Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection.

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.

Evaluation of wound healing activity of cow urine ark in diabetic Wistar albino rats.

AIM: To evaluate wound healing activity of cow urine ark in diabetic rats. MATERIALS AND METHODS: Streptozotocin-induced diabetic Wistar albino rats were randomly divided into six groups (n = 6). Three groups - diabetic control, active control (glibenclamide), and treatment (cow urine ark) were operated for excision wounds (EWs). Rats in these groups received distilled water 1 ml/day, glibenclamide 0.5 mg/kg body weight/day, and cow urine ark 5.5 ml/kg body weight/day orally till complete healing of the EWs. EWs were evaluated for wound contraction on 3rd, 7th, and 11th day and for reepithelization on 11th day. The other three groups were operated for incision wounds (IW) as well as dead space wounds (DW) in the same animal which received the above agents orally for 11 days. IWs were analyzed for wound breaking strength and DWs were analyzed for dry weight, hydroxyproline content, and histology of granulation tissue. RESULTS: EWs showed significantly increased wound closure in the treatment group as compared to the diabetic as well as active control groups at 3rd (P < 0.001) and 11th (P < 0.05) post-wounding day and to the only diabetic control group at 7th (P < 0.01) post-wounding day. IWs showed significant improvement in wound breaking strength in the treatment as compared to diabetic (P < 0.001) and active control (P < 0.01) groups. DWs showed significant increase in hydroxyproline content of granulation tissue in the treatment as compared to diabetic control (P < 0.001) and active control (P < 0.001) groups. Wound breaking strength and hydroxyproline content also significantly increased in the active control group compared to diabetic control (P < 0.001 and P < 0.05, respectively). Granulation tissue dry weight was significantly increased in treatment and active control groups as compared to diabetic control (P < 0.001). CONCLUSION: Cow urine ark increases granulation tissue formation as well as collagen content. Wound contraction was also significantly improved. The cow urine ark could be potentially effective in promoting healing of diabetic wounds by increasing granulation tissue formation and collagen content, however, further studies are required for its clinical application.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis.

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64-1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44-1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71-1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55-0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54-0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data.

BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each day's delay). INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING: F Hoffmann-La Roche.

Anti-urolithiatic effect of ethanolic extract of Pedalium murex linn. fruits on ethylene glycol-induced renal calculi.

PURPOSE: To evaluate effect of ethanolic extract of Pedalium murex Linn. fruits on experimental model of calcium oxalate nephrolithiasis. MATERIALS AND METHODS: Thirty-six male Wistar albino rats were randomly divided in 6 groups.Normal controls received distilled water for 28 days. Other five groups received ethylene glycol(1% v/v) in distilled water for 28 days. Pedalium murex ethanolic extract was given 200 mg/kg and 400 mg/kg orally in distilled water for 28 days in prophylactic groups (III and IV) and from 15th to 28th days in treatment groups (V and VI). The urea, creatinine, random blood sugar, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin and calcium were measured on 28th day. 24 hr urinary oxalate and volume were measured on day 0 and 28. On day 28, kidneys were removed, weighed and subjected to histopathological examination. Calcium oxalate crystallization was evaluated by renal histopathology and in-vitro method of mineralization.All parameters were analyzed by Kruskal-Wallis or one-way ANOVA with post-hoc test. RESULTS: Pedalium murex showed significant improvement in renal function and kidney weight inprophylactic groups as compared to ethylene glycol controls. It did not show any effect on urinary oxalate, urine volume and any other serological parameters. Calcium oxalate crystallization was significantly reduced in all the Pedalium murex treated groups (P < .05). Calcium oxalate and phosphate mineralization were also inhibited by 33% and 57%. CONCLUSION: Ethanolic extract of Pedalium murex fruits possess significant activity for prevention of renal calculi.

Central anti-cholinergic syndrome induced by single therapeutic dose of atropine.

A 55 years old male patient, who is planned for bronchoscopy developed central anti-cholinergic syndrome due to therapeutic dose of atropine. Withdrawal of atropine has improved the symptoms. Thereafter, instillation of atropine as eye drops leads to reappearance of symptoms. The reaction was definite according to Naranjo's algorithm. It was severe and definitely preventable according to Modified Hartwig and Siegel's scale and Modified Schumock and Thornton scale respectively. Central anti-cholinergic syndrome may be due to variation in the genetic susceptibility (Idiosyncrasy) to atropine. Idiosyncratic reaction on administration of atropine as a pre-anesthetic medication or eye drops should be kept in mind while prescribing.

Epilepsy: Novel therapeutic targets.

Despite of established and effective therapy for epilepsy, 20-25% patients develop therapeutic failure; this encourages finding newer drugs. Novel approaches target receptors which remain unaffected by conventional therapy or inhibit epileptogenesis. AMPA receptor antagonists have shown faster and complete protection compared to diazepam. Protein kinase (PK) plays an important role in the development of epilepsy. PK inhibitors such as K252a, VID-82925, and Herbimycin A have been found effective in inhibition of spread of epileptiform activity and epileptogenesis. Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors classified into three groups. Group 1 mGluRs antagonist and Groups 2 and 3 mGluRs agonists inhibited pentylenetetrazole-induced kindled seizures. Combined use of these agents has also shown favorable results. Mammalian target of rapamycin (mTOR) plays a central role in multiple mechanisms of epileptogenesis. mTOR causes transcription, induction of proapoptotic proteins, and autophagy inhibition. Rapamycin was effective in suppression of recurrent seizures as well as in tuberous sclerosis and acute brain injury model. 5% CO(2) showed potent effects on cortical epileptiform activity and convulsions in animal epilepsy models and in humans with drug-resistant partial epilepsy. It is found to be rapidly acting, safe and cheap, thus it can be a good option in emergency for suppression of seizure. Neurosteroids are considered as fourth generation neuromessengers, they act as positive allosteric modulators of γ-aminobutyric acid (GABAA) receptors. Clinical trial of ganaxolone, an allopregnanolone analogue, has shown a beneficial role in pharmacoresistant epilepsy. However, most of these drugs are tested in early phases of development and the possible use and safety in epilepsy has to be proven in clinical trials.

Cross sensitivity between ciprofloxacin and levofloxacin for an immediate hypersensitivity reaction.

Seven years old male child (24 kg weight) diagnosed as a case of sub acute appendicitis treated with ciprofloxacin, immediately developed multiple erythmatous papules. Reaction subsided after withholding ciprofloxacin and treatment with dexamethasone and chlorpheneramine maleate. It was developed again when treated with levofloxacin and subsided after withdrawal. IgE binding at 7(th) position of core structure of fluoroquinolones likely to be the mechanism. As all the fluoroquinolones have similar core structure, hypersensitivity to one may have cross sensitivity to other fluoroquinolones. It is advisable to avoid other fluoroquinolones and switch over to other group of antibiotics when hypersensitivity to one occurs.

Adverse drug reaction profile of oseltamivir in Indian population: A prospective observational study.

OBJECTIVES: To analyze the pattern of adverse drug reactions (ADRs) of oseltamivir and its comparison with available data. MATERIALS AND METHODS: Suspected or confirmed cases of H1N1 influenza A on therapeutic regimen and close contacts of cases H1N1 influenza A on prophylactic regimen of oseltamivir were included. Data were collected by personal interview after obtaining written informed consent. Causality, severity, and preventability assessments were done by using Naranjo's scale, modified Hartwig and Siegel's scale, and modified Schumock and Thornton Scale, respectively. Data were expressed in proportions. Frequency of ADRs in therapeutic and prophylactic groups were compared with phase III trial of oseltamivir by using Chi-square test. RESULTS: Total 294 patients were interviewed. In prophylactic group, 107 of 257 (41.63%) and in therapeutic, group 23 of 37 (62.16%) developed ADRs. ADRs reported in therapeutic group was significantly (P = 0.029) higher as compared with prophylactic group. Frequently observed ADRs in both the groups were gastritis, nausea, vomiting, diarrhea weakness, sedation, loneliness, sadness, headache, and abdominal pain. Naranjo's algorithm showed all ADRs in probable category in prophylactic group, 27.78% probable and 72.22% possible reactions in therapeutic group. Severity assessment showed 76% mild and 24% moderate reactions in therapeutic group, 89% mild and 11% moderate reactions in prophylactic group. Severity of ADRs was significantly higher in therapeutic group. Most of ADRs were in nonpreventable category, except gastritis, nausea and vomiting were in definitely preventable category. CONCLUSION: Oseltamivir is well tolerated in Indian population. Gastrointestinal side effects are most common and preventable.