Quinazolinone-based benzenesulfonamides with low toxicity and high affinity as monoamine oxidase-A inhibitors: Synthesis, biological evaluation and induced-fit docking studies.

The research in selective monoamine oxidases (MAO-A and MAO-B) inhibitors has been increased due to their therapeutic value for neurodegenerative diseases. In this study, 4-((2-(aryl)-4-oxoquinazolin-3(4H)-yl)amino)benzenesulfonamides were synthesized and their MAOs inhibition potentials were investigated applying in vitro fluorometric technique. The most potent compounds 7 and 8 against MAO-A had IC50 values of 0.058 ± 0.002 and 0.094 ± 0.003 µM, respectively, while the reference moclobemide had an IC50 value of 6.061 µM. Compounds 7 (>1724 times) and 8 (>1063 times) more selective and reversible inhibitors of MAO-A rather than MAO-B. Toxicity studies of 7 (IC50 = 210.23 µM) and 8 (IC50 = 259.27 µM) showed that compounds can be considered as non-toxic towards SH-SY5Y cell line at their effective concentrations against MAO-A. In silico docking simulations successfully explained the observed activities and also highlighted structural water molecules to play a key role in the ligand-enzyme interactions. Calculated molecular descriptors are also obeying Lipinski's rule of five and brain/blood partition coefficients, a critical parameter in neurodegenerative diseases. These reversible inhibitors can have considerable advantages compared to irreversible inhibitors which may possess serious pharmacological side effects.

Fecal elastase levels in children diagnosed with functional abdominal pain-not otherwise specified.

BACKGROUND: Although the exact pathophysiology of functional gastrointestinal diseases remains unclear, numerous etiologies have been blamed, including visceral hypersensitivity, gastrointestinal motility disorders, psychological factors, intestinal mucosal inflammation, intestinal microbiota, and post-infectious syndromes. In the present study, we aimed to evaluate pancreatic insufficient patients diagnosed with functional abdominal pain-not otherwise specified (FAP-NOS) according to Rome IV criteria. METHODS: The study included a total of 110 patients aged 4-17 years who were diagnosed with FAP-NOS according to Rome IV criteria. The control group consisted of 80 patients with no gastrointestinal disorders and chronic diseases. Glucose, amylase, lipase, pancreatic amylase, immunoreactive trypsinogen (IRT) and fecal elastase (FE-1) levels were examined for each patient. RESULTS: No significant difference was found between the two groups with regard to lipase, pancreatic amylase, IRT, and serum glucose levels. However, the amylase levels were significantly higher and the FE-1 levels were significantly lower in the study group compared to the control group (p=0.007 and p < 0.001). The cut-off value detected in in ROC analysis for the diagnostic value of FE-1 in predicting FAP-NOS was found to be 140.107 µg/g. Based on this value, the sensitivity, specificity, PPV, and NPV of FE-1 were 82.1%, 66.2%, 77%, 73%, respectively. Accordingly, the likelihood of FE-1 in providing a positive value in patients with FAP-NOS was almost 9 times higher than in individuals without FAP-NOS. CONCLUSIONS: FE-1 levels were significantly lower in children diagnosed with FAP-NOS and we consider that this difference could be attributed to malabsorption secondary to dysbiosis as there is not enough data.

Static postural balance evaluation and an investigation of the relationship with joint health in children with severe haemophilia: a controlled cross-sectional study.

INTRODUCTION: Recurrent hemarthroses disturbing force/movement control are likely to impair postural balance. AIM: To investigate the possible changes in static postural balance parameters in children with haemophilia (CwH) and to reveal its relationship with Haemophilia Joint Health Score (HJHS). METHODS: Twenty-one CwH aged 6-18 who had haemophilic arthropathy in at least one lower limb joint and 21 healthy peers were evaluated by using a force platform. Centre of pressure (CoP) signals were displayed as a map in both anteroposterior direction (APD) and mediolateral direction (MLD) by statokinesigram. Accordingly, the amplitude, velocity and standard deviation of CoP displacements along with the perimeter and ellipse area were measured. Assessments were made under eyes opened and eyes closed in bipedal stance for 60 s. Joint health and muscle strength were evaluated with HJHS and digital dynamometer, respectively. RESULTS: Velocity and amplitude of CoP displacements in MLD were increased in CwH (p˂0.05). It was also found that these parameters were moderate correlated with the clinical score of the lower limb joints (p˂0.05). In CwH, standard deviation of CoP displacements in the APD was significantly higher in eyes closed, while standard deviation in MLD was significantly higher in eyes opened (p˂0.05). CONCLUSION: Disturbances during bipedal stance reveal the need for balance evaluation in CwH. Increased mediolateral oscillations may be an early sign of disorders of the musculoskeletal system in CwH. In addition to improving joint health, postural balance exercises that increase MLD stability have to be included in the rehabilitation programme of CwH.

Identification of three novel pathogenic ITGA2B and one novel pathogenic ITGB3 mutations in patients with hereditary Glanzmann's thrombasthenia living in Eastern Turkey.

Glanzmann's thrombasthenia (GT) is an autosomal recessive disorder in which the underlying problem is the lack or dysfunction of the GpIIb/IIIa receptor on the platelet surface. The present study determines the genetic mutation typology and analyzes the association between mutation types and clinical findings in patients diagnosed with GT who were followed up in Department of Pediatric Hematology of the Yüzüncü Yil University School of Medicine. The medical charts of 17 patients who underwent therapy and that were followed up in the Department of Pediatric Hematology of the Yüzüncü Yil University Dursun Odabas Medical Center between January 2008 and April 2018 were reviewed retrospectively. Data on such patient characteristics as present genetic mutations, age, gender, age at diagnosis, presenting symptoms, clinical findings, and platelet count and volume were garnered from the patient records. Of the 12 patients identified with genetic mutations, six had the same type of mutation, while four were identified with novel mutations that have to date not been defined in literature. Of these four mutations, three were located in the ITGA2B gene and one in the ITGB3 gene. The present study identified no significant association between the genetic and clinical findings of the patients. Novel mutations were identified in four cases in the present study. No association was found between the mutation type, and the bleeding scores and bleeding phenotypes of the patients. Further studies involving a larger number of patients are required to determine the relationship between the genotypes and clinical findings in patients with GT.

Muscle strength and joint health in children with hemophilia: a cross-sectional study.

BACKGROUND AND OBJECTIVES: We aimed to evaluate joint health in children with hemophilia (CwH) and to investigate the effects of hemarthrosis on the musculoskeletal system. METHOD: Forty-one CwH aged between 6-18 years participated in the study. Joint health status was evaluated according to Hemophilia Joint Health Score (HJHS). Pain intensity level was assessed in resting and in activity using Visual Analog Scale. Range of motion was measured with goniometer and muscle strength was assessed with digital dynamometer. Arthropathic joints were examined in three groups named knee, elbow and ankle. RESULTS: Physical examination revealed arthropathy findings to be found in 29 knee, 19 elbow and 18 ankle joints. The median of flexion angle of the affected side were 120°, 122° and 12° for the knee, elbow and ankle and extension losses of these joints were 5°, 7° and 0, respectively. In CwH having knee and elbow arthropathy, index joint HJHS was found to be significantly higher than those with ankle arthropathy (p < 0.01). The flexor and extensor muscle strength significantly decreased in 11 CwH with unilateral elbow arthropathy compared to the non-arthropatic side (p < 0.05). In 15 CwH with unilateral ankle arthropathy decreased in the extensor muscle strength (plantarflexors) (p < 0.05). Extension loss showed a good correlation with index HJHS of elbow, knee and ankle joints, respectively. (rs= 0.599, 0.576, 0.606, p < 0.01). We observed that the muscle strength of elbow flexors/extensors and ankle extensors were significantly decreased compared to the non-arthropathic side. However this situation was not detected in knee joint despite having highest index HJHS. CONCLUSION: Our findings indicate that hemarthrosis may cause more muscle strength loss in the upper extremity than the lower extremity. Furthermore, extension loss was found to be an important parameter in physical examination of hemophilic arthropathy. Musculoskeletal system should be evaluated comprehensively at regular intervals and when necessary rehabilitative treatment should be planned.

Multicenter Hospital-Based Prospective Surveillance Study of Bacterial Agents Causing Meningitis and Seroprevalence of Different Serogroups of Neisseria meningitidis, Haemophilus influenzae Type b, and Streptococcus pneumoniae during 2015 to 2018 in Turkey.

The etiology of bacterial meningitis in Turkey changed after the implementation of conjugated vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) in the Turkish National Immunization Program (NIP). Administration of Hib vaccine and PCV-7 (7-valent pneumococcal conjugate vaccine) was implemented in NIP in 2006 and 2009, respectively. In 2011, PCV-7 was replaced with PCV-13. Meningococcal vaccines have not yet been included in Turkish NIP. This prospective study comprised 27 hospitals located in seven regions of Turkey and represented 45% of the population. Children aged between 1 month and 18 years who were hospitalized with suspected meningitis were included. Cerebrospinal fluid (CSF) samples were collected, and bacterial identification was made according to the multiplex PCR assay results. During the study period, 994 children were hospitalized for suspected meningitis, and Hib (n = 3, 2.4%), S. pneumoniae (n = 33, 26.4%), and Neisseria meningitidis (n = 89, 71%) were detected in 125 samples. The most common meningococcal serogroup was MenB. Serogroup W comprised 13.9% (n = 5) and 7.5% (n = 4) of the meningococci in 2015 to 2016 and 2017 to 2018, respectively. Serogroup C was not detected. There were four deaths in the study; one was a pneumococcus case, and the others were serogroup B meningococcus cases. The epidemiology of meningococcal diseases has varied over time in Turkey. Differing from the previous surveillance periods, MenB was the most common serogroup in the 2015-to-2018 period. Meningococcal epidemiology is so dynamic that, for vaccination policies, close monitoring is crucial.IMPORTANCE Acute bacterial meningitis (ABM) is one of the most common life-threatening infections in children. The incidence and prevalence of ABM vary both geographically and temporally; therefore, surveillance systems are necessary to determine the accurate burden of ABM. The Turkish Meningitis Surveillance Group has been performing a hospital-based meningitis surveillance study since 2005 across several regions in Turkey. Meningococcus was the major ABM-causing agent during the 2015-to-2018 period, during which MenB was the dominant serogroup.

Evaluation of Renal Function Disorder With Urinary Neutrophil Gelatinase-associated Lipocalin Level in Patients With ß-Thalassemia Major.

BACKGROUND AND AIM: Neutrophil gelatinase-associated lipocalin (NGAL) is found in the granules of human neutrophils, with many diverse functions. Expression of NGAL is induced under various pathophysiological conditions, for example, infection, inflammation, kidney injury, cardiovascular disease, burn injury, and intoxication, and it has an important antiapoptotic and anti-inflammatory role. PATIENTS AND METHODS: A total of 37 patients with thalassemia disease ß-thalassemia major (24 male and 13 female individuals) and 37 healthy controls (17 male and 20 female) were enrolled in this study. All patients were regularly transfused, and all of them were using oral chelator, deferasirox. RESULTS: NGAL and cystatin C levels were significantly higher in the case group than in the control group. CONCLUSION: In patients with ß-thalassemia major, renal damage can occur owing to regular blood transfusion. Urinary NGAL levels in these patients may be considered as a marker for early renal injury.

Typhoid Fever Accompanied With Hematopoetic Lymphohistiocytosis and Rhabdomyolysis in a Refugee Child.

Typhoid fever is an acute and systemic infectious disease that is specific to humans and is caused by Salmonella typhi. Patients may present with different findings ranging from simple fever to multiple organ failure. Hemophagocytosis and rhabdomyolysis are rare complications of typhoid fever. In this study, we presented a case of hemophagocytic lymphohistiocytosis and rhabdomyolysis in a 14-year-old girl who migrated from Mosul, Iraq, 1 month ago.

Use of a High-Purity Factor X Concentrate in Turkish Subjects with Hereditary Factor X Deficiency: Post Hoc Cohort Subanalysis of a Phase 3 Study.

Hereditary factor X (FX) deficiency is a rare bleeding disorder more prevalent in countries with high rates of consanguineous marriage. In a prospective, open-label, multicenter phase 3 study, 25 IU/kg plasma-derived factor X (pdFX) was administered as on-demand treatment or short-term prophylaxis for 6 months to 2 years. In Turkish subjects (n=6), 60.7% of bleeds were minor. A mean of 1.03 infusions were used to treat each bleed, and mean total dose per bleed was 25.38 IU/kg. Turkish subjects rated pdFX efficacy as excellent or good for all 84 assessable bleeds; investigators judged overall pdFX efficacy to be excellent or good for all subjects. Turkish subjects had 51 adverse events; 96% with known severity were mild/moderate, and 1 (infusion-site pain) was possibly pdFX-related. These results demonstrate that 25 IU/kg pdFX is safe and effective in this Turkish cohort (ClinicalTrials.gov identifier: NCT00930176).

Initial Lymphocyte Count as Prognostic Indicator for Childhood Immune Thrombocytopenia.

Acute ITP is a benign, self-limiting disease. Chronic ITP is diagnosed when thrombocytopenia persists beyond 12 months. The main objective of the present study was to examine whether absolute lymphocyte counts at diagnosis has predictive value with chronic ITP. A total of 601 patients diagnosed as ITP between 1995 and 2014 were retrospectively evaluated. CBCs with differential counts were performed at presentation for 601 patients. Absolute lymphocyte counts at presentation were independently predictive of disease duration. The male to female ratio was almost 1:1 and 25.9 % (156/601) of the patients had chronic ITP. We determined that age >6.75 year, platelet counts >6.950/mm3 and absolute lymphocyte counts ≤2.050/mm3 was associated with a significant risk for developing chronic ITP. Absolute lymphocyte counts at the time of diagnosis were predictive variables for the development of chronic ITP. Further researches are needed to confirm the current finding and to assess the underlying pathophysiology with the course of the ITP in observational studies.

Cutaneous side effects of doxycycline: a pediatric case series.

OBJECTIVE: Brucellosis is highly endemic in Turkey and doxycycline is commonly used for its treatment. The present study aimed at documenting the cutaneous side effects of doxycycline in pediatric brucellosis patients in Turkey. MATERIALS AND METHODS: Pediatric patients with brucellosis that were treated between February 2014 and January 2016 were analyzed retrospectively, and those that developed doxycycline-related cutaneous side effects were identified. Demographic data, epidemiological history, physical examination findings, laboratory test results, anti-brucellosis treatment regimen, duration of follow up and outcome were recorded. RESULTS: Among the 189 brucellosis patients, 141 treated with doxycycline plus rifampicin. Seven patients (5%) (two female and five male) developed doxycycline-related cutaneous side effects. Mean duration of treatment before the onset of cutaneous side effects was 9.5 weeks. Doxycycline therapy was continued in five of these patients and was changed in two patients. In the patients that continued to receive doxycycline the cutaneous side effects gradually improved. CONCLUSIONS: Cutaneous side effects of doxycycline should always be a consideration, especially in regions in which brucellosis is endemic and doxycycline is commonly used to treat it.

Brucellar Aortitis and Meningoencephalitis in an Adolescent.

Brucellosis can affect any organ system and result in possible complications. We present an adolescent male who had brucellar aortitis and meningitis simultaneously. Brucellar aortic involvement is a rare complication of brucellosis and can occur without concomitant endocarditis. Here, the patient was managed with prolonged antibiotic therapy without any surgery.

An analysis of children with brucellosis associated with haemophagocytic lymphohistiocytosis.

This retrospective study included seven paediatric cases aged from 4 to 14 (10.2±3.4) years with pathologically proved haemophagocytic lymphohistiocytosis from a single institution during 2009 and 2013. Over this time period, 496 patients with brucellosis were diagnosed. None of the patients (3 boys and 4 girls) had a history of any haematologic disorder. All patients had an anamnesis for recently consumed unpasteurised homemade dairy products or had a contact history with sheep and/or cows. The diagnosis of brucellosis was confirmed by standard tube agglutination test in all patients; titres were 1: 1280 in seven patients. Blood culture was positive for Brucella melitensis in three patients (42%). Bone marrow cultures were positive for B. melitensis in four patients (57%). Fever was present in all patients (100%) with haemophagocytic lymphohistiocytosis. The other most common symptoms were malaise, myalgia, anorexia, sweating and weight loss. In addition, sweating was observed in five patients, and lymphadenopathy, petechiae, and weight loss were observed in one patient. Hepatomegaly, splenomegaly, and hepatosplenomegaly were found in four (57%), six (85%) and four (57%), patients, respectively. Haemophagocytosis was documented in bone marrow examinations of all children except in two cases. All patients recovered completely, and their peripheral blood counts returned to normal by 2 to 4 weeks after antibiotic treatment of brucellosis.

Evaluation of the Hemostatic Disorders in Adolescent Girls with Menorrhagia: Experiences from a Tertiary Referral Hospital.

Bleeding disorders are a common cause of menorrhagia in the adolescent age group. We aimed to evaluate the incidence of hemostatic disorders, using clinical and laboratory findings of bleeding disorders in adolescent girls with menorrhagia. A retrospective chart review used to evaluate adolescent girls with menorrhagia who were referred to Yuzuncu Yil University Pediatric Hematology clinic between January 2010 and December 2014. Out of 52 patients referred for investigation, 50 patients were included in the study. The mean age and mean menarche age were 14.8 ± 1.42 (range: 12-17) and 12.47 ± 0.55, respectively. In 42 % (n = 21) of patients, anemia was detected. In 22 % (n = 11) of patients, a bleeding disorder was detected: five cases with von Willebrand disease, two cases with acute immune thrombocytopenic purpura, one case with Bernard-Soulier syndrome, one case with Glanzmann thrombasthenia, one case with aplastic anemia and one case with factor X deficiency. The remaining 39 out of the 50 patients were finally diagnosed with dysfunctional uterine bleeding. When compared the patients with bleeding disorders and without bleeding disorders, bleeding from other sites, including gingival bleeding or epistaxis, low platelet counts and prolonged activated partial thromboplastin time were found statistically more frequent in patients with bleeding disorders (p < 0.05). Menorrhagia in adolescents is frequently associated with underlying bleeding disorders. Adolescents with heavy menstrual bleeding and a history of nose or gingival bleeding should be evaluated for congenital bleeding disorders.

Hematologic Findings in Children With Brucellosis: Experiences of 622 Patients in Eastern Turkey.

The aim of the present study was to present the hematologic findings of 622 cases diagnosed with acute brucellosis. Medical records of children with brucellosis, admitted to Yuzuncu Yil University Hospital over a 6-year period, were analyzed retrospectively. Three hundred ninety-seven (63.8%) patients were male and 225 (36.2%) were female. The mean age was 11 years (range, 1 to 16 y). The mean hematologic values were as follows: hemoglobin 9.4 (3.4 to 17) g/dL, hematocrite 28% (12% to 50%), leukopenia 2.8 (1.1 to 33)×10/L, leukocytosis 13.7 (1.1 to 33)×10/L, and platelets 79 (3 to 972)×10/L. An overall 28.6% of patients were found to have anemia, alone or in combination with leukopenia or thrombocytopenia. Sixteen percent of patients had thrombocytopenia, 13.9% had leukopenia, 7.7% had pancytopenia, and 4% had both leukopenia and thrombocytopenia. Hematologic complications such as anemia, thrombocytopenia, and leukopenia are more frequently seen in acute brucellosis cases. However, acute brucellosis should also be considered in the differential diagnosis in the presence of other hematologic abnormalities such as severe thrombocytopenia, bicytopenia, and pancytopenia.

Diagnostic evaluation of our patients with hemophilia A: 17-year experience.

AIM: Hemophilia A is a rare inherited bleeding disorder resulting from factor VIII deficiency and is a group of diseases characterized by intra-articular and intramuscular bleeding. In this study, we aimed to retrospectively evaluate the treatment outcomes, demographic and clinical characteristics of our patients who were treated and followed up for last 17 years in our pediatric hematology unit with a diagnosis of Hemophilia A. MATERIAL AND METHODS: The medical records of 83 patients who were diagnosed with Hemophilia A and followed up between 1997 and 2014 in our hospital's pediatric hematology clinic were reviewed retrospectively. The demographic data, prophylaxis state, development of inhibitors and clinical characteristics of the patients were evaluated. RESULTS: When the complaints at presentation were examined, it was found that 27 (32%) patients had hemarthrosis, 24 (29%) patients had ecchymosis and hematoma, 13 (16%) patients had prolonged bleeding after trauma or cut, 10 (12%) patients had gingival, mouth or nose bleeding, 4 (5%) patients had prolonged bleeding after circumcision, 4 (5%) patients had gastrointestinal bleeding, 1 (1%) patient had hematuria. Fifty (60%) patients were considered severe hemophilia A, 20 (24%) patients were considered moderate hemophilia A and 13 (16%) patients were considered mild hemophilia A according to factor activity. Among severe hemophilia A patients, primary prophylaxis was being administered in 2 (2%) patients and secondary prophylaxis was being administered in 40 (48%) patients. Inhibitor positivity was found in 8 (10%) of these patients. It is found that hemophilic artropathy developed in 17 patients and 8 of these 17 patients had undergone radioisotope synovectomy. CONCLUSIONS: Treatment of severe bleeding in hemophilia A patients should be performed in hospital and the presence of inhibitor must be investigated in cases of uncontrolled bleeding where adequate doses of factor concentrates have been administered for treatment. In order to decrease the development of inhibitor, prophlaxis should be suggested to patients rather than repetetive treatment when bleeding occurs. The radioactive synovectomy should not be overlooked in countries like ours in which factors can not be used adequately.

Frequency of the p.Gly262Asp mutation in congenital Factor X deficiency.

INTRODUCTION: Congenital factor X (FX) deficiency is a rare bleeding disorder inherited as an autosomal recessive trait with an incidence of 1 : 500 000-1 000 000. A total or partial deficiency of FX causes an impairment of clot formation, leading to a haemorrhagic disease, which manifests with bleeding symptoms of different severity, also unprovoked. AIM: We analysed the clinical manifestations, laboratory phenotype and genotype in 12 patients from Turkey affected with severe FX deficiency. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT), FX activity (FX:C) and FX antigen level (FX:Ag) were measured, and mutation analysis was performed for all patients. RESULTS: The most frequent bleeding episodes in patients were epistaxis and easy bruising (11/12, 91%), followed by haemarthroses (10/12, 83%). FX:C was <1% in 11 patients, and 4% in one. FX:Ag was reduced in all patients, consistent with type II deficiency. Direct sequencing of the factor X gene (F10) identified two different mutations: the novel 33 bp in-frame deletion p.Thr176_Gln186, c.526_558del, which seems to be associated with milder bleeding symptoms and the c.785G>A, p.Gly262Asp missense mutation (previously reported as Gly222Asp), which is associated with severe bleeding symptoms. CONCLUSION: The p.Gly262Asp missense mutation was identified in 11 of the 12 patients in this study. Previously published cases on the same p.Gly262Asp mutation were Iranian patients originating from the border between Turkey and Iran suggesting that this mutation may be candidate as a good tool for mutational screening analysis in this area.

Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005-2012 in Turkey. A multicenter prospective surveillance study.

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey.

Recognizing true H5N1 infections in humans during confirmed outbreaks.

INTRODUCTION: The goal of this study was to evaluate whether any characteristics that are evident at presentation for urgent medical attention could be used to differentiate cases of H5N1 in the absence of viral testing. METHODOLOGY: Information about exposure to poultry, clinical signs and symptoms, treatments, and outcomes was abstracted from existing data in the global avian influenza registry (www.avianfluregistry.org) using standardized data collection tools for documented and possible cases of H5N1 infection who presented for medical attention between 2005-2011 during known H5N1 outbreaks in Azerbaijan, Indonesia, Pakistan and Turkey. RESULTS: Demography, exposure to poultry, and presenting symptoms were compared, with only the common symptoms of fever and headache presenting significantly more frequently in confirmed H5N1 cases than in possible cases. Reported exposure to  infected humans was also more common in confirmed cases. In contrast, unexplained respiratory illness, sore throat, excess sputum production, and rhinorrhea were more frequent in possible cases. Overall, oseltamivir treatment showed a survival benefit, with the greatest benefit shown in H5N1 cases who were treated within two days of symptom onset (51% reduction in case fatality). CONCLUSION: Since prompt treatment with antivirals conferred a strong survival benefit for H5N1 cases, presumptive antiviral treatment should be considered for all possible cases presenting during an outbreak of H5N1 as a potentially life-saving measure.