Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day, 1.37 ± 2.745 hours for safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia.
The pathogenesis of dengue virus infection is attributed to complex interplay between virus, host genes and host immune response. Host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity as well as genetic factors are major determinants of disease susceptibility. NS1 protein and anti-DENV NS1 antibodies were believed to be responsible for pathogenesis of severe dengue. The cytokine response of cross-reactive CD4+ T cells might be altered by the sequential infection with different DENV serotypes, leading to further elevation of pro-inflammatory cytokines contributing a detrimental immune response. Fcγ receptor-mediated antibody-dependent enhancement (ADE) results in release of cytokines from immune cells leading to vascular endothelial cell dysfunction and increased vascular permeability. Genomic variation of dengue virus and subgenomic flavivirus RNA (sfRNA) suppressing host immune response are viral determinants of disease severity. Dengue infection can lead to the generation of autoantibodies against DENV NS1antigen, DENV prM, and E proteins, which can cross-react with several self-antigens such as plasminogen, integrin, and platelet cells. Apart from viral factors, several host genetic factors and gene polymorphisms also have a role to play in pathogenesis of DENV infection. This review article highlights the various factors responsible for the pathogenesis of dengue and also highlights the recent advances in the field related to biomarkers which can be used in future for predicting severe disease outcome.
Clinical diagnosis of scrub typhus is often difficult because the symptoms are very similar to those of other febrile illness such as dengue, leptospirosis, malaria and other viral hemorrhagic fevers. Though better diagnostic tests are available for rickettsial diseases and scrub typhus elsewhere, the Weil-Felix test is still commonly used in India, mainly because microimmunofluorescence assays (M-IFA) were not available in India till recently and relevant staff had insufficient training. The present study was performed to investigate the performance of M-IFA, IgM ELISA, and Weil-Felix test on 546 non-repeated serum samples from subjects suspected of having scrub typhus. One hundred and forty-three of these 546 samples were positive by M-IFA; these cases were also confirmed clinically to have scrub typhus based on their dramatic responses to doxycycline therapy. IgM ELISA was positive in 122 of the 143 M-IFA positive cases and the Weil-Felix test in 96. Though the Weil-Felix test is a heterophile agglutination test, it was found in this study to have good specificity but far too little sensitivity to use as a routine diagnostic test. IgM ELISA can be a good substitute for M-IFA. Incorporation of multiple prototype antigens on M-IFA slides is likely one of the reasons for its superior performance. As newer and better diagnostic assays become available for scrub typhus diagnosis in developed countries, it will be imperative to also use such tests in other endemic countries to prevent over-or under-diagnosis of scrub typhus.
Herbicide poisoning is most common method of suicide in India and it is associated with high morbidity and mortality. Among different herbicidal poisonings the most predominantly found poisonings are paraquat and glyphosate. These compounds are highly toxic and their poisonings require proper management techniques. High fatality is seen in these cases which are mainly due to its inherent toxicity and lack of effective treatment. Common symptoms of these poisonings includes gastrointestinal corrosive effects with mouth and throat, epigastric pain and dysphagia, acid-base imbalance, pulmonary edema, shock and arrhythmia. Long term health effects include pulmonary fibrosis, renal failure, hepatic failure, heart failure, multi-organ failure or death. No proven antidote exists for these poisonings. So the treatment is mainly supportive. Initially gastric lavage or whole-gut irrigation using adsorbents such as Fuller's earth, bentonite or activated charcoal is recommended. In case of renal failure hemodialysis or hemoperfusion may be considered. However novel approaches like treatment with N-acetylcysteine, vitamin C, vitamin E, cyclophosphamide may also be helpful.
AIM: To study the value of platelet count to spleen diameter ratio as a noninvasive parameter for diagnosing esophageal varices (EVs) in liver cirrhosis.METHODS: The laboratory and ultrasonographic variables were prospectively evaluated in 150 patients with liver cirrhosis. Only stable patients were included in the study. Patients with active gastrointestinal bleeding at the time of admission were excluded. All patients underwent screening upper gastrointestinal endoscopy.RESULTS: The platelet count, spleen diameter and platelet count to spleen diameter ratio in patients with EVs were significantly different from patients without EVs. The platelet count to spleen diameter ratio had the highest accuracy among the three parameters. By applying receiver operating characteristic curves, a platelet count to spleen diameter ratio cut-off value of 1014 was obtained, which gave positive and negative predictive values of 95.4% and 95.1%, respectively. The accuracy of this cut-off value as evaluated by applying receiver operating characteristic curves was 0.942 (95% CI 0.890 to 0.995).CONCLUSION: Among the noninvasive parameters studied, platelet count to spleen diameter ratio had the highest accuracy for diagnosing EVs. However, the evidence for the noninvasive diagnosis is not yet sufficient to replace endoscopy as a diagnostic screening tool for EVs in all cirrhotic patients. The platelet count to spleen diameter ratio may be a useful tool for diagnosing EVs in liver cirrhosis noninvasively when endoscopy facilities are not available.
S. aureus is a significant cause of BSI with a case fatality rate comparable to those of other developing nations. The upsurge in MRSA rates is alarming in our setup. Antibiotic stewardship and strict control of antibiotic use must be implemented by health care professionals to curb the increasing trend in MRSA BSIs.
Leptospirosis and dengue fever are increasingly seen as causes of tropical febrile illness and often are clinically indistinguishable. This two-year prospective study from a tertiary care centre comprised 200 patients including 68 men (mean 34.8 years) with dengue and 73 (mean 46.19 years) with leptospirosis. Oliguria, icterus, muscle tenderness, anaemia, leukocytopenia, thrombocytopenia, elevated erythrocyte sedimentation rate (ESR), acute renal failure (ARF) and hypoalbuminaemia appeared more commonly in leptospirosis in comparison to dengue. Eighteen per cent mortality was observed in leptospirosis compared to one per cent in dengue. ARF, hyperbilirubinaemia, acute respiratory distress syndrome (ARDS), creatine kinase (CK) elevation and thrombocytopenia were predictors of death in leptospirosis and thrombocytopenia, ARDS and ARF predictors of death in dengue. On receiver operating characteristics (ROC) analysis, leucocytosis >11000/mm(3), ESR >40 mm, serum creatinine >2 mg/dL, total serum bilirubin >2 mg/dL, CK >500 U/L and serum albumin <3 mg/dL were more likely to be an indication of leptospirosis at presentation compared to dengue.
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