Population attributable numbers and fractions of deaths due to smoking: a pooled analysis of 180,000 Japanese

Objective

Age- and sex-specific population attributable fraction (PAF) and premature deaths attributable to smoking were estimated from a pooled analysis of cohort studies in Japan.

Methods

A pooled analysis of individual participant data from 13 well-qualified cohort studies throughout Japan (a total of 183,251 Japanese aged 40-89, 69,502 men and 113,749 women; the baseline years between 1987 and 1995 with average 10 years of follow-up) was performed. Poison regression model was used to estimate age- and sex-specific hazard ratios, and their PAFs of all-cause deaths and number of annual premature deaths attributable to smoking were estimated.

Results

Overall PAF attributable to smoking was 24.6% in men and 6.0% in women. The estimated number of annual premature deaths due to smoking was 121,854 (men: 109,998; women: 11,856) in Japan. The age-specific PAF was largest in men aged 60-69 (47.7%) and in women aged 50-59 (12.2%). In the older group aged 70-79 and 80-89, PAF was 15.4% and 8.0% in men and 3.5% and 1.5% in women, respectively.

Conclusions

Age-specific PAFs attributable to smoking in Japanese men are much larger than that reported from other Asian countries.     

Smoking prevalence and smoking attributable mortality in Italy, 2010

Objective

To provide updated information on smoking prevalence and attributable mortality in Italy.

Method

A representative survey on smoking was conducted in 2010 on a sample of 3020 Italian adults (1453 men and 1567 women). We used SAMMEC software to update smoking attributable mortality in Italy.

Results

In 2010, 21.7% of Italians (23.9% of men and 19.7% of women) described themselves as current smokers. Smoking prevalence was higher in men than in women in all age groups, except for the middle-aged population (45-64 years; 25.6% in men and 25.9% in women). Age-standardized smoking prevalence was higher in men than in women among less educated subjects and in southern Italy. No substantial difference was observed either in educated subjects or in northern and central Italy. Overall, 71,445 deaths in Italy (52,707 men and 18,738 women, 12.5% of total mortality) are attributable to smoking.

Conclusion

The overall smoking prevalence of 21.7% in 2010 is the lowest registered over the last 50 years. Since 1998, smoking related deaths declined by almost 15%. Given that Italy has now reached the final stage of the tobacco epidemic, anti-smoking strategies should focus on support for smoking cessation.     

Considerable variation in NNT - a study based on Monte Carlo simulations

Objective

The aim of this analysis was to explore the variation in measures of effect, such as the number-needed-to-treat (NNT) and the relative risk (RR).

Study Design and Setting

We performed Monte Carlo simulations of therapies using binominal distributions based on different true absolute risk reductions (ARR), number of patients (n), and the baseline risk of adverse events (p₀) as parameters and presented results in histograms with NNT and RR. We also estimated the probability of observing no or a negative treatment effect, given that the true effect is positive.

Results

When RR is used to express treatment effectiveness, it has a regular distribution around the expected value for various values of true ARR, n, and p₀. The equivalent distribution of NNT is by definition nonconnected at zero and is also irregular. The probability that the observed treatment effectiveness is zero or negative when the true value is positive depends on n, p₀, and the true ARR. In some cases, this probability is even higher than 50%.

Conclusion

For realistic values of true ARR, n, and p₀, the observed NNT varies much more than the observed ARR and RR. Clinicians should use NNT cautiously when expressing treatment benefits.     

How many deaths are attributable to smoking in the United States? Comparison of methods for estimating smoking-attributable mortality when smoking prevalence changes

Background

The number of smoking-attributable deaths is commonly estimated using current and former smoking prevalences or lung cancer mortality as an indirect metric of cumulative population smoking. Neither method accounts for differences in the timing with which relative risks (RRs) for different diseases change following smoking initiation and cessation. We aimed to develop a method to account for time-dependent RRs.

Methods

We used birth cohort lung cancer mortality and its change over time to characterize time-varying cumulative smoking exposure. We analyzed data from the American Cancer Society Cancer Prevention Study II to estimate RRs for disease-specific mortality associated with current and former smoking, and change in RRs over time after cessation.

Results

When lung cancer was used to measure cumulative smoking exposure, 254,700 male and 227,000 female deaths were attributed to smoking in the US in 2005. A modified method in which RRs for different diseases decreased at different rates after cessation yielded similar but slightly lower estimates [251,900 (male) and 221,100 (female)]. The lowest estimates resulted from the method based on smoking prevalence [225,800 (male) and 163,700 (female)].

Conclusions

Although all methods estimated a large number of smoking attributable deaths, future efforts should account for temporal changes in smoking prevalence and in accumulation/reversibility of disease-specific risks.     

Mortality attributable to smoking in Vietnamese men in 2008

Objective

Smoking prevalence among Vietnamese men is among the highest in the world. Our aim was to provide estimates of tobacco attributable mortality to support tobacco control policies.

Method

We used the Peto–Lopez method using lung cancer mortality to derive a Smoking Impact Ratio (SIR) as a marker of cumulative exposure to smoking. SIRs were applied to relative risks from the Cancer Prevention Study, Phase II. Prevalence-based and hybrid methods, using the SIR for cancers and chronic obstructive pulmonary disease and smoking prevalence for all other outcomes, were used in sensitivity analyses.

Results

When lung cancer was used to measure cumulative smoking exposure, 28% (95% uncertainty interval 24–31%) of all adult male deaths (> 35 years) in Vietnam in 2008 were attributable to smoking. Lower estimates resulted from prevalence-based methods [24% (95% uncertainty interval 21–26%)] with the hybrid method yielding intermediate estimates [26% (95% uncertainty interval 23–28%)].

Conclusion

Despite uncertainty in these estimates of attributable mortality, tobacco smoking is already a major risk factor for death in Vietnamese men. Given the high current prevalence of smoking, this has important implications not only for preventing the uptake of tobacco but also for immediate action to adopt and enforce stronger tobacco control measures.     

Treatments effects from randomized trials and propensity score analyses were similar in similar populations in an example from cardiac surgery

Objective

Analyses comparing randomized to nonrandomized clinical trials suffer from the fact that the study populations are usually different. We aimed for a comparison of randomized clinical trials (RCTs) and propensity score (PS) analyses in similar populations.

Study Design and Setting

In a systematic review, we “meta-matched” RCTs and PS analyses that compared the off- and the on-pump technique in coronary artery bypass grafting. “Meta-confounders” were summarized in a “meta-propensity score” and were used for “meta-matching.” We compared treatment effects between RCTs and PS analyses for 10 previously defined binary clinical outcomes in this “meta-matched” population as differences in “meta-odds ratios.”

Results

For all clinical outcomes, the estimated differences in “meta-odds ratios” were below an absolute value of 0.15, all confidence intervals included the null.

Conclusions

In our example, treatment effects of off-pump versus on-pump surgery from RCTs and PS analyses were very similar in a “meta-matched” population of studies, indicating that only a small remaining bias is present in PS analyses.     

Residential fungal growth and incidence of acute respiratory illness during the first two years of life

Background

Whether or not indoor mold growth causes acute childhood respiratory illness is controversial.

Objective

To determine the influence of indoor fungus on the incidence of acute respiratory illness episodes during the first two years of life.

Methods

Fungal indicators were measured in homes of children followed by daily symptom diaries and twice monthly telephone contact up to two years.

Participants

357 children born in Prince Edward Island, Canada.

Results

Generally, fungal contamination was not excessive with a geometric mean mold surface area (MSA) of 1012 cm² (geometric standard deviation (GSD) 24.2). The annual mean illness episodes per child were 6.85 (Standard Deviation (SD) 2.80). The incidence of respiratory illness episodes was not significantly related to any of the mold indicators: Analysis of variance (ANOVA) derived F-statistic (p values) was 0.14 (0.7090) for mold surface area.

Conclusions

In homes not selected by degree of fungal contamination, fungal burden was generally not excessive and was not found to be a risk factor for acute respiratory illness episodes during the first two years of life.     

Population studies of the effectiveness of mammographic screening

Objective

To examine population data to see whether survival from breast cancer has improved differentially in screened and unscreened women and examine published studies on mammographic screening to determine whether there is evidence that screening is no longer effective.

Methods

Data was reviewed on trends in breast cancer specific survival among women participating and not participating in the British Columbia Breast Screening Program. Population studies of mammographic screening published between 2000 and 2010 with breast cancer mortality as the outcome were also reviewed.

Results

Breast cancer specific survival in British Columbia improved more in screening participants than non-participants, HR = 0.74 (0.58,0.93) between the periods 1990-4 and 2000-4. Among the published studies of mortality between 2000 and 2010 selected from different jurisdictions all had found a reduction in breast cancer mortality although this was not always statistically different from zero. Studies had used a range of designs and evaluative methods which may have contributed to the magnitude of the effect reported.

Conclusion

No evidence was found in the British Columbia data and the published studies reviewed, that treatment or other changes, had caused mammographic screening to become ineffective.     

Risk of smoking and body mass index for incidence of diabetes mellitus in a rural Japanese population

Objective

To assess the risk of smoking, body mass index (BMI), and both for incidence of diabetes in a rural Japanese population.

Method

This study was a 10.1-year cohort study of 2070 men and 3802 women aged 40-69 years without diabetes at baseline who underwent a health check-up at one central hospital in Nagano Prefecture. Participants were classified according to a combination of smoking status and BMI. Participants were followed from 1990 to 2006. The incidence of diabetes was determined from fasting and random levels of plasma glucose, HbA_1c levels or being under medical treatment for diabetes.

Results

Diabetes developed in 595 of the participants during 59,111 person-years of follow-up. In men, the multivariable-adjusted hazard ratios for incidence of diabetes compared with non-smokers of normal weight were as follows: 3.36 (2.02-5.60) in current smokers with normal weight and 1.70 (0.87-3.34) and 3.93 (2.22-6.96) in obese non-smokers and obese current smokers, respectively. In men the population-attributable fraction of diabetes onset due to current smoking, obesity and both were 22.0%, 2.5% and 11.2%, respectively.

Conclusion

Regardless of BMI, smoking is an important risk factor for diabetes in male populations with a high prevalence of smoking.     

The quality of safety reporting in trials is still suboptimal: survey of major general medical journals

Objective

To evaluate whether the quality of reporting harms improved after the publication of the Extension of the Consolidated Standards of Reporting Trials (CONSORT) statement and predictors that influence the safety reporting in randomized controlled trials (RCTs)

Study Design and Setting

Systematic survey of published RCTs assessing drugs. In MEDLINE, we identified 228 RCTs published in Annals of Internal Medicine, British Medical Journal, Journal of American Medical Association, The Lancet, and The New England Journal of Medicine in 2003 and 2006.

Results

The reporting of harms have improved over time both in quality and extent of space. However, the mean score as an overall measure of adequacy in reporting harms was 0.58 in 2003 and increased to 0.67 in 2006, indicating a moderate safety reporting. Safety was more adequate in trials with statistically significant results for efficacy, private funding, primary harms outcome, and anti-infective, antineoplasmatic, or immunosuppressive agents.

Conclusion

The use of the Extension of the CONSORT statement may be associated with improving the quality of safety reporting in RCTs, but there are still deficiencies that need to be corrected to use quantitative objective evidence for harms in performing meta-analyses and making therapeutic decisions.     

Young women's perceptions of pregnancy risk and use of emergency contraception: findings from a qualitative study

Background

Advance provision of emergency contraception (EC) has increased use but not impacted on pregnancy or abortion rates. Here we describe young women's EC use and experiences of unprotected sex to explore why this difference occurs.

Methods

In-depth interviews with twenty 20-year-old women from eastern Scotland.

Results

The majority (16) had used EC; 10 reported some experience of unprotected sex. EC use followed contraceptive failure and unexpected or unplanned, but not frequent, unprotected sex. Acknowledging the need for EC requires recognition of pregnancy risk. Those reporting frequent unprotected sex misperceived their pregnancy risk and did not use EC. This group was from socially disadvantaged backgrounds, and all became pregnant.

Conclusions

EC remains an important “backup” contraceptive and should continue to be widely available. With high levels of unprotected sex, nonuse of EC and unintended pregnancies, further efforts are required to improve the sexual and reproductive health outcomes of disadvantaged young women.     

Malaria severity criteria and prognostic factors among children in Dakar

Introduction

Severity factors associated with malaria as well as prognostic factors for death were assessed at the Dakar Centre Hospitalier National d’Enfants Albert Royer de Fann (CHNEAR).

Patients and methods

A prospective study was carried out from January 1 to December 31, 2007 involving children from 0 to15 years of age, admitted for plasmodium falciparum malaria with positive thick drop examination, meeting at least one of the WHO 2000 malaria severity criteria. Acidosis was not studied.

Outcome

The rate of severe malaria cases in our hospital was 6.4%. The sex ratio was 1.4 and the median age of patients at 91 months. A peak was observed during the 4th trimester (75.5%). Convulsions (52.5%) and obtundation (49.4%) were the most common signs of clinical severity while hyperparasitemia and severe anemia ranged at 27.2% and 21.6%, respectively. Lethality was 11.1 % and the main death risk factors were young age (p = 0.025), coma (p = 0.007), respiratory distress (p = 0.04), or hypoglycemia (p = 0.001).

Conclusion

Reducing malaria hospital mortality in Senegal may be obtained by proper management of poor prognostic factors such as coma, respiratory distress, and hypoglycemia.     

Reviews assessing the quality or the reporting of randomized controlled trials are increasing over time but raised questions about how quality is assessed

Objective

Many reviews specifically aimed to assess the quality of randomized controlled trials (RCTs). We evaluated the quality of reporting in such reviews.

Study Design and Setting

PubMed and the Cochrane library were searched for all reviews assessing the quality of RCTs between 1987 and 2007, and experts in the field were also contacted.

Results

We found 177 reviews published from 1987 to 2007, 58% of which were published after 2002. Of these, 131 (74%) focused on the quality of RCTs, 44 (25%) on quality of reporting, and 2 (1%) assessed both. The search strategy was well reported (92%). The criteria for assessment were reported in 97% of the reviews but were defined in only 38%. Seventy-four different items and 26 different scales were identified. Allocation sequence generation and concealment were reported in 41% and 40%, respectively, but their adequacy was assessed in 20% and 29%, respectively; scales were used in 40% and Consolidated Standards of Reporting Trials (CONSORT) checklist in 12%.

Conclusion

The number of methodological reviews has dramatically increased in recent years. Despite an improved reporting of the methodology, how quality is assessed still raises important issues. Heterogeneity of criteria used and lack of definition may limit the relevance of these reviews.     

Descripción de las agresiones sexuales atendidas en el servicio de urgencias de un centro hospitalario de referencia

Objective

To describe the factors related to adult sexual assaults attended in a referral hospital in the city of Barcelona (Spain).

Methods

We carried out an individual-based cross-sectional study of sexual assaults treated in the emergency department between 2005 and 2008.

Results

A total of 712 patients (95.5% female) were treated. The median age of assaulted women was 25 years. Complaints were made in 87.5% of cases and assaults were made by a single attacker in 84.5%. When the perpetrator was known, the profile of the victim (p ≤ 0.05) was as follows: the victim was assaulted at home (81.5%), the perpetrator acted alone (94.2%), the mechanism of aggression was penetration (89.3%) and the attack took place during the week (63.3%).

Conclusions

Analysis of sexual assaults allows for different risk groups to be established, which facilitates the development of specific protocols and guidelines for effective aid and full treatment.     

Randomized controlled trials of herbal interventions underreport important details of the intervention

Objective

To examine the quality of reporting and predictors of reporting in randomized clinical trials (RCTs) of herbal medicine interventions.

Study Design and Setting

We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, and Academy of Microscope Enhanced Dentistry up to December 2007 for any English language RCT of 11 commonly used herbal medicine interventions. Two individuals separately and independently assessed all trials using the Consolidated Standards of Reporting Trials (CONSORT) checklist for herbal medicines interventions. We randomly selected 100 of these trials, extracted a set of potential predictor variables identified through a literature search and consultation with experts, and performed a conceptually driven stepwise elimination regression analyses for predictor variables.

Results

The 406 trials reported on average 38% of the information suggested in the checklist. Regression analyses revealed better overall reporting in trials with a participant flow diagram (P = 0.008), those of Panax quinquefolius (P = 0.018), and those published in more recent years (P = 0.02).

Conclusion

Our results indicate that RCTs of herbal medicine interventions frequently do not report important characteristics of the intervention. Trialists should refer to the CONSORT for herbal medicines when reporting their trials.     

A triple combination strategy corrects population stratification bias and saves genotyping cost

Objective

The case-control association study has gained popularity for mapping disease-susceptibility gene(s) of complex human diseases. However, the study is prone to population stratification bias.

Study Design and Setting

The authors proposed a triple combination strategy of stratum matching, genomic control, and multiple DNA pooling for population-based case-control association studies. Monte Carlo simulation showed that the type I error rates are well controlled using this strategy.

Results

As for power, it increases under the following situations: (1) more accurate stratum matching, (2) more null markers for genomic control, (3) more DNA pooling sets, and (4) more accurate DNA pooling measurement.

Conclusion

The triple combination strategy corrects population stratification bias and saves genotyping cost.     

Systematic review reveals heterogeneity in definition of a clinically relevant difference in pain

Objective

To describe the pain decrease considered as clinically relevant when designing a trial and reporting its results.

Methods

A systematic review of the literature in MEDLINE was conducted to select randomized controlled trials (RCTs) with pain as a primary outcome. Data extracted included the definition (terms and values) of a clinically relevant difference in pain, the type of pain studied (acute or chronic), the level of application (group or individual) of the clinically relevant difference, and the reference justifying the choice of value for clinically relevant difference.

Study Design and Setting

Seventy-four trials were included, and only 16 articles justified the choice of a value for clinically relevant difference with a reference citation. The values chosen for the clinically relevant relative decrease in pain varied from 4 to 40 mm or from 15% to 55% at the group level and from 20 to 50 mm at the individual level. In seven articles, the authors confused the application of the reference value at the individual or group level.

Conclusion

Our review revealed a great heterogeneity in definition, format, and values of what is considered a clinically relevant difference in pain in RCTs of analgesics, and standardizations are advisable.     

Survival distributions impact the power of randomized placebo-phase design and parallel groups randomized clinical trials

Objectives

The study evaluated the power of the randomized placebo-phase design (RPPD)—a new design of randomized clinical trials (RCTs), compared with the traditional parallel groups design, assuming various response time distributions. In the RPPD, at some point, all subjects receive the experimental therapy, and the exposure to placebo is for only a short fixed period of time.

Study Design and Setting

For the study, an object-oriented simulation program was written in R. The power of the simulated trials was evaluated using six scenarios, where the treatment response times followed the exponential, Weibull, or lognormal distributions. The median response time was assumed to be 355 days for the placebo and 42 days for the experimental drug.

Results

Based on the simulation results, the sample size requirements to achieve the same level of power were different under different response time to treatment distributions. The scenario where the response times followed the exponential distribution had the highest sample size requirement. In most scenarios, the parallel groups RCT had higher power compared with the RPPD.

Conclusion

The sample size requirement varies depending on the underlying hazard distribution. The RPPD requires more subjects to achieve a similar power to the parallel groups design.     

Optimism bias leads to inconclusive results-an empirical study

Objective

Optimism bias refers to unwarranted belief in the efficacy of new therapies. We assessed the impact of optimism bias on a proportion of trials that did not answer their research question successfully and explored whether poor accrual or optimism bias is responsible for inconclusive results.

Study Design

Systematic review.

Setting

Retrospective analysis of a consecutive-series phase III randomized controlled trials (RCTs) performed under the aegis of National Cancer Institute Cooperative groups.

Results

Three hundred fifty-nine trials (374 comparisons) enrolling 150,232 patients were analyzed. Seventy percent (262 of 374) of the trials generated conclusive results according to the statistical criteria. Investigators made definitive statements related to the treatment preference in 73% (273 of 374) of studies. Investigators’ judgments and statistical inferences were concordant in 75% (279 of 374) of trials. Investigators consistently overestimated their expected treatment effects but to a significantly larger extent for inconclusive trials. The median ratio of expected and observed hazard ratio or odds ratio was 1.34 (range: 0.19-15.40) in conclusive trials compared with 1.86 (range: 1.09-12.00) in inconclusive studies (P < 0.0001). Only 17% of the trials had treatment effects that matched original researchers’ expectations.

Conclusion

Formal statistical inference is sufficient to answer the research question in 75% of RCTs. The answers to the other 25% depend mostly on subjective judgments, which at times are in conflict with statistical inference. Optimism bias significantly contributes to inconclusive results.     

The potential impact of an HIV vaccine with limited protection on HIV incidence in Thailand: a modeling study

Background

The RV144 trial on the ALVAC/AIDSVAX candidate HIV vaccine, carried out in Thailand, showed short-lived protection against infection.

Methods

Using a deterministic compartmental model we explored the potential impact of this vaccine on heterosexual HIV transmission in Thailand. Both one-off vaccination strategies, as well as strategies with regular boosting, either annually or every two years, were explored. Both targeting the general adult population and prioritizing sex workers were modeled. The impact of risk compensation among high risk groups, as well as whether higher levels of safe sex in high risk groups could be an alternative to vaccination, was studied.

Results

One-off vaccination campaigns had only transient effects, and boosting appears to be a key component of successful vaccination campaigns. Intensive vaccination campaigns may reduce HIV incidence by up to 75% after 10 years of vaccination. Targeting only sex workers has a smaller impact but has a more favorable cost-benefit ratio. Risk compensation has the potential of undoing much of the benefits of a vaccination program and may even increase incidence. In contrast, higher levels of safe sex among sex workers would provide a viable alternative to vaccinating this group.

Discussion

The new vaccine holds promise for controlling HIV in Thailand and similar countries. In view of the short lived protection of the vaccine, regular boosting of immunity as well as avoidance of risk compensation are essential. Targeting sex workers would achieve the greatest reduction in incidence per vaccination and may be considered for expensive vaccines but its cost-effectiveness has to be compared to alternatives.