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Waveguide structures have got popularity because of its extensive application in radar system of naval ships and aircrafts. Waveguide models provide high probability of small target detection and reduce rate of false target detection. There are a large number of studies on the waveguide slotted in the wide wall. Researches concerning the narrow wall of the waveguide are much less known. An edge slotted waveguide antenna array based on semicircular end of inclined slots radiating waveguide is proposed. Length of the inclined slot is extended to the adjacent broad wall with semicircular cutting. This extended length increases the resonant length and hence higher gain is obtained. Semicircular cutting at the end of the slot reduces cross-polarization component hence side lobe level obtained are low. Narrow wall inclined slotted waveguide is analyzed and designed to operate in X-band. The radiating slots are etched and rotated alternatively on the broadened top plate with semicircular cutting into the adjacent walls. This technique deletes the radial component of the propagating wave and adds the axial component of the propagating wave. Semicircular cutting increases the resonant length and enhances the gain of the antenna. Designed waveguide structure provides high gain, and cross-polarization component is minimized. Gain of 26 dB is obtained from the simulation results obtained in HFSS (High frequency Software Simulation) and side lobe level obtained is around 20 dB while hardware design provides the gain of 24.5 dB measured on VNA (Vector Network Analyzer) keeping the side lobe level minimum.

Background/Aim: To study the changing pattern of acute intestinal obstruction at a teaching institute. Patients and Methods: It is a prospective descriptive study conducted at a teaching hospital during the period from June 2004 to June 2009. All patients with clinical or radiological evidence of acute intestinal obstruction were included in this study regardless of the gender of the patient. Patients below the age of 10 years were excluded from the study. The treatment strategy was planned ranging from conservative treatment to emergency laparotomy after resuscitation and rehydration of the patient. Details of individual patients were recorded on a pro forma sheet and data analyzed statistically on SPSS version 14. Results: A total of 229 patients with acute intestinal obstruction were admitted and treated. The mean age of the study population was 43.08 ± 13.07 years. Postoperative adhesions accounted for 41% (n= 95) of the total cases, followed by abdominal tuberculosis (25%, n= 58), obstructed/ strangulated hernias of different types (18%, n= 42). There was an obvious change in the pattern of etiology of acute intestinal obstruction as the common causes were postoperative adhesions and abdominal tuberculosis instead of obstructed inguinal hernias. Conclusion: An increase in the adhesive obstruction and a concomitant decrease in the incidence of obstructed hernias indicate a changing trend towards early operation before it gets complicated. Abdominal tuberculosis is emerging as another common cause of acute bowel obstruction.

Avian leukosis is a significant viral disease affecting chicken populations globally, including Bangladesh, resulting in high mortality and morbidity rates and causing substantial economic losses in the commercial poultry industry. This study aimed to detect avian leukosis virus (ALV) during recent outbreaks in Bangladesh, utilising a molecular-based approach. A total of 14 liver samples were collected from the suspected layer flocks in Bangladesh. The diagnosis of ALV infection in chickens was confirmed through necropsy, histopathological examinations, reverse transcription-polymerase chain reaction (RT-PCR), and sequence analysis. Gross observations revealed severe liver enlargement with scattered white nodules on the surface in the infected chickens. Histopathological observations showed the infiltration of huge mononuclear inflammatory cells in the periportal area of liver and microvesicular fatty degeneration and necrosis of some hepatocytes. RT-PCR results identified three samples positive for the env gene of ALV. Sequence analysis of the env genes demonstrated high homology among the identified strains (97%-98%) and with reference strains (92%-96%) at the nucleotide level. The phylogenetic tree revealed close relatedness of the three identified strains to reference strains from India, USA, and China. Mutational analysis indicated several mutations throughout the envelope glycoprotein of the identified strains. Protein structure analysis showed minor changes in the hydrophobic region of the envelope protein of the identified strains. In conclusion, this study, the first detailed investigation in Bangladesh, contributes to understanding ALV epidemiology, highlights genetic diversity, and emphasises the necessity for further investigations and the implementation of effective control measures in the affected regions., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

The novel antimalarial ganaplacide combined with lumefantrine solid dispersion formulation (LUM-SDF) was effective and well tolerated in the treatment of uncomplicated falciparum malaria in adults, adolescents, and children in a multinational, prospective, randomized, active-controlled Phase II study conducted between August 2017 and June 2021 (EudraCT 2020-003284-25, Clinicaltrials.gov NCT03167242). Pharmacokinetic data from that study are reported here. The trial comprised three parts: a run-in part in 12 adult/adolescent patients treated with a single dose of ganaplacide 200 mg plus LUM-SDF 960 mg assessed potential pharmacokinetic (PK) interactions between ganaplacide and lumefantrine; in Part A, adult/adolescent patients received one of the six ganaplacide-LUM-SDF regimens or artemether-lumefantrine; and in Part B, three dose regimens identified in Part A, and artemether-lumefantrine, were assessed in children aged 2 to <12 years, with body weight ≥10 kg. A rich blood sampling schedule was used for all 12 patients in the PK run-in part and a subset of patients (N = 32) in Part A, with sparse sampling for remaining patients in Parts A (N = 275) and B (N = 159). Drug concentrations were determined by a validated protein precipitation and reverse phase liquid chromatography with tandem mass spectrometry detection method. Parameters including AUC inf , AUC last , AUC 0-t , C max, and t max were reported where possible, using non-compartmental analysis. In the PK run-in part, there was no notable increase in ganaplacide or lumefantrine exposure when co-administered. In Parts A and B, ganaplacide exposures increased with dose, but lumefantrine exposure was numerically under dose-proportional. Lumefantrine exposure was higher with ganaplacide-LUM-SDF than with artemether-lumefantrine, although high variability was observed. Ganaplacide and lumefantrine exposures (C max and AUC 0-24 h ) were comparable across age and body weight groups. Drug exposures needed for efficacy were achieved using the dose regimen 400 mg ganaplacide plus lumefantrine 960 mg once daily for 3 days under fasted conditions., (© 2024 Novartis. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: Human immunodeficiency virus (HIV) and sexually transmitted infections (STIs) can cause severe and fatal complications; knowledge about these diseases is essential for promoting safe sex practices and modifying behaviours that are harmful to one's health. This study investigates Syrian people's understanding, attitudes, and behaviors towards HIV/AIDS and STIs, aiming to identify factors promoting safe sex practices and modifying harmful behaviors., Methods: This online cross-sectional study was conducted in Syria between 3 September and 23 November 2022, involving all 18+ individuals. The questionnaire was adapted from a previous study containing 74 questions from five sections: socio-demographic information, knowledge and practice regarding STIs, knowledge and practice regarding HIV/AIDS, attitude towards HIV/AIDS, and attitude regarding STIs and analyzed using descriptive and multivariate logistic regression., Results: The study involved 1073 participants mostly aged between 18-30, with 55.3% females. Over half had good awareness of STIs and HIV/AIDS, with 55% and 63% respectively. Specifically, the overall knowledge level of STI type, signs/symptoms, risks of transmission, preventive methods, and complications for untreated STIs were (45.7%), (52.9%), (58.1%), (66.1%), and (59.6%), respectively. Medical field respondents had higher knowledge of HIV (P-value < 0.05, OR = 2)., Conclusion: Our results show that Syrian people have a knowledge level of STIs and HIV was moderate. However, the attitude toward STIs was negative, as less than half of the participants had a good attitude. It is essential to solve these knowledge gaps, especially in low-income countries such as Syria.

Polycystic Ovarian Syndrome (PCOS) is a prevalent metabolic and hormonal disorder affecting women of reproductive age. Limited data exists on Syrian women's PCOS awareness and health behaviors. This study aimed to gauge PCOS prevalence, knowledge, awareness, and health-related practices among Syrian women. A cross-sectional online survey was conducted from 11 February to 27 October 2022, targeting Syrian women aged 18-45. Collaborators from specific medical universities distributed a questionnaire adapted from a Malaysian paper through social media platforms. Out of 1840 surveyed Syrian women, 64.2% were aged 21-29, and 69.6% held bachelor's degrees. Those with a bachelor's degree exhibited the highest mean knowledge score (12.86), and women previously diagnosed with PCOS had a higher mean knowledge score (13.74) than those without. Approximately 27.4% were confirmed PCOS cases, and 38.9% had possible cases. Women with PCOS were 3.41 times more likely to possess knowledge about the condition. The findings suggest a moderate level of PCOS knowledge and health-related practices among Syrian women, emphasizing the need for increased awareness. Consistent local PCOS screening programs, in collaboration with obstetrics and gynecology professionals, are crucial for improving understanding and clinical symptom recognition of this condition among Syrian women.

Background: Emergence of drug resistance demands novel antimalarial drugs with new mechanisms of action. We aimed to identify effective and well tolerated doses of ganaplacide plus lumefantrine solid dispersion formulation (SDF) in patients with uncomplicated Plasmodium falciparum malaria., Methods: This open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial was conducted at 13 research clinics and general hospitals in ten African and Asian countries. Patients had microscopically-confirmed uncomplicated P falciparum malaria (>1000 and <150 000 parasites per μL). Part A identified the optimal dose regimens in adults and adolescents (aged ≥12 years) and in part B, the selected doses were assessed in children (≥2 years and <12 years). In part A, patients were randomly assigned to one of seven groups (once a day ganaplacide 400 mg plus lumefantrine-SDF 960 mg for 1, 2, or 3 days; ganaplacide 800 mg plus lumefantrine-SDF 960 mg as a single dose; once a day ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; once a day ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; or twice a day artemether plus lumefantrine for 3 days [control]), with stratification by country (2:2:2:2:2:2:1) using randomisation blocks of 13. In part B, patients were randomly assigned to one of four groups (once a day ganaplacide 400 mg plus lumefantrine-SDF 960 mg for 1, 2, or 3 days, or twice a day artemether plus lumefantrine for 3 days) with stratification by country and age (2 to <6 years and 6 to <12 years; 2:2:2:1) using randomisation blocks of seven. The primary efficacy endpoint was PCR-corrected adequate clinical and parasitological response at day 29, analysed in the per protocol set. The null hypothesis was that the response was 80% or lower, rejected when the lower limit of two-sided 95% CI was higher than 80%. This study is registered with EudraCT (2020-003284-25) and ClinicalTrials.gov (NCT03167242)., Findings: Between Aug 2, 2017, and May 17, 2021, 1220 patients were screened and of those, 12 were included in the run-in cohort, 337 in part A, and 175 in part B. In part A, 337 adult or adolescent patients were randomly assigned, 326 completed the study, and 305 were included in the per protocol set. The lower limit of the 95% CI for PCR-corrected adequate clinical and parasitological response on day 29 was more than 80% for all treatment regimens in part A (46 of 50 patients [92%, 95% CI 81-98] with 1 day, 47 of 48 [98%, 89-100] with 2 days, and 42 of 43 [98%, 88-100] with 3 days of ganaplacide 400 mg plus lumefantrine-SDF 960 mg; 45 of 48 [94%, 83-99] with ganaplacide 800 mg plus lumefantrine-SDF 960 mg for 1 day; 47 of 47 [100%, 93-100] with ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; 44 of 44 [100%, 92-100] with ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; and 25 of 25 [100%, 86-100] with artemether plus lumefantrine). In part B, 351 children were screened, 175 randomly assigned (ganaplacide 400 mg plus lumefantrine-SDF 960 mg once a day for 1, 2, or 3 days), and 171 completed the study. Only the 3-day regimen met the prespecified primary endpoint in paediatric patients (38 of 40 patients [95%, 95% CI 83-99] vs 21 of 22 [96%, 77-100] with artemether plus lumefantrine). The most common adverse events were headache (in seven [14%] of 51 to 15 [28%] of 54 in the ganaplacide plus lumefantrine-SDF groups and five [19%] of 27 in the artemether plus lumefantrine group) in part A, and malaria (in 12 [27%] of 45 to 23 [44%] of 52 in the ganaplacide plus lumefantrine-SDF groups and 12 [50%] of 24 in the artemether plus lumefantrine group) in part B. No patients died during the study., Interpretation: Ganaplacide plus lumefantrine-SDF was effective and well tolerated in patients, especially adults and adolescents, with uncomplicated P falciparum malaria. Ganaplacide 400 mg plus lumefantrine-SDF 960 mg once daily for 3 days was identified as the optimal treatment regimen for adults, adolescents, and children. This combination is being evaluated further in a phase 2 trial (NCT04546633)., Funding: Novartis and Medicines for Malaria Venture., Competing Interests: Declaration of interests CW, KC, ID, RP, HC, and DM are employees of Novartis. GS and CR are employees and stockholders of Novartis. ACM and MEG are employees of Medicines for Malaria Venture. MPG received fees from Novartis for advisory work related to malaria. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: This study aimed to evaluate the gap between guidelines and local clinical practice for diagnosis and treatment of uncomplicated and severe malaria, the patient characteristics, diagnostic approach, treatment, and compliance to standard guideline recommendations., Methods: This was a multicentre, observational study conducted between October 2020 and March 2021 in which patients of all ages with symptoms suggestive of malaria and who visited a healthcare facility were prospectively enrolled in six countries in sub-Saharan Africa (The Democratic Republic of the Congo, Mozambique, Nigeria, Rwanda, The United Republic of Tanzania, and Zambia)., Results: Of 1001 enrolled patients, 735 (73.4%) patients had confirmed malaria (based on overall judgment by investigator) at baseline (uncomplicated malaria: 598 [81.4%] and severe malaria: 137 [18.6%]). Of the confirmed malaria patients, 533 (72.5%) were administered a malaria rapid diagnostic test. The median age of patients was 11 years (range: 2 weeks-91 years) with more patients coming from rural (44.9%) than urban (30.6%) or suburban areas (24.5%). At the community level, 57.8% of patients sought advice or received treatment for malaria and 56.9% of patients took one or more drugs for their illness before coming to the study site. In terms of early access to care, 44.1% of patients came to the study site for initial visit ≥ 48 h after symptom onset. In patients with uncomplicated malaria, the most prescribed treatments were artemisinin-based combination therapy (ACT; n = 564 [94.3%]), primarily using artemether-lumefantrine (82.3%), in line with the World Health Organization (WHO) treatment guidelines. In addition, these patients received antipyretics (85.6%) and antibiotics (42.0%). However, in those with severe malaria, only 66 (48.2%) patients received parenteral treatment followed by oral ACT as per WHO guidelines, whereas 62 (45.3%) received parenteral treatment only. After receiving ambulatory care, 88.6% of patients with uncomplicated malaria were discharged and 83.2% of patients with severe malaria were discharged after hospitalization. One patient with uncomplicated malaria having multiple co-morbidities and three patients with severe malaria died., Conclusions: The findings of this study suggest that the prescribed treatment in most patients with uncomplicated malaria, but not of those with severe malaria, was in alignment with the WHO recommended guidelines., (© 2023. The Author(s).)

Heterogeneous multiprocessors can offer high performance at low energy expenditures. However, to be able to use them in hard real-time systems, timing guarantees need to be provided, and the main challenge is to determine the worst-case schedule length (also known as makespan) of an application. Previous works that estimate the makespan focus mainly on the independent-task application model or the related multiprocessor model that limits the applicability of the makespan. On the other hand, the directed acyclic graph (DAG) application model and the unrelated multiprocessor model are general and can cover most of today's platforms and applications. In this work, we propose a simple work-conserving scheduling method of the tasks in a DAG and two new approaches to finding the makespan. A set of representative OpenMP task-based parallel applications from the BOTS benchmark suite and synthetic DAGs are used to evaluate the proposed method. Based on the empirical results, the proposed approach calculates the makespan close to the exhaustive method and with low pessimism compared to a lower bound of the actual makespan calculation., (© The Author(s) 2021.)

The study aimed to determine the efficacy of a safe and well-tolerated dose and regimen of tobramycin inhalation powder (TIP) on Pseudomonas aeruginosa sputum density in patients with bronchiectasis.This is a phase II, double-blind, randomised study in bronchiectasis patients aged ≥18 years with chronic P. aeruginosa infection. Patients were randomised 1:1:1 to either cohort A: three capsules of TIP once daily (84 mg); cohort B: five capsules once daily (140 mg) or cohort C: four capsules twice daily (224 mg). Within each cohort, patients were further randomised 2:2:1 either to TIP continuously, TIP cyclically (alternating 28 days of TIP and placebo) or placebo for 16 weeks, respectively and were followed up for 8 weeks.Overall, 107 patients were randomised to cohorts A (n=34), B (n=36) and C (n=37). All three TIP doses significantly reduced the P. aeruginosa sputum density from baseline to day 29 versus placebo in a dose-dependent manner (p≤0.0001, each). A smaller proportion of patients in the continuous-TIP (34.1%) and cyclical-TIP (35.7%) groups experienced pulmonary exacerbations versus placebo (47.6%) and also required fewer anti-pseudomonal antibiotics (38.6% on continuous TIP and 42.9% on cyclical TIP) versus placebo (57.1%) although not statistically significant. Pulmonary exacerbation of bronchiectasis was the most frequent (37.4%) adverse event. Overall, TIP was well tolerated, however, 23.4% of the patients discontinued the study drug due to adverse events.Continuous- and cyclical-TIP regimens with all three doses were safe and effective in reducing the P. aeruginosa sputum density in patients with bronchiectasis and chronic P. aeruginosa infection., Competing Interests: Conflict of interest: E. Polverino reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and personal fees from Bayer, Menarini, Grifols, Zambon, Pfizer, Chiesi, Teva, Shire, Insmed and Polyphor, and grants from Chiesi and Grifols, outside the submitted work. Conflict of interest: J.D. Chalmers reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and grants and personal fees from GSK, Boehringer-Ingelheim, AstraZeneca, Pfizer, Bayer Healthcare, Grifols, Napp, Aradigm corporation, and Insmed, outside the submitted work. Conflict of interest: H.A.W.M. Tiddens reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and personal fees from Vertex and Gilead, grants and personal fees from Novartis, and grants from Roche, Vertex, Chiesi and Vectura, outside the submitted work. Conflict of interest: H. Goossens reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study. Conflict of interest: M. Tunney reports grants from European Union IMI grant in collaboration with Novartis, during the conduct of the study; and grants from European Union, Novartis and Alaxia SAS, outside the submitted work. Conflict of interest: F.C. Ringhausen reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and grants, personal fees and non-financial support from Aposan, AstraZeneca, Bayer, Boehringer Ingelheim, Celtaxsys, Chiesi, Corbus, Grifols, InfectoPharm, Insmed, MSD, Novartis, PARI, Parion, Polyphor, Vertex and Zambon, outside the submitted work. Conflict of interest: A.T. Hill reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study. Conflict of interest: R. Pathan reports other from Novartis, outside the submitted work. Conflict of interest: G. Angyalosi reports other from Novartis, outside the submitted work. Conflict of interest: F. Blasi reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and grants and personal fees from AstraZeneca, Bayer, Grifols, Pfizer, Chiesi, GSK, Guidotti, Menarini, Novartis, Teva, Zambon and Insmed, outside the submitted work. Conflict of interest: S.J. Elborn reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and grants from Novartis, and personal fees from Vertex, Galapagos and Ionis, outside the submitted work. Conflict of interest: C.S. Haworth reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and grants and personal fees from Aradigm, Chiesi, Gilead, Grifols, GSK, Insmed, International Biophysics, Janssen, Mylan, Novartis, Teva, Vertex and Zambon, outside the submitted work. Conflict of interest: M.R. Loebinger reports grants from European Union IMI Grant (in collaboration with Novartis), during the conduct of the study; and personal fees from Bayer, Grifols, Astra Zeneca, Insmed and Polyphor, outside the submitted work., (Copyright ©ERS 2021.)

Objective: The purpose of this study was to evaluate if the cognitive benefit of rivastigmine is affected by the presence of orthostatic hypotension (OH) in patients with Parkinson's disease dementia (PDD)., Methods: We conducted a post hoc analysis on 1,047 patients with PDD from 2 randomized controlled trials comparing rivastigmine versus placebo at week 24 (n = 501) and rivastigmine patch versus capsule at week 76 (n = 546). A drop ≥ 20 mm Hg in systolic blood pressure (SBP) or ≥ 10 in diastolic blood pressure (DBP) upon standing classified subjects as OH positive (OH+); otherwise, OH negative (OH-). The primary end point was the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) at week 24 and the Mattis Dementia Rating Scale (MDRS) at week 76, using intention-to-treat with retrieved dropout at week 24 and observed cases at week 76, consistent with the original analyses., Results: Overall safety was comparable between OH+ (n = 288, 27.5%) and OH- (n = 730, 69.7%), except for higher frequency of syncope (9.2%) in the OH+ placebo arm. The placebo-adjusted effect of rivastigmine on ADAS-Cog at week 24 was 5.6 ± 1.2 for OH+ and 1.9 ± 0.9 in OH- (p = 0.0165). Among subjects with OH, the MDRS change from baseline at week 76 was higher for rivastigmine capsules versus patch (10.6 ± 2.9 vs -1.5 ± 3.0, p = 0.031). The overall prevalence of OH was lower for rivastigmine than placebo at week 24 (28.3% vs 44.6%, p = 0.0476)., Interpretation: The cognitive benefit from rivastigmine is larger in patients with PDD with OH, possibly mediated by a direct antihypotensive effect. ANN NEUROL 2021;89:91-98., (© 2020 American Neurological Association.)

Background: Secukinumab, a human monoclonal antibody that selectively targets interleukin-17A, is highly efficacious in the treatment of moderate-to-severe psoriasis, starting at early time points, with a sustained effect and a favorable safety profile., Methods: Patients with moderate-to-severe plaque psoriasis were randomized to secukinumab 300 mg, secukinumab 150 mg, or placebo self-administered by prefilled syringe at baseline, weeks 1, 2, and 3, and then every four weeks from week 4 to 48. Efficacy responses (≥ 75/90/100% improvement in Psoriasis Area and Severity Index [PASI 75/90/100] and clear/almost clear skin by Investigator's Global Assessment 2011 modified version [IGA mod 2011 0/1]) were measured to week 52. Patient-reported usability of the prefilled syringe was evaluated by the Self-Injection Assessment Questionnaire to week 48., Results: The efficacy of secukinumab increased to week 16 and was maintained to week 52. With secukinumab 300 mg at week 52, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 83.5%/68.0%/47.5% and 71.5% of patients when analyzed by multiple imputation, respectively, and by 75.9%/62.1%/43.1% and 63.8% of patients when analyzed by nonresponder imputation, respectively. With secukinumab 150 mg at week 52, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 63.5%/50.3%/31.1% and 43.6% of patients when analyzed by multiple imputation, respectively, and by 61.0%/49.2%/30.5% and 42.4% of patients when analyzed by nonresponder imputation, respectively. Self-reported acceptability of the prefilled syringe was high throughout the study. The incidence of adverse events (AE) was well balanced between groups, with AEs reported in 74.4% of patients receiving secukinumab 300 mg and 77.3% of patients receiving secukinumab 150 mg. Nasopharyngitis was the most common AE across both secukinumab groups., Conclusion: Self-administration of secukinumab by prefilled syringe was associated with robust and sustained efficacy and a favorable safety profile up to week 52. , , J Drugs Dermatol. 2016;15(10):1226-1234.

Background: This subgroup analysis of the European Cubicin Outcomes Registry Experience evaluated the safety and effectiveness of daptomycin in children and adolescent patients (<18 years)., Methods: Clinical outcomes at the end of therapy were assessed as success (cured or improved), failure or nonevaluable. Safety was assessed for up to 30 days post treatment., Results: Eighty-one children and adolescent patients were included in this study. The most common primary infections were bacteremia (19.8%), complicated skin and soft-tissue infection (18.5%), osteomyelitis (13.6%), endocarditis (12.3%), foreign body/prosthetic infection (12.3%), uncomplicated skin and soft-tissue infection (9.9%) and other (13.6%). Daptomycin doses ranged from 4 to >10 mg/kg/day. Median duration of therapy was 12.5 (interquartile range, 7-25; mean, 16.7; standard deviation, 12.8) days. Staphylococcus aureus (46.7%) was the most commonly isolated pathogen (23.8% methicillin-resistant S. aureus). Forty-nine (60.5%) patients completed daptomycin therapy without further antibiotics, 27 (33.3%) switched to another antibiotic, 4 (4.9%) discontinued because of adverse events (AEs) and 1 (1.2%) discontinued because of other reason. Overall, 75 (92.6%; 95% confidence interval: 95.2-100.0%) patients achieved clinical success; 39 of 41 (95.1%) patients receiving daptomycin monotherapy and 36 of 40 (90.0%) patients receiving concomitant antibiotics. Six (7.4%) patients reported AEs, including 1 patient with increased blood creatine phosphokinase. Three (3.7%) patients had serious AEs; 1 (1.2%) had a serious AE possibly related to daptomycin., Conclusion: Daptomycin, alone or combined with other antibiotics and/or surgery, demonstrated high clinical success rates against a wide variety of infections and was well tolerated in children and adolescents.

Background: Pooled data from two large registries, Cubicin(®) Outcomes Registry and Experience (CORE; USA) and European Cubicin(®) Outcomes Registry and Experience (EU-CORE; Europe, Latin America, and Asia), were analyzed to determine the characteristics and clinical outcomes of daptomycin therapy in patients with Gram-positive infections across wide geographical regions., Methods: Patients receiving at least one dose of daptomycin between 2004 and 2012 for the treatment of Gram-positive infections were included. Clinical success was defined as an outcome of 'cured' or 'improved'. Post-treatment follow-up data were collected for a subset of patients (CORE: osteomyelitis and orthopedic foreign body device infection; EU-CORE: endocarditis, intracardiac/intravascular device infection, osteomyelitis, and orthopedic device infection). Safety was assessed for up to 30 days after daptomycin treatment., Results: In 11,557 patients (CORE, 5482; EU-CORE, 6075) treated with daptomycin (median age, 62 [range, 1-103] years), the most frequent underlying conditions were cardiovascular disease (54.7 %) and diabetes mellitus (28.0 %). The most commonly treated primary infections were complicated skin and soft tissue infection (cSSTI; 31.2 %) and bacteremia (21.8 %). The overall clinical success rate was 77.2 % (uncomplicated SSTI, 88.3 %; cSSTI, 81.0 %; osteomyelitis, 77.7 %; foreign body/prosthetic infection (FBPI), 75.9 %; endocarditis, 75.4 %; and bacteremia, 69.5 %). The clinical success rate was 79.1 % in patients with Staphylococcus aureus infections (MRSA, 78.1 %). An increasing trend of high-dose daptomycin (>6 mg/kg/day) prescribing pattern was observed over time. Clinical success rates were higher with high-dose daptomycin treatment for endocarditis and FBPI. Adverse events (AEs) and serious AEs possibly related to daptomycin therapy were reported in 628 (5.4 %) and 133 (1.2 %) patients, respectively., Conclusions: The real-world data showed that daptomycin was effective and safe in the treatment of various Gram-positive infections, including those caused by resistant pathogens, across wide geographical regions.

Introduction: Daptomycin, a rapid concentration-dependent bactericidal antibiotic, is approved at a dose of 4 mg/kg/day for the treatment of complicated skin and soft tissue infections (cSSTI) and at a dose of 6 mg/kg/day for the treatment of Staphylococcus aureus right-sided infective endocarditis (RIE) and bacteremia associated with cSSTI and RIE. Studies have reported the successful use of high-dose daptomycin (>6 mg/kg/day) in patients with difficult-to-treat infections. The present analysis evaluated the effectiveness and safety of high doses (>6 mg/kg/day) of daptomycin for the treatment of different Gram-positive infections., Methods: European Cubicin(®) Outcomes Registry and Experience (EU-CORE) is a non-interventional, multicenter, retrospective, patient registry designed to collect real-world data from patients treated with daptomycin between 2006 and 2012. Clinical outcomes were assessed at the end of daptomycin treatment for three dose groups: ≤6, >6 to <8, and ≥8 mg/kg/day. Safety was assessed for up to 30 days post-daptomycin treatment., Results: Of the 6075 patients enrolled in EU-CORE, 4892 patients received daptomycin doses ≤6 mg/kg/day, while 1097 patients received high doses (>6 mg/kg/day). The primary infections with the largest proportion of patients treated with a high dose (>6 mg/kg/day) were osteomyelitis (37.1%), foreign body/prosthetic infection (31.6%), and endocarditis (27.6%). S. aureus was identified in 42.9% of patients with positive cultures treated with either ≤6 or >6 mg/kg/day. The overall clinical success rate was 82.0% (899/1097) with high doses (>6 mg/kg/day) and 80.3% (3928/4890) with doses ≤6 mg/kg/day. Numerically higher clinical success rate was observed for endocarditis and foreign body/prosthetic infection, as well as for coagulase-negative staphylococcal and enterococcal infections, with high-dose daptomycin treatment. There were no new or unexpected safety findings at doses >6 mg/kg/day., Conclusion: These results suggested that daptomycin at doses >6 mg/kg/day was effective and well tolerated. High-dose daptomycin is a potential therapeutic option in patients with difficult-to-treat Gram-positive infections., Funding: This study was funded by Novartis Pharma AG.

Introduction: The European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)) was a retrospective, non-interventional, multicenter study which evaluated the safety and effectiveness of daptomycin therapy in patients with Gram-positive infections including infective endocarditis (IE)., Methods: Data from the EU-CORE registry were collected for patients with IE who had received at least one dose of daptomycin between January 2006 and April 2012, across 18 countries in Europe (12), Latin America (5) and Asia (1). Clinical outcomes were assessed as success (cured or improved), failure or non-evaluable. Adverse events (AEs) were recorded during treatment and for up to 30 days post-treatment; follow-up data were collected for 2 years., Results: Of 6075 patients included in the EU-CORE registry, 610 were diagnosed with IE as primary infection; 149 (24.4%) right-sided IE (RIE), 414 (67.9%) left-sided IE (LIE), and 47 (7.7%) with both right- and left-sided IE (BRLIE). Overall clinical success was achieved in 80.0% of patients (RIE 88.6%, LIE 76.6% and BRLIE 82.9%). Success rates for methicillin-resistant Staphylococcus aureus (MRSA) infections were 90.9%, 71.7% and 66.6% in patients with RIE, LIE and BRLIE, respectively. The overall sustained clinical success rate in patients followed for up to 2 years was 86.7% (RIE 93.5%, LIE 88.3% and BRLIE 77.8%). AEs deemed possibly related to daptomycin in the investigator's opinion were reported in 2 (1.3%) RIE, 18 (4.3%) LIE and 1 (2.1%) BRLIE patients. There were 11 (1.8%) patients (2 with RIE, 8 with LIE and 1 with BRLIE) with AEs of creatine phosphokinase elevation reported as possibly related to daptomycin., Conclusion: Data from this real-world clinical setting showed that daptomycin was well tolerated and effective for the treatment of LIE and BRLIE in addition to RIE caused by Gram-positive bacteria, including MRSA. Two-year follow-up data showed that a high proportion of patients had a sustained response.

Introduction: The objective of this analysis was to describe in real-life settings the clinical outcomes and safety associated with daptomycin treatment in a cohort of patients with complicated skin and soft tissues infection (cSSTI)., Methods: All patients with cSSTI who had received at least one dose of daptomycin between January 2006 and April 2012 were identified from a non-interventional, multicenter, retrospective registry (European Cubicin(®) Outcome Registry and Experience; EU-CORE(SM))., Results: Of the 6075 patients included in the EU-CORE registry, 1927 (31.7%) were diagnosed with cSSTI (male, 63.8%; median age, 63 years). The most frequent underlying diseases were cardiovascular disease (58.1%) and diabetes mellitus (40.7%). The most frequent cSSTIs included surgical site infections (34.9%), wound infections (20.2%) and diabetic foot infections (19.9%). The most frequently prescribed doses of daptomycin were 4 mg/kg/day (38.9%) and 6 mg/kg/day (35.2%). A total of 1126 (58.4%) patients received antibiotics prior to daptomycin treatment; treatment failure (53.7%) was the most common reason for switching to daptomycin. The majority of hospitalized patients (61.8%) were treated with concomitant antibiotics. Among patients with positive cultures, Staphylococcus aureus (51.9%; 673/1297) was the most common pathogen. The overall clinical success rate was 84.6%; for infections caused by S. aureus, the success rate was 87.2% (methicillin susceptible, 87.8%; methicillin resistant, 87.0%). Adverse events possibly related to daptomycin treatment were reported in 2.4% of patients and adverse events led to drug discontinuation in 2.4% of patients., Conclusion: Daptomycin treatment resulted in high clinical success rates in patients with different cSSTI subtypes, the majority of whom having failed previous antibiotic therapy. Daptomycin was well tolerated and there were no new or unexpected safety findings.

Introduction: The aim of this analysis was to describe in real-world settings the clinical outcomes and safety associated with daptomycin treatment in patients with neutropenia and Gram-positive infections., Methods: Patients with an absolute neutrophil count (ANC) ≤1000 cells/mm(3) who received at least one dose of daptomycin between 2006 and 2012 were selected from a non-interventional, multicenter, retrospective registry (European Cubicin(®) Outcome Registry and Experience; EU-CORE(SM))., Results: Of the 6075 patients enrolled in EU-CORE, 446 (7.3%) had an ANC ≤ 1000 cells/mm(3) at baseline or during daptomycin therapy; they were all included in efficacy and safety populations. Half of the patients had severe neutropenia (ANC ≤ 100 cells/mm(3)). Most patients had hematologic malignancy (60.5%), an immunosuppressed state (39.7%) or had undergone a transplant (27.8%). The most common primary infections were bacteremia (42.2%) and complicated skin and soft tissue infection (13.9%). Cultures were positive for 68.6% (254/370) of patients with available culture results; coagulase-negative staphylococci (43.7%; 111/254) and Staphylococcus aureus (18.9%; 48/254) were the most commonly isolated primary pathogens. Median duration of daptomycin therapy was 10.0 (range 1-98) days. Most patients (82.8%) received antibiotics concomitantly with daptomycin; the most common were carbapenems (51.2%), penicillins (42.1%), and aminoglycosides (19.9%). The overall clinical success rate (cured or improved) associated with daptomycin was 77.1%. Adverse events possibly related to daptomycin treatment were reported in seven (1.6%) patients and led to drug discontinuation in 27 (6.1%) patients., Conclusion: The study results suggest that daptomycin is an effective therapeutic option for the treatment of a broad range of Gram-positive infections in patients with neutropenia, and has a good safety profile., Funding: This study was funded by Novartis Pharma AG.

Introduction: The aim of this study was to evaluate the clinical outcomes and safety of daptomycin therapy in patients with serious Gram-positive infections., Methods: Patients were enrolled in the European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)), a non-interventional, multicenter, observational registry. The real-world data were collected across 18 countries (Europe, Latin America, and Asia) for patients who had received at least one dose of daptomycin between January 2006 and April 2012. Two-year follow-up data were collected until 2014 for patients with endocarditis, intracardiac/intravascular device infection, osteomyelitis, or orthopedic device infection., Results: A total of 6075 patients were enrolled. The most common primary infections were complicated skin and soft tissue infection (31.7%) and bacteremia (20.7%). Staphylococcus aureus was the most frequently reported pathogen (42.9%; methicillin-resistant S. aureus [MRSA], 23.2%), followed by Staphylococcus epidermidis and other coagulase-negative staphylococci (CoNS, 28.5%). The most commonly prescribed dose of daptomycin was 6 mg/kg/day (43.6%), and the median duration of therapy was 11 (range 1-300) days. Overall clinical success rate was 80.5%, and was similar whether daptomycin was used as first-line (82.9%) or second-line (79.2%) therapy. Clinical success rates were high in patients with S. aureus (83.9%; MRSA 83.0%) and CoNS (including S. epidermidis, 82.5%) infections. The majority of patients with endocarditis or intracardiac/intravascular device infection (86.7%) or osteomyelitis/orthopedic device infection (85.9%) had a sustained response during the 2-year follow-up period. There were no new or unexpected safety findings., Conclusion: Results from real-world clinical experience showed that daptomycin is a valuable therapeutic option in the management of various difficult-to-treat Gram-positive infections., Funding: This study was funded by Novartis Pharma AG.

Background: Daptomycin has proven efficacy in patients with Gram-positive complicated skin and soft tissue infections (cSSTIs), including those caused by Staphylococcus aureus, regardless of methicillin susceptibility., Objective: This study was undertaken to evaluate the efficacy and safety of daptomycin in elderly patients., Study Design: This was an open-label, multicentre, randomized phase IIIb study conducted in hospitalized patients, Patients: Patients aged ≥65 years with a diagnosis of Gram-positive cSSTIs with or without bacteraemia were included. In addition, infections were required to be of sufficient severity to require inpatient hospitalization and treatment with parenteral antibiotics for at least 96 h. The main exclusion criterion was the presence of a non-complicated SSTI that could heal by itself or be cured by surgical removal of the site of infection., Intervention: Patients were randomized (2:1) to intravenous daptomycin or pooled intravenous standard therapies (semi-synthetic penicillin or vancomycin, referred to as the 'comparator'). Duration of treatment was between 5 and 14 days for cSSTIs without bacteraemia and between 10 and 28 days for cSSTIs with bacteraemia., Main Outcome Measure: The primary objective was descriptive comparison of clinical success in clinically evaluable patients at test of cure, 7-14 days post treatment. Secondary objectives were microbiological outcome, duration of treatment and safety., Results: In total, 120 patients were randomized (81 to daptomycin; 39 to the comparator) and 102 patients completed the study. Baseline characteristics were similar between the two groups. Common infections included cellulitis, ulcers and abscesses; six patients had bacteraemia [five documented (daptomycin, n = 3; comparator, n = 2); and one suspected (daptomycin, n = 1)]. Test-of-cure clinical success rates were numerically higher for daptomycin than for the comparator [89.0 % (65/73) vs. 83.3 % (25/30); odds ratio 1.65 (95 % confidence interval 0.49-5.54)]. For patients with S. aureus infections, cure rates were 89.7 % (35/39) versus 69.2 % (9/13), respectively; percentage points difference, 20.5 (95 % confidence interval -12.2 to 50.9)]. Rates of adverse events (AEs) and serious AEs were similar in both treatment arms; however, discontinuation rates for AEs/serious AEs were lower for daptomycin than for the comparator (3.8 % vs. 10.0 %). Three serious AEs were considered to be related to the study drug: one case each of pancytopenia (semi-synthetic penicillin), renal failure (vancomycin) and asymptomatic increase in creatine phosphokinase concentrations (daptomycin)., Conclusion: In elderly patients, for whom data were previously limited, the efficacy and safety of daptomycin have been confirmed, including for infections caused by S. aureus, regardless of methicillin susceptibility.

Objectives: Infective endocarditis (IE) is a complex infection associated with high mortality. Daptomycin, a cyclic lipopeptide antibiotic highly active against Gram-positive bacteria, has recently been incorporated into IE treatment guidelines. This retrospective analysis provides insights into the use of daptomycin in IE in the European Cubicin(®) Outcomes Registry Experience (EU-CORE(SM)) between 2006 and 2010., Patients and Methods: Three hundred and seventy-eight (10%) of 3621 enrolled patients received daptomycin for treatment of IE. Two hundred and fifty-nine (69%) had left-sided IE (LIE) and 182 patients (48%) underwent concomitant surgery., Results: Staphylococcus aureus was the most frequently identified pathogen (n=92; methicillin susceptible, n=50) and daptomycin was used empirically in 134 patients. Among cases of second-line therapy (n=312), the most common reason for switching to daptomycin was failure of the previous regimen (including glycopeptides and penicillins). Daptomycin was administered at 6 mg/kg in 224 patients and at ≥ 8 mg/kg in 72 patients. Clinical success rates were 80% overall, 91% for right-sided IE (RIE) and 76% for LIE, with similar rates seen for infections caused by methicillin-susceptible S. aureus (84%) and methicillin-resistant S. aureus (81%). The clinical success rate in patients treated with ≥ 8 mg/kg daptomycin was 90% [n=72 (RIE, 91%; LIE, 89%)]. No new safety signals were observed., Conclusions: In patients with IE registered in EU-CORE, daptomycin was most frequently used as second-line treatment after treatment failure. The majority of patients had LIE and most commonly received daptomycin for the treatment of staphylococcal infections. Clinical success was high in this difficult-to-treat population. The role of doses ≥ 8 mg/kg per day in the empirical treatment of IE deserves further investigation.

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated., Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52., Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52., Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B.

Software tools for the flexible examination of genomic sequence information derived from populations of organisms in a geospatial context are few in number, closely tied to Web-based resources, generally focused on one or a few loci or haplotypes, and typically produce a global phylogeny as a summary of relatedness. We sought instead to produce a portable, self-contained analysis tool that is efficiently focused on a geospatial display of specifically chosen polymorphism frequencies or combination frequencies from very large data sets of genome-scale sequence from multiple individuals. PolyLens is a Java-based, integral visual analytical toolkit which can systematically process population genomic data, visualise geographic distributions of genealogical lineages, and display allele distribution patterns. PolyLens is designed for users to visualise specific DNA sequences within each individual and its related location information in the existing data set.

Objective: To investigate the pattern of presentation, severity, factors responsible for delayed presentation and outcome of breast cancer in patients presenting to a teaching hospital of Jamshoro., Methods: It's a prospective descriptive study of 103 malignant breast lumps treated at a tertiary care teaching hospital over a period of 8 years. All patients were admitted through Outpatients department and were thoroughly examined and investigated. Treatment offered was based on triple assessment and ranged from lumpectomy to toilet mastectomy depending upon the stage of disease. The variables studied were recorded on a proforma and analyzed on SPSS version 12 for measuring frequencies and using Chi square test where applicable., Results: The mean age of the study population was 39.17 +/- 6.019 years and a range of 22 to 54 years. The frequency of advanced malignancy was alarmingly high in younger patients. Intra- ductal carcinoma was the commonest tumour in 93 (90%) patients, while the remaining included lobular (07) and Paget's disease (03). The high figures of advanced disease at presentation is attributed to lack of knowledge and education, poverty and local customs of women not exposing themselves even to the physicians. In addition, there is a substantial delay in the referral of patients from under privileged, remote areas where patients continue to receive symptomatic treatment till such time that disease becomes incurable., Conclusion: Advanced breast disease is common in younger patients belonging to underprivileged and remote rural areas. Great efforts are required to educate people so as to make early diagnosis possible

Objectives: To study the spectrum of presentation and outcome of different treatment modalities in Fournier's gangrene., Methods: It's a prospective analysis of 73 diagnosed patients of Fournier's gangrene admitted and treated in surgical department of a public sector university from June 2000 to June 2008. All patients were admitted through casualty with varying proportions of necrotizing infection of the perineal and genital fascia, with gangrene of the overlying skin. After resuscitation and preliminary investigations, including culture of the necrotic tissue, the patients were treated either conservatively by broad spectrum antibiotics, cardiopulmonary support, nutritional and fluid support or surgically by repeated aggressive wound debridement under anaesthesia. The behaviour of the disease, different modalities of treatment offered, response and outcome of the management were all collected on a proforma for statistical analysis on SPSS version 12., Results: Seventy three patients with a mean age of 57.32 +/- 13.87 years and range of 33-86 years presented with varying degrees of Fournier's gangrene. Of the total population, 67 (91.78%) were males and 6 (8.213%) were females. Fifty nine (80.82%) patients had one or the other co-morbidity with maximum number (n = 44, 60.2%) having diabetes mellitus. State of diabetes control was found to be an important prognostic factor. A source of infection was identified in skin, ano-rectal and perineal regions in 42 (57.53%) patients. Thirteen (17.80%) patients died despite aggressive conservative or surgical treatment., Conclusion: Fournier's gangrene continues to be a lethal disease despite overall improvement in the antibiotic spectrum and surgical techniques. Diabetes remains the most important prognostic factor in the outcome of disease.

Background: Advancing age with its associated co-morbidities increases the likelihood of postoperative complications as well as conversion rate during laparoscopic cholecystectomy. Recent studies have also questioned efficacy of this procedure in geriatric patients. The present study assesses the safety and applicability of laparoscopic cholecystectomy in geriatric patients. The objective of the present study was to asses safety and applicability of laparoscopic cholecystectomy in the elderly patients of 65 years and above., Methods: This is a prospective analysis of 173 patients, over 65 years of age, who underwent laparoscopic cholecystectomy from December 2002 to November 2006 at Liaquat University Hospital, Jamshoro. Patients presenting with complicated and uncomplicated gallstone disease were included in the study population and all of them were operated laparoscopically. The data included demographic details, co-morbidities, underlying biliary pathology, indications for surgery, operative and postoperative complications, morbidity and mortality, and hospital stay. The statistical analysis of the data performed on SPSS version 10., Results: Laparoscopic cholecystectomy undertaken in 173 elderly patients with a mean age of 69.72 years, out of whom 52 (30.05%) were males and 121 (69.94%) were females. Co-morbid conditions were identified in 53.17% (n = 92) patients and included hypertension in 38 patients (21.96%), Diabetes Mellitus in 23 patients (13.29%), COPD in 19 (10.98%) patients, Coronary artery disease in 9 (5.20%) and cardiac arrhythmias in 3 (1.73%) patients. Indications for surgery included simple biliary colic in majority of patients (69.94%) and complicated stone disease in 52 (30.05%) subjects. There were 37 (21.38%) emergency laparoscopic cholecystectomies and 136 (78.61%) patients were operated electively. Mean operative time was 100 minutes with a SD 29.03. Fourteen (8.09%) patients required conversion to OC (Open Cholecystectomy) due to various reasons. Mean hospital stay was 6.28 days. Overall 23 (13.29%) patients developed postoperative complications. One patient died of acute MI on 2nd postoperative day., Conclusion: There is no undue risk in laparoscopic cholecystectomy in the elderly population and the procedure can be regarded as safe as in patients below 65 years of age.