocher had already highlighted this problem: ‘Since we have adhered strictly to this procedure, the hoarseness, formerly so frequently observed after operation, has now become exceptional’. Subsequently in 1919 Halsted wrote in ‘The Operative Story of Goitre’: ‘Kocher, neat and precise, operating in a relatively bloodless manner, scrupulously removed the entire gland, doing little damage outside its capsule, Billroth, operating more rapidly, and, as I recall his manner, with less regard for the tissues and less concern for the hemorrhage, might easily have removed the parathyroids or at least have interfered with their blood supply, and have left fragments of the thyroid’ .et al., on the best surgical approach for treating multinodular goiter [et al. in their prospective randomized study demonstrated that the essential advantages of the ultrasonic dissector were a significant shorter OT, decreased amount of blood loss and reduction of parathyroid injury [In the systematic review of Rouwen r goiter , the user goiter ,21; thesr goiter . Defeched injury . This laP = 0.00001), intraoperative blood loss  (P = 0.04) and overall drainage volume  (P = 0.00001) in the patients underwent thyroidectomy with UAS. Our analysis showed that the patients who were treated with UAS did not present more favorable results in incidence of postoperative transient complications but similar results about permanent complications .Our study shows a relevant advantage of cost-effectiveness in patients treated with UAS; there is a statistically significant reduction in the OT  (vs. 0.83% in CT) and transient hypocalcaemia (8.4% in UAS vs. 7.5% in CT). There was no significant difference in the incidence of permanent laryngeal nerve palsy (0.8% in UAS vs. 1.04% in CT) and permanent hypocalcaemia (2.48% in UAS vs. 1.66% in CT). The level of surgeons’ experience is an important factor which can influence the onset of these complications; the use of UAS can only help surgical action but cannot replace the experience of the surgeon.The only significant advantage shown in the present study is represented by an improved cost-effectiveness secondary to a reduction of the usage of operating room space for patients treated with UAS, due to a significant reduction of operative time. Our analysis showed that the patients who were treated with UAS did not present more favorable results in terms of postoperative transient complications: transient laryngeal nerve palsy (1.49% in UAS CI = Confidence interval; CT = Conventional technique; OT = Operating time; UAS = Ultrasonic dissector; WMD = Weighted means difference.The authors declare that they have no competing interests.All authors read and approved the final manuscript.


The Schroth method has proven to be an effective treatment for patients suffering from adolescent idiopathic scoliosis (AIS); however, its impact on patients who have undergone surgical intervention to correct scoliosis and who suffer from postural imbalances along with diminished respiration is unknown.The aim of this study was to examine the effects of Schroth therapy on a 21-year-old female with AIS after spinal fusion.During an evaluation in December 2011, one month after spinal fusion (T10-Pelvic), the patient's clinical sagittal profile demonstrated a significant forward trunk inclination of 5 cm. Angle of Trunk Rotation (ATR) was 5° in the thoracic and 4° in the lumbar. Quality-of-life score was 3.3 (SRS 22 questionnaire). Body image was 3 ). Pain score was 4 using the Visual Analog Scale (VAS). Force vital capacity (FVC) was 2.1 liters. Chest expansion was 1.9 cm in the subaxillary, 2.2 cm in the nipple line and -2.0 cm around the waist. Positive bilateral Thomas Test for hip flexors and knee extensors. Gluteus maximus and medius strength -4/5 bilateral, quadratus lumbarum -3/5 bilaterally. Decreased abdominal and trunk extensor strength. Single-leg stance was 5 seconds right and 6 seconds left.The physical therapy regimen included modified application of the Schroth exercises for patient with spinal fusion. The patient trained three 1-hour sessions per week for a duration of 10 weeks at an outpatient clinic, and was instructed to apply the learned principles during her daily activities and home exercise program, which consisted of 30-minute sessions five days per week. The patient is currently in treatment.After the 10 week treatment period, the patient had demonstrated preliminary measurable improvement. The clinical trunk inclination reduced to 2.5 cm, the ATR had decreased to 3° in the thoracic and 2° in the lumbar. Quality-of-life score and body image showed improvement with a score of 4.5 on the SRS 22 and 5 on the TAPS. Pain score diminished to 1. FVC increased to 2.8 liters and chest expansion to 2.8 cm, 3.1 cm and 1 cm at measured locations. Gluteus maximus and medius bilaterally +4/5 and hip flexors and knee extensors improved in flexibility. The patient felt more comfortable with her appearance and reported satisfaction with the results.These preliminary findings may suggest that physical therapy utilizing the Schroth Method, with modification for fusion, may be a useful way to treat patients after spinal fusion.


Despite programmed screening in the Netherlands, the decrease in incidence of cervical carcinoma lags behind. We analysed screening results preceding carcinoma cases, timeliness in case of follow-up, and FIGO  stages as efficiency parameters for screening were taken.We analysed 286 women with cervical cancer between 2005 and 2007 for cytology history preceding carcinoma, hierarchically arranging cytology history (if present) into three groups: ‘screened’, ‘work-up’, and ‘underscreened’ (>6 yrs before diagnosis). For screen- and work-up smears, we analysed timeliness. FIGO stage was measured in relation to cytology history.P=0.51). A total of 108 out of 286 (36.4%) women were underscreened, and 73 out of 286 (25.5%) were unscreened. Advanced carcinoma or FIGO stage ⩾2B in screened women was 16.0 vs 48.7% in work-up, underscreened, or unscreened (P<0.001).A total of 105 out of 286 (36.7%) women with cervical carcinoma were screened preceding the diagnosis. Delayed time intervals in case of abnormal cytology were 43.5% for borderline/mild dyskaryosis (BMD) and 38.0% for BMD . Improvement of attendancy is needed to meet the standard of quality for screening programmes.Women with cervical cancer are underscreened and have poor timeliness in case of abnormal cytology. Being un- or underscreened correlates significantly with higher cervical cancer stages, especially in older women (aged ⩾49 years;  Cervical cancer is preceded by well-defined premalignant lesions, which can be identified by detecting abnormal cells in Papanicolaou smear. Cervical screening by cytology with adequate treatment have resulted in a decrease in incidence and mortality of cervical carcinoma  within tCoverage of the screening programme is currently 77% . EarlierHere we analysed 286 women, with cervical carcinoma from the region Noord-Holland/Flevoland in the Netherlands, diagnosed between 2005 and 2007. We analysed the relationship between the FIGO  stage of the detected carcinoma and the associated screen status. In addition, we analysed whether the smear was made within or outside the screening programme, and the compliance for referral to the gynaecologist in case of an abnormal smear.All cytological and histological results carried out in the Netherlands are excerpted in the Pathological National Automated Archive (PALGA), a centralised database. Since 1991, coverage is at least 95% (n=48). This left 307 298 numbers of smears of which 286 (0.09%) women were diagnosed with histologically confirmed cervical carcinoma. Cervical smears were registered as either inside- or outside the screening programme. This study was approved by the ethical committee of PALGA.In total, our query in PALGA provided 337 830 smears of which 334 cases (0.10%) with index-diagnosis histologically confirmed cervical carcinoma in 2005–2007 and living in one region of the Netherlands. Group of records, presumably belonging to a single person, were ‘eyeballed’  to filter out administrative twins by checking domicile, initials, and apparent inconsistencies in clinical history (t=0). From this point, we did a retrospective research in the preceding time period to determine their last cytological examination. Three time frames were defined as follows: ‘unscreened’ , ‘underscreened’ (last smear taken >6 years before the diagnosis: the work-up smear not included), or ‘screened’ (smear taken between 1 and ⩽6 years before the diagnosis). We defined cytology obtained less than 1 year preceding the diagnosis as a ‘work-up smear’.Screening histories of the 286 cases of carcinoma from PALGA database were analysed for presence or absence of cytology history. For each woman, we took time point with cervical carcinoma diagnosis . For this sub-analysis of ‘within the screening programme’, we have chosen the upper age as 63 years, as the Dutch screening programme invites women up to age 60 years (with a cutoff at 63 years because of a possible follow-up time) and for lower age as 29 years, as women can be invited from the age of 29 years onwards. The number of eligible women (29–63 years) was 217 for this sub-analysis with respect to the the screening programme .In case of multiple abnormal smears in the screening history , we accepted the first abnormal smear as the starting point. If women had only multiple normal smear results in the screened period, we analysed the time interval between the last smear before the diagnosis and at the time of diagnosis. All analyses were performed using SPSS 15.0 software .Work-up smears for diagnosis were defined as all cases of cytology obtained <1 year before the diagnosis rather than 6 months, because we considered women with a ⩾BMD preceded by BMD cytology in the period from 12 to 6 months before the diagnosis to represent women who should have had a severe abnormality in the first smear, and thus be representative for women with signs and symptoms of carcinoma. We have taken this into account plus allowing a few months delay in repeat. Thus, we end the period for work-up smears at 1 year before the diagnosis.Women are invited in the Netherlands into the programme in the year they turn 30 years of age. Actually, at the time of screening they may still be 29 years. Similarly, at the second invitation, women may be still 34 years of age.Women with a normal smear results will be invited again for the next screening round. Women with borderline/mild dyskaryosis (BMD) are advised to repeat the smear after 6 and 18 months. If at least one of the repeated cytology smears is read as BMD or worse, the woman will be referred to a gynaecologist for colposcopy. Women with >BMD (moderate dyskaryosis or worse) are referred immediately to a gynaecologist. Women with inadequate smears (not suitable for diagnosis) are advised to repeat the test after 6 weeks.n=195). Two cases with inadequate smears without follow-up were excluded, leaving a total of 193 cases. After tabulating smear results, the time interval was categorised in two periods that is, not delayed and delay in diagnosis.Among the women with cervical carcinoma, we analysed the time interval between the first abnormal smear cytology and the histologically confirmed diagnosis. For timeliness, women were categorised as ‘not delayed’ or ‘delay in diagnosis’ . Absence was defined as having no smear in the screened period. Furthermore, we also analysed the FIGO stage in relation to the cytology result of women with a smear taken in the screened period, allowing insight in whether an inadequate cytology advice results in a later detection of carcinoma. Both types of analyses were stratified by age eligibility for screening invitation, or other ages. These analyses were also stratified by age . The anan=217, aged 29–63) for receiving an invitation within the context of a screening programme and a non-eligible group , or >63 years (n=63) for falling outside invitational cohorts. The number of women without any smear in the period preceding the diagnosis was 1 out of 6 (16.7%), 37 out of 217 (17.1%), and 35 out of 63 (55.6%) for women aged 29, 29–63, and >63 years, respectively , carcinoma of endometrial origin or metastasis. Age ranged between 25 and 93 years old . We divided the remaining 286 women into an eligible group  cytology, respectively. Furthermore, 15 out of 105 (14.3%) had >BMD, but cervical cancer was diagnosed more than a year later, suggestive of time delays. For women with only a work-up smear preceding the diagnosis, the results show a different pattern: >BMD was found in 75 out of 90 women (83.3%). The results of cytology in the group of women screened >6 years before the diagnosis resembled the first group: 12 out of 18 women (66.7%) had a normal cytology result, 5 out of 18 women (27.8%) had BMD cytology result, and only 1 out of 18 (5.6%) had >BMD (had >BMD .n=18), with respect to the time interval between the last negative smear and the diagnosis of carcinoma, into a subgroup with the last smear made 7–11 years previously for diagnosis and a group with the last smear made ⩾11 years before diagnosis. We could not find a significant difference in cytology result. However, it should be realised that the number of women in the subgroups was very small for a meaningful analysis (data not shown).In addition, we have sub-divided our group of underscreened women (n=67) and inadequate (n=2) cytology results of women in the screened period, as shown in vs 27 out of 53 (50.9%) outside the programme.The normal  with >BMD in the screened period again had >BMD, one woman (6.7%) had BMD, and two women (13.3%) had no smear in the work-up for diagnosis period (not shown). Similarly, for women with BMD in the screened period, 13 out of 21 (61.9%) had >BMD, 3 out of 21 (14.3%) had BMD, 1 woman (4.8%) had a normal cytology result, and 4 women (19.0%) had no smear in the work-up period. Again, the distribution of the indication smear is equal for both the groups (data not shown).n=217) for programmed screening (aged 29–63 years) and having at least one smear ⩽6 years before diagnosis , only women eligible (P<0.001), of whom 75 out of 99 (75.8%) had a programmed smear and 24 out of 99 (24.2%) had the smear taken outside the screening programme, which was statistically significant (P<0.001).Only 99 of 217 women (45.6%) actually had a smear taken in the screened period (A further 78 out of 217 (35.9%) women had a work-up smear only, divided between 29 out of 78 (37.2%) (aged 29–63 years) for invitational cytology and 49 out of 78 (62.8%) outside the screening programme . In totaP=0.51).For timeliness, we divided the interval as ‘not delayed’ and ‘delay in diagnosis’ . In the group of women with >BMD cytology smear, 88 out of 142 (62.0% 95% CI: 53.5–70.0) showed no delay for diagnosis. In the group, women with BMD, 26 out of 46 (56.5% 95% CI: 41.1–71.1) had no delay in diagnosis. Delay in diagnosis for women with >BMD and BMD were observed in 54 out of 142 (38.0%) and 20 out of 46 (43.5%) women, respectively. Overall, 60.6% of the women had no delay in diagnosis (95% CI: 53.3–67.7). The difference in delay in diagnosis of between women with >BMD and BMD cytology smears was not significantly lower (n=23) or time information was lacking (n=2).We also analysed the work-up smears of women who had a normal smear  in the period >6 years before the diagnosis. In total, 10 of these 12 women had >BMD (83.3%) and 2 out of 12 women (16.7%) had again normal cytology result. A total of 6 out of 18 women with ⩾BMD result (one woman with >BMD and five women with BMD) >6 years before diagnosis were categorised as delay in diagnosis. Together, with the 75 women with >BMD and 11 women with BMD, the total >BMD and BMD cases are 142 and 46, respectively. For the remaining 25 women, timeliness was not applicable, as they had had either normal cytology  in the percentage of screen smear. However, when we compare FIGO stage group 1B with 2A–2B, we notice a significant difference . Also a difference can be noticed when we compare the group 2A–2B with 3A–4 .When comparing the FIGO stage 1A with 1B, there is statistically no difference . Furthermore, we also analysed whether the differences between FIGO stage and two age groups (29–63 vs <29 and/or >63 years) were significant. The result showed a significant value at P<0.001  had significantly lower screen smear compared with the group with low-grade FIGO stage (1A or 1B) P<0.001; . In the n=100) in relation to their cytology smear result  no significant differences were found .When we analysed FIGO stage of women with a screen smear  who had no smear in the screened period, compared with women who had their smear in the same period . In addition, we analysed whether a correlation could be found between the mode of screening and severe FIGO stage found among women (aged 34–63 years) who had their smear taken in the screened period. No statistical difference was found .We then analysed FIGO stage in relation to screen smear e strata . We notiOur data show that only 36.7% (105 out of 286) of women diagnosed with cervical carcinoma in the region of Noord-Holland/Flevoland between 2005 and 2007 were appropriately screened. If restricted to eligible women for receiving an invitation for cervical screening (aged 29–63 years), this percentage was 45.6% (99 out of 217). This finding is in agreement with a meta-analysis study, showing that about 46.2% women had a smear in the screened period  that were ‘screened’ had a normal cytology result . A meta-vs 34.6%. P<0.001; Furthermore, our data show that 75 out of 217 (34.5%) women from the eligible age cohorts had been screened within the screening programme  in the aP=0.51). This suggests that significant improvement can be made in both the compliances with repeats as well as re-dressing delays in workup.The result of timeliness between the first abnormal smear ⩽6 years, preceding the diagnosis and histologically confirmed diagnosis, showed in 62.0% (95% CI: 53.5–70.0%) no delay in diagnosis among women with >BMD as cytology diagnosis and in 56.5% (95% CI: 41.1–71.1%) among women with BMD (P=0.009), whereas 1.4-fold higher cervical carcinoma stage (stages 3A–4) was found among women without screen smear compared with women with screen smear and at 2A–2B FIGO stage (P=0.047). Furthermore, a trend can be seen in the relation between the higher stages and age of women. The older women (age ⩾49 years) without a smear in the screened period showed significantly higher FIGO stages compared with older women who had a smear in the same period (P<0.001). This indicates that non-screened older women are at higher risk for high-stage cervical cancer.The correlation between the FIGO stage and women with or without a cytology smear in screened period showed a difference for higher stages: a 1.7-fold higher cervical carcinoma stage (stages 2A–2B) was observed in carcinoma-bearing women (aged 29–63 years) without cytology history compared with women at 1B FIGO stage (P<0.001). Even if women screened outside the screening programme were included, the percentage would be 45.6%, which is similar to as reported in the literature  had participated in an organised programmed screening between 1 and ⩽6 years before diagnosis (95% CI: 28.2–40.9% terature .+/CIN3+ lesions, particularly in women who did not attend the previous round of screening (There are several options to improve the participation rate in organised screening programme.


Liver transplantation (LT) is the only treatment option for patients with advanced liver disease. Currently, liver donation to these patients, considering priorities, is based on the Model for End-Stage Liver Disease (MELD). MELD score is a tool for predicting the risk of mortality in patients with advanced liver disease. However, few studies have so far been conducted in Iran on the efficacy of MELD score of these patients.This study reviews the present status of the MELD score and introduces a new model for optimal prediction of the risk of mortality in Iranian patients with advanced liver disease.Data required were collected from 305 patients with advanced liver disease who enrolled in a waiting list (WL) in Imam Khomeini Hospital from May 2008 to May 2009. All of the patients were followed up for at least 3 years until they died or underwent LT. Cox regression analysis was applied to select the factors affecting their mortality. Survival curves were plotted. Wilcoxson test and receiver operating characteristics curves for survival predictive model were used to compare the scores. All calculations were performed with the SPSS (version 13.0) and R softwares.During the study, 71 (23.3%) patients died due to liver cirrhosis and 43 (14.1%) underwent LT. Viral Hepatitis (43.7%) is the most common cause of end-stage liver disease among Iranian patients. A new model (NMELD) was proposed with the use of the natural logarithms of two blood serum variables  and the patients' age (year) by applying the Cox model:NMELD = 10 × (0.736 × ln (bilirubin) – 1.312 × ln  + 0.025 × age + 1.776)The results of the Wilcoxon test showed that there is a significant difference between the usual MELD and our proposed NMELD scores (P < 0.001). Receiver operating characteristics curve for survival predictive model indicated that the NMELD score is more efficient compared with the MELD score in predicting the risk of mortality. Since serum creatinine was not significant in NMELD score, further studies to clarify this issue are suggested. Gastrointestinal and liver diseases are among the most common causes of morbidity in Iran and constitute a substantial proportion of mortality, which imposes enormous economic consequences , 2. ProgLT is recognized as the only way to treat patients with cirrhosis. The aim of this study was to determine the best time for LT and the factors influencing these patients’ mortality. Optimal allocation of the few available donor livers for WL is essential. In this study, the survival rate of patients awaiting LT for one, two and three years, and the related influential factors were examined. Here, we attempt to provide a more efficient scoring system than the previous for predicting the mortality risk of patients with advanced liver disease.We evaluated all of the patients with advanced liver disease on the WL for LT in Imam Khomeini Hospital  during May 2008 to May 2009. They were followed up for 3 years. The required data included demographic features, cause of cirrhosis and laboratory test results. Child-Pugh (CP) score was evaluated by five parameters: ascites, encephalopathy, bilirubin, prothomobin time and albumin. CP scores of all participants were calculated according to the method summarized in MELD calculations were done on the natural logarithms (ln) of three variables in blood serum: total bilirubin, creatinine and the international normalized ratio (INR) of prothrombin. MELD score was calculated by the following formula:MELD = 9.6 × ln (creatinin mg/dL) + 11.2 × ln (INR) + 3.8 × ln (bilirubin mg/dL) + 6.43According to the United Network for Organ Sharing (UNOS) modifications, the laboratory values below 1.0 were rounded to 1 to avoid negative scores, and the maximum serum creatinine considered within the MELD equation was 4.0 mg/dL. In this paper, CP and MELD scores were calculated at the beginning of the study for all patients. Censorship group included the patients that underwent LT during this period or did not die by the end of the study. The univariate Cox regression models were applied separately to discriminate each significant factor. The adjusted survival and hazard functions were estimated using a multivariate Cox regression model. Factors associated with P-values of less than 0.20 for the previous stage (univariate Cox models) were candidates for multivariate analysis. In all models, factors with P Values < 0.05 were considered to be significant . The resOf the 305 patients, 126 (41.3%) were females and 179 (58.7%) were males. The mean age of the patients was 40.67 (± 14.39) (Mean ± (Standard Deviation) (M ± SD) years. The age range was between 18 and 71 years. During the study, 71 (23.3%) patients died due to complications of liver cirrhosis and 43 (14.1%) underwent LT. Survival rate at one, two and three years after enrolling in the WL was 82%, 73% and 66%, respectively. Survival rate at one, two and three years for patients with MELD scores < 10 was 95%, 90% and 79%, for 9 < MELD < 20 was 89%, 79% and 75%, and for MELD > 19 was 55%, 40% and 27%, respectively.In Group 2, 83 (40.7%) were females and 121 (59.3%) were males. 48 (23.5%) patients in this group died due to complications of liver cirrhosis and 27 (13.2%) underwent LT. The mean age of the patients was 41.6 (± 0.98) (Mean ± (Standard Error) (M ± (SE)) years. The age range was between 18 and 65 years. In univariate analysis, continuous variables showed a significant association with the patients’ age (P = 0.009), ln (bilirubin) (P < 0.001), ln  (P < 0.001) and ln (INR) (P < 0.001). Categorical variables revealed an association between ascites (P < 0.045) and encephapolathy (P = 0.013). The results of univariate analysis are shown in Cox multiple regression analysis indicated that there is a statistically significant correlation between ln (bilirubin), ln  and age, and the risk of mortality. The results of multivariate analysis are shown in The score of the optimal model was calculated via the below formula:A = 0.979 × ln (bilirubin) – 1.745 × ln  + 0.033 × ageBy linear regression, we found that the best linear fit between A (as independent variable) and the MELD score (as dependent variable) was provided by a line with the slope of 7.519 and an intercept of 17.661. The correlation between the two was good with R = 0.560. Based on the above analysis, the scores obtained from the model can be derived from the below formula. Here, we’ve termed it the ‘New MELD (NMELD)’ score:NMELD = 10 × (0.736 × ln (bilirubin) – 1.312 × ln  + 0.025 × age + 1.776)To avoid negative scores, serum bilirubin values below 1.0 were rounded to 1 and serum albumin values over 5.4 were rounded to 5.4; the obtained scores were rounded to the nearest integer. All analyses for modeling of NMELD were done based on the data collected from Group 2. In Group 1, 42 (41.6%) individuals were females and 59 (58.4%) were males. 23 (22.8%) patients in this group died due to complications of liver cirrhosis and 16 (15.8%) underwent LT. The mean age of the patients was 40.2 (± 1.53) years. The age range was between 18 and 71 years.Comparison of accuracy of the NMELD Score (Dash Line) Using the Covariates of ln (Bilirubin), ln (Albumin) and age vs. MELD Score (Solid Line) Using the Covariates of ln (Bilirubin), ln (INR) and ln (Creatinine). Lines Plot the Estimates of Incident/Dynamic AUC (t) Versus Time Under the Assumption of Proportional Hazards. LT has been accepted as an effective method for the recovery of health in patients with advanced liver disease. However, the increasing discrepancy between the number of patients on WLs and the number of available donor livers has a major impact on the mortality of these patients . DiseaseAmong the 305 patients in this study, who were listed for LT from May 2009 to May 2012, the most common etiology of liver disease was viral hepatitis (34.7%). This is in contrast with the findings of the Malinchoc et al. study, conducted at a medical center in the USA where alcoholic liver cirrhosis was the most prevalent (38.8% to 90.5%) followed by viral hepatitis (4.8% to 10.4%), and also with the results of a study by Sumskiene et al. in Lithuania where alcoholic liver cirrhosis was the most prevalent (28.9%) followed by viral hepatitis (17.8%) , 41. Thi


Neonatal sepsis is still a leading cause of death among newborns. Therefore a protein-microarray for point-of-care testing that simultaneously quantifies the sepsis associated serum proteins IL-6, IL-8, IL-10, TNF alpha, S-100, PCT, E-Selectin, CRP and Neopterin has been developed. The chip works with only a 4 μL patient serum sample and hence minimizes excessive blood withdrawal from newborns. The 4 μL patient samples are diluted with 36 μL assay buffer and distributed to four slides for repetitive measurements. Streptavidin coated magnetic particles that act as distinct stirring detection components are added, not only to stir the sample, but also to detect antibody antigen binding events. We demonstrate that the test is complete within 2.5 h using a single step assay. S-100 conjugated to BSA is spotted in increasing concentrations to create an internal calibration. The presented low volume protein-chip fulfills the requirements of point-of-care testing for accurate and repeatable (CV < 14%) quantification of serum proteins for the diagnosis of neonatal sepsis. It is caused by microbial pathogens including bacteria, virus and fungi. The survival rates increase enormously with an early stage diagnosis which allows timely administration of antibiotics. Neonatal sepsis is still a leading cause of death among newborns since symptoms are often wrongly interpreted due to their unspecific and late occurrence . HoweverSepsis is a condition caused by pathogenic microorganisms but induced by the immune response through excessive release of growth factors, cytokines and inflammation- and coagulation factors into the systemic circulation. Those factors can be exploited as specific biomarkers enabling early and reliable diagnosis. The cytokines interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10) and tumor necrosis factor alpha  and the serum proteins C-reactive protein (CRP), procalcitonin (PCT), S-100 and E-Selectin have been identified as a specific and accurate biomarker panel for the early diagnosis of sepsis. The clinically relevant ranges as well as the cut-off values of the respective serum proteins that allow discrimination between healthy and septicaemic patients are outlined in Herein we aim at the further development of a sepsis chip for point-of-care testing of neonatal sepsis. This is achieved by: (a) the reduction of required patient sample volume, (b) the reduction of assay steps and incubation times and (c) the integration of an internal calibration. The chip for biomarker detection of sepsis comprises multi-analyte on-chip immunoassays which include both sandwich  and binding inhibition formats . The combination of both assay formats allows analysis of the selected biomarkers on one chip despite the large heterogeneity of the analytes regarding cut-off concentration . In our 50), limit of detection (LOD), limit of quantification (LOQ), and inter- and intra-array variations.In order to prevent excessive blood withdrawal from newborns, the biochip was further miniaturized to operate with a five-fold reduced sample volume. The assay performance of the miniaturized chip is then compared with the classical format and evaluated using assay parameters like analyte concentration halfway between the zero point and the upper asymptote  coupled through the glass slide into the reaction solution. To account for the antibody spot kinetics, thus the migration of the analytes in solution towards the spot and across the surface we included bi-functional streptavidin coated magnetic particles (Strep.MPs), which act as both micro-mixer and detection reagent for the biotinylated antibodies. Strep.MPs in the sizes of 130 nm, 500 nm and 1 μm were tested. In addition, the assay procedure was further optimized by reducing assay steps and incubation times. Furthermore the calibration was integrated on the chip  presenting a point-of-care device suitable for use in neonates.In general, assay miniaturization provokes loss in assay sensitivity due to e.g., diffusion limitations. While a sample volume of 50 μL, as used for the classical chip, is mixed properly during incubation on the rotational shaker, a sample volume of 10 μL, as used for the miniaturized chip, is too small to be moderately mixed under the same incubation conditions. Different theoretical considerations have been made concerning the impact of diffusion on the antibody antigen kinetics for immunoassays on solid surfaces –17. For et al.  develope2.2.1.Chip platform used was the proprietary ARChip Epoxy , Anti IL2.2.All washing steps were performed via centrifugation at 16,200 g-force number for 6 min (Eppendorf Centrifuge 5417C). Five hundred μL of a 1 mg/mL 500 nm magnetic particles suspension are coated with functionalized silica by adding 200 μL GOPS and sonicating for 90 min, then an additional 10 μL of GOPS was added and the particles were sonicated  for another 90 min. The particles were washed twice with 1× PBS and resuspended in 1× PBS. Particles were washed 3× with 0.5 mM MES buffer (pH 5.0) by centrifugation and resuspended in 250 μL MES buffer. 50 μL Dy647-streptavidin (1 mg/mL Stock) and 50 μL PEG 6000 were added and incubated for 2 h on a rotational shaker at maximum speed . The reaction was vortexed every 30 min. The particles were washed twice with PBS and resuspended in 30 mM ethanolamine containing 1% BSA for 30 min to quench the reaction. The particles were washed 3× and resuspended in 500 μL 1× PBS containing 0.05% Tween 20 and 0.1% BSA (pH 7.4) and stored at 4 °C until use. The particle concentration was estimated to be 200 μg/mL. The protocol was adapted from .2.3.Capture antibodies were diluted in printing buffer “na” (1× PBS (pH 7.2)/0.01% Na-deoxycholate) to concentrations of 0.4 μg/mL for IL-6, IL-8, IL-10 and 0.5 μg/mL for TNF alpha, S-100, procalcitonin and E-Selectin. The proteins CRP and neopterin conjugated to BSA were diluted in printing buffer “cb” (1× PBS (pH 7.2)/0.005% CHAPS, 0.01% BSA) to concentrations of 0.5 mg/mL each. The appropriate spotting conditions  were established in previous research . The pro2.4.S-100 protein was conjugated to BSA to improve immobilization on ARChip Epoxy. The conjugate was prepared by incubating 100 μL S-100 (0.5 mg/mL Stock) with 1 mg EDC for 10 min on an orbital shaker. An additional 10 μL BSA (5 mg/mL) were added and the reaction was allowed to proceed for 4 h. Zero to 218.7 ng/mL S-100-BSA-conjugate in buffer “cb” was then spotted onto the chip.2.5.2, 100 mM NaCl, 0.1% Tween in a ratio of 1:10. This corresponds to 20 μL patient serum sample diluted with 180 μL Tris buffer for the classical chip and 4 μL patient serum sample diluted with 36 μL Tris buffer for the miniaturized chip.Surface blocking was performed for 30 min in 1× PBS (pH 7.2)/0.1% Tween 20 in order to remove any unbound probes and to deactivate reactive surface groups. Slides were washed twice in 1× PBS (pH 7.2) and dried using compressed air. Assay buffer used consists of CRP free human serum and 0.1 M Tris (pH 7.4), 10 mM CaCl2.5.1.The protocol of the “classical sepsis chip” has been introduced before . BrieflyCalibration standards were prepared by serial dilution of mixes of analytes in CRP-free serum and diluted with assay buffer 1:10. For the so called “external calibration” nine spiked standards were applied. After washing three times with 1× PBS (pH 7.2)/0.1% Tween-20, slides were incubated for 45 min with 50 μL biotinylated antibody mixes with end concentrations of 1 μg/mL each. After washing three times, slides were incubated with 4 μg/mL Dy647 streptavidin for 45 min. All incubation steps were carried out on the orbital shaker  at maximum speed at room temperature. Slides were washed and dried using compressed air and stored in the dark until scanning.2.5.2.While the classical chip was processed in the FastFrame that provides wells that are 7 mm in length and width the low volume chip was arranged in silicon miniwells  with incubation chambers of 4.5 mm in diameter. Those wells were small enough for a sample of 10 μL to completely cover the wells harboring the arrays. 10 μL patient serum sample or standard dilution series diluted 1:10 with assay buffer was incubated for 2.5 h in a humid chamber on the magnetic stirrer  at 450 rpm to allow sample mixing. The standard dilution series was spiked with appropriate amounts of antigen, biotinylated antibodies (1 μg/mL) and strep.MPs. (4 μg/mL). Detection occured via labeling with a biotinylated antibody against Cy3/Cy5 and Cy3 labeled streptavidin (1 μg/mL each). Slides were washed and dried using compressed air and stored in the dark until scanning.2.6.ex: 635 nm, λem: 670 nm) were recorded using the Genepix 4000B non-confocal scanner . Data were analyzed with the Genepix 6.0 software. The photomultiplier tube (PMT) voltage was held constant throughout the scans for each analyte to allow data comparison.Fluorescence signals  were excluded. Standard curves were set up with GraphPad Prism 5.0 using the five parameter logistic fit.50 value  is defined as the concentration halfway between the zero point and the upper asymptote when the value of the asymmetric factor is 1. The limit of detection (LOD) is defined as lowest concentration that can be detected and was calculated by the mean zero concentration + three standard deviations (SD) of the blank [inter% = SD/mean × 100) and the intra-array variability to the variation within one array (CVintra% = SD of one triplicate/mean of one triplicate × 100). Recoveries were calculated to identify the accuracy of the assay displaying the % relation between the calculated concentrations and the expected concentrations.The IChe blank . The limhe blank . The int3.3.1.50 values, CVs and LODs of the resulting calibration curves were defined as criteria for assay performance. The assay designs used in the classical and miniaturized chip are presented in To prevent excessive blood withdrawal from newborns the sepsis chip was miniaturized by applying a fivefold reduced sample volume. The main challenge in the realization of the miniaturized protein chip was developing the appropriate incubation and stirring system to maintain good assay performance with respect to sensitivity, reproducibility and accuracy. IC50 value was taken as evaluation parameter since it lies within the ascending slope providing the highest precision of the measurement and a good reference point for comparison of different treatments. For the classical chip the IC50 values for IL-6, S-100, E-Selectin and CRP are 46 pg/mL, 10 ng/mL, 170 ng/mL and 4.7 μg/mL respectively, while for the miniaturized chip they were 82 pg/mL, 19 ng/mL, 202 ng/mL and 2.5 μg/mL. This demonstrates that reduction of the sample volume leads to losses in sensitivity. Obviously, sample volumes of 10 μL are too small to be properly mixed on the orbital shaker during incubation. Thus, strep.MPs were implemented as so-called stirring detection reagents in the assay to accelerate the antibody antigen kinetics. Acceleration of diffusion processes is a common issue and magnetic particles have been previously outlined as successful tool to provide sample mixing in microscale devices [et al. [et al. [50 values . devices , 22. In  [et al.  reported [et al.  used ant [et al.  and anti [et al.  magneticNano-sized and micro-sized strep.MPs  were applied to the miniaturized assay to assess potential concerns about steric hindrance, but the assay performance was similar no matter what particle size was used.Comparison of the miniaturized protein chip with and without strep.MPs shows that sensitivity is increased by a factor of 2 (for E-Selectin and CRP) to 4 (for IL-6 and S-100) through the addition of strep.MPs. In Section 3.2.1 this method will be further advanced in that fluorescent strep.MPs will be implemented as stirring detection reagent.3.2.3.2.1.et al. [As outlined in et al.  showed t3.2.2.50, CV and LOD as measures for the assay performance. While for the detection of IL-6, S-100 and E-Selectin sandwich immunoassays were performed, a binding inhibition test was done for CRP. To guarantee a fast and effective treatment of the disease, a rapid diagnosis and thus short assay times are essential. However, in order to achieve short assay times, a compromise must be made between incubation time, assay sensitivity and data reproducibility. In order to determine the lowest incubation time necessary to perform a sensitive and accurate chip analysis three different incubation times were tested and evaluated using IC50 values. IC50 values are listed in 50 is similar for IL-6 and E- Selectin after 2 h and 2.5 h incubation, there are significant differences observed for S-100 and CRP. Sensitivity was drastically reduced for all tested biomarkers, if incubated for only 1.5 h. Interestingly, reproducibility of data was not affected and remained the same (CV < 14%) regardless what incubation time or analyte was used.In summary, a 2 h incubation step is most likely sufficient for the diagnosis of neonatal sepsis. While assay sensitivity remains unchanged for IL-6 and E-Selectin, assay sensitivity is slightly decreased for S-100 and for CRP. For diagnostic purposes the right balance between incubation time and sensitivity has to be specified individually according to the clinical requirements.3.3.The optimized low volume protein chip as described in Section 3.2 was tested for quantification of “patient” samples and evaluated in a recovery experiment. The assay performance was assessed by recovery values calculated as the relation of interpolated and expected concentrations. Recoveries that lie within 70 and 130% are considered as acceptable in clinical diagnosis indicating reasonable accuracy of the assay . Three “Mean intra-array variations of 11.8%, 10.3%, 12.4% and 13.3% for IL-6, S-100, E-Selectin and CRP respectively are obtained. Average inter-array variability of the four tested markers was 11.7% which indicates a good chip-to-chip reproducibility. Figures of merit are summarized in 3.4.For calibration of the protein microarray and quantification of the unknown sample a standard dilution series was prepared for each assay . To do so, nine spiked antigen mixes replicated four times were applied to 36 wells. This leaves 12 wells for patient samples  when using a set of four slides. To reduce the effort and further simplify the protein-chip the calibration was directly integrated on the chip . Several attempts to provide a one patient, one biochip format have been made by immobilization of the protein  or the d50 3.38 ng/mL, CVinter 12%; external calibration: LOD 0.241 ng/mL, LOQ 0.976 ng/mL, IC50 2.84 ng/mL, CVinter 13%). 2) of 0.968) was observed: most values cluster within the 95% confidence band (grey dotted lines) of the fit line. The significance of the linear correlation is confirmed by a p-value below 0.01%. The mean intra-array variation was 10.4% for the external and 10.8% for the internal calibration.The calibration curves are almost identical both in terms of shape and maximal signal intensities which is in accordance with the assay parameters obtained  were processed on the chip to evaluate the accuracy of the calibration curves calculated from the %-relation between interpolated concentrations and expected concentrations. The recoveries obtained were 70% and 103% when interpolating to the external calibration and 70% and 83% when interpolating to the internal calibration. The recoveries are within 70–130% which is appropriate for clinical purposes.4.We have presented herein a protein chip that fulfills the requirements for point-of-care diagnostics in terms of miniaturization, assay time and internal calibration. A sample volume of 40 μL which corresponds to 4 μL patient serum sample diluted 1:10 with assay buffer is sufficient to quantify sepsis associated serum proteins. The optimized low volume chip is especially attractive for diagnosis in neonates since the reduced sample volume minimizes stress and pain caused through excessive blood withdrawal. Sample mixing to overcome diffusion limitations is ensured through the addition of streptavidin coated magnetic particles (strep.MPs) acting as both stirring and detection components. Fluorescence labeling of the streptavidin coated magnetic particles further accelerates and simplifies the assay assembly resulting in a single step assay that is accomplished within 2.5 h. We demonstrated that for some analytes (exemplarily shown for IL-6 and E-Selectin) an incubation time of 2 h is sufficient to allow sensitive and accurate quantification. For some analytes (exemplarily S-100 and CRP) shortening of the incubation time to 2 h accounts for decreased sensitivity calling for variation of the incubation time according to the requirements with respect to assay sensitivity and assay time. The establishment of an internal calibration makes the protein chip even more attractive for point-of-care applications since it further simplifies the device in terms of quality control and handling. The low volume protein-chip allows accurate determination of the sepsis biomarkers with good reproducibility (CV < 14%). Recoveries are within the clinically acceptable range (70–130%).


We aimed to describe haemodynamic changes when haemodialysis is instituted in the critically ill. Three hypotheses are tested: (1) the initial session is associated with cardiovascular instability; (2) the initial session is associated with more cardiovascular instability compared to subsequent sessions; and (3) looking at unstable sessions alone, there will be a greater proportion of potentially harmful changes in the initial sessions compared to subsequent ones.Data were collected for 209 patients, identifying 1,605 dialysis sessions. Analysis was performed on hourly records, classifying sessions as stable/unstable by a cut-off >±20% change in baseline physiology (HR/MAP). Data from 3 hours prior to and 4 hours after dialysis were included, and average and minimum values derived. Three time comparisons were made . Initial sessions were analysed separately from subsequent sessions to derive two groups. If a session was identified as being unstable, then the nature of instability was examined by recording whether changes crossed defined physiological ranges. The changes seen in unstable sessions could be described as to their effects: being harmful/potentially harmful, or beneficial/potentially beneficial.P = 0.68, reinforcing the lack of significant variance.Discarding incomplete data, 181 initial and 1,382 subsequent sessions were analysed. A session was deemed to be stable if there was no significant change (>±20%) in the time-averaged or minimum MAP/HR across time comparisons. By this definition 85/181 initial sessions were unstable . Therefore Hypothesis 1 is accepted. This compares to 44% of subsequent sessions (95% CI 41.1 to 46.3). Comparing these proportions and their respective CI gives a 95% CI for the standard error of the difference of -4% to 10%. Therefore Hypothesis 2 is rejected. In initial sessions there were 92/1,020 harmful changes. This gives a proportion of 9.0% (95% CI SEM 7.4 to 10.9). In the subsequent sessions there were 712/7,248 harmful changes. This gives a proportion of 9.8% (95% CI SEM 9.1 to 10.5). Comparing the two unpaired proportions gives a difference of -0.08% with a 95% CI of the SE of the difference of -2.5 to +1.2. Hypothesis 3 is rejected. Fisher's exact test gives a result of Our results reject the claims that using haemodialysis is an inherently unstable choice of therapy. Although proportionally more of the initial sessions are classed as unstable, the majority of MAP and HR changes are beneficial in nature.


Identify epilepsy-associated factors and calculate measures of impact, stigma, quality of life (QOL), knowledge-attitude-practice (KAP) and treatment gap in Prey Veng, Cambodia.This first Cambodian population-based case-control study had 96 epileptologist-confirmed epilepsy cases and 192 randomly selected matched healthy controls. Standard questionnaires, which have been used in similar settings, were used for collecting data on various parameters. Univariate and multivariate regression was done to determine odds ratios. Jacoby stigma, 31-item QOL, KAP etc were determined and so were the factors associated with them using STATA software. Treatment gap was measured using direct method.Multivariate analyses yielded family history of epilepsy, difficult or long delivery, other problems beside seizures , and eventful pregnancy of the subject's mother as factors associated with epilepsy. There was high frequency of seizure precipitants esp. those related to sleep. Population attributable risk (%) was: family history (15.0), eventful pregnancy of subject's mother (14.5), long/difficult birth (6.5), and other problem beside seizures (20.0). Mean stigma  was mainly related to treatment efficacy. Mean QOL  was mainly related to treatment regularity. Cause or risk factor could be determined in 56% of cases. Treatment gap was 65.8%.Factors in pre- and perinatal period were found to be most crucial for epilepsy risk in Cambodia which inturn provides major prevention opportunities. A global action plan for treatment, stigma reduction and improvement of QOL should be set-up in this country. Medical and social domains of epilepsy in Cambodia are poorly investigated. Based on a first-ever large population-based door-to-door representative study (N = 16510), the lifetime prevalence of epilepsy in Prey Veng province is 5.8/1000 This population-based study was conducted in Prey Veng province and was an extension of the earlier population-based epilepsy prevalence study that was conducted in the same population To determine case histories and KAP, we used detailed questionnaires that are already used in several population-based surveys in similar REP settings. Information on stigma was derived using the Jacoby stigma questionnaire There were 96 cases and 192 matched controls. There were slightly more (53.1%) male epilepsy cases and the median age of the cases was 24.0 years, SD±13.6, range 3–70. Those <20 years represented 65.6% of the cases and the most frequent age group was 12–20 years (30.2%). On the other hand, 53.2% controls were males and the median age of controls was 28.0 years . Five (2.6%) controls had some health problem, namely two subjects with chronic headache and one subject each with sleep disturbance, gastric ulcer, and weakness. All controls had a normal neurological clinical exam.Generalised epilepsy consisted of tonic-clonic seizures (76.0%), absence (1.0%) and myoclonic seizures (3.1%) whereas partial epilepsy consisted of simple and complex partial seizures (12.5%), and olfactory partial seizures (1.0%). Mixed seizures consisted of 6.2% cases and 0.2% cases remained unclassified.Factors associated with epilepsy and their respective odd's ratios are provided in We enquired about several seizure precipitants among our cases and their presence was positively reported in the following manner: having seizures within one hour of awakening from sleep (18.7%), lack of sleep (18.6%), during sleep (16.4%), stoppage of treatment (13.1%), emotional disturbance (12.0%), alcoholism (5.4%), menstruation (4.3%), and hyperventilation (3.1%). Rest did not report any seizure precipitant.The difference in proportions of various risk factors between case and control population was calculated. Excess proportion of risk factors was observed among cases than controls in the following manner: abnormal pregnancy of the subject's mother  followed by other problem beside seizures , long or difficult birth  and family history of epilepsy .Case fraction (CF) is the proportion of exposed among total study population. These fractions were calculated for various risk factors in our population and were: 14.5% (95% CI 3–50) from positive epilepsy family history, 10.0% (95% CI 4–21) from eventful pregnancy of the subject's mother, 6.2% (95% CI 4.7–7.5) from long or difficult birth, and 7.6% (95% CI 5.9–8.2) from other problems beside seizures .The Attributable risk indicates the amount of epilepsy that can be attributed to a factor among the group exposed to a risk factor. The fractions (in %) for various risk factors in our population were: 66.6% (95% CI 50–86) from positive epilepsy family history, 89.8% (95% CI 85–92) from eventful pregnancy of the subject's mother, 88.2% (95% CI 83–93) from long or difficult birth, and 92.6% (95% CI 88–95) from other problems beside seizures . These figures indicate that 66.6–92.6% of those exposed to one of these factors could avoid having epilepsy as outcome.The population attributable risk percentage (PARP) expresses the increase of risk in the general population (over that for a population which had no exposure) which is due to the exposure. It is the measure of weight of risk factor on the occurrence of a disease and in turn indicates the proportion of cases that can be eliminated from the total population if the factor is eliminated. We calculated the attributable risk for each factor that we obtained by using standard formula for case-control studies. We obtained population attributable risk of 15.0% (95% CI 4–51) from positive epilepsy family history, 14.5% (95% CI 7–27) from eventful pregnancy of the subject's mother, 6.5% (95% CI 1–21.0) from long or difficult birth, and 20.0% (95% CI 9–41.0) from other problems beside seizures . This risk also implies that the relation of these factors with epilepsy is causal at least statistically and overall in Cambodia a cause/risk factor can therefore be evidently determined in at least 56.0% of cases. Causal Pie Model for population of Cambodia is given in KAP , precipitants (sleep disturbance p = 0.05), seizure type (tonic-clonic p = 0.05), quality of life , treatment .We enquired about stigma by using three-question jacoby scale . The meaKnowledge: In our population about half of cases (53.6%) considered epilepsy as contagious. Hereditary (41.5%), saliva (21.5%), sharing food plate , rubbing shoulders or shaking hands (5.8%), gas emission (1.9%) and others (3.9%) were reported to be possible sources for contagion. Most (84.3%) cases considered their epilepsy as treatable and mainly by modern medicines (91.5%). Origin of epilepsy was largely unknown (56.3%) or natural (43.7%) and none of our cases reported origin of their epilepsy as supernatural. Attitude: Others were reported to be highly protective of cases (98.9%), education and marriage respectively was considered possible by 68.7% and 33.3% of cases. Limitation in marriage possibilities was considered to be due to hereditary nature of epilepsy (53.9%), fear of contamination (23.8%), inviting bad luck (15.8%) and fear of seizure (6.5%). Twenty-two (22%) cases reported taboos: fear of contamination (52.4%) and inviting bad luck (47.6%). Practice: Seizures were reported to interrupt work (63.5%) or to practice sports (30.3%) but they were reported to not interrupt travelling (47.9%), attending social functions (79.1%), talking with others about their epilepsy (57.2%), or sharing same smoke pipe and food plate (75%).Details are presented in All cases were enquired about their treatment history. Traditional treatment was being used by 18.7%  and was mainly prescribed by subject himself (40.0%) or by traditional healer (53.3%) or someone else (6.6%). Traditional treatment was mainly herbal (60%) and nature of treatment for rest was mineral, mixed or unknown. None had animal product based treatment. Only 4 cases (26.6%) were taking traditional treatment regularly and its efficacy (subject's view) was good (6.6%), moderate (13.3%), bad (46.6%) or indeterminable (33.3%). Modern treatment was being used by 34.3% cases . Out of these, 42.2% were taking modern treatment regularly and its efficacy (subject's view) was good (21.2%), moderate (54.6%), bad (18.1%), or none and unknown in 6.0% cases. Forty-three percent (43%) were not on any treatment and treatment type was unknown in 4.1% cases. The treatment gap was 65.8%.worry QOL ; cognition QOL . Factors that were considered to be nearly significant were the following: cognition QOL , medication QOL .The QOL using QOLIE-31 is measured on a scale from 0 to 10, with 10 representing the best possible quality of life and 0 representing worst possible quality of life. The median overall QOL was 5.0 (SD±1.4), We conducted a first-ever large representative population-based matched case-control study in Cambodia that had epilepsy as a primary objective and used robust case-finding methods. All epilepsy cases were confirmed by epileptologists and each case had two matched controls randomly selected from the same source population. We aimed to identify factors that might have been associated with epilepsy in this population and in multivariate analysis, most of our risk factors were maternal-child-health related signifying the importance of this period for risk of having epilepsy. These factors are not different with results from other populations that had predominant generalised seizures  and epilepsy onset at a young age Factor that was most significantly  found was «other problems beside seizures» and this mainly included mental retardation and hyperthermia. Mental retardation is independently associated with the risk of having epilepsy Other factors that we obtained in our results were also pre- and perinatal such as eventful pregnancy of the subject's mother and long or difficult birth. These factors are independently and causally related to the development of lifetime and active epilepsy A positive family history increases the risk to have epilepsy by two- to three-fold Even though most seizures are considered to occur spontaneously, they can be precipitated by several endogenous or exogenous (seizure inducing and seizure triggering) factors. We enquired about presence of seizure precipitants and many cases reported a presence of seizure precipitants. Our frequency of precipitating factors is much higher than other studies rd of epilepsy individuals vis-a-vis thwarting concealment due to fear of stigma or of anxiety, shame or self-exclusion etc. Stigma is often associated with epilepsy Epilepsy since long is considered to be a contagious disorder and in our study nearly 54% cases reported epilepsy as a contagious disorder, mainly through hereditary route (41.5%), saliva (21.5%), sharing food plate (17.6%), sexual route (7.8%), rubbing shoulder/shaking hands (5.8%). However, some of the contagions reportedly observed in other populations were not reported by our population for instance reporting of breath, urine, faeces, blood, sperm and genital secretions as contagions Median overall QOL in our population was 5.0±1.4, The score for seizure worry was (36.3±22.1) lowest and highest for medication effects (median score of 83.3±24.0), a pattern that is also seen in nearby Asian populations Treatment gap that is observed in our population is not different from some populations although much lower than some other populations such as Pakistan, Laos etc Strengths of this study lies in its population-based design and use of standard procedures for epilepsy cases and their controls. Results from all major aspects of epilepsy are addressed in this study. Weakness of our study is similar to other case-control studies conducted in such settings due to the possibility of recall bias.This study identified challenges and opportunities for Cambodia in relation to epilepsy, Our results show that in at least 56.0% of cases the causative or risk factor can be evidently determined in Cambodia. The epilepsy-associated factors  obtained in this population are preventable in nature. These factors thus provide opportunity for prevention by at least 41.0% should exposure to these risk factors is eliminated in the general population of Cambodia. Prevention of epilepsy can be aimed through strengthening of usual maternal and child health service (MCH). This prevention proportion matches with the results from other resource-poor populations through control of similar factors Consistent and sufficient treatment remains one major challenge particularly in many resource-poor populations. Since traditional healers are usually approached for treatment needs, by minority of cases in this population though, it might be necessary to engage them in case identification, ascertainment and their treatment in future studies. They might be essential to bridge the gap between treatment and the target population since it is likely that neither traditional nor modern treatment can sufficiently address all epilepsy individuals alone.


The objective of this study was to investigate the effect of beta blocker on cardiac recovery and rhythm during cardiac surgeries. Sixty surgical rheumatic heart disease patients were received esmolol 1 mg/kg or the same volume of saline prior to removal of the aortic clamp. The incidence of cardiac automatic re-beat, ventricular fibrillation after reperfusion, the heart rate after steady re-beat, vasoactive drug use during weaning from bypass, the posterior parallel time and total bypass time were decreased by esmolol treatment. In conclusion: Esmolol has a positive effect on the cardiac recovery in cardiopulmonary bypass surgeries. It has been well documented that early administration of beta-adrenergic antagonist during CPB or within 10 minutes after releasing of aortic clamp contributes to left ventricular function . Also, cThe study protocol followed the Declaration of Helsinki and was approved by the Ethics and Research Committee of Nanjing Medical University . The study was performed in a prospective randomized manner after all the patients signed written informed consents.60 rheumatic heart disease patients undergoing elective single mitral valve replacements were enrolled in our study. Patients were randomly assigned to two groups by a computer program. 30 patients received esmolol 1 mg/kg prior to removal of the aortic clamp, while 28 received the same volume of saline. 2 patients were excluded because of cardiopericarditis. The cardiac recovery of patients was assessed on the basis of:(1) the heart auto re-beat ratio (the heart beat returns spontaneously without ventricular fibrillation or a temporary pacemaker); (2) the recovery time (time from reperfusion to steady heart beat); (3) the ratio of atrial fibrillation during weaning; (4) Ventricular fibrillation after primary re-beat (5) heart rate after steady re-beat; (6) heart rate 10 minutes after re-beat, and (7) temporary peri-operative pacemaking, (8) vasoactive drug use during weaning from CPB. We also recorded the bypass associated time.The data were analyzed with the software SPSS 11.0. The quantitative data were expressed as mean ± SD, and the difference was compared using one-factor analysis of variance. The qualitative data were compared with chi-square analysis. Fisher's exact test was used when the minimum expected count was less than five. P < 0.05 was considered to be significant.Following esmolol treatment, the heart underwent re-beat automatically in 26 patients, as compared to 10 patients in the control group (P < 0.001). Ventricular fibrillation after primary re-beat happened in 9 cases in control but only 1 case in esmolol group (P = 0.005). The recovery durations were 4.1 ± 1.3 min in the treatment group, and 4.4 ± 1.5 min in controls (P = 0.407). The heart rate after steady re-beat was 89.6 ± 14.9 bpm in control but 49.9 ± 14.6 in treatment group (P < 0.001). The heart rate after successful re-beat 10 minutes later was 94.8 ± 14.3 bpm in control but 91.5 ± 10.5 in treatment group (P = 0.310). Atrial fibrillation was found in 11 cases in control and 10 cases in esmolol group (P = 0.786). Two of the control group required temporary pacemaker, compared to 3 patients in the treatment group (P = 1.000). Eleven patients in control group needed vasoactive drug during weaning from bypass while only three in esmolol group (P = 0.014). . The posterior parallel time (time from unclamping to weaning) was 29.6 ± 8.9 minutes in control group and 24.3 ± 7.8 minutes in esmolol group (P = 0.007). The bypass time was 69.9 ± 9.0 minutes in control group and 63.7 ± 10.9 minutes in esmolol group (P = 0.022). (Figure Our study found a positive effect of beta blocker on the prevention of ventricular arrhythmia in surgical heart disease patients. In addition, we also identified that esmolol increased the auto re-beat success rate, decreased the incidence of ventricular fibrillation after primary re-beat, and maintained better myocardial oxygen delivery and consumption balance without prolonging bypass time. On the contrary, esmolol treatment prior to removal of the aortic clamp decreased the posterior bypass time.Esmolol treatment did not increase the need for temporary cardiac pacemaker in order to maintain the target heart rate after bypass. Because it is a very short acting beta blocker, and it seldom depresses the heart rate or contractility when administered in the early stage. In addition, esmolol improved the cardiac recovery and the heart oxygen delivery and consumption balance, which increased the myocardial energy stores and thereby benefit for the weaning process.More and more physicians incline to use beta blocker to treat various arrhythmias including ventricular arrhythmia in non-surgical patients -11. And In conclusion, esmolol has a positive effect on the cardiac recovery in CPB surgeries.CPB: cardiopulmonary bypass; CABG: coronary artery bridge grafting.The authors declare that they have no competing interests.First author: SJ participated in the sequence alignment and drafted the manuscript.Second author: DZ participated in the design of the study and performed the statistical analysis.Correspondence author: QY conceived of the study, and participated in its design and coordination.All authors have read and approved the final manuscript.


These studies mostly rely on a limited number of monitors which introduces exposure error, and excludes rural and suburban populations from locations where monitors are not available, reducing generalizability and potentially creating selection bias.Many studies report significant associations between PM2.5 exposures on emergency hospital admissions of the elderly in the Mid-Atlantic region.We performed case-crossover analysis for each admission type, matching on day of the week, month and year and defined the hazard period as lag01 (a moving average of day of admission exposure and previous day exposure).Using prediction models developed by our group, daily PM2.5 exposure was estimated across the Mid-Atlantic . We then investigated the short-term effects of PM2.5 and hospitalization for all outcomes examined. For example, for every 10-µg/m3 increase in short-term PM 2.5 there was a 2.2% increase in respiratory diseases admissions (95% CI = 1.9 to 2.6), and a 0.78% increase in cardiovascular disease (CVD) admission rate (95% CI = 0.5 to 1.0). We found differences in risk for CVD admissions between people living in rural and urban areas. For every10-µg/m3 increase in PM 2.5 exposure in the ‘rural’ group there was a 1.0% increase (95% CI = 0.6 to 1.5), while for the ‘urban’ group the increase was 0.7% (95% CI = 0.4 to 1.0).We observed associations between short-term exposure to PM2.5 exposure was associated with hospital admissions for all respiratory, cardio vascular disease, stroke, ischemic heart disease and chronic obstructive pulmonary disease admissions. In addition, we demonstrate that our AOD  based exposure models can be successfully applied to epidemiological studies investigating the health effects of short-term exposures to PM2.5.Our findings showed that PM Using meta-regression, Zanobetti and colleagues examined whether this association was modified by season and community specific PM2.5 composition, after controlling for seasonal temperature as a surrogate for ventilation. They found that for every 10 µg/m3 increase in 2-day averaged PM2.5 exposure there was an increase of 1.9% (95% CI: 1.3 to 2.4) in CVD, 2.2% (95% CI: 1.1 to 3.4) in MI, 1.8% (95% CI: 1.3 to 2.5) in CHF, 2.7% (95% CI: 1.3 to 4.2) in diabetes, and 2.1% (95% CI: 1.2 to 2.9) in respiratory admissions.A key study conducted by Zanobetti and colleagues 2.5 and ultrafine particles (particulate matter with a diameter of less than 100 nanometres in diameter) on emergency hospital admissions for cardiac and respiratory diseases. More specifically, they evaluated the effect of PM exposures on emergency hospital admissions in Rome between 2001–2005 on acute coronary syndrome, heart failure, lower respiratory tract infections, and COPD. PM data were collected daily at one central fixed monitor. Data were analyzed with a case-crossover analysis using a time-stratified approach. Belleudi and colleagues reported an immediate impact of same-day to exposure to PM2.5 on hospitalizations for acute coronary syndrome of 2.3% (95% CI: 0.5% to 4.2%) and an increase of 2.4% for heart failure (95% CI: 0.3% to 4.5%). The effect on lower respiratory tract infections showed an increase of 2.8% (95% CI: 0.5% to 5.2%) for a 2-day lag.Belleudi and colleagues 2.5 data was available only for one in three or one in six days. In addition, all these studies were limited to populations living close to monitoring stations and thus did not include individuals living in suburban and rural areas where no monitoring stations were available. Further, geographic differences in the daily variability of exposure were usually not captured.Most previous studies have been limited by the lack of high spatial and temporal resolution of daily exposure data. For many of the previous US studies PM2.5 exposures for epidemiological studies, and applied it to data from the Mid-Atlantic region of the U.S. 2.5 on a daily basis throughout the Mid-Atlantic states. In this paper, we use our model generated predictions to study the association between short-term PM2.5 exposure and emergency hospital admissions among elderly (aged 65 and older) included in the Medicare program across the Mid-Atlantic region. Medicare is a national social insurance program, administered by the U.S. federal government since 1966,that guarantees access to health insurance for Americans aged 65 and older. We take advantage of our geographic resolution to examine the effect of space dependent modifiers such as poverty or education, as well as effect estimate differences between more and less urbanized settings. In addition, our study investigates the entire population of a region, rather than selected locations near monitoring sites as commonly done in previous studies.We have recently presented a new method of assessing temporally- and spatially-resolved PMThis study was approved by the institutional review boards of the Harvard School of Public Health. The US Medicare data is previously collected administrative data and does not require individual patient consent. All Hospital admittance records were anonym zed.The presented study’s spatial domain included the Mid-Atlantic region comprising of Washington D.C., and the states of Delaware, Maryland, New Jersey, Pennsylvania, Virginia, New York and West Virginia .2 with a population of 57,999,568. The average size of population in the Mid-Atlantic zip codes for the general population is 9095 and 1246 for people 65 and over. The median zip code population is 2818 for the general population and 420 for people 65 and over. Around 36.2% of the Medicare population in our analysis  live within 30 km of a monitor station (more ‘urban’ areas) while 63.8%  live farther then 30 km from a monitoring station . In general the ‘rural’ population is poorer with lower median income levels of $37,327 compared to $49,928 in the ‘urban’ areas and lower levels of education, with only 13.9% of people holding bachelor level degrees compared to 23.0% in the ‘urban’ areas. The data cover an area of 495,486 km2.5 exposures for the years 2000–2006 were assessed using our recently developed prediction models 2.5 predictions at a 10×10 km spatial resolution across the study area  and IMPROVE  monitoring networks and AOD data from the Moderate Resolution Imaging Spectroradiometer (MODIS) satellites. We also incorporated land use regression  and meteorological variables . In stage 1 of the model, we calibrate the AOD grid-level observations to the PM2.5 monitoring data collected within 10 km of an AOD reading. The first stage of the model consists of a mixed model for observed PM2.5 (containing both fixed and day-specific random effects for the intercept), the AOD slopes, and the temperature slopes. We then incorporate the additional spatial, temporal (daily), and spatio-temporal covariates as predictors in the PM2.5 model. To accommodate the fact that daily AOD data missingness is not random, the first stage model incorporates inverse probability weighting (IPW) to potentially prevent bias in the regression coefficient estimates and thus in the resulting estimations. To accommodate the fact that the PM-AOD calibration factors can vary spatially between large regions, we divided the Mid Atlantic area into regions. The intercept, AOD, and temperature random effects in the model are nested within regions of the study. In stage 2 of the model, we estimate PM2.5 concentrations in grid cells without monitors but with available AOD measurements using the stage 1 fit. Finally, in stage 3 of the model, we estimated daily PM2.5 concentration levels for all grid cells in the study domain for days when AOD data were unavailable. Using the PM2.5 predictions obtained from the first stage of the model as the response, we fit a model containing a smooth function of latitude and longitude (of the grid cell centroid) and a random intercept for each cell. This is similar to universal kriging, extended to include the mean of the PM2.5 monitors on that day  and random cell-specific slope. To allow for temporal variations in the spatial correlation, a separate spatial surface was fit for each two-month period of each year. Using this method provides additional information about the concentration in the missing grid cells that simple kriging would not. To validate our model, we repeatedly divided the data randomly into 90% and 10% splits. Predictions for the held-out 10% of the data were made from the model fit of the remaining 90% of the data. This “out of sample” process was repeated ten times, and cross-validated (CV) R2 values were computed. Even for location-day combinations without AOD data our model performance was still excellent (mean out-of-sample R2 = 0.81). Both the stage 1 and stage 3 models yielded very small predictions errors (RMSPE - Root of the mean squared prediction errors) −1.1 µg/m3 and 1.4 µg/m3 respectively, indicating a strong model performance. Further, CV results revealed no bias in the predicted concentrations (Slope of observed vs. predicted = 0.97–1.01).We used ground PM2.5 exposure estimates were generated by our prediction models. These PM2.5 daily predictions were matched to zip codes using ArcGIS and SAS based on spatial location and date. For more detailed information on the prediction model please refer to Kloog et al PMIndividual hospital admittance records were obtained from MEDICARE and cover hospitalization for all residents of age 65 and older, for all available years (2000–2006). We defined cases as those with an emergency admission and a primary discharge diagnosis using ICD-9  for all respiratory (ICD 9 460–519), CVD (ICD 9 390–459), IHD (ICD 9 410–414),COPD (ICD 9 490–496) and stroke (ICD 9 434) related admissions. These records included information such as age, sex, date of admission, race/ethnicity, and zip code of residence.2.5 to compare to previous studies We choose broader areas for the leading admission causes  since one would expect the broader admission data to produce less noisy estimates for two reasons. First, the counts are higher and therefore there is more power to examine CVD admissions. Secondly, studies of misdiagnosis in hospital administrative records show that the broader the categories, the less the amount of misclassification. We also were interested in specifically looking at the COPD and stroke admissions sub category associations with PMSocioeconomic variables were obtained through the US Census Bureau from the 2000 social, economic and housing characteristics datasets ocioeconomic variables used included the following zip code level information: Percent of minorities, age, education (people with no high school education) and median income.Temperature data were obtained through the National Climatic Data Center (NCDC) Zip code-specific admissions were matched with our exposure estimates for each 10×10 km grid cell. We used a case-crossover analysis approach, which was developed as a variant of the case-control design to study the effects of transient exposures on acute events 2.5 was included in the model as a potential confounder.The data were analyzed using conditional logistic regression . Temperature with the same moving average as PM2.5 association with admissions. In addition we examined interactions between exposure and both income level (low vs high income groups) and gender.Case-crossover analyses lend themselves to the analysis of effect modification and thus we looked at several interactions. Specifically, in the largest admission group (CVD) we investigated whether the subject residence within 30 km of a monitor or farther than 30 km from monitor modified the PMTo investigate the robustness of our results, various sensitivity analyses were run on the CVD and all respiratory admissions. Specifically, we analyzed other averaging periods: lag02 (a moving average of day of admittance exposure and 2-days of previous exposure) and lag 0 (day of admittance exposure) vs. lag01 (a moving average of day of admittance exposure and previous day exposure). We also matched control days to be days within the same month and year, with the same temperature (rather than the same day of week), to control for temperature by matching rather than modeling Descriptive statistics are presented in 3 increase in PM2.5 by cause of admission. For example, for all respiratory admissions, we found a 2.2 percent increase in admissions (95% CI = 1.9 to 2. 6). For CVD admissions, we found a 0.8 percent increase (95% CI = 0.5 to 1.0). COPD, IHD and stroke all showed similar increase in admission rates  in the PM2.5 associations with CVD between people living closer to monitor areas (‘urban’ group) and farther away , between the income level groups (high and low) and small differences between the genders  and very similar in lag02 compared to the main lag01 analysis . The results from matching control days to be days with the same temperature resulted in very similar results to the main analysis. For CVD, we found a 1.0 percent increase in admission rate (95% CI = 0.6 to 1.3).The results from the sensitivity analysis were consistent with the primary analysis. Both for CVD and all respiratory admissions, when using lag0 or lag02 PM2.5 exposures generated by our novel prediction model and increased hospital admissions in an elderly population (aged 65 and older) in the Mid-Atlantic States. These associations were positive for all respiratory, CVD, COPD,IHD and stroke admission causes tested. We also found differences in the PM2.5 associations between people living closer to monitor areas and farther away, between the income level groups and small differences between the genders. The associations observed in our analysis are broadly consistent with the associations observed in many recent case-crossover analysis examining associations between short-term PM2.5 exposures and hospital admissions In this paper we examine associations between PM2.5 was larger in the less densely populated areas, which were not previously included in most analyses. This is of great importance to risk assessment studies since it may provide some evidence about the differential toxicity of fine particles between ‘urban’ and ‘rural’ Mid-Atlantic elderly populations. In less urban areas secondary particles, for example sulfate, represent a larger fraction of fine particle mass compared to those in urban areas. Acidic sulfate compounds such as ammonium bisulfate and sulfuric acid which are present in fine particles measured in the Mid-Atlantic region inter alia tumor promotion 2.5 exposures and hospital admissions. The use of our spatiotemporal model reduces exposure misclassification that may exists in, for example, time series studies that use a single exposure metric for daily exposure in an entire metropolitan area. Such error is a mixture of classical exposure error, which likely biases the effect estimates downward, and Berkson error, which increases the confidence interval To the best of our knowledge, this is the first time that all the population in the Mid-Atlantic area, and not just those close to monitors, have been included in an analysis of the association between PMThere are a few limitations in the presented study. The spatial resolution (zip codes for the Medicare data) are not individual addresses, but those are not available because of privacy concerns. In addition, the use of 10×10 km for the satellite data could be improved as well. However, as satellite remote sensing evolves and progresses, higher spatial resolution data (such as 1×1 km) should become available soon and will further reduce exposure error 2.5 exposures. In addition, we have demonstrated that our AOD-based exposure models can be successfully applied to epidemiologic studies investigating the health effects of short-term exposures to PM2.5. This is because these models make it possible to estimate spatially-resolved PM2.5 exposures for specific zip codes. In addition, they can be used to assess exposures for large regions which allows for the inclusion of both urban and rural populations. This provides more generalizable results for risk assessment.In conclusion, our findings indicate that hospital admissions for all respiratory, CVD, IHD, COPD and stroke were associated with PM


Differences in the incidence of hospital-acquired infections among European hospitals are due to a range of factors such as case mix, variable infection control policies and practices, and culture. The PROHIBIT study aims at inventorying and analysing national and local infection prevention policies and practices in Europe. The aim of this study is to test two interventions of proven efficacy, a hand hygiene (HH) improvement campaign and an extensive central venous catheter (CVC) bundle, in reducing CVC-related bloodstream infection (CRBSI).Fourteen hospitals from 11 countries take part with ≥ one intensive care units (ICU) since January 2011. Primary outcome is CRBSI, secondary outcomes compliance with HH and the CVC bundle. After a baseline of 6 months, every 3 months 3 hospitals were randomized to implement one or both interventions following a stepped wedge design. The last 2 started in July 2012 and the study ends in June 2013. The HH strategy followed the World Health Organization guidelines while the CRBSI prevention strategy is based on a successfull programme of the University of Geneva hospitals.The mean  baseline CRBSI rate was 2.5/1000 CVC days (2.2-2.8) with an interhospital range of 0.0-10.0. The incidence of most CVC bundle hospitals was ≤1.0 at baseline already. The mean rate upon the intervention was 0.9 . The mean baseline CVC bundle compliance of 4.3% increased to 40.6% for all hospitals. The mean baseline HH compliance of 48.6% (range: 16.9-67.1), improved to 60.0% for all hospitals (range: 36.1-85.3). Multivariate Cox regression, stratified per hospital, revealed that the HH intervention alone and both interventions combined were associated with reduced CRBSI incidence densities (HR 0.4 and 0.5 respectively).Our findings confirm variation of CRBSI incidence densities among European ICUs. The interventions appear effective particularly in hospitals with higher baseline rates. This needs to be confirmed in the final analysis including competing risks and sensitivity analyses.None declared.


Results. There were found, in the group of adenocarcinoma tubulare, SUVmax 1.5–23.1 (7.46 ± 4.57), in mucinous adenocarcinoma, SUVmax 2.3–10.3 (5.5 ± 2.4), in undifferentiated carcinoma, SUVmax 3.1–13.6 (7.28 ± 3.25), in adenocarcinoma partim mucocellulare, SUVmax 2–25.3 (7.7 ± 6.99), and, in normal gastric wall, SUVmax 1.01–2.55 (1.84 ± 0.35). For the level of 2.6 cut-off value between the normal wall and neoplasm FLT uptake from ROC analysis, all but five gastric cancers showed higher accumulation of FLT than noninfiltrated mucosa. Conclusion. Gastric cancer presents higher accumulation of 18F-FLT than normal, distended gastric mucosa. Significantly higher accumulation was shown in cancers better differentiated and with higher cellular density.The aim of the study was to evaluate the usefulness of 18F-FLT PET/CT in the detection and differentiation of gastric cancers (GC). 104 consecutive patients (57 cases of adenocarcinoma tubulare (G2 and G3), 17 cases of mucinous adenocarcinoma, 6 cases of undifferentiated carcinoma, 14 cases of adenocarcinoma partim mucocellulare, and 10 cases of end stage gastric cancer) with newly diagnosed advanced gastric cancer were examined with FLT PET/CT. For quantitative and comparative analyses, the maximal standardized uptake value (SUV Gastric cancer (GC) is an aggressive neoplasm with very poor prognosis. In Poland, in 2010, a number of 5364 people died (3486 men and 1878 women) due to gastric cancer. During the last 4 decades, both morbidity and mortality have dropped significantly in Poland from the 1st place at the beginning of the 1970s to the 4th most common cancer related death in men and the 7th in females FLT uptake in the normal gastric wall the SUVmax was measured in the area of normal gastric wall indicated on the basis of gastroscopy in 25 out of 104 patients in the study. The number of patients was limited to 25, as it was sufficient to further statistical analysis.In order to assess the [18F]FLT was synthesized in our laboratory using R&D Syncrom module (Raytest) following the standard operating procedure (SOP). Radiosynthesis of [18F]FLT is based on [18F]fluoride displacement of a protected nosylate precursor. A simple three-step synthesis was used to prepare radiochemically pure [18F]FLT—98% ± 0.98%, at the end of synthesis within 45 min and with a 15% ± 7.6% radiochemical yield.FLT (3′-Fluoro-3′deoxythymidine-) PET. They have compared the accumulation of FLT and FDG in gastric cancer and showed that FLT PET was more sensitive than FDG PET, especially in tumors with no or low FDG uptake. This publication opened the new era in the stomach cancer PET diagnostics, but the authors concentrated only on the primary advanced tumors. Presented above data and results of other studies suggest that FDG is not ideal tracer for this type of cancers.The asm only . Kawamurasm only  analyzedasm only  evaluateasm only  publishe18F-FDG PET in the diagnosis of gastric cancer concluded that FDG uptake is lower in nonintestinal than in intestinal Lauren type tumors. They described that only 60% of locally advanced GC were detected by FDG PET, but even 83% of intestinal type tumors were PET positive, when only 41% of diffused ones were seen. We found also lower accumulation of 18F-FLT in nonintestinal gastric cancers—mean SUVmax = 6.84 versus 7.69 found in intestinal type tumors, but the difference was not statistically significant. It can suggest that cell proliferation is higher in intestinal GC Lauren type. The results Stahl et al. described for FDG PET were the same as those we found for FLT PET, showing higher uptake in nonmucus-containing GC with FLT SUVmax = 7.27 versus 5.50 in mucinous adenocarcinoma. In this work, FDG SUVmax was 7.2 in nonmucinous neoplasms versus 3.9 in mucus-containing ones. It can show that not only metabolic increase characterizes solid GC but higher cell proliferation as well. The uptake of both FDG and FLT was also higher in low-grade GC than in high-grade cancers. The differences were statistically significant for both radiopharmaceuticals . We showed that detection of GC using 18F-FLT PET was successful in 89 out of 94 patients (95% sensitivity) with 5 false negative cases . In these 5 cases, the FLT uptake was within the range of noninvaded gastric wall, while, in all others, there was a great variety of SUVmax values. Only tumors with relatively lower cellular density (mucinous type) accumulated FLT significantly less than other ones. Histopathological types of gastric cancer donot reflect their ability to FLT accumulation which was supposed to be strongly related to cellular proliferation within the tumors. Kameyama et al. [max for FLT (7 ± 3.3) was significantly lower than that for FDG (9.4 ± 6.3)  even if it did not correlate with KI-67 index. This was not the case in FDG uptake, but the number of patients enrolled into the study counted only 21 patients. High-grade tumors are frequently necrotic, so the mean cellularity can be lower in low-grade cancers. In our paper, we showed that FLT SUVmax was significantly lower in cancers with lower cellular density—similar to results of Kameyama group. FLT uptake has been shown to be lower in cancer with higher mucinous content and probably lower cellularity (18.1% of patients with mucinous adenocarcinoma) but simultaneously higher in better differentiated tumors. It is suspected that FLT uptake is not a simple result of proliferation alone, but can use an additional mechanism related to nucleoside transporters. It should be carefully studied in further works. Due to possibility to indicate a low cohesive cancer type, we hope it can be useful in predicting prognosis, planning treatment, and monitoring response in patients with gastric cancer.Analyzing the pathomorphological cancer structure, we compared independently some present or absent features within the cancer types. Stahl et al.  in publia et al.  in his smax. The optimal cut-off value between the cancer and mucosal accumulation was found at the level of 2.6 with sensitivity of 95% and an acceptable FN ratio of 5%. FLT PET/CT accumulation is significantly higher in regions of higher cellular density and cellular proliferation as well as in better differentiated neoplasm.We found that all gastric cancer types presented higher mean accumulation of FLT when compared to noninfiltrated gastric wall as measured by SUV


Pulmonary complications are frequently occurring medical complications after aneurysmal subarachnoid hemorrhage (aSAH) . Early rWe conducted a retrospective study in 137 consecutively admitted patients with aSAH, admitted between October 2007 and October 2011 to the ICU of a university hospital. ERD was defined as increased need for ventilatory support the second or third day after admission (Table P = 0.14). ERD showed a trend towards an association with mortality . A clear association was found between absence of ERD and functional outcome with ordinal logistic regression analysisMean age of the patients was 55.9 (± 12.7) and 63.5% was female. A total 46.7% of the patients developed DCI. Mortality was 25.6%. Forty percent of the patients were classified as having ERD. ERD was not associated with DCI .(0.98 point increase in GOS score at 3 to 6 months; 95% CI = 0.14 to 1.82; ERD within 72 hours after admission is associated with increased risk of poor functional outcome after aSAH, but not DCI. Further investigations are required to assess whether prevention of ERD may improve outcome.