Jo Leonardi-Bee

A systematic review of worldwide incidence of nonmelanoma skin cancer

Background  Nonmelanoma skin cancer (NMSC) is the most common cancer affecting white‐skinned individuals and the incidence is increasing worldwide.

Blood Pressure and Clinical Outcomes in the International Stroke Trial

Background and Purpose— Among patients with acute stroke, high blood pressure is often associated with poor outcome, although the reason is unclear. We analyzed data from the International Stroke Trial (IST) to explore the relationship between systolic blood pressure (SBP), subsequent clinical events over the next 2 weeks, and functional outcome at 6 months in patients with acute stroke. Methods— We included in the analysis 17 398 patients from IST with confirmed ischemic stroke. A single measurement of SBP was made immediately before randomization. Clinical events within 14 days of randomization were recorded: recurrent ischemic stroke, symptomatic intracranial hemorrhage, death resulting from presumed cerebral edema, fatal coronary heart disease, and death. Survival and dependency were assessed at 6 months. Outcomes were adjusted for age, sex, clinical stroke syndrome, time to randomization, consciousness level, atrial fibrillation, and treatment allocation (aspirin, unfractionated heparin, both, or neither). Results— A U-shaped relationship was found between baseline SBP and both early death and late death or dependency: early death increased by 17.9% for every 10 mm Hg below 150 mm Hg (P <0.0001) and by 3.8% for every 10 mm Hg above 150 mm Hg (P =0.016). The rate of recurrent ischemic stroke within 14 days increased by 4.2% for every 10–mm Hg increase in SBP (P =0.023); this association was present in both fatal and nonfatal recurrence. Death resulting from presumed cerebral edema was independently associated with high SBP (P =0.004). No relationship between symptomatic intracranial hemorrhage and SBP was seen. Low SBP was associated with a severe clinical stroke (total anterior circulation syndrome) and an excess of deaths from coronary heart disease (P =0.002). Conclusions— Both high blood pressure and low blood pressure were independent prognostic factors for poor outcome, relationships that appear to be mediated in part by increased rates of early recurrence and death resulting from presumed cerebral edema in patients with high blood pressure and increased coronary heart disease events in those with low blood pressure. The occurrence of symptomatic intracranial hemorrhage within 14 days was independent of SBP.

Blood Pressure Reduction and Secondary Prevention of Stroke and Other Vascular Events: A Systematic Review

Background— High blood pressure is a risk factor for stroke recurrence. We assessed the effectiveness of lowering blood pressure in preventing recurrent vascular events in patients with previous stroke or transient ischemic attack. Summary of Review— We performed a systematic review and meta-regression of completed randomized controlled trials that investigated the effect of lowering blood pressure on recurrent vascular events in patients with prior ischemic or hemorrhagic stroke or transient ischemic attack. Trials were identified from searches of 3 electronic databases (Cochrane Library, EMBASE, MEDLINE). Seven randomized controlled trials, with 8 comparison groups, were included. Lowering blood pressure or treating hypertension with a variety of antihypertensive agents reduced stroke (odds ratio [OR], 0.76; 95% CI, 0.63 to 0.92), nonfatal stroke (OR, 0.79; 95% CI, 0.65 to 0.95), myocardial infarction (OR, 0.79; 95% CI, 0.63 to 0.98), and total vascular events (OR, 0.79; 95% CI, 0.66 to 0.95). No effect was seen on vascular or all-cause mortality. Heterogeneity was present for several outcomes and was partly related to the class of antihypertensive drugs used; angiotensin-converting enzyme inhibitors and diuretics separately, and especially together, reduced vascular events, while &bgr;-receptor antagonists had no discernable effect. The reduction in stroke was related to the difference in systolic blood pressure between treatment and control groups (P =0.002). Conclusions— Evidence from randomized controlled trials supports the use of antihypertensive agents in lowering blood pressure for the prevention of vascular events in patients with previous stroke or transient ischemic attack. Vascular prevention is associated positively with the magnitude by which blood pressure is reduced.

High Blood Pressure in Acute Stroke and Subsequent Outcome. A Systematic Review

Abstract—High blood pressure (BP) is common in acute stroke and might be associated with a poor outcome, although observational studies have given varying results. In a systematic review, articles were sought that reported both admission BP and outcome (death, death or dependency, death or deterioration, stroke recurrence, and hematoma expansion) in acute stroke. Data were analyzed by the Cochrane Review Manager software and are given as odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs). Altogether, 32 studies were identified involving 10 892 patients. When all data were included, death was significantly associated with an elevated mean arterial BP ([MABP] OR, 1.61; 95% CI, 1.12 to 2.31) and a high diastolic BP ([DBP] OR, 1.71; 95% CI, 1.33 to 2.48). Combined death or dependency was associated with high systolic BP ([SBP] OR, 2.69; 95% CI, 1.13 to 6.40) and DBP (OR, 4.68; 95% CI, 1.87 to 11.70) in primary intracerebral hemorrhage (PICH). Similarly, high SBP (+11.73 mm Hg; 95% CI, 1.30 to 22.16), MABP (+9.00 mm Hg; 95% CI, 0.92 to 17.08), and DBP (+6.00 mm Hg; 95% CI, 0.19 to 11.81) were associated with death or dependency in ischemic stroke. Combined death or deterioration was associated with a high SBP (OR, 5.57; 95% CI, 1.42 to 21.86) in patients with PICH. In summary, high BP in acute ischemic stroke or PICH is associated with subsequent death, death or dependency, and death or deterioration. Moderate lowering of BP might improve outcome. Acute BP lowering needs to be tested in 1 or more large, randomized trials.

Prenatal and Passive Smoke Exposure and Incidence of Asthma and Wheeze: Systematic Review and Meta-analysis

OBJECTIVES: Exposure to passive smoke is a common and avoidable risk factor for wheeze and asthma in children. Substantial growth in the prospective cohort study evidence base provides an opportunity to generate new and more detailed estimates of the magnitude of the effect. A systematic review and meta-analysis was conducted to provide estimates of the prospective effect of smoking by parents or household members on the risk of wheeze and asthma at different stages of childhood. METHODS: We systematically searched Medline, Embase, and conference abstracts to identify cohort studies of the incidence of asthma or wheeze in relation to exposure to prenatal or postnatal maternal, paternal, or household smoking in subjects aged up to 18 years old. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by using random effects model. RESULTS: We identified 79 prospective studies. Exposure to pre- or postnatal passive smoke exposure was associated with a 30% to 70% increased risk of incident wheezing (strongest effect from postnatal maternal smoking on wheeze in children aged ≤2 years, OR = 1.70, 95% CI = 1.24–2.35, 4 studies) and a 21% to 85% increase in incident asthma (strongest effect from prenatal maternal smoking on asthma in children aged ≤2 years, OR = 1.85, 95% CI = 1.35–2.53, 5 studies). CONCLUSIONS: Building upon previous findings, exposure to passive smoking increases the incidence of wheeze and asthma in children and young people by at least 20%. Preventing parental smoking is crucially important to the prevention of asthma.

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.

Environmental tobacco smoke and fetal health: systematic review and meta-analysis

Objective: To determine the effects of environmental tobacco smoke (ETS) exposure on birth outcomes. Design: A systematic review and meta-analysis was performed in accordance with MOOSE guidelines. MEDLINE, EMBASE, CINAHL and LILACS (up to October 2007), were searched and also reviews and reference lists from publications, with no language restrictions. Pooled mean differences and odds ratios (ORs) with 95% confidence intervals were estimated using data extracted from papers, based on random effect models. Setting: Comparative epidemiological studies. Patients: Pregnant women or women who have given birth. Exposures: Maternal exposure to ETS during pregnancy. Main outcome measures: Mean birth weight and proportion of premature infants. Results: 58 studies were included; 53 used cohort designs, 23 ascertaining ETS exposure prospectively and 30 retrospectively; 5 used case–control designs. In prospective studies, ETS exposure was associated with a 33 g (95% CI 16 to 51) reduction in mean birth weight, and in retrospective studies a 40 g (95% CI 26 to 54) reduction. ETS exposure was also associated with an increased risk of low birth weight (birth weight <2500 g; prospective studies: OR 1.32, 95% CI 1.07 to 1.63; retrospective studies: OR 1.22, 95% CI 1.08 to 1.37). The risk of small for gestational age (<10th centile) birth was significantly associated with ETS exposure only in retrospective studies (OR 1.21, 95% CI 1.06 to 1.37). There was no effect of ETS exposure on gestational age. Conclusions: Exposure of non-smoking pregnant women to ETS reduces mean birth weight by 33 g or more, and increases the risk of birth weight below 2500 g by 22%, but has no clear effect on gestation or the risk of being small for gestational age.

Rehabilitation therapy services for stroke patients living at home: systematic review of randomised trials.

BACKGROUND Stroke-unit care can be valuable for stroke patients in hospital, but effectiveness of outpatient care is less certain. We aimed to assess the effects of therapy-based rehabilitation services targeted at stroke patients resident in the community within 1 year of stroke onset or discharge from hospital. METHODS We did a systematic review of randomised trials of outpatient services, including physiotherapy, occupational therapy, and multidisciplinary teams. We used Cochrane collaboration methodology. FINDINGS We identified a heterogeneous group of 14 trials (1617 patients). Therapy-based rehabilitation services for stroke patients living at home reduced the odds of deteriorating in personal activities of daily living (odds ratio 0.72 [95% CI 0.57-0.92], p=0.009) and increased ability of patients to do personal activities of daily living (standardised mean difference 0.14 [95% CI 0.02-0.25], p=0.02). For every 100 stroke patients resident in the community receiving therapy-based rehabilitation services, seven (95% CI 2-11) would not deteriorate. INTERPRETATION Therapy-based rehabilitation services targeted at selected patients resident in the community after stroke improve ability to undertake personal activities of daily living and reduce risk of deterioration in ability. These findings should be considered in future service planning.

Exposure to parental and sibling smoking and the risk of smoking uptake in childhood and adolescence: a systematic review and meta-analysis

Background There is increasing evidence that contact with other smokers, particularly in the family, is a strong determinant of risk of smoking uptake. A systematic review and meta-analysis of the magnitude of these effects is reported. Methods Studies were identified by searching four databases to March 2009 and proceedings from international conferences. Meta-analyses were performed using random effects, with results presented as pooled ORs with 95% CIs. Results 58 studies were included in the meta-analyses. The relative odds of uptake of smoking in children were increased significantly if at least one parent smoked (OR 1.72, 95% CI 1.59 to 1.86), more so by smoking by the mother (OR 2.19, 95% CI 1.73 to 2.79) than the father (OR 1.66, 95% CI 1.42 to 1.94), and if both parents smoked (OR 2.73, 95% CI 2.28 to 3.28). Smoking by a sibling increased the odds of smoking uptake by 2.30 (95% CI 1.85 to 2.86) and smoking by any household member by 1.92 (95% CI 1.70 to 2.16). After adjusting for overestimation of RRs it is estimated that, in England and Wales, around 17 000 young people take up smoking by the age of 15 each year as a consequence of exposure to household smoking. Conclusions Parental and sibling smoking is a strong and significant determinant of the risk of smoking uptake by children and young people and, as such, is a major and entirely avoidable health risk. Children should be protected from exposure to smoking behaviour, especially by family members.

Trends in incidence of skin basal cell carcinoma. Additional evidence from a UK primary care database study.

We determined the trends in incidence of skin basal cell carcinoma (BCC) using a primary care population‐based cohort study in the UK. 11,113 adults with a BCC diagnosis were identified from a total of 7.22 million person‐years of data between 1996 and 2003 from the Health Improvement Network database. From a random subsample of BCC cases identified from the database, 93% were confirmed by hospital letter and/or pathology report. The incidence of BCC was 153.9 per 100,000 person‐years (95% CI 151.1, 156.8) and was slightly higher in men as compared to women (Incidence Rate Ratio 1.10, 95% CI 1.06, 1.14). There was a 3% increase year on year across the study period (IRR 1.03, 95% CI 1.01, 1.04), with the largest increase in incidence seen in the 30–39 year age groups, although this did not reach statistical significance. Our study indicates 53,000 new cases of BCC are estimated every year in the UK and figures are continuing to rise on a yearly basis. Incidence rates are highest for men and in particular in the older age categories. These findings are consistent with those reported for various other populations. We have also found an increase in incidence in ages 30–39, which may suggest a cohort effect of increasing ultraviolet exposure in successive younger generations. This may have a huge public and service impact in future years in countries such as the UK, with predominantly fair‐skinned population, with high leisure exposure to ultraviolet light. Our findings underline the need for more elaborate preventive measures.