We aimed to determine the demographic and clinical features of patients with Behcet’s disease (BD) in Southeastern Turkey.In this study, files of 132 patients with BD  who were diagnosed with BD according to the International Study Group criteria at the Department of Dermatology of Dicle University Faculty of Medicine from 2005 to 2009 were evaluated retrospectively. Demographical and clinical characteristics of the cases were recorded.Mean age of the cases was 32.40 ± 9.4 years (range 15 - 59 years) and male/female ratio was 0.73. The mean age at diagnosis was 28.71 ± 9.1 years. Six cases were diagnosed as juvenile BD (4.45%). Oral aphthous lesions (100%) and genital ulcers (94%) were found to be the most common findings of the disease, followed by pathergy positivity (75%), papulopustular lesions (74.2%), erythema nodosum (43.2%), thrombophlebitis (6.8%) and extragenital ulcers (6.1%). Systemic involvement was noted as joint involvement in 79.5%, ocular involvement in 28.8%, vascular involvement in 9.8%, pulmonary involvement in 2.3%, neurologic involvement in 2.3% and genitourinary system involvement in 0.8%. There was no significant difference between mucocutaneous findings and systemic involvement ratios of male and female cases.Demographic and clinical features of BD may vary according to geographical region, gender and ethnicity. We hope that this study will contribute to the epidemiologic data of BD which may exhibit different clinical and demographic features in different parts of the world. Behcet’s disease (BD) is a chronic multisystemic disorder characterized by oral ulcers, genital ulcers, cutaneous lesions, ocular, articular, neurological and vascular involvement. BD most often affects patients in their second or third decade, but can occur at any age. There seems to be a little male predominance but this finding varies from country to country. Although this predominance is seen almost all over the world, it is more common in Turkey, Iran, Japan, Korea and China . In prevFiles of 132 patients who were diagnosed by the criteria of the International Study Group  of BD atOur study included 132 cases whose ages ranged from 15 to 59 years. The mean age of cases was 32.4 ± 9.4 years. The mean ages of males and females were 34.57 ± 8.68 years and 30.8 ± 9.51 years, respectively (P < 0.05). Seventy-six (57.6%) cases were female and 56 (42.4%) cases were male. Male/female ratio was 0.73. The most common age range was between 26 and 35 years (39.4%). Mean age is lower in female patients in BD. A comparison of the sexes for age revealed a statistically meaningful difference (P < 0.05).Age at onset of symptoms was 24.2 ± 9.1 years in females and 27.2 ± 8.4 years in males (P < 0.05). Age at onset of symptoms ranged from 8 to 54 years. Duration of disease in patients ranged from 1 to 16 years. The average duration of illness was 4.05 ± 2.9 years. The mean age at diagnosis was 28.71 ± 9.0 years. The ages at diagnosis of males and females were 30.8 ± 8.55 years and 27.17 ± 9.22 years, respectively (P < 0.05). Female and male patients were compared for the initial age of symptoms of the disease, with statistically meaningful differences (P < 0.05).Comparison of the ages of the patients by sex and the initial age of the symptoms, duration of the disease and diagnosis ages for BD is summarized in Patients with initial symptoms at age 16 years or younger were considered as having juvenile BD. In our study, the prevalence of juvenile BD was found to be 4.54% among patients with BD. Clinical features of juvenile cases are shown in Oral aphthae was observed in all of the 132 patients (100%). Oral aphthae was found in the form of minor ulcer in 73 (55.3%) patients, major ulcer in seven (5.3%) patients, and minor and major ulcer in 52 (39.4%) patients. The number of lesions was less than 5 in 93 (70.5%) patients, and between 5 and 10 (27.3%) in 36 patients. The frequency of attacks was found between 3 and 5 in 100 (75.8%) patients. A comparison of male and female patients for the number of oral aphthae showed less than five lesions in 43.4% of males and 79% of females. This difference was found to be statistically significant (P < 0.05). No statistically significant differences were found among sexes for the size of lesions, improvement time and frequency of attacks.Genital ulcer was determined in 124 patients (94%). Genital ulcers were detected in 93% (52/56) of male patients and 95% (72/76) of female patients. The initial symptom of BD was genital ulcer in three of the female patients. The most frequent locations of genital ulcers were 85% in the scrotum in the male and labiums and vulva in the female. There was genital scarring due to previous lesions in 55.3% of the patients. The prevalence of extragenital ulcers was found 6.1%. A comparison of male and female patients for the number and size of genital ulcer lesions, and the frequency of attacks found no statistically meaningful difference (P > 0.05) between them.Forty-three (32.6%) patients had a single genital ulcer lesion, and 81 (61.3%) had two or more genital ulcer lesions. Fifty-five (41.7%) patients experienced one attack, and 69 (52.2%) patients experienced two and more attacks annually. Seventy-three (55.3%) patients had scar tissues of former lesions. Cicatricial lesions of former lesions were seen more in male patients than in female patients and this difference was found to be statistically meaningful.Erythema nodosum was found in 57 (43.2%) patients. Erythema nodosum was more common in female patients, with no statistically meaningful difference (P > 0.05).Papulopustular lesions were found in 43 (76.7%) male and 55 (72.3%) female patients. A positive pathergy test was found in 42 (75%) male patients, and 57 (75%) female patients. No statistically meaningful differences were found between the sexes for papulopustular lesions and positive pathergy.Less common skin findings such as furunculosis in two male patients, Sweet’s syndrome-like lesions in one male and in one female, leg ulcers and stasis dermatitis in one male patient, and recurrent erythema multiforme-like lesions in one female patient were noted.Ocular involvement was noted in 38 (28.8%) patients (panuveitis in 25 (18.9%) patients, anterior uveitis in six (4.5%) patients, posterior uveitis and iridocyclitis in two (1.5%) patients, and intermediate uveitis, retinal vasculitis, retinal detachment and keratitis in one (0.8%) patient). Ocular symptoms such as decreased vision, burning, pain, itching and redness were found in 24.2% of patients.Of 105 patients (79.54%) with joint complaints, monoarthralgia was seen in 21 (15.9%) patients, oligoarthralgia in 39 (29.5%), polyarthralgia in 40 (30.3%), monoarthritis in 24 (18.2%), oligoarthritis in five (3.8%), and poliathrtitis in one (0.8%).Deep vein thrombosis was seen in five (3.8%) patients . There was superior vena cava thrombosis, superior vena cava syndrome and pulmonary thromboembolism in a female. There was osteonecrosis of the femoral head and abdominal aortic aneurysm in a female. A 22-year-old male with pulmonary involvement died due to massive pulmonary hemorrhage.Sixty-two (47.0%) patients had gastrointestinal tract complaints such as abdominal pain, indigestion, heartburn, diarrhea, nausea and vomiting, melena and/or hematochezia and weight loss.When family history was evaluated, 15 (11.4%) patients had BD, 24 (18.2%) patients had recurrent aphthous stomatitis (RAS) and four (3.0%) patients had both BD and RAS in their family history.BD is most common in young adults between the second and fourth decades. Although it can begin at any age, it is rare in children and adults over 50 years of age. The average age of onset of BD has been reported as 25.6 years old in Turkey .The age at onset of first symptoms and age of diagnosis of BD may vary. Uslu et al found the average age of onset of symptoms as 27.1 years, and Karincaoglu et al found the average age of onset of symptoms between 16 and 25 years in their study , 11. In Although most studies report that BD is more common in male, gender rate may vary from study to study , 7. TursSkin lesions are common in BD. Oral ulcers is the most common and unchanging symptom of the BD. It is seen as the first symptom in 70% of patients, and prevalence of oral ulcers in patients with BD was reported in Turkey to be 100%, in Iran 96.8%, in Japan 98.2%, in Korea 97.5%, in Morocco 100% and in UK 100% . Also thIn previous studies, prevalence of papulopustular lesions was reported in Turkey as 54-72.3%, 40% in China, and 41-49% in Europe . In our In different studies, prevalence of erythema nodosum-like lesions was reported as 15-78%  [Prevalence of positive pathergy test of patients with BD was found to be 50-80% in Turkey, 44% in Japan, and 12-52% in Europe , 16. In Eye involvement, which is one of the most important organ involvement, is 40-70% in patients with BD . Eye invNeurological involvement is usually seen in the first 5 years, it has a high risk of morbidity and mortality, and it occurs more commonly in males with BD , 18. PrePrevalence of vascular involvement was reported by Alpsoy et al as 4.4%, Tursen et al as 7%, Uslu et al as 9.1%, Karincaoglu et al as 16.1% , 14. In The actual prevalence of pulmonary involvement is not known. Prevalence of vascular involvement was reported in Turkey to be 1-1.1%, in Europe 0-17%, and in Taiwan 3% . In our Prevalence of gastrointestinal involvement varies in different societies such as 1.4-5% in Turkey, 14% in France, 14% in Britain and 50-60% in Japan . In our Involvement of the genitourinary system is seen in about 5% of patients with BD , 18, 19.Juvenile BD is rare, and it is used to define patients under 16 years who satisfy the diagnostic criteria of the disease. Patients with juvenile BD comprise 3-7% of all patients with the disease. Among patients with BD, the prevalence of juvenile BD was reported in Turkey to be 2-10.5%, and 1.6% in Japan . In our Our study revealed no significant differences between male and female patients for mucocutaneous  and systemic involvements. The study found that our patients had a higher incidence of mucocutaneous findings, with no meaningful difference between the sexes. The study found a higher incidence of joint complaints and sacroiliitis among female patients, with more common eye involvement in male patients. However, these differences were not considered significant. The study found a significantly high level of headache in female patients. This study found that our patients with BD had parallel demographic and clinical findings with previous studies, with no meaningful difference.In conclusion, the demographic and clinical features of BD may vary according to different geographical regions, gender and ethnicity. Mucocutaneous findings were more common in our patients, which is relatively similar to other studies conducted in Turkey. We hope that this study will contribute to the epidemiology of BD that may vary in clinical and demographic features in different regions of the world.


To determine the efficacy of terlipressin and albumin in improving renal functions in patient with hepatorenal syndrome (HRS) and to identify factors determinant of better response.In this quasi experimental interventional study patients of liver cirrhosis and ascites with HRS type I were treated with intravenous albumin and incremental dosage of terlipressin based on response with maximum dose of 12mg/day. Decline of creatinine below 1.5mg/dl was defined as complete response. Factors predictive of response to therapy were determined via linear regression analysis.Twenty four patients were included with male to female ratio 3.8/1(19/5) and mean age 53.3 (±10.06). Complete response to terlipressin/albumin was seen in 14 (58.3%)patients, seven (29.2%) achieved partial response with > 25% creatinine decline while three (12.5%) had no response. Lower serum creatinine at diagnosis , absence of hyperkalemia  and absence of portal vein thrombosis  are associated with response to treatment in HRS. Baseline serum creatinine  was independent predictor of response to therapy in multivariate analysis.Terlipressin and albumin is an effective treatment for HRS type I. Patients with lower baseline serum creatinine are more likely to respond to this therapy. Hepatorenal syndrome is a fatal but potentially reversible complication of end stage liver disease. It is defined as impairment of renal function in a patient with liver cirrhosis in the absence of any alternative identifiable cause of renal failure.4What triggers HRS remained the source of controversy over many years. Now we have consensus that splanchnic arterial vasodilatation resulting from excess of vasodilators in circulation in a patient with cirrhosis is the primary trigger for HRS.Combination of splanchnic vasoconstrictor along with intravenous albumin for volume expansion is treatment of choice for HRS as per Acute Dialysis Quality Initiative (ADQI) work group recommendations.11Inasmuch as we have effective therapeutic options for variceal bleeding, ascites or encephalopathy, we are encountering increasing number of patients with HRS. Identification of cost effective treatment for HRS in our patients with cirrhosis is urgently needed. Moreover, in view of potential side effects related to vasoactive drug, we would like to limit this treatment to patients most likely to respond by identifying factors associated with better outcome. Objective of our study was to determine the effectiveness of terlipressin in combination with albumin in patients with HRS Type-1 in improving renal functions and to identify factors associated with favorable outcome of this treatment.This experimental design cohort study was carried out at The Doctors Hopsital & Medical Center from January 2008 to June 2015. Only patients with Type-1 HRS were included. Sampling technique was non-probability purposive convenient sampling. Patients with cirrhosis and ascites, as confirmed on abdominal ultrasound who had doubling of creatinine above 2.5mg/dl within two weeks were included. HRS was confirmed by absence of shock at admission, absence of hypovolemia as confirmed by “failure to improve renal function (decrease in creatinine < 1.5 mg/dl) following atleast 2 days of diuretic withdrawl (if on diuretics), and volume expansion with albumin at 1 g/kg/day up to a maximum of 100g/day”, no current or recent treatment with nephrotoxic drugs, absence of parenchymal renal disease as defined by proteinuria < 0.5 g/day, no haematuria (< 50 red cells/high power field) and normal renal ultrasound.After detailed clinical history and examination, complete blood count, liver function tests, renal function tests, serum electrolytes, urine complete examination and abdominal ultrasound were carried out in all patients. All patients were given intravenous albumin 1g/kg up to maximum of 100 gm to exclude hypovolemia before confirmation of HRS. Ascitic fluid was examined for differential count, biochemistry and culture.Patients were treated with terlipressin, initially 2mg/day along with intravenous albumin 20mg/day. Response was evaluated through monitoring of vital signs, daily urine output, daily serum creatinine and clinical condition of patient. If serum creatinine failed to decline by 25% of baseline value after three days, dose was increased to 4mg, 8mg and 12mg/day progressively. Maximum dose limit was 12mg/day. Dose of terlipressin was not increased further in case of favorable response defined as ≥ 25% reduction in creatinine within three days time or maximum dose limit reached. Complete response to terlipressin in combination with albumin was defined as decline in serum creatinine < 1.5 mg/dl. Decline of more than 25% of baseline creatinine but not below 1.5 mg/dl in creatinine value was regarded as partial response. Less than 25% decline in baseline creatinine with maximum dose possible was defined as No response.Patients with variceal bleeding, spontaneous bacterial peritonitis or portosystemic encephalopathy were treated as per standard protocol. Patients with complete or partial response and improvement in their clinical condition were advised medications and evaluation by liver transplantation unit at discharge. In case of no response, due to absence of alternative treatment options urgent liver transplantation was recommended.® 20. Quantitative variables were expressed as mean ± standard deviation (SD) while qualitative variables were given as percentage. Complete, partial or no response were given as percentage. Univariate analysis to identify variables associated with response to treatment were determined using chi squareχ2 for qualitative and unpaired two tailed student’s t test for quantitative variables. Variables with p value ≤0.1 were used for multivariate analysis for independent prediction of response to therapy by multivariate linear regression analysis. Reciever operating characteristic (ROC) curve was used to identify cut off value of variables predictive of response to therapy.Statistical analysis was carried out using SPSSTotal of 24 patients diagnosed with HRS Type-I were included. Male to female ratio was 3.8/1(19/5) with mean age of 53.3 (±10.06) years. Hepatitis C was responsible for liver cirrhosis in 21(87.5%) patients, one (4.2%) patient had hepatitis B, whereas two were negative for both hepatitis B and C. Hepatocellular carcinoma was already diagnosed in 10 (41.75%) patients. On clinical evaluation all patients had ascites and jaundice, 13 (54.2%) presented with abdominal pain, 9 (37.5%) with fever, 23 (95.8%) complained of oliguria, 22 (91.7%) had portosystemic encephalopathy, four (16.7%) presented with upper gastrointestinal bleeding and three (12.5%) complained of dyspnea. Ascites was mild to moderate in 16 (66.6%) patients while 8 (33.4%) had tense ascites. Spontaneous bacterial peritonitis was confirmed on ascitic fluid analysis in seven (29.1%) patients. All patients were in Child Pugh Turcotte (CTP) class C with mean score of 13.46 (±1.1) whereas mean Model for End stage Liver Disease (MELD) score was 36.6 (±5.5). Only one (4.2%) patient had MELD score less than 30, 16(66.7%) had score between 30-39 while 7(29.2%) had score of 40. Hyponatremia was present in 16 (66.7%) patients while 7 (29.2%) had hyperkalemia.Maximum dose of terlipressin used was 2mg/day in 5 (20.8%), 4mg/day in 16(66.7%) patients and 8mg/day in 3 (12.5%) patients.Complete response of HRS to terlipressin/albumin was seen in 14 (58.3%) patients, seven (29.2%) achieved partial response while three (12.5%) had no improvement in renal profile. Mean time to achieving serum creatinine <1.5 mg/dl in patients with complete response was 5.14 (±1.14) days. Of patients with complete response, 13 (92.8%) were discharged and referred for liver transplantation while 1 (7.2%) died due to worsening encephalopathy. Among patients with partial response, maximum dose limit of terlipressin was not reached as 5 (71.4%) died during treatment, one due to hyperkalemia induced arrythmia and 4 due to multi-organ failure whereas two (28.6%) were shifted to transplant center during treatment. All three patients with no response died during hospital admission. Referral for transplantation was possible in 15 (62.5%) patients while 9 (37.5%) died during treatment.We compared variables noted during study between patients with complete response and those who failed to achieve complete response to terlipressin/albumin, to identify predictors of successful treatment of HRS as given in Hepatorenal syndrome is one of the dreadful terminal complications encountered in patients with advanced cirrhosis. Failure to treat HRS especially type 1 is invariably fatal.Complete response to combination of terlipressin and albumin was seen in 58.3% of patient in our study. In a study of 119 patients with HRS by Heidemann J et al., response rate was 55%.16Important query to be answered is “Does this benefit translate in survival improvement”? Gluud LL et al. reviewed 5 randomized trials available on vasoconstrictor/albumin therapy in HRS and cumulative data showed reduced mortality with treatment (RR 0.76 95% CI 0.61-0.95).19High baseline serum creatinine, hyperkalemia, and portal vein thrombosis on ultrasound were identified as bad prognostic indicators in univariate analysis of our patients but only baseline creatinine stood the test of multivariate analysis as independent predictor of response to treatment with terlipressin in combination with albumin. Nazar A noted that bilirubin ≥ 10mg/dl and rise in mean arterial pressure (MAP) of ≥ 5mm are associated with poor response to therapy and lower baseline creatinine results in faster recovery.Our study is limited by the absence of control group but as terlipressin is now recommended along with albumin for HRS Type- I, control group was not possible. Studies with larger number of patients comparing terlipressin with other vasoconstrictor agents may further enrich our knowledge regarding factors associated with better response. Identification of these factors will enable us to limit this costly treatment to patients most likely to respond thus saving cost of treatment. Very few studies pertaining treatment of HRS are available in literature from our region. As more and more centers are developing liver transplantation services in our country, studies like ours will enable us to select better treatment option to bridge patients of HRS to liver transplantation.Terlipressin along with albumin is an effective therapeutic intervention for HRS type I. Patients with lower baseline serum creatinine are more likely to respond to this therapy.


Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. The aim of this study was to assess efficacy and safety of individualized homeopathic treatment post-hoc test).A randomized, placebo-controlled, double-blind, double-dummy, superiority, three-arm trial with a 6 week follow-up study was conducted. The study was performed in a public research hospital in Mexico City in the outpatient service of homeopathy. One hundred thirty-three peri- and postmenopausal women diagnosed with major depression according to DSM-IV (moderate to severe intensity) were included. The outcomes were: change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression, Beck Depression Inventory and Greene Scale, after 6 weeks of treatment, response and remission rates, and safety. Efficacy data were analyzed in the intention-to-treat population . Fluoxetine was not different from placebo in Greene Climacteric Scale.Homeopathy and fluoxetine are effective and safe antidepressants for climacteric women. Homeopathy and fluoxetine were significantly different from placebo in response definition only. Homeopathy, but not fluoxetine, improves menopausal symptoms scored by Greene Climacteric Scale.NCT01635218ClinicalTrials.gov http://www.trialsjournal.com/content/14/1/105. Major depression disorder (MDD) is a chronic and frequently disabling disorder. The risk for MDD is approximately 1.5 to 3 times higher in women than in men, with an estimated lifetime prevalence in women of 21.3% . The risRecent studies have demonstrated a significant association between menopausal transition and a higher risk for developing depression, with risk rising from early to late perimenopause and decreasing during postmenopause. It has been postulated that during perimenopause the risk for mood disorders may be increased for women with sensitivity to normal hormonal fluctuations . A numbeThe Diagnostic and Statistical Manual of Mental Disorders, abbreviated as DSM, is the diagnostic tool that serves as a universal authority for psychiatric diagnosis. The DSM-5 was recently published on 2013 . Depresset al published a meta-analyses of clinical trial data submitted to the US Food and Drug Administration (FDA) and revealed a mean drug-placebo difference in improvement scores of 1.8 points, whereas the National Institute for Clinical Excellence (NICE) used a drug-placebo difference of 3 points as a criterion for clinical significance  HRSD score points after six weeks, corresponding an effect size = 0.45 (largest difference between any two groups to be detected/expected within group standard deviation = diff/de). To detect an effect size = 0.45, in a 3-group design (1:1:1), using F-Test, with a 5% risk of type 1 error, and 83% power, 63 patients per group were expected to be required considering also a 10% drop-out rate.Sample size calculation was estimated using G*Power  and report forms where participants wrote daily any adverse event.All data were entered electronically on data sheets designed for the study. Original study forms were entered and kept on files at the JMH. Participants files were stored in numerical order in a secure and accessible place and manner. Participants files will be maintained in storage for a period of five years after completion of the study. All forms related to the study data were kept in locked cabinets. Access to the study data was restricted.All patients under randomization were included in the primary efficacy population (intention-to-treat population), regardless whether or not they adhered to the treatment protocol or provided complete data sets. Only patients who withdrew their consent to use their personal data were excluded from the analysis. The flow of participants through the trial is presented in a CONSORT diagram.First, the three groups were compared in order to verify that there are not significant differences among them at baseline to confirm they are comparable after randomization. Demographic characteristics were summarized using means and standard deviation for continuous data  and relative frequencies for qualitative data . The baseline demographic characteristics among groups were compared with the use of chi square test or by one-way independent measures of analysis of variance (ANOVA) as required. Continuous data were represented by means and standard deviation, whereas categorical data were represented by a frequency table.versus placebo; (2) fluoxetine versus placebo. The main statistical analysis compared primary and secondary outcomes measurements among groups at weeks 4 and 6. The primary outcome (change in mean HRSD score) and secondary outcomes (change in mean BDI and GS scores) among groups at baseline and weeks 4 and 6, were analyzed by one-way ANOVA to provide a statistical test of whether or not the means of the three groups are all equal. The statistical significant ANOVA result (p<0.05) suggests rejecting the global null hypothesis H0 . Owing to the study is a three-arm trial, adjustment for multiple comparisons was accomplished with Bonferroni method which requires that the p-value for each comparison be less than or equal to 0.05 divided by the total number of study comparisons. This guarantees that the probability of at least one type I error is less than 0.05.Data were analyzed with SPSS statistical software (version 17.0). We compared: (1) IHT Eta squared [between-groups sum of squares/total sum of squares] was calculated by hand to determine effect size. Responder rates were compared among groups using chi square test. Relative risk and odds ratio with 95% CI, and number needed to treat (NNT) were also determined. Statistical significance was set at p<0.05 level for all analysis. Steps taken in the design and data collection stages were observed carefully in order to prevent missing data, but this was difficult to completely achieve. Missing data were as a result of loss to follow-up and were handled by sensitivity analysis (SA). A multiple imputation technique (MI) was performed using multiple imputed datasets which yield unbiased estimates, and also accounts for the within and between dataset variability. Five imputations were performed in SPSS (version 17.0).Statistical analysis for repeated measurements was not prespecified in the study protocol. A mixed effect model analysis with random intercept and slope was used to assess the rate of change in HRSD, BDI and GS scores, among groups over the 6-week treatment interval.All patients who received at least one dose of study drugs were considered in the safety analysis. Adverse events were translated to Medical Dictionary for Regulatory Activities terms (MeDRa terms), quantified, and compared among groups using chi square test.Baseline characteristics of participants are summarized in There were no significant differences among groups with respect to risk factors for depression . Sixty-fvs 20.6 (2.9) [95% CI (19.7–21.5)] in fluoxetine group vs 20.7 (3.1) [95% CI (19.8–21.7)] in placebo group . Mean (SD) baseline score in BDI was 26.3 (7.2) [95% CI (24.1–28.4)] in IHT group vs 25 (7.8) [95% CI (22.7–27.3)] in fluoxetine group vs 27 (9.0) [95% CI (24.2–29.8)] in placebo group . Mean (SD) baseline score in GS was 35.3 (8.5) [95% CI (32.7–37.9)] in IHT group vs 33.2 (10.1) [95% CI (30.5–36.5)] in fluoxetine group vs 37.9 (11.5) [95% CI (34.3–41.4)] in placebo group .vs 11.7 (3.7) [95% CI (10.5–12.9)] in fluoxetine group vs 15.0 (3.7) [95% CI (15.9–18.3)] in placebo group . Bonferroni post hoc test determined that means differed in IHT group vs placebo group (p = 0.0) and fluoxetine group vs placebo group (p = 0.0). IHT group was better than placebo in 5.0 points (p = 0.00); fluoxetine group was better than placebo in 3.2 points (p = 0.00). Means did not differ in IHT group vs fluoxetine group (p = 0.082).After six weeks follow-up, there were significant differences among groups in HRSD. Mean (SD) score in HRSD was 9.9 (3.0) [95% CI (9.0–10.9)] in IHT group With respect to BDI, after six weeks of treatment, there were no significant differences among the three groups . In the IHT group baseline score decreased from 26.3 (7.2) [95% CI (24.1–28.4)] to 12 (6.1) [95% CI (10.1–13.9)], fluoxetine group decreased from 25.0 (7.8) [95% CI (22.7–27.3)] to 14.2 (7.8) [95% CI (11.7–16.7)] and placebo group, from 27.0 (9.0) [95% CI (24.2–29.8)] .vs 23.1 (12.3) [95% CI (19.2–27.1)] in fluoxetine group vs 26.8 (11.7) [95% CI (22.8–30.7)] in placebo group . Bonferroni post hoc test showed that IHT was better than placebo in 8.6 points (p = 0.02). Means did not differ in fluoxetine group vs placebo group (p = 0.424). Also, there were no differences in fluoxetine group vs IHT group (p = 0.115)  score in GS was 18.1 (7.8) [95% CI (15.7–20.6)] in IHT group = 0.115) .t = 6.44, p = 0.00, 95% CI (1.93–3.63)] and the fluoxetine group had 1.31 points higher than IHT in HRSD score .The improvements in the three treatment groups in HRSD, BDI and GS are shown in Figs. t = 1.13, p = 0.258, 95% CI (−0.894–3.32)] and the fluoxetine group had 1.82 points higher than IHT in BDI score  (The rate of change in BDI score was −7.17 points (p = 0.00) for IHT during the 6-week treatment interval. The placebo group had 1.21 points higher than IHT in BDI score [(5–3.88)] .t = 2.49, p = 0.03, 95% CI (0.689–5.78)]; the fluoxetine group had 3.62 points higher than IHT in GS score  (The rate of change in GS score was −8.65 points (p = 0.00) for IHT during the 6-week treatment interval. The placebo group had 3.28 points higher than IHT in GS score [(–6.168)] .2 = 18.1, 2 df, p = 0.00). Neither IHT nor fluoxetine group differed from placebo group on the remission definition (7 or less points in HRSD). Only 15.9% had remission of depression after six weeks of treatment in IHT group, 15.2% in fluoxetine group and 4.7% in placebo group .Two patients need to be treated for one to benefit (decrease of 50% or more on HRSD baseline score) in an IHT compared to placebo after a 6-week treatment. Thus IHT is protective for depression after 6-week treatment , but no statistical significance was found in benefit from a 6-week IHT according to remission definition (7 or less points in HRSD)  . In caseWith respect to adverse events, Only one patient taking fluoxetine had increased anxiety and insomnia, so it was necessary to interrupt the medication and prescribe an IHT. This reaction did not threaten patient's life. This was the only case that the pharmacist told the homeopathic doctor the medication the patient was taken (fluoxetine). Then it was necessary to prescribed an IHT and the patient did not continue in the previously allocated intervention. In the rest of participants, all the adverse events were very mild and tolerable and medication was not interrupted. In the IHT group, 11.4% felt a mild homeopathic aggravation followed by clinical improvement. It was not necessary to stop study medication.In compliance with RedHot Guidelines, The results were assessed for robustness through sensitivity analysis. Missing data were handled using a multiple imputation technique. The primary efficacy outcome and the two secondary outcomes were analyzed by this technique. Five imputations were performed and results remained unchangeable with respect to the primary analysis in all imputations.The results of this study indicate that both IHT and fluoxetine are effective antidepressant treatments for women in peri- and posmenopausal stage. This clinical trial is based on: (1) CONSORT guidelines for reporting randomized trials with parallel groups ; (2) Repet al reported improvement in depression in outpatient patients with moderate to severe depression using individualized homeopathic Q-potencies. They conducted a non-inferiority trial comparing homeopathy with fluoxetine, but a placebo group was not included due to ethical reasons  in a synthesis of RCTs. They concluded that few well-controlled studies, have documented response rates for extended treatment with a single effective antidepressant. In the Gibbons' study remission rate was 82%, with 75% achieving remission by 140 days (twenty weeks). For fluoxetine, 23% of patients who were unimproved at eight weeks showed full remission at twelve weeks [Nevertheless, there is an impact if the results are analyzed with different cut-off points in HRSD. In spite of the overall results of this study which indicate that both, IHT and fluoxetine improve depression in climacteric women, IHT and fluoxetine were significantly more effective than placebo according to the HRSD definition of response only. Response rates of IHT and fluoxetine are similar to those published in other studies . Neitherfinition . Translave weeks . Therefoet al. They reported the highest remission rates  after a 4-week follow-up; 76.9 and 72.4% for fluoxetine and homeopathy, respectively, after eight weeks of treatment [et al, reported that menopause is related to a worse antidepressant treatment response [versus placebo differences vary substantially as a function of baseline severity. They suggest that the magnitude of benefit of antidepressant treatment compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms [et al concluded that baseline severity do not affect antidepressant response.Different results were published by Adler reatment . Low remresponse . As prevsymptoms , 46. HowOtherwise, an important point to consider is NNT. From a public health perspective this is an enormous difference and indicates that for every two treated patients with IHT during six weeks, an additional patient treated will respond. So IHT could be a proven and low cost treatment that improves depression in many women in climacteric stage. Mexico has a big population of low-income women without social security that cannot buy antidepressant medication. Homeopathy could be considered as a health care option for these women. In case of fluoxetine, for every three treated patients during six weeks, an additional patient treated will respond.vs placebo. Further studies with an adequate study design and sample size are needed to confirm whether IHT is equivalent or non-inferior to fluoxetine in climacteric depressive women.Although in the HOMDEP-MENOP study there was no statistical difference between IHT and fluoxetine, this study was not designed to prove if IHT is not worse or equivalent to fluoxetine. It is important to take into account the relative futility of trying to compare the efficacy of active antidepressants in a conventional study. Snappin explains that it is fundamentally impossible to prove that two treatments have exactly equivalent effects. Therefore, equivalence trials aim to show that the effects differ by no more than a specific amount  . If two et al investigated the demographic influences for BDI in a non-clinical Spanish speaking population and found that those with lower education tended to report higher severity of individual symptoms [Besides the positive results in HRSD, no statistical differences were found among groups in BDI score. Both, HRSD and BDI are standardized instruments that assessed depression severity, but BDI is self-administered. Participants received instructions to respond correctly. BDI requires elementary school as a minimum to be able to answer the test, and although all participants studied elementary school, some difficulties to understand and answer the test were observed with this instrument, so maybe this could biased the results. BDI has been used in Mexican population in other diseases such as rheumatoid arthritis. Dawes symptoms .It is well known that there is an association between domestic violence or abuse and mental health problems . The preet al stated that 'a study design in which the selection of a suitable, individualized homeopathic medicine occurs during the double-blind randomized phase evaluates not only the efficacy of homeopathy, but also the efficiency of the homeopath in selecting and managing that medicine' [Although individual prescriptions are necessary in classical homeopathy, they have been considered as an obstacle for a double-blind trial in homeopathy . Adler eedicine' . The HOMWith respect to climacteric complaints, results from GS score showed that IHT is effective for improving symptoms of women at this stage. Despite the main objective of this study was to prove efficacy of IHT for depression, other climacteric symptoms which are frequently associated with this condition were evaluated. Many observational studies have confirmed the effectiveness of homeopathic treatment for climacteric women . The effThe HOMDEP-MENOP study demonstrated the efficacy of IHT for climacteric complaints associated with moderate to severe depression in a RCT. Many women that cannot use hormonal replacement therapy could benefit from homeopathy. However, there are some limitations that require consideration. For example, the HOMDEP-MENOP study did not evaluate the frequency and severity of vasomotor symptoms separately. Hot flushes are one of the most common symptoms in peri- and postmenopause. Approximately, 70% of women could experience them without being depressive, as well as depression could be experienced without vasomotor symptoms . A varieet al reported that a growing evidence suggests that SSRIs are effective in the management of hot flushes [et al concluded that venlafaxine and paroxetine are more consistent in effectively reducing the frequency and severity of vasomotor symptoms based on many studies, and fluoxetine should be considered second or third-line option if patients fail therapy with or cannot tolerate first-line medication [2C receptors, which modulate brain norepinephrine and dopamine systems. Therefore, fluoxetine causes activation and weight loss. Fluoxetine has activating properties, and this can lead to problems, such as insomnia and agitation [Fluoxetine was not different from placebo in GS score. This finding also deserves a possible explanation. Because norepinephrine and serotonin are both involved in the development of menopausal symptoms, it is plausible to expect that an agent that is designed to modulate these systems might be effective in reducing the frequency and severity of these symptoms . Carroll flushes . Althoug flushes . Thus, tdication . Fluoxetgitation . GS evalIn conclusion, IHT and fluoxetine are effective antidepressants for improving depression in climacteric women after a 6-weeks treatment. In the remission definition, IHT and fluoxetine were not different from placebo, so further studies are necessary to prove the effectiveness of IHT in a longer period of time. IHT also improves menopause symptoms according to GS, but well-designed RCTs are required to deeply study the efficacy of homeopathy specifically in climacteric symptoms.S1 CONSORT Checklist(PDF)Click here for additional data file.S1 Protocol(PDF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.


Background. We aimed to assess incidentally discovered hepatocellular carcinoma (iHCC) over time and to compare outcome to preoperatively diagnosed hepatocellular carcinoma (pdHCC) and nontumor liver transplants. Methods. We studied adults transplanted with a follow-up of at least one year. Patients were divided into 3 groups according to diagnosis of hepatocellular carcinoma. Results. Between 1990 and 2010, 887 adults were transplanted. Among them, 121 patients (13.6%) had pdHCC and 32 patients (3.6%) had iHCC; frequency of iHCC decreased markedly over years, in parallel with significant increase in pdHCC. Between 1990 and 1995, 120 patients had liver transplants, 4 (3.3%) of them had iHCC, and only 3 (2.5%) had pdHCC, while in the last 5 years, 263 patients were transplanted, 7 (0.03%) of them had iHCC, and 66 (25.1%) had pdHCC (P < 0.001). There was no significant difference between groups regarding patient survival; 5-year survival was 74%, 75.5%, and 77.3% in iHCC, pdHCC, and non-HCC groups, respectively (P = 0.702). Patients with iHCC had no recurrences after transplant, while pdHCC patients experienced 17 recurrences (15.3%) (P = 0.016). Conclusions. iHCC has significantly decreased despite steady increase in number of transplants for hepatocellular carcinoma. Patients with iHCC had excellent outcomes with no tumor recurrence and survival comparable to pdHCC. Incidental hepatocellular carcinoma (iHCC) is defined as preoperatively undiagnosed hepatocellular carcinoma (HCC) found on explant pathology of patients transplanted for benign disease. It is not uncommon .Recent advancements in diagnostic imaging have resulted in a marked increase in sensitivity for detection of smaller lesions , which sThis study included all adult patients who underwent liver transplantation at University of Alberta Hospital between October 1990 and December 2010 and had at least one year of follow-up. Thirty-two patients had incidentally diagnosed HCC (iHCC). We divided patients into three groups: patients with iHCC presented group 1, group 2 included recipients with pdHCC, and group 3 presented patients transplanted due to non-HCC indications. We compared the groups regarding incidence, characteristics of patients, histopathological characteristics, recurrence, and patient survival. Data were collected prospectively in an electronic database  and were analyzed retrospectively. We also divided transplants into 5-year periods to study trend of iHCC and pdHCC over time.πr3) based on the maximum diameter of each tumor [From program inception in 1989, screening of cirrhotic patients on the waiting list was done on an irregular basis and then was done using abdominal ultrasound and serum alpha-fetoprotein (AFP). Since 2006, screening has been done using contrast-enhanced computed tomography or magnetic resonance imaging: every 6 months for cirrhotic patients on the waiting list with no known HCC and every 3 months for patients who have known HCC. Preoperative diagnosis of HCC depended on contrast-enhanced computed tomography and/or magnetic resonance imaging, with biopsy only in cases with nondiagnostic imaging. A lesion was considered HCC if it showed enhancement in the early arterial phase with washout in the late phase or if the lesion had marked increase in size with follow-up, according to AASLD guidelines [P value < 0.05 was considered significant and all statistics were done using SPSS  version 16.Data were summarized as mean ± SD for continuous variables and frequency (%) for categorical factors. Groups were compared using one-way ANOVA and chi-square test. Post hoc test (Bonferroni method) was used for paired comparisons. Survival curves were done using the Kaplan-Meier method and compared using the Log-rank test. This cohort includes 887 adult patients (>18 years old) who were transplanted at our institution. A total of 734 (82.8%) patients were transplanted due to non-HCC indications and 153 (17.2%) patients had HCC; of them 121 (13.6%) patients were pdHCC and 32 (3.6%) had been diagnosed based on explant pathology (iHCC). Patients with iHCC represented 21% of all HCC cases. Mean age at time of transplant was 50.9 ± 10.6 years with a follow-up of 4.5 ± 4.1 years.P < 0.001)  of them had iHCC, and only 3 (2.5%) had pdHCC. These figures changed dramatically between 2006 and 2010; 263 patients underwent transplant, 7 (0.03%) of them had iHCC, and 66 (25.1%) had pdHCC (< 0.001) .P < 0.001). Autoimmune liver diseases including primary sclerosing cholangitis, primary biliary cirrhosis, and autoimmune hepatitis were significantly higher in nontumor patients (<0.001). Prevalence of alcoholic liver disease was comparable in the 3 groups (P = 0.109). Patients who had pdHCC had significantly better condition at time of transplant as reflected by the lower MELD and Child-Pugh scores . Patients with iHCC and pdHCC had significantly higher HCV infection (<0.001). HBV infection was significantly more prevalent among pdHCC patients compared to patients with iHCC and non-HCC patients   .Patients with iHCC had 12 (37.5%) cumulative deaths with a mean time from transplant to death of 3.5 ± 3.1 years. The cause of death was bacterial infection in 3 patients, malignancy in 2 patients (metastatic pancreas cancer and posttransplant lymphoproliferative disease), chronic rejection in two patients, multiorgan failure in 2 patients, cardiovascular and neurological complications in 2 patients, and suicide in one.In pdHCC, 33 patients (27.3%) died, with a mean time from transplant to death of 3.0 ± 3.9 years. Causes of death included recurrence of HCC in 14 patients, other malignancies in 2 patients, cardiovascular disease in 5 patients, and bacterial infections in 3 patients. The remaining patients were lost due to hemorrhage (1 patient), recurrence of primary disease (2), chronic rejection (1), multiorgan failure (2), neurological complications (1), and pulmonary complications (2). In the non-HCC patients, 256 died during the follow-up period.P = 0.016) . Recurrence free survival at 5 years after transplant was 100% in group 1 and 80.4% in group 2 (= 0.016) .3 with 50% of patients having tumor volume of less than 2.6 cc3. Follow-up was done by transplant centers for 17 patients and nontransplant centers for 15 patients. Initially, abdominal ultrasound and serum AFP were used for screening; the highest pretransplant AFP ranged from 3 to 41. Since 2006, screening for all patients on waiting list is done using contrast-enhanced CT or magnetic resonance imaging (MRI) scans every 6 months with AFP.In this study, we analyzed the outcome of 887 adult patients who received liver transplant in our center over a period of 20 years and found that 32 out of the 153 patients with HCC were diagnosed by pathological examination of the explant only. No patient with iHCC experienced recurrence of malignancy and survival was comparable to patients with pdHCC, perhaps because of more severe preoperative liver disease in the iHCC group as reflected by higher MELD and Child-Pugh scores.Over a period of 20 years, incidence of HCC has increased steadily. In the first 5 years, only 2.5% of transplant patients had pdHCC, while in the last five years, 25% of cases had pdHCC. Despite increasing incidence of HCC over time, incidentally discovered HCC has decreased significantly. In the first five years, iHCC represented 3.3% of cases, while in the last five years iHCC dropped to 0.03%. iHCC represented 21% of all cases diagnosed with HCC and constituted 3.6% of all adult transplanted patients which is comparable to the published literature, where prevalence of iHCC among transplanted HCC cases has varied from 4.2% to 40% . Kishi eIn our cohort, the relative proportion of iHCC among all transplanted patients with HCC decreased steadily from 62.5% in the first 5 years to reach 14.7% in the last 5 years. This dramatic decline likely reflects both significant improvement in diagnostic imaging and increasing experience in the diagnostic teams as well as close monitoring of patients. Reported sensitivities of contrast-enhanced MRI for detection of HCC of all sizes are 33%–90% and 50%–80% for lesions smaller than 2 cm and 4%–33% for lesions smaller than 1 cm .However, not all lesions were small; some of the missed lesions were larger than 2 cm, which should raise another issue about periodic screening for patients at risk of developing HCC and also about where to do the screening. Since 2006, our center started to do screening for cirrhotic patients on the liver transplant waiting list every 6 months using contrast-enhanced CT or MR scans with serum AFP which was associated with an increased incidence of pdHCC in parallel with decreasing incidence of iHCC. Few cases that followed the protocol had small lesions that had enhancement with contrast but were atypical in appearance and difficult to characterize. One patient had a large iHCC that was missed on imaging; this patient had screening by his primary care center. Reviewing iHCC cases revealed that about half of them were screened by primary care centers. A study from Japan  showed tIn this study, we did not find dramatic difference regarding incidence of iHCC among different liver diseases. In East Asian countries, there is high prevalence for HCC among HBV carriers. A study from Hong Kong  showed aP = 0.084). Patient survival at 1 year and 5 years was 78% and 58% in iHCC group and 90% and 70% in pdHCC group. They had recurrence in 13% of iHCC patients and 22% recurrence in pdHCC patients (P = 0.486). In another study of 53 patients [P < 0.05). Survival at 1 year and 5 years was 82% and 82% in iHCC group and 78% and 57% in pdHCC patients. In our cohort, iHCC patients did not have any recurrence during the follow-up; however, they did not have a survival advantage over patients with pdHCC. Survival at 1 year and 5 years was 90.6% and 72.5% in iHCC group and 86.3% and 71.9% in pdHCC group, respectively. We suspect that the iHCC patients did not achieve better survival than pdHCC patients due to their poorer general condition at time of transplant as reflected from their significantly higher MELD and Child-Pugh scores, notwithstanding the reality that high MELD score is a weak prognostic factor for mortality of HCC patients after liver transplantation [Outcome of iHCC varies between centers. In a study of 198 HCC patients , 51 patipatients , 11 patiantation . Patient3 and alpha-fetoprotein of <400 ng/mL [It could be expected that most of all incidental HCC would be within Milan criteria. Surprisingly, we found 24% of our iHCC cohort was beyond Milan based on the explant pathology. Six out of 8 cases were beyond Milan based on the number of lesions. All iHCC cases were within the TTV/AFP criteria utilized in our center since 2007, which are based on total tumor volume of <115 cc00 ng/mL . As the 00 ng/mL , 15, 17.In conclusion, we found patients with iHCC to have excellent tumor related outcome with no tumor recurrence and survival comparable to non-HCC patients and pdHCC patients. The incidence of iHCC has decreased dramatically over years, while the incidence of HCC as the primary listing diagnosis for liver transplantation has continued to increase in many centers. This study provides further evidence that the number of HCC lesions should not be used alone for excluding patients from transplantation, as it may exclude patients with favorable outcome.


One of the common causes of morbidity in patients with RA is pulmonary involvement. Some studies have shown that the possible abnormal results of pulmonary function tests in rheumatoid disease are higher than usual. We aimed to evaluate the prevalence of spirometric abnormalities in patients with RA.This case-control study was conducted on 99 patients with RA who referred to a rheumatology clinic in Qazvin, northwest Iran. Sixty five age- and sex-matched healthy controls were recruited as well. History taking, physical examination, laboratory tests and spirometry were performed for the participants. RA severity was assessed according to Disease Activity Score 28 (DAS28). The data were processed using SPSS software version 16. Chi square and student's t test and multiple logistic regressions were used as appropriated.28 was 2.5 (±1.1). Dyspnea was the most common respiratory complaint (6.1%). Three (3%) patients had mild restrictive, 2 (2%) patients mild obstructive, and one (1%) patient moderate obstructive diseases. In the control group, only one participant had mild restrictive pulmonary disease (P<0.05). A significant decrease of FEF25 , FEF50 , FEF75  and FEF25-75  was observed in patients compared with the control group. We found no correlation between the patients’ age, duration and severity of the disease, and laboratory tests with spirometric indices.The mean (±SD) age of the patients was 46 (±10.5) years. The mean (±SD) duration of disease was 4.8 (±5.4) years, and the mean (±SD) DASIt is recommended that patients with RA be visited on a regular basis and PFT be done for them for the early diagnosis of pulmonary involvement. Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease with an unknown origin. It can have various systemic presentations; however the main characteristic of the diseases is symmetrical inflammatory synovitis, which affects the peripheral joints. The lung can be involved frequently in rheumatological diseases. This involvement can be caused by different etiologies such as drug toxicity, infection, or specific manifestations of the immune process  reduction in such patients to smoking, and not to the rheumatoid process  + 0.28 * sort (number of swollen joints 0- 28) + 0.70 * ln  + 0.014 * Vas general health patients (mm)25%-75%), FEF75, FEF50, FEF25, forced vital capacity (FVC), forced expiratory volume (FEV1), FEV1/FVC and peak expiratory flow (PEF). Based on the ATS criteria, those who had an FEV1/FVC of less than 70%, were identified as having obstructive disease; its severity was determined according to FEV1 decline. The patients with normal FEV1/FVC and decreased FVC (<80%) were diagnosed as having restrictive disease; its severity was determined by the decrease in FVC.Decrease in patients’ functionality was evaluated based on the used functional class in rheumatoid arthritis  and confidence interval of the variables. P values less than 0.05 were considered as statistically significant.Data were analyzed using SPSS software, version 16. The group data was introduced with the mean and standard deviation. Quantitative and qualitative data were analyzed using student's Overall, 99 patients and 65 health controls were studied. The mean (±SD) age of the studied patients in the case group was 46 (±10.5) years (range: 19-73). 89 (89.9%) patients were women and 10 (10.1%) were men. The control group consisted of 10 (15.4%) men and 55 (84.6%) women with a mean (±SD) age of 45.6 (±7.9) years . The difference in the mean ages of the patients in the case and control groups was not statistically significant (P=0.5). Also, there was no difference in sex distribution between these 99 patients and the 65 controls. None of the patients and controls smoked.The mean (±SD) duration of RA was 4.8 (±5.4) years. Of the 99 patients with RA, 81 (81.8%) patients were receiving methotrexate, 97 (98%) hydroxychloroquine, 3 (3%) sulfasalazine, and 1 (%1) was receiving non-steroidal anti inflammatory drug (NSAID). All the patients were receiving prednisolone.The mean (±SD) age of the patients at the onset of the disease was 41 (±11.3) years (range: 8-67). There were only six (1.6%) patients who had pulmonary complaints. Three (3%) patients had sputum and 5 (5.1%) patients had cough. All these six patients complained from dyspnea along with other symptoms, which was the most frequent reported pulmonary symptom.28 was 2.5 (±1.1) in the case group, which shows that many patients had DAS28 <2.6 which was the characteristic of the recovery phase of the disease.The mean (±SD) ESR in the patients was 17.5 (±11.6) (range: 2-60). 87 (87.9%) patients were in functional class I, 11 (11.1%) in class II, and one (1%) in class III. No patient was in the functional class IV. The mean (±SD) DAS25 , FEF50 , FEF75 , and FEF25-75  were significantly lower in the case group compared with the control group.Small airway involvement in patients with RA was confirmed. In pulmonary function studies, 93 (93.9%) patients were normal, 3 (3%) had mild restrictive, 2 (2%) mild obstructive, and one (1%) moderate obstructive diseases. In the control group, 64 (98.5%) individuals had normal tests and only one (1.5%) participant had mild restrictive pulmonary disease (P<0.05).We found no correlation between the patients’ age, duration and severity of the disease, and laboratory tests with spirometric indices.25-75, FEF75, FEF50, and FEF25 were significantly lower in the case group compared with the control group. This fact indicated small airway involvement in patients with RA. Many studies have been conducted on the prevalence of pulmonary disorders in the patients with RA. In such studies, various pulmonary tests including spirometry and high resolution CT have been performed for the assessment of the existence and the type of lung involvement. Based on the results of these studies the incidence of lung involvement in patients with RA was reported to be 38-65%  with PFT abnormalities. There was no significant correlation between laboratory tests , with PFT abnormalities either. Similar results were derived from the studies of There was no correlation between age and PFT abnormalities in our study. This was in contrast with the report of In our study, there was no significant correlation between the prevalence of PFT abnormalities with sex, which is in accordance with Our study had some limitations. Firstly, the patients in our study were selected from a university hospital, which could create bias in selecting patients with more severe involvement compared with patients at the community level, although all our patients were recruited from the hospital's outpatient clinic. The second limitation of our study was that we could not used additional pulmonary tests (including body-box) to evaluate the restrictive lung diseases more accurately. This test was not available in our center.Pulmonary involvement can be seen in patients with RA. While pulmonary involvement has a significant role in the mortality and morbidity of such affected patients, since the involvement progresses gradually with few signs and symptoms, most patients may not have obvious complaints. Therefore, it is recommended that patients with RA be visited on a regular basis and PFT be done for them for the early diagnosis of pulmonary involvement.


Salmonella enterica subsp. enterica serovar Enteritidis is generally considered to benefit from molecular techniques like multiple-locus variable-number of tandem repeats analysis (MLVA), which allow early detection and confinement of outbreaks. Here, a surveillance study, including phage typing, antimicrobial susceptibility testing and MLVA on 1,535 S. Enteritidis isolates collected between 2007 and 2012, was used to evaluate the added value of MLVA for public health surveillance in Belgium. Phage types PT4, PT8, PT21, PT1, PT6, PT14b, PT28 and PT13 dominate the Belgian S. Enteritidis population. The isolates of S. Enteritidis were most frequently susceptible to all antibiotics tested. 172 different MLVA profiles were detected, of which 9 frequent profiles included 67.2% of the S. Enteritidis population. During a serial passage experiment on selected isolates to investigate the in vitro stability of the 5 MLVA loci, no variations over time were observed indicating that the MLVA profiles were stable. The MLVA profile of isolates originating from different outbreaks in the Democratic Republic of the Congo (DRC) between 2010 and 2011 were distinct from any of the MLVA profiles found in Belgian isolates throughout the six year observational period and demonstrates that MLVA improves public health surveillance of S. Enteritidis. However, MLVA should be complemented with other subtyping methods when investigating outbreaks is caused by the most common MLVA profile.Surveillance of  Salmonella infections commonly cause self-limiting gastroenteritis, but severe infections including bacteraemia and meningitis have also been reported.Salmonellosis constitutes an important public health problem throughout the world with approximately 93.8 million illnesses and 155,000 deaths each year [In Belgium, non-typhoidal salmonellosis is, after campylobacteriosis, the most frequently reported foodborne illness .almonella infections are caused by consumption of contaminated food, person-to-person transmission, waterborne transmission and numerous environmental and animal exposures.SSalmonella comprises more than 2,579 serotypes [S. Enteritidis emerged in the 80’s in Europe and in America. The serotype is capable of systemic colonization of poultry, consequently leading to a contamination of eggs and poultry meat. With the introduction of a vaccination campaign in layer flocks in 2005, the incidence of human salmonellosis in Belgium drastically decreased [http://bacterio.wiv-isp.be) [The genus ecreased . The tot-isp.be) .Salmonella spp. contaminations in the entire food chain  together with sanitary measurements are essential to detect and prevent human Salmonella infections.Surveillance programs that timely detect Salmonella and Shigella (NRCSS) [Salmonella isolates from meat and meat products, isolated in the context of the official zoonosis monitoring program of the Federal Agency for the Safety of the Food Chain (FASFC), are also transferred to the NRCSS for serotyping and genotyping. In consequence the NRCSS possesses the most comprehensive and up to date data collection on human salmonellosis and Salmonella food chain contamination in Belgium [S. Enteritidis isolates are characterised by phage typing [Salmonella, depending on the molecular characteristics of both phage and phage receptor on the bacterial surface [In Belgium, data on human salmonellosis cases are centralized in the National Reference Centre for  (NRCSS) . In addi Belgium . Typing  Belgium . Traditie typing . This te surface . Phage t surface . The adv surface .S. Enteritidis. The advantage of PFGE is its relatively good discriminatory power. However, PFGE is time-consuming and laborious to perform which makes it less suitable for typing a large number of isolates. In addition, rigorous standardization of the applied protocols is necessary [Pulse field gel electrophoresis (PFGE) is generally accepted as being the “gold standard” for the genotyping of ecessary .S. Enteritidis has been published [More recently, a multilocus variable number of tandem repeat analysis (MLVA) harmonized protocol for subtyping of ublished ,11. ThisS. Enteritidis by comparing, within a panel of isolates submitted to NRCSS over the 6-year period 2007–2012, the MLVA profiles with the results of phage typing and antibiotic susceptibility testing and by evaluating the in vitro stability of MLVA loci in a serial passage experiment.The objective of the current study was to evaluate the potential of MLVA typing for surveillance and outbreak detection of human Salmonella strains isolated from human patients by peripheral clinical laboratories were transferred to NRCSS for serotyping  that were serotyped as Enteritidis, a random subset  of 1,498 isolates (34.3%) were analysed by phage typing, antimicrobial susceptibility testing and MLVA.In Belgium, and 2012 ). DuringIn addition, 37 isolates  collected during outbreaks in Congo between 2010 and 2011  [Serotyping of e scheme . Phage tKingdom) . A frequEscherichia coli ATCC 25922 strain. Multidrug resistance (MDR) was defined as resistance to 4 or more antibiotics.The susceptibility to 13 antibiotics was determined by the disk diffusion (Kirby-Bauer) method following recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and using Bio-Rad  disks . InhibitMLVA was performed as described previously . Liquid in vitro stability of the 5 MLVA loci was evaluated in 20 S. Enteritidis isolates with a frequent MLVA profile and a frequent phage type, in 2 S. Enteritidis isolates with a rare MLVA profile but with a frequent phage type and in 5 S. Enteritidis isolates from different outbreaks in the Democratic republic of the Congo (DRC) between 2010 and 2011. A single colony from a culture grown overnight on LB agar at 37°C was inoculated into 5 ml LB broth and incubated overnight at 37°C without shaking. Next, a series of 50 passages at a rate of two passages per day was performed by inoculating 20 μl of culture into 5 ml fresh LB broth and incubating at 37°C without shaking. Glycerol (25% v/v) stocks (-80°C) were made before each 5th passage. MLVA was performed on heated liquid cultures after every fifth passage, as described above, leading to a total of 363 typing tests [The ng tests .S. Enteritidis isolates was created in BioNumerics 6.5  using the categorical coefficient and no priority rules for the algorithm.A minimum spanning tree based on MLVA profiles of S. Enteritidis isolates with Simpson’s index of diversity (D) [The discriminatory power of phage typing, antibiotic susceptibility testing and MLVA was evaluated in the 1,498 randomly sampled sity (D)  and Shansity (D) . Shannonsity (D) .In the sample population of Belgian human isolates , 42 distinct phage types were present, nevertheless 1294 (86.4% of the sample population) isolates were attributed to the frequent phage types PT4 (19.0%), PT8 (18.6%), PT21 (16.3%), PT1 (11.7%), PT6 (8.5%), PT14b (4.6%), PT28 (4.1%) and PT13 (3.4%). The isolates with frequent phage types were not equally distributed over time . Phage tThe PT4 prevalence remained fairly stable until 2012 when a drastic and statistically significant (P < 0.001) increase was noted with a peak of 37.8%. The proportions of phage types PT28 and PT13 equally increased during the 6-year period. PT28 peaked in 2011 with a prevalence of 15.1% and this peak differed significantly from the values of the other years . On the other hand, PT6 remained stable until 2010 when a significantly decreased to 5.6% in 2012 was noted (0.05>p>0.02). Both PT1 and PT21 decreased significantly (P<0.001) during the study period showing a 2012 prevalence of 5.6% and 5.9% respectively. In 2010, PT14b showed a unique peak of 20.8% which was significant different (P<0.001) from the values found in the other years. Other phage types comprised each less than 3% of the isolate panel.S. Enteritidis were generally susceptible to all antibiotics tested (87.0%).Overall, the isolates of Eight point five percent % of isolates were resistant to nalidixic acid and 3.3% to ampicillin. Proportion of Nalidixic acid and ampicillin resistant isolates varied between 5.3% and 13.7% and 1.25% and 5.04%, respectively over the 6-year period.S. Enteritidis belonging to PT1 and PT14b showed resistance to nalidixic acid in 20.5% and 21.7% of the cases respectively.Prevalence of resistance to other antibiotics was between 0.1% for ciprofloxacin, 0.7% for cefotaxime and 1.4% for sulfamethoxazole .S. Enteritidis (1.3%).Multi-resistance to at least ≥ 4 antibiotics was quite uncommon across all S. Enteritidis isolates typed with MLVA targeting 5 loci, a total of 172 distinct MLVA profiles were detected. The highest number of different alleles was seen at locus SENTR5 (15), followed by loci SENTR6 (12), SENTR4 (7), SENTR7 (4) and SE3 (2).Among the 1,498 S. Enteritidis isolate (5.9% of the sample population), while 9 frequent MLVA profiles (5.2% of the MLVA profiles) comprised 67.2% of the S. Enteritidis isolates (S. Enteritidis isolates (Eigthy nine rare MLVA profiles (51.7% of the MLVA profiles) were detected in only one isolates . The MLVisolates .The isolates with frequent MLVA profile were not equally distributed over the years of the study period . ProfileAmong the most frequent phage types, the number of distinct MLVA profiles ranged from 15 for PT14b and to 51 for PT4 .Except for phage type PT13 and PT21, which showed a dispersed population of many different MLVA profiles, the most common MLVA profile for each phage type belonged to one of the frequent MLVA profile , Fig. 2belog(S), where S is the number of subtypes. Shannon’s E is a measure for the evenness of the subtype distribution [Diversity indices are commonly used as a measure for the discriminatory power, defining the ability to distinguish between unrelated isolates , of a suribution  and has To evaluate the added value of MLVA in case of outbreak detection, a subset of 37 isolates representative for sampling date and geography originating from different outbreaks in the Democratic republic of the Congo (DRC) between 2010 and 2011 were included in this study.MLVA typing of the 37 isolates revealed two major profiles: 2–13–3–3-NA (n = 16) and 2–15–3–3-NA (n = 14). In addition, there were three minor profiles: 2–14–3–3-NA and 2–16–3–3-NA  and profile 1–15–3–3–1 (1 isolate from a patient in Ngeba).The respective MLVA profiles were distinct from any of the MLVA profiles found in Belgian isolates throughout the six year observational period. The differences between 5 of the 6 detected MLVA profiles were minor and can be attributed to one variation of tandem repeat number in only one locus (SENTR5).in vitro stability of the number of tandem repeats in the MLVA loci, 27 S. Enteritidis isolates (22 isolates from Belgium and 5 from DRC) were subjected to a serial passage experiment  proving that a better discrimination was achieved by combining the phage typing method and MLVA. This is also demonstrated by the diversity and distribution indices. On the contrary, MLVA or phage typing might be sufficient to distinguish a cluster of isolates with rare MLVA profiles or phage types. This was also the case for the 37 outbreak isolates presented in this study.S. Enteritidis isolates, we observed that all the MLVA profiles remained stable in vitro proving the stability of the results obtained by this technique.In addition to the discriminatory power of a subtyping method, the stability of the assessed markers should be taken into account. From our serial passage experiment on S. Enteritidis collected during the 6-year period 2007–2012, and can thus improve public health surveillance. However, outbreak detection with MLVA is not straightforward, since for isolates with a frequent MLVA profile, phage typing is still necessary to achieve an unique, combined subtyping result. MLVA should be complemented with other subtyping methods when the investigated outbreak is caused by the most common MLVA profile.In conclusion, based on Simpson’s and Shannon’s indices, MLVA has a high discriminatory power for the 1,498


Acute gastroenteritis is a serious cause of child mortality and morbidity in resource-limited countries. A viral etiology is most common, and rotavirus and norovirus are reported to be the leading causative agents. There are still few epidemiological data on the simultaneous occurrence of these viruses in Morocco. The aim of this study was to provide useful epidemiological data on the gastroenteritis associated with rotavirus and norovirus among children aged less than 5 years.From January to December 2011, 335 samples were tested for rotavirus and norovirus using enzyme-linked immunosorbent assay, reverse-transcription-polymerase chain reaction (RT-multiplex PCR) and real-time RT-PCR. Partial sequences of the norovirus were phylogenetically analyzed to determine the genotype.The overall rates of rotavirus and norovirus infections were 26.6% and 16.1%, respectively. Mixed viral infections were detected in 9 of 335 stool specimens (2.7%).The most common genotype combination in the rotavirus strains was G1[P8] (51.7%), followed by G2[P4] (10.1%), G2[P8] (4.5%), G9[P8] (3.4%), G4[P8] (3.4%), and G1[P6] (2.3%). Among patients positive for norovirus, 42 (77.8%) tested positive for GII and 12 (22.2%) for GI. Thirty-three (78.6%) of the norovirus GII-positive cases were successfully characterized. Genotype GII.4 was the most prevalent , followed by GII.3 , GII.13 , GII.16 , and GII.17 .This study suggests that in Morocco, norovirus is the most frequent cause of acute gastroenteritis after rotavirus, but further enteric viruses need to be integrated in the surveillance system so that a conclusion could be drawn. Acute gastroenteritis is a very common disease in young children. It is characterized by massive inflammation of the gastrointestinal tract membranes, leading to frequent vomiting and/or diarrhea. Although regarded as a short-term intestinal disorder, acute gastroenteritis can cause severe dehydration, leading to further complications and hospitalization -3.Reoviridae (group A rotaviruses), Caliciviridae (noroviruses), Adenoviridae (adenoviruses 40/41), and Astroviridae (astroviruses) , G2P[4], G3P[8], G4P[8], and G9P[8], . RemarkaNorovirus is considered the second most frequent cause of severe childhood gastroenteritis after rotavirus . Its preFew data are available on the etiology of acute gastroenteritis among young children in Morocco. Only one study reports the detection of norovirus in shellfish in Morocco. Norovirus were detected in 30% of samples, with an equal representation of GI and GII strains, but were much more frequently found in cockles or clams than in oysters .The report of a national survey performed in 1998, describing the causes of child deaths, revealed that a high rate of mortality among children aged less than 5 years was attributed to diarrheal diseases. The number of these deaths in 1 year is estimated to be 6000 . In 2006In countries where the rotaviral vaccine has been introduced, there has been a decline in morbidity related to rotavirus-associated gastroenteritis. However, a mathematical increase of the percentage involved in gastroenteritis cases related to norovirus has been reported. Norovirus has consequently been designated the predominant cause of gastroenteritis in hospitalized children ,27,28.To address the paucity of data regarding norovirus infections, we assessed the features of acute gastroenteritis related to rotavirus and norovirus in four regions of Morocco.This prospective study was carried out as part of the regional rotavirus gastroenteritis surveillance network of the eastern Mediterranean region of the World Health Organization. The survey covered four geographically different regions of Morocco: the University Children’s Hospital in Rabat , Mohamed V Hospital in Tanger , Al Farabi Hospital in Oujda (eastern region), and Prefectoral Hospital in Beni-Mellal (southern region).In total, 335 fecal specimens were collected from children aged less than 5 years who were hospitalized or required medical care for acute gastroenteritis; Fourty six were from Rabat, 44 were from Tanger, 25 were from Beni-Mellal and 220 were from Oujda. The criteria for gastroenteritis were defined as follows: the acute onset of three or more loose stools, and/or two or more vomiting episodes a day that were not related to any other diagnosis, regardless of the fever conditions; stools with blood traces were excluded. A complete clinical examination was performed and a questionnaire was completed to collect the demographic data and clinical histories of the subjects.Stools were collected within the first 48 h of admission. Rotaviral infections were screened with an enzyme-linked immunosorbent assay . The sensitivity of the test was 96.6% (83.0–99.9%) and its specificity was 96.4% (81.6–99.9%). Rotavirus-reactive samples were stored at −70°C until their molecular characterization with reverse transcription-polymerase chain reaction (RT-multiplex PCR) ,25. RotaNorovirus infections were assessed using real-time RT-PCR with oligonucleotide primers and probes as described previously ,33, and The PCR products were sequenced with the same primers as were used for their amplification, with the ABI Prism BigDye Terminator Ready Reaction Cycle Sequencing Kit  and an ABI 3100 Genetic Analyzer (Applied Biosystems). DNA was sequenced in both directions using the BigDye Terminator cycling methodology (Applied Biosystems) and an ABI 3130xl Genetic Analyzer (Applied Biosystems). Sequences were aligned using ClustalW included in the Mega5.2 software . A phyloThe nucleotide sequence data were submitted to GenBank and assigned the accession numbers KJ162359–KJ162391.Informed consent was obtained from the parents or legal guardians of minors. The Ethics Office from the WHO and the Moroccan Ministry of Health deemed this surveillance as public health practice.2 and Fisher’s tests (EpiInfo version 3.4) and the Mann–Whitney test was used to compare the Vesikari score values. The level of statistical significance was set at 95%. The Fisher’s test is particularly useful when the expected value is less than five.Qualitative variables were compared with χAmong the 335 children enrolled in the study, 184 were boys and 151 were girls; the sex ratio  was 1.22. Their ages ranged between 1 and 59 months, with a median age of 12 months. The main clinical parameters related to acute gastroenteritis recorded in our study were the period of diarrhea, number of vomiting episodes, dehydration, and fever.All the patients studied had diarrhea for periods of 1–15 days, with a median duration of 2 days. The median number of vomiting episodes was five episodes per day among all the children, with a range of 0–15 episodes per day. Sixty-four percent of sufferers showed a high rate of vomiting episodes, and 61.3% experienced fever. Of the children enrolled, 30% showed moderate dehydration and 40% severe dehydration. Children aged less than 12 months were the most severely affected, with an estimated dehydration rate of 49%.The estimated rate of the rotaviral infection was 26.6% (89/335). The age of the children affected with rotavirus was between 2 and 59 months, with a median age of 12 months. The great majority (36%) of rotaviral infections occurred in children aged 6–12 months . Twenty-six patients (33.33%) experienced moderate dehydration, but 8 of the 78 rotavirus-infected children 10.26%) showed no symptoms of dehydration . Rabat and Tanger which are coastal cities had the highest percentages of norovirus positivity, during the study period. The difference between the coastal sites and non-coastal sites was statistically significant Table .The age The median period of diarrhea among the norovirus-infected patients was 2 days and the median number of vomiting episodes was five events per day. Of the 43 detected cases of noroviral infection, severe dehydration occurred in 13 (30.23%) children and 13 (30.23%) showed moderate dehydration. No dehydration was recorded in 17 norovirus-infected children (39.53%)  patients and were recorded in children with a median age of 24 months. The median period of diarrhea was 3 days and the median number of vomiting episodes was four per day.Of the nine patients with mixed rotavirus–norovirus infections, two showed severe dehydration (22.22%) and four (44.44%) showed moderate dehydration. Three of the nine coinfected children (33.33%) showed no signs of dehydration. The majority of rotavirus-norovirus dual infections were recorded between April and May , followed by G2P[4] (10.1%), G2P[8] (4.5%), G9P[8] 3.4%), G4P[8](3.4%) and G1P[6] (2.3%). A high prevalence of mixed strains was found (22.5%) and 2.1% of strains could not be typed  carried genotype GII and 12 (22.2%) carried genotype GI. A subset of the norovirus samples positive for GII was selected for sequence analysis, and 33 were successfully characterized in region C of the viral genome. The prevailing genotype was GII.4, accounting for 81.8% of infections (n = 27), whereas genotypes GII.3 and GII.13 each accounted for 6.1% of infections (n = 2).Other genotypes, GII.16 and GII.17, were each represented by one strain . The nucleotide sequence analysis showed that GII.4 was the most prevalent genotype. The variant strain designated “GII.4 variant Sydney 2012” was identified in two samples. A sequence analysis of these two samples based on a 302-bp sequence of the capsid gene (C-region) showed 99% identity with the variant Sydney 2012.A representative phylogenetic tree based on the nucleotide sequences of the capsid region (C-region) was constructed with the neighbor-joining method  tested positive for rotavirus and 16.1% (n = 54) for norovirus. Our results are consistent with several studies undertaken elsewhere, indicating that norovirus is the most common cause of acute gastroenteritis, after rotavirus -38.After the introduction of a rotavirus vaccine in the United States, hospitalizations related to acute gastroenteritis were 45% lower than 2 years earlier . A substIn Morocco, prior the implementation of the national immunization program with rotavirus vaccine, circulating isolates of rotavirus were genotyped in our facilities. From June 2006 to May 2009, 1388 stool samples were collected from children less than 5 years of age admitted for diarrhea in different regions of Morocco. Overall, 41.7% (579 of 1388) of the stools samples tested were positive for rotavirus. Genotyping of 548 (95%) samples demonstrated that G1P[8] (55%) was the most prevalent strain, followed by G9P[8] (11.3%), G2P[4] (9.1%), G4P[8] (0.9%), and G3P[8] (0.4%). Several other strains were identified including G1P[4] (0.2%), G1P[6] (0.9%), G2P[6] (4.3%), G2P[8] (0.2%), G3P[6] (0.4%), G3P[4] (0.2%), and G9P[6] (0.2%). A high prevalence of mixed infections was found  of which G1G2P[8] (4%) and G1G3P[8] (3.6%) accounted for the majority. Considerable diversity of rotavirus genotypes was present among circulating strains in Morocco . After iBecause the Moroccan childhood immunization program was implemented with a rotavirus vaccine in 2010, it is likely that norovirus-associated gastroenteritis will increase relative to rotavirus-associated gastroenteritis, as described by Patel et al.  and PaynBoth viruses were detected in all age groups examined in this study. The peak detection rate occurred between 6 and 12 months of age for rotavirus, with a median age of 12 months, and between 12 and 24 months of age for norovirus, with a median age of 14 months, as was also shown in a French study . These fDuring this 1-year survey, cases of rotavirus- and norovirus-associated gastroenteritis were recorded throughout the year, except in October and February, when no case of rotavirus and norovirus was detected, respectively. We observed one peak for rotavirus in January and two peaks for norovirus, in June. The increased rates of noroviral infection in spring and summer have been documented previously in Libya and Spain ,44. The In Morocco, spring and summer seasons are commonly associated with increased consumption of seafood particularly oysters, which is known as a risk factor for acquiring norovirus infection ,46. Raban = 27) was the predominant genotype, followed by GII.3 (n = 2) and GII.13 (n = 2), GII.16 (n = 1), and GII.17 (n = 1). Several global studies have demonstrated the prevalence of the GII.4 genotype and our results are consistent with them  and KJ162362 [Tanger/M687/2011/MOR]). This variant was first identified in March 2012 in Australia  and in DDual rotavirus-norovirus infections were detected in 2.7% of our study samples. Approximately the same rate was reported (2.1%) in a Polish study , but ourOur findings highlight the need to strengthen the surveillance of gastroenteritis and extend it to others regions in Morocco. This will allow us to monitor changes in the epidemiology of rotavirus- and norovirus-associated gastroenteritis and to identify dynamic shifts in the circulating strains.The authors declare that they have no competing interests.ME, MB, SA, and RE designed the epidemiological study, participated in its design and coordination, and gave their final approval to the version to be published. ME performed the molecular studies, participated in the sequence alignment, and drafted and edited the manuscript. HO and KS were involved in drafting the manuscript. NE performed the laboratory tests on the human stool samples. LB performed the statistical analysis and participated in its design. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/14/300/prepub


ATP8B1 or ABCB11 account for the majority of cholestasis with low GGT. But the ranges for GGT in patients with ATP8B1 or ABCB11 deficiency are unclear. This study tried to unravel the features of GGT in these patients that improve diagnostic efficiency.Genetic defects in ATP8B1 and/or ABCB11 from January 2012 to December 2015. Additional 17 patients with ATPB81 or ABCB11 deficiency diagnosed between January 2004 and December 2011 were also enrolled in this study. 600 population-matched children served as controls. Clinical data were obtained by retrospectively reviewing medical records.This study enrolled 207 patients with chronic cholestasis who were ordered to test for X2 = 10.363, P = 0.001). The remaining 96 patients exceeded the ranges described above and failed to receive a genetic diagnosis. These patients accounted for 43.8% of sequencing cost.A total of 26 patients were diagnosed with ATP8B1 deficiency and 30 patients were diagnosed with ABCB11 deficiency. GGT levels were similar between the two disorders at any observed month of age, but varied with age. The peak GGT value was <70U/L in the 2nd~6th month of life, <60U/L in the 7th~12th month and <50U/L beyond one year. GGT levels in patients with a genetic diagnosis were different from that in patients without a genetic diagnosis and controls. Larger ranges for GGT were found in patients without a genetic diagnosis. Some controls had GGT≥70U/L in the 2nd~6th month. Of the 207 patients, 39 (18.8%) obtained a genetic diagnosis. 111 patients met the ranges described above, including all the 39 patients with ATP8B1 or ABCB11 deficiency. The sensitivity was 100.0%. The rate of a positive molecular diagnosis increased to 35.1% (39/111 vs. 39/207, GGT levels in patients with ATP8B1 or ABCB11 deficiency varied with age. The peak GGT value was <70U/L in the 2nd~6th month of life, <60U/L in the 7th~12th month and <50U/L beyond one year. Cholestasis is one of the most common manifestations of liver disease in infancy and affects about 1 in 2500–5000 live births. A range of hepatobiliary disorders, that involve the process of bile acid biosynthesis, bile secretion and excretion, can result in cholestasis .ATP8B1, and can present as either progressive familial intrahepatic cholestasistype 1 (PFIC1) or benign recurrent intrahepatic cholestasis type 1 (BRIC1)  for non-normality. Comparison of GGT levels between two groups was done by the nonparametric Mann-Whitney test. Comparison of GGT levels among three or more groups was performed by the nonparametric Kruskal-Wallis H test. The difference between two ratios was tested by Chi-square test. 26 patients fulfilled the definition of ATP8B1 deficiency, including 1 heterozygote with weak canalicular GGT expression, 17 compound heterozygotes and 8 homozygotes . 30 diff30 patients were diagnosed with ABCB11 deficiency, including 4 homozygotes, 24 compound heterozygotes and 2 heterozygotes with absent BSEP expression . SequencP = 0.819). GGT levels in patients without a genetic diagnosis were higher than that in patients with a genetic diagnosis . In addition, no significant difference was found when the rates of CMV infection were compared between patients with and without a genetic diagnosis .Only serum ALT and GGT activities in patients without a genetic diagnosis were different from that in the ATP8B1 deficiency and the ABCB11 deficiency simultaneously when liver function test results at presentation were compared among the three groups . HoweverA comparison of GGT levels between the ATP8B1 deficiency and the ABCB11 deficiency revealed that GGT levels were similar between the two disorders at any observed month of age . HoweverX2 = 78.430, P = 0.000; nd month of life were similar to that in the 3rd month. But GGT levels in the 2nd~3rd month were higher than that in the 4th~6th month, while they were similar among the 4th~6th month. When GGT levels were compared among the 7th~12th month, the difference was not significant. GGT levels in the 7th~12th month were higher than that beyond 1 year, but were lower than that in the 2nd~3rd month and the 4th~6th month.Significant difference was observed when GGT levels were compared among different ages by month in patients with a genetic diagnosis . But relatively larger ranges were found in patients without a genetic diagnosis and controls. Serum GGT activities in controls reached adult range (<50U/L) in the 7th month of life. However, one patient with ATP8B1 deficiency and two patients with ABCB11 deficiency had GGT≥50U/L in the 7th~12th month. Serum GGT activities of 117 tests revealed that the peak GGT value in patients with a genetic diagnosis was lower than 60U/L in the 7th~12th month. All patients with a genetic diagnosis had GGT<50U/L beyond one year, while 37.2% of patients lacking a genetic diagnosis still had GGT≥50U/L.Similar ranges for GGT were found in patients with a genetic diagnosis in the 2th month . Serum GATP8B1 and/or ABCB11 between January 2012 and December 2015, received a molecular diagnosis. The overall rate of a positive molecular diagnosis was 18.8%. GGT levels of 111 (53.6%) patients were found to meet the ranges described in patients with a genetic diagnosis. All the 39 patients with ATP8B1 or ABCB11 deficiency were included in the 111 patients. The sensitivity was 100.0%. The rate of a positive molecular diagnosis increased to 35.1% . 67 (60.4%) of the 111 patients were ordered to test for both genes, 21 (31.3%) obtained a molecular diagnosis. The 21 patients included 3 patients whose causal gene was identified when the second gene was tested. 44 of the 111 patients were ordered to test for ATP8B1 or ABCB11 only, 18 (40.9%) received a molecular diagnosis . GGT activities of the remaining 96 (57.1% of subjects lacking a genetic diagnosis and 46.4% of the 207 patients) patients exceeded the ranges described above. These patients failed to fulfill the definition of ATP8B1 or ABCB11 deficiency, and accounted for 43.8% of sequencing cost  at 6 months old. Therefore, we concluded that GGT<70U/L in the 2nd~6th month, <60U/L in the 7th~12th month and <50U/L beyond one year were important features of patients with ATP8B1 or ABCB11 deficiency.Similar to healthy infants –12, GGT eviously  and contATP8B1 and ABCB11. However, the rates of a positive molecular diagnosis were similar between patients testing for both genes and patients testing for one gene (P = 0.301). This might attribute to clinic and laboratory differences between the two disorders as reported previously [It was known that ATP8B1 deficiency and ABCB11 deficiency accounted for the majority of patients with low GGT. These explained why 60.4% of patients whose GGT levels met the ranges described above were ordered to test for both eviously . We propeviously ) also caeviously  or wholeeviously  might beATP8B1 and/or ABCB11 could be assigned to a molecular diagnosis. 46.4% of patients had GGT activities over the ranges described above. Of these patients, other genetic defects should be taken into consideration. If these patients were waived from testing for these genes, the rate of positive molecular diagnosis would increase greatly. Meanwhile, 43.8% of the sequencing cost would have been saved.In fact, the ranges for GGT in patients with ATP8B1 or ABCB11 deficiency were unclear when genetic tests were ordered. This caused some patients with elevated GGT were ordered to test for the two genes and resulted in a low rate of positive molecular diagnosis. According to our data, only 18.8% of patients who tested for nd~6th month, <60U/L in the 7th~12th month and <50U/L beyond one year of age. If only patients whose GGT levels met the ranges were ordered to test for these genes, the overall rate of a positive molecular diagnosis would have increased greatly. This also resulted in approximately 1/2 of sequencing cost saving.GGT levels in the ATP8B1 deficiency were similar to that in the ABCB11 deficiency at any observed month of age. Similar to healthy infants, GGT levels in these patients also varied with age. But GGT levels in these patients were different from that in patients without a genetic diagnosis and controls. The peak GGT value was <70U/L in the 2S1 Checklist(DOC)Click here for additional data file.S1 Table(DOC)Click here for additional data file.


The chronically critically ill patient comes from an acute critical patient who survived the initial insult and did not recover their physiological baseline functions, depending on life support for weeks to months, especially on mechanical ventilation support. In literature, the most frequent definitions are the tracheostomy need or length of stay of at least 8 days in ICU.Describe and compare clinical and epidemiological data of chronic and acute critically ill patients in severe sepsis and septic shock.Historical cohort. We analyzed 1293 patient charts from 4 intensive care units from January to December 2013. Patients were included if had at least 18 years old and had severe sepsis or septic shock with a minimum survival of 24 hours after the diagnosis. The cases were divided into 2 cohorts: the chronic critical patient  and the acute critical patient .We analyzed 352 cases of severe sepsis (33.2%) and septic shock (66.8%). The average age was 65 (range 18 to 98), and 53.1% were men. The APACHE II average score was 20.9. Lung (58% vs 43.3% p = 0.017) and bloodstream (25% vs 7.5% p < 0.001) were the most prevalent sepsis focuses in the chronic cohort, but in the acute cohort were abdomen (22.2% vs 1% p < 0.001) and urine (15.5% vs 5% p = 0.007). There was no significant difference comparing SOFA, leukocytes, lactate and PCR, except the maximum respiratory frequency and the maximum temperature, these variables tended to have larger average values in chronically critical patients . When comparing life support need, there was an increased use of mechanical ventilation (86.9% vs 73.3% p = 0.01) and lower use of dobutamine (7% vs 17.5% p = 0.019) by chronically critically ill patients. The most common class of antibiotics in the chronic cohort was carbapenems  and in the acute cohort it was anti-Pseudomonas penicillin (31% vs 16.2% p = 0.007). The largest duration of antibiotic therapy was on chronically critically ill patients (7.3 days vs 9.6 days p < 0.001). Analyzing the outcomes, the length of stay in the chronic group was higher (27.1 days vs 11.9 days p < 0.001). Also, the mortality rate until the 21st day of stay in ICU was higher in the acute cohort than in the chronic cohort, although the mortality rate in 60 days was higher in the chronic cohort .The profile of chronically critically ill is different from the acute patient. Chronic ill patients have more lung and blood infection as well as dependence on mechanical ventilation as life support. Besides, the chronically critically ill have a higher survival rate in the first 21 days in ICU; however, after that period, they begin to show a progressively higher mortality.


Studies suggest that rates of anaphylaxis, the most severe form of an allergic reaction, are increasing in Pediatric Emergency Departments (PED). Significant gaps still exist regarding the prevalence, triggers and temporal trends of anaphylaxis in Canada. The Cross-Canada Anaphylaxis Registry (C-CARE) was created with the primary goal of determining the societal burden of anaphylaxis in Canada; our aim was to use C-CARE to examine temporal trends in anaphylaxis rates.Over a 2-year period (April 2011 to April 2013), children presenting to the Montreal Children’s Hospital PED with anaphylaxis were recruited. The treating physician documented characteristics and triggers of anaphylactic reactions using a standardized data entry form. Charts of all PED patients were reviewed to identify anaphylactic cases that were missed in prospective recruitment.Among 81,677 PED visits in Year 1, 168 anaphylaxis cases were identified (0.21%) versus 218 anaphylaxis cases among 78,650 PED visits in Year 2 (0.27%), yielding a difference of 0.06%  between the two years. The median age of anaphylaxis was 4.8 years (IQR: 2.3-10.1) in Year 1 and 5.9 years (IQR 2.1-11.1) in Year 2. There was a slightly higher male predominance in cases of anaphylaxis in both Year 1  and Year 2 . The major triggers in both years were food allergens (87.5% and 80.6% respectively) with peanut being the most predominant (29.5% and 20.6%) followed by tree nuts (15.5% and 14.8%). Severe anaphylaxis  was found in 7.1%  of patients from Year 1 versus 3.7%  in Year 2.There was a greater rate of anaphylaxis in the second year of the C-CARE study. In both years, food allergens were found to be the most common trigger with peanuts being the most common food. These results are comparable to the increasing rates of anaphylaxis seen in other westernized countries. Future studies in the Montreal Children’s Hospital as well as in other centers are required to establish temporal trends in anaphylaxis rates, triggers and reaction characteristics.