A Two Wave Analysis of Hospitalizations and Mortality from Seasonal and Pandemic 2009 A (H1N1) Influenza in Saurashtra, India: 2009-2011.

BACKGROUND: During May 2009, India reported the confirmed case of 2009 A (H1N1) influenza reported and in August 2009, Saurashtra region made the first report. AIM: We describe the clinico-epidemiological characteristics of patients who were hospitalized with 2009 A (H1N1) influenza infection and seasonal influenza in Saurashtra region. SUBJECTS AND METHODS: A total of 1726 patients suffering from A (H1N1) influenza and seasonal influenza were admitted in the different hospitals of Rajkot city of Saurashtra region during September 2009-February 2011. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm the infection. The clinico-epidemiological features of the patients were closely monitored. Data were analyzed by Chi square or Fisher's exact test, using Epi Info software (version 3.5.1) of the Center for Disease Control (CDC). RESULTS: Among the patients hospitalized due to influenza, 29.6% (511/1726) were laboratory confirmed cases of A (H1N1) influenza while the rest 70.4% (1215/1726) were cases of seasonal influenza. A median time of 5 days was observed from the onset of illness to laboratory confirmed diagnosis of A (H1N1) influenza. The median duration of hospital stay of such patients was 2-32 days. All admitted A (H1N1) influenza patients received Oseltamivir drug, but only 14.9% (76/511) received it within 2 days of onset of illness. 24.9% (127/511) of those admitted for A (H1N1) influenza died as compared to 5.3% (65/1215) of those suffering from seasonal influenza. The most common symptoms were cough, fever, sore throat and shortness of breath in both the groups of patients. The prevalence of any coexisting morbidity in those with A (H1N1) influenza was 31.3% (160/511) while in those with seasonal influenza it was 19.4% (236/1215). The common coexisting morbidities were hypertension, diabetes mellitus, chronic pulmonary diseases and pregnancy. Pneumonia was reported in 91% positive patients with chest radiography. CONCLUSION: Though the clinico-epidemiological pattern of the A (H1N1) influenza patients were comparable to that of those suffering from seasonal influenza, a fivefold higher mortality was noted in A (H1N1) influenza patients. Hypertension, pregnancy, pneumonia on chest X-ray, and receiving antiviral treatment within 2 days of illness onset were mainly reported among A (H1N1) influenza patients.

A clinical study to compare the efficacy and safety of pregabalin sustained release formulation with pregabalin immediate release formulation in patients of diabetic peripheral neuropathic pain.

OBJECTIVE: To compare the efficacy and safety of sustained release (SR) formulation of pregabalin with immediate release (IR) formulation in patient with diabetic peripheral neuropathic pain. MATERIALS AND METHODS: In this open label, randomized, comparative, multicentric study, the primary efficacy measure was reduction in visual analogue scale (VAS) of short form McGill pain questionnaire (SF-MPQ) score from baseline to last visit. The secondary evaluation measures included reduction in SF-MPQ descriptive score and present pain intensity score and change in clinical global impression - improvement of illness (CGI-I) and clinical global impression - severity of illness (CGI-S) from baseline to last visit. Total duration of the study was 12 weeks. Safety evaluation was done by recording treatment emergent adverse events and laboratory investigations at baseline and end of treatment. RESULTS: Of 265 randomized patients, 133 received pregabalin SR tablets and 132 pregabalin IR. Patients randomized to both treatments responded to respective treatments. The least square means of VAS score in both the groups were reduced significantly (P <0.01). Reduction in both groups was similar (P = ns). At the end of the trial in both the groups, there was a significant reduction in the SF-MPQ descriptive score (P <0.01), severity of illness as well as clinically significant improvement in the symptoms. Difference between the groups for CGI-I (P = 0.37) and CGI-S (P = 0.41) score was not statistically significant. Treatment in both the groups was found safe and well tolerated. CONCLUSION: The study shows that the pregabalin SR is safe and effective in patients of diabetic peripheral neuropathic pain. The results of the study demonstrated that pregabalin SR has comparable efficacy and safety as pregabalin IR.

Absence of ocular malignant transformation after sub-retinal delivery of rAAV2/2 or integrating lentiviral vectors in p53-deficient mice.

Insertional mutagenesis following gene therapy with gammaretroviral vectors can cause the development of lymphoproliferation in children with X-linked severe combined immunodeficiency. In experimental studies, recombinant adeno-associated virus (rAAV) vectors have also been reported to increase susceptibility to carcinogenesis. The possibility of vector-induced transformation in quiescent ocular cells is probably significantly lower than in mitotically active cells, but given the increasing number of clinical applications of rAAV and lentiviral vectors for ocular disease, a specific assessment of their oncogenic potential in the eye is important. In this study, we investigated the effect of rAAV2/2 and integrating HIV-1 vectors upon the incidence of ocular neoplasia in p53 tumour-suppressor gene-knockout (p53(-/-)) mice, which are highly susceptible to intraocular malignant transformation. Subretinal injections of high titre rAAV2/2 or integrating HIV-1 vectors induced no tumours in p53(-/-) or p53(+/-) animals, nor significantly affected their natural longevity. We conclude that any insertional events arising from subretinal delivery of these vectors appear insufficient to cause intraocular malignancy, even in highly susceptible animals. These findings support the continued development of these vectors for ocular applications.

IVIVR in oral absorption for fenofibrate immediate release tablets using dissolution and dissolution permeation methods.

In a previous study it has been demonstrated that a dissolution/permeation (D/P) system can discriminate between different immediate release fenofibrate formulations. The fractions permeated were correlated with fenofibrate's in vivo exposure in rats following p.o. administration. In the present study more detailed investigations are presented using data from six fenofibrate tablets tested in vivo in humans. In these pharmacokinetic studies no significant differences between formulations in AUC but in Cmax were found. Differences between the Cmax values were not explained by the dissolution characteristics of the tablets but were rationalized on the basis of micellar entrapment and diminished mobility of the active ingredient by surfactants in the formulations. This was demonstrated by a permeation system using dialysis membranes. Thus a permeation step in addition to dissolution measurement may significantly improve the establishment of an IVIV relationship.

IVIVR in oral absorption for fenofibrate immediate release tablets using dissolution and dissolution permeation methods.

In a previous study it has been demonstrated that a dissolution/permeation (D/P) system can discriminate between different immediate release fenofibrate formulations. The fractions permeated were correlated with fenofibrate's in vivo exposure in rats following p.o. administration. In the present study more detailed investigations are presented using data from six fenofibrate tablets tested in vivo in humans. In these pharmacokinetic studies no significant differences between formulations in AUC but in Cmax were found. Differences between the Cmax values were not explained by the dissolution characteristics of the tablets but were rationalized on the basis of micellar entrapment and diminished mobility of the active ingredient by surfactants in the formulations. This was demonstrated by a permeation system using dialysis membranes. Thus a permeation step in addition to dissolution measurement may significantly improve the establishment of an IVIV relationship.

Retinal nerve fiber thickness in inflammatory demyelinating diseases of childhood onset.

PURPOSE: To evaluate retinal nerve fiber layer thickness (RNFLT) using optical coherence tomography (OCT) in children with acquired demyelinating diseases. METHODS: This is a cross-sectional study of patients seen between 2006-2008 at the Pediatric MS Center of the Jacobs Neurological Institute. Consensus definitions for pediatric demyelinating disease were followed. All children received OCT testing and assessment of visual acuity (VA) using Snellen and low contrast letter acuity (LCLA) charts. RESULTS: Thirty-eight children diagnosed with acquired demyelinating disease, 15 healthy controls, and five children with other neurological disorders (OND) were included. Average RNFLT in healthy controls was 107 +/- 12 microm(n = 30) versus 108 +/- 5 microm (n = 10) in OND controls. In children with multiple sclerosis, average RNFLT +/- SD was 99 +/- 14 microm in unaffected (n = 24) versus 83 +/- 12 micromin eyes affected by optic neuritis ("affected eyes") (n = 10). Average RNFLT in children with acute disseminated encephalomyelitis and transverse myelitis was 102 +/- 15 microm in unaffected (n = 18) versus 67 +/- 17 microm in affected eyes (n = 6). In children with optic neuritis (ON), average RNFLT +/- SD was 97 +/- 13 microm in unaffected (n = 5) versus 89 +/- 12 microm in affected eyes (n = 9). Differences between children with demyelinating disease and controls and between ON and nonON eyes were statistically significant (P < 0.001). Bivariate correlations of RNFLT with LCLA (P = 0.002) and VA (P < 0.001) were significant. CONCLUSIONS: OCT may be a valuable tool for the assessment and monitoring of anterior optic pathway dysfunction in children with demyelinating diseases.

AAV-mediated gene therapy for retinal disorders: from mouse to man.

A wide range of retinal disorders can potentially be treated using viral vector-mediated gene therapy. The most widely used vectors for ocular gene delivery are based on adeno-associated virus (AAV), because they elicit minimal immune responses and mediate long-term transgene expression in a variety of retinal cell types. Proof-of-concept experiments have demonstrated the efficacy of AAV-mediated transgene delivery in a number of animal models of inherited and acquired retinal disorders. Following extensive preclinical evaluation in large animal models, gene therapy for one form of inherited retinal degeneration due to RPE65 deficiency is now being tested in three concurrent clinical trials. Here, we review different approaches for treating inherited retinal degenerations and more common acquired retinal disorders using AAV-based vectors.

Temporal decline in the prognostic impact of a recurrent acute myocardial infarction 1985 to 2002.

OBJECTIVE: To investigate trends in case-fatality and prognostic impact from recurrent acute myocardial infarction (re-AMI) during 1985-2002. DESIGN: Retrospective cohort study using nationwide administrative data from Denmark. SETTINGS: National registries on hospital admissions and causes of death were linked to identify patients with first AMI, re-AMI and subsequent prognosis. PATIENTS: Patients > or =30 years old with a discharge diagnosis of AMI during 1985-2002 were tracked for first hospital admission for re-AMI 1 year after discharge. MAIN OUTCOME MEASURES: One-year case-fatality. RESULTS: 166 472 patients were identified with a first AMI; 14 123 developed re-AMI. One-year crude case-fatality from first AMI/re-AMI was 39% versus 43% in 1985-1989 and 25% versus 29% in 2000-2002, respectively. In 1985-89, 35 795 patients survived to discharge (71%); of these 2.5% experienced reinfarction within 30 days (early reinfarction) and an additional 9.0% reinfarction within days 31-365 (late re-AMI). Re-AMI carried a poor prognosis in 1985-1989 compared to no re-AMI with age- and sex-adjusted relative risk of 1-year case-fatality of 7.5 (95% CI: 6.9 to 8.5) from early re-AMI and 11.7 (95% CI: 11.0 to 12.4) from late re-AMI. In 2000-2002, 23 552 patients (86%) survived to discharge; 4.4% had early re-AMI and 6.6% late re-AMI. Adjusted relative risk of 1-year case-fatality had declined to 2.1 (95% CI: 1.9 to 2.5) from early re-AMI and 5.6 (95% CI: 5.1 to 6.2) from late re-AMI compared to patients without reinfarction. CONCLUSION: Prognosis after AMI has improved substantially during the latest two decades and extends to patients with re-AMI.

Reduced lung function and risk of atrial fibrillation in the Copenhagen City Heart Study.

Chronic obstructive pulmonary disease has been associated with a high frequency of arrhythmias. Few studies have analysed the role of reduced lung function in predicting atrial fibrillation (AF). The aim of the present study was to investigate the relationship between forced expiratory volume in one second (FEV1) and risk of first episode of AF in a prospective study. Data from 13,430 males and females without previous myocardial infarction, who participated in the Copenhagen City Heart Study, were analysed. New AF was assessed at re-examination after 5 yrs and by hospital admission for AF during a period of 13 yrs. Multivariate analyses were used with adjustment for cardiopulmonary risk factors. There were 62 new cases of AF at 5-yr follow-up (0.58%) and 290 cases (2.20%) diagnosed at hospitalisations. Risk of new AF at re-examination was 1.8-times higher for FEV1 between 60-80% of predicted compared with FEV1 > or = 80% after adjustment for sex, age, smoking, blood pressure, diabetes and body mass index. The risk of AF hospitalisation was 1.3-times higher for FEV1 between 60-80% and 1.8-times higher for FEV1 < 60% compared with FEV1 > or = 80%, when additional adjustment was made for education, treatment with diuretics and chest pain at activity. The authors conclude that reduced lung function is an independent predictor for incident atrial fibrillation.

Lipid hydroperoxide stimulates retinal neovascularization in rabbit retina through expression of tumor necrosis factor-alpha, vascular endothelial growth factor and platelet-derived growth factor.

To test the hypothesis that oxidative damage associated with tissue hypoxia plays a role in neovascularization, a lipid hydroperoxide (LHP) was injected into the vitreous of rabbits. Single injections of LHP (50-600 microg) caused a sustained retinal neovascularization visualized clinically by ophthalmoscopy and confirmed by microscopy. Vasodilators, i.e. histamine and nitric oxide, peaked at 6h and 7 days, respectively. The levels of both tumor necrosis factor-alpha and interleukin-1alpha peaked at 12h and dropped to basal levels by 24h. Expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta peaked at 24h and were sustained throughout the following 3 weeks, and platelet-derived growth factor was also elevated throughout the same period. Upregulation of these five angiogenic cytokines, but not basic fibroblast growth factor, occurred prior to the appearance of neovascularization. Leakage of fluorescein at the tips of new vessels was demonstrated by fluorescein angiography. Linoleic hydroperoxide induced neovascularization, but saturated or unsaturated native C-18 fatty acids had no effect. The cascade of multiple, angiogenic cytokines induced by LHP may interact to promote sustained neovascularization.

Pancreatic abscess: is there a role for conservative therapy?

Pancreatic abscess is a serious complication of acute pancreatitis and non-operative management has been reported to carry a mortality of nearly 100%. We present five patients with pancreatic abscess, who were successfully treated with antibiotics alone. All 5 patients had acute pancreatitis followed by prolonged fever and development of an abdominal mass. The diagnosis was confirmed in each of them by a contrast enhanced CT scan and an ultrasound guided aspiration of pus from the pancreatic mass. The choice of antibiotics was decided by the culture reports in two cases and by Gram's staining in the remaining three patients. We attribute the success of antibiotic therapy in our patients to early diagnosis by CT scan and guided aspiration as well as the absence of any unfavourable risk factors. This study suggests that a select group of patients with pancreatic abscess may be managed conservatively with antibiotics.

Paroxysmal nocturnal hemoglobinuria with hepatic vein thrombosis presenting as hepatic encephalopathy.

We present a patient with paroxysmal nocturnal hemoglobinuria with diffuse hepatic central vein thrombosis who presented with encephalopathy and recovered from the hepatic manifestations with antihepatic coma measures alone.

Macroamylase in the pleural fluid of a patient with lymphoma.

A patient with a macroamylase in pleural fluid is described. A diagnosis of recurrent pleural effusion due to chronic relapsing pancreatitis had been made on the basis of hyperamylasemia, high pleural fluid amylase, and abdominal pain. The amylase in the pleural fluid as well as the serum was ultimately characterized as a macroamylase on electrophoresis and chromatography. A diagnosis of lymphoma subsequently became obvious. The pathogenesis of the macroamylase in the pleural effusion and the association of macroamylasemia with malignant disease is discussed.