Sudhir Venkatesan

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 days 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 days 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.

Impact of Neuraminidase Inhibitor Treatment on Outcomes of Public Health Importance During the 2009–2010 Influenza A(H1N1) Pandemic: A Systematic Review and Meta-Analysis in Hospitalized Patients

Background. The impact of neuraminidase inhibitor (NAI) treatment on clinical outcomes of public health importance during the 2009–2010 pandemic has not been firmly established. Methods. We conducted a systematic review and meta-analysis, searching 11 databases (2009 through April 2012) for relevant studies. We used standard methods conforming to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random effects models. Results. Regarding mortality we observed a nonsignificant reduction associated with NAI treatment (at any time) versus none (OR, 0.72 [95% CI, .51–1.01]). However we observed significant reductions for early treatment (≤48 hours after symptom onset) versus late (OR, 0.38 [95% CI, .27–.53]) and for early treatment versus none (OR, 0.35 [95% CI, .18–.71]). NAI treatment (at any time) versus none was associated with an elevated risk of severe outcome (OR, 1.76 [95% CI, 1.22–2.54]), but early versus late treatment reduced the likelihood (OR, 0.41 [95% CI, .30–.56]). Conclusions. During the 2009–2010 influenza A(H1N1) pandemic, early initiation of NAI treatment reduced the likelihood of severe outcomes compared with late or no treatment. PROSPERO Registration. CRD42011001273.

Neuraminidase inhibitors: who, when, where?

Although the neuraminidase inhibitors (NIs), oseltamivir and zanamivir were first licensed in 1999, their clinical effectiveness is still hotly debated. Two rigorous systematic reviews and meta-analyses of the data from clinical trials conducted in community settings against relatively benign influenza, both suggest that reductions in symptom duration are extremely modest, under one day. Whilst one of these reviews could find no evidence of reductions in complications, the most recent review reported clinically meaningful and statistically significant reductions in the likelihood of requiring antibiotics (44%) and hospitalizations (63%) in adult patients with confirmed influenza, treated with oseltamivir. A further meta-analysis of observational data from the 2009 influenza A(H1N1) pandemic suggested that, in hospitalised patients, NIs significantly reduced mortality in adults by 25% overall, and by 62% if started within 48 hours of symptom onset, compared with no treatment. But, the effectiveness of NIs in children is far less clear. Taken together, these data suggest that NIs should be reserved for patients with influenza who are at high-risk of complications, or when clinically assessed found to be markedly unwell, or rapidly deteriorating. In such patients, treatment should be initiated empirically, as soon as possible, preferably with follow-on virological confirmation.

Factors determining intention to quit tobacco: exploring patient responses visiting public health facilities in India

IntroductionIntention to quit and setting a quit date are key steps in the process towards improving quit rates and are thus an integral part of tobacco cessation efforts. The present study examined various motivating factors of “intention to quit” and “setting a quit date” in patients visiting public health facilities in two states of India.MethodsA total of 1569 tobacco-users visiting public health facilities in 12 districts of the states of Andhra Pradesh and Gujarat were assessed through an interviewer-administered questionnaire. Bivariate and multivariable logistic regression was performed to assess the effect of socio-demographic characteristics, nicotine dependence, previous quit attempts and motivational factors on “intention to quit within 30 days” and “setting a quit date”.ResultsOnly 12% of patients intended to quit tobacco within 30 days and about 11% of them were ready to set a quit date. Respondents aged above 25 years were 53% less likely to quit tobacco within 30 days when compared to those below 25 years (95% Confidence Intervals [CI]: 0.22 to 0.99). Smokeless tobacco users were associated with an odds ratio (OR) of 2.05 (95% CI: 1.15 to 3.65) for “setting a quit date” when compared to smokers. Those with 1 to 5 previous quit attempts (in the past twelve months) were associated with an OR of 2.2 (95% CI: 1.38 to 3.51) for “intention to quit” and 2.46 (95% CI: 1.52 to 3.96) for “setting a quit date”. “Concern for personal health” and “setting an example for children” were associated with ORs of 3.42 (95% CI: 1.35 to 8.65) and 2.5 (95% CI: 1.03 to 6.03) respectively for “setting a quit date”.ConclusionsThis study is amongst the first in India to explore factors associated with the “intention to quit” and “setting a quit date” among patients visiting public health facilities. Our findings suggest that socio-economic and individual-level factors are important factors depicting intention to quit and setting a quit date. We recommend the need for well-defined studies to understand the long term effects of factors influencing tobacco cessation for patients visiting public health facilities in India.

Impact of outpatient neuraminidase inhibitor treatment in patients infected with influenza A(H1N1)pdm09 at high risk of hospitalization: an Individual Participant Data (IPD) meta-analysis

Summary Our findings suggest that in populations at high risk for hospital admission, patients with laboratory-confirmed or clinically diagnosed A(H1N1)pdm09 infection, NAI treatment in the community or outpatient settings is associated with reduced likelihood of subsequent hospital admission.

Cohort study of preoperative blood pressure and risk of 30-day mortality after elective non-cardiac surgery

Background Preoperative blood pressure (BP) thresholds associated with increased postoperative mortality remain unclear. We investigated the relationship between preoperative BP and 30-day mortality after elective non-cardiac surgery. Methods We performed a cohort study of primary care data from the UK Clinical Practice Research Datalink (2004-13). Parsimonious and fully adjusted multivariable logistic regression models, including restricted cubic splines for numerical systolic and diastolic BP, for 30-day mortality were constructed. The full model included 29 perioperative risk factors, including age, sex, comorbidities, medications, and surgical risk scale. Sensitivity analyses were conducted for age (>65 vs <65 years old) and the timing of BP measurement. Results A total of 251 567 adults were included, with 589 (0.23%) deaths within 30 days of surgery. After adjustment for all risk factors, preoperative low BP was consistently associated with statistically significant increases in the odds ratio (OR) of postoperative mortality. Statistically significant risk thresholds started at a preoperative systolic pressure of 119 mm Hg (adjusted OR 1.02 [95% confidence interval (CI) 1.01-1.02]) compared with the reference (120 mm Hg) and diastolic pressure of 63 mm Hg [OR 1.24 (95% CI 1.03-1.49)] compared with the reference (80 mm Hg). As BP decreased, the OR of mortality risk increased. Subgroup analysis demonstrated that the risk associated with low BP was confined to the elderly. Adjusted analyses identified that diastolic hypertension was associated with increased postoperative mortality in the whole cohort. Conclusions In this large observational study we identified a significant dose-dependent association between low preoperative BP values and increased postoperative mortality in the elderly. In the whole population, elevated diastolic, not systolic, BP was associated with increased mortality.

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

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.

Effects of five preoperative cardiovascular drugs on mortality after coronary artery bypass surgery: A retrospective analysis of an observational study of 16, 192 patients.

BACKGROUND Statins reduce risk from coronary artery bypass graft (CABG) surgery, but the influence of angiotensin-converting enzyme inhibitors, alpha-2 adrenergic agonists, calcium channel blockers and beta-blockers is less clear. OBJECTIVES We investigated the association of each of these drugs with perioperative risk, accounting for different confounders, and evaluated the class, dose-response and long-term protective effect of statins. DESIGN A retrospective analysis of observational data. SETTING United Kingdom. PATIENTS Sixteen thousand one hundred and ninety-two patients who underwent CABG surgery during the period 01 January 2004 to 31 December 2013 and contributed data to Primary Care Clinical Practice Research Datalink. EXPOSURE VARIABLES Cardiovascular drugs. OUTCOME MEASURE Perioperative mortality within 30 days of surgery. STATISTICAL ANALYSIS Five multivariable logistic regression models and a further Cox regression model were used to account for preexisting cardiovascular and other comorbidities along with lifestyle factors such as BMI, smoking and alcohol use. RESULTS Exposure to statins was most prevalent (85.1% of patients), followed by beta-blockers (72.8%), angiotensin-converting enzyme inhibitors (60.5%), calcium channel blockers (42.8%) and alpha-2 adrenergic agonists (1.2%). The mortality rate was 0.8% in patients not prescribed statins and 0.4% in those on statins. Statins were associated with a statistically significant reduced perioperative mortality in all five logistic regression models with adjusted odds ratios (OR) (95% confidence interval, 95% CI) ranging from 0.26 (0.13 to 0.54) to 0.35 (0.18 to 0.67). Cox regression for perioperative mortality [adjusted hazard ratio (95% CI) 0.40 (0.20 to 0.80)] and 6-month mortality [adjusted hazard ratio (95% CI) 0.63 (0.42 to 0.92)] produced similar results. Of the statin doses tested, only simvastatin 40 mg exerted protective effects. The other cardiovascular drugs lacked consistent effects across models. CONCLUSION Statins appear consistently protective against perioperative mortality from CABG surgery in multiple models, an effect not shared by the other cardiovascular drugs. Further data are needed on whether statins exert class and dose-response effects.

Physician and patient concordance of report of tobacco cessation intervention in primary care in India

BackgroundTobacco cessation interventions by physicians hold promise in improving quit rates. The 5As intervention (‘Ask’, ‘Advise’, ‘Assess’, ‘Assist’ and ‘Arrange’) is an evidence-based approach for tobacco cessation. However, little is known about adherence with the tobacco cessation interventions in primary care in India. In the present study we assessed physicians’ adherence with the 5As intervention and explored physician and patient concordance on the report of 5As intervention for tobacco cessation.MethodsWe used data from two cross-sectional surveys conducted in 12 districts of Andhra Pradesh and Gujarat in India. The surveys were administered simultaneously to both patients attending, and physicians working in health facilities providing primary care. Health facilities were selected by systematic random sampling and patients were recruited by simple random sampling. Common health facilities where both surveys were performed were identified, and individual patients were matched to their physicians through a unique matching code to obtain the two study samples.ResultsSlight agreement was observed between the physician and patient responses on ‘Ask’ and ‘Arrange’ component of the 5As intervention. The ‘Advise’, ‘Assess’ and ‘Assist’ components showed low agreement. Slightly higher levels of agreement were seen on all components of the 5As, except ‘Advise’, for those patients who had made an attempt to quit.ConclusionsOur study suggests an urgent need for revising current strategies in order to strengthen the ‘Advise’, ‘Assess’, and ‘Assist’ interventions in tobacco cessation in primary care settings. Patient surveys should be used routinely in assessing fidelity and provider adherence for large scale behavioral health programs.

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

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.