Mario Chen-Mok

Prevalence of Rheumatic Heart Disease in Children and Young Adults in Nicaragua

Rheumatic heart disease (RHD) results in morbidity and mortality that is disproportionate among individuals in developing countries compared to those living in economically developed countries. The global burden of disease is uncertain because most previous studies to determine the prevalence of RHD in children relied on clinical screening criteria that lacked the sensitivity to detect most cases. The present study was performed to determine the prevalence of RHD in children and young adults in León, Nicaragua, an area previously thought to have a high prevalence of RHD. This was an observational study of 3,150 children aged 5 to 15 years and 489 adults aged 20 to 35 years randomly selected from urban and rural areas of León. Cardiopulmonary examinations and Doppler echocardiographic studies were performed on all subjects. Doppler echocardiographic diagnosis of RHD was based on predefined consensus criteria that were developed by a working group of the World Health Organization and the National Institutes of Health. The overall prevalence of RHD in children was 48 in 1,000 (95% confidence interval 35 in 1,000 to 60 in 1,000). The prevalence in urban children was 34 in 1,000, and in rural children it was 80 in 1,000. Using more stringent Doppler echocardiographic criteria designed to diagnose definite RHD in adults, the prevalence was 22 in 1,000 (95% confidence interval 8 in 1,000 to 37 in 1,000). In conclusion, the prevalence of RHD among children and adults in this economically disadvantaged population far exceeds previously predicted rates. The findings underscore the potential health and economic burden of acute rheumatic fever and RHD and support the need for more effective measures of prevention, which may include safe, effective, and affordable vaccines to prevent the streptococcal infections that trigger the disease.

Vasectomy by ligation and excision, with or without fascial interposition: a randomized controlled trial [ISRCTN77781689]

BackgroundRandomized controlled trials comparing different vasectomy occlusion techniques are lacking. Thus, this multicenter randomized trial was conducted to compare the probability of the success of ligation and excision vasectomy with, versus without, fascial interposition (i.e. placing a layer of the vas sheath between two cut ends of the vas).MethodsThe trial was conducted between December 1999 and June 2002 with a single planned interim analysis. Men requesting vasectomies at eight outpatient clinics in seven countries in North America, Latin America, and Asia were included in the study. The men were randomized to receive vasectomy with versus without fascial interposition. All surgeons performed the vasectomies using the no-scalpel approach to the vas. Participants had a semen analysis two weeks after vasectomy and then every four weeks up to 34 weeks. The primary outcome measure was time to azoospermia. Additional outcome measures were time to severe oligozoospermia (<100 000 sperm/mL) and vasectomy failure based on semen analyses.ResultsWe halted recruitment after the planned interim analysis, when 841 men had been enrolled. Fascial interposition decreased time to azoospermia (hazard ratio [HR], 1.35; P < 0.0001) and time to severe oligozoospermia (HR, 1.32; P < 0.0001) and reduced failures based on semen analysis by about half, from 12.7% (95% confidence interval [CI], 9.7 to 16.3) to 5.9% (95% CI, 3.8 to 8.6) (P < 0.0001). Older men benefited less from fascial interposition than younger men in terms of the speed of achieving azoospermia. However, the number of vasectomy failures was reduced to a similar degree in all age groups. Slightly more adverse events occurred in the fascial interposition group, but the difference was not significant. These failure rates may appear high to practitioners in countries such as the USA, but they are similar to results from other careful studies of ligation and excision techniques.ConclusionFascial interposition significantly improves vasectomy success when ligation and excision is the method of vas occlusion. A limitation of this study is that the correlation between postvasectomy sperm concentrations and risk of pregnancy is not well quantified.

Effectiveness of vasectomy using cautery

BackgroundLittle evidence supports the use of any one vas occlusion method. Data from a number of studies now suggest that there are differences in effectiveness among different occlusion methods. The main objectives of this study were to estimate the effectiveness of vasectomy by cautery and to describe the trends in sperm counts after cautery vasectomy. Other objectives were to estimate time and number of ejaculations to success and to determine the predictive value of success at 12 weeks for final status at 24 weeks.MethodsA prospective, non-comparative observational study was conducted between November 2001 and June 2002 at 4 centers in Brazil, Canada, the UK, and the US. Four hundred men who chose vasectomy were enrolled and followed for 6 months. Sites used their usual cautery vasectomy technique. Earlier and more frequent than normal semen analyses (2, 5, 8, 12, 16, 20, and 24 weeks after vasectomy) were performed. Planned outcomes included effectiveness (early failure based on semen analysis), trends in sperm counts, time and number of ejaculations to success, predictive value of success at 12 weeks for the outcome at 24 weeks, and safety evaluation.ResultsA total of 364 (91%) participants completed follow-up. The overall failure rate based on semen analysis was 0.8% (95% confidence interval 0.2, 2.3). By 12 weeks 96.4% of participants showed azoospermia or severe oligozoospermia (< 100,000 sperm/mL). The predictive value of a single severely oligozoospermia sample at 12 weeks for vasectomy success at the end of the study was 99.7%. One serious unrelated adverse event and no pregnancies were reported.ConclusionCautery is a very effective method for occluding the vas. Failure based on semen analysis is rare. In settings where semen analysis is not practical, using 12 weeks as a guideline for when men can rely on their vasectomy should lessen the risk of failure compared to using a guideline of 20 ejaculations after vasectomy.

Frequency and patterns of early recanalization after vasectomy.

BackgroundOur understanding of early post-vasectomy recanalization is limited to histopathological studies. The objective of this study was to estimate the frequency and to describe semen analysis patterns of early recanalization after vasectomy.MethodsCharts displaying serial post-vasectomy semen analyses were created using the semen analysis results from 826 and 389 men participating in a randomized trial of fascial interposition (FI) and an observational study of cautery, respectively. In the FI trial, participants were randomly allocated to vas occlusion by ligation and excision with or without FI. In the cautery study, sites used their usual cautery occlusion technique, two with and two without FI. Presumed early recanalization was based on the assessment of individual semen analysis charts by three independent reviewers. Discrepancies were resolved by consensus.ResultsPresumed early recanalization was characterized by a very low sperm concentration within two weeks after vasectomy followed by return to large numbers of sperm over the next few weeks. The overall proportion of men with presumed early recanalization was 13% (95% CI 12%–15%). The risk was highest with ligation and excision without FI (25%) and lowest for thermal cautery with FI (0%). The highest proportion of presumed early recanalization was observed among men classified as vasectomy failures.ConclusionEarly recanalization, occurring within the first weeks after vasectomy, is more common than generally recognized. Its frequency depends on the occlusion technique performed.

A comparison of vas occlusion techniques: cautery more effective than ligation and excision with fascial interposition

BackgroundVasectomy techniques have been the subject of relatively few rigorous studies. The objective of this analysis was to compare the effectiveness of two techniques for vas occlusion: intraluminal cautery versus ligation and excision with fascial interposition. More specifically, we aimed to compare early failure rates, sperm concentrations, and time to success between the two techniques.MethodsWe compared semen analysis data from men following vasectomy using two occlusion techniques. Data on intraluminal cautery came from a prospective observational study conducted at four sites. Data on ligation and excision with fascial interposition came from a multicenter randomized controlled trial that evaluated the efficacy of ligation and excision with versus without fascial interposition. The surgical techniques used in the fascial interposition study were standardized. The surgeons in the cautery study used their customary techniques, which varied among sites in terms of type of cautery, use of fascial interposition, excision of a short segment of the vas, and use of an open-ended technique. Men in both studies had semen analyses two weeks after vasectomy and then approximately every four weeks. The two outcome measures for the analyses presented here are (a) time to success, defined as severe oligozoospermia, or <100,000 sperm/mL in two consecutive semen analyses; and (b) early vasectomy failure, defined as >10 million sperm/mL at week 12 or later.ResultsVasectomy with cautery was associated with a significantly more rapid progression to severe oligozoospermia and with significantly fewer early failures (1% versus 5%).ConclusionThe use of cautery improves vasectomy outcomes. Limitations of this comparison include (a) the variety of surgical techniques in the cautery study and differences in methods of fascial interposition between the two studies, (b) the uncertain correlation between sperm concentrations after vasectomy and the risk of pregnancy, and (c) the use of historical controls and different study sites.

Termination of a randomized controlled trial of two vasectomy techniques

Family Health International (FHI) and EngenderHealth conducted a multicenter, randomized controlled trial to evaluate a fascial interposition (FI) component of a vas occlusion procedure for male sterilization. A data monitoring committee (DMC) was established to provide independent review of the interim report. The DMC met to review the interim report after enrollment of 552 men. As planned, an estimate of the hazard ratio (HR) for successful vasectomy for the FI group versus the no-FI group controlling for age of the participant and level of experience of the surgeon was obtained for the interim report using Coxs proportional hazards regression. The main analysis comparing time to vasectomy success, defined as two consecutive azoospermic semen samples, was highly significant and met the prespecified level for stopping enrollment (HR=1.54, p<0.01). However, a troublesome age by vasectomy technique interaction became apparent in the analysis. FI was clearly beneficial for younger males. However, the trend for older men was not as clear. The DMC recommended continuing the trial to better study this interaction and obtain more data to clarify the effect of FI for older men. After consulting further with the DMC, the study statisticians presented the interim report to senior management at FHI. A meeting between FHI senior management and the DMC followed. After much deliberation, trial enrollment was terminated. Follow-up of participants already enrolled in the study continued as planned. This paper presents the issues involved in the decision to terminate the study.

Nondifferentiable errors in beta-compliance integrated logistic models

In a classical measurement error model, true regressors, though unknown, vary stochastically around the true level. In inhalation toxicology, environmental epidemiology, and some other problems, the administered dose may not be completely absorbed into the system, resulting in a stochastic compliance where the actual dose intake is smaller in magnitude, so the classical measurement error models may not be tenable. We introduce some logistic models for stochastic compliance of various types incorporating a Beta-compliance distribution. These compliance-adjusted models are categorized into three types: (i) Low (or near zero) dose levels, (ii) moderate dose levels, and (iii) high dose levels, resulting in different forms. The bootstrap method is incorporated to draw statistical conclusions based on BAN estimators.

Nondifferentiable errors in beta-compliance integrated logistic models : Numerical results

In dose-response models, there are cases where only a portion of the administered dose may have an effect. This results in a stochastic compliance of the administered dose. In a previous paper (Chen-Mok and Sen, 1999), we developed suitable adjustments for compliance in the logistic model under the assumption of nondifferential measurement error. These compliance-adjusted models were categorized into three types: (i) Low (or near zero) dose levels, (ii) moderate dose levels, and (iii) high dose levels. In this paper, we analyze a set of data on the atomic bomb survivors of Japan to illustrate the use of the proposed methods. In addition, we examine the performance of these methods under different conditions based on a simulation study. Among all three cases, the adjustments proposed for the moderate dose case do not seem to work adequately. Both bias and variance are larger when using the adjusted model in comparison with the unadjusted model. The adjustments for the low dose case seem to work in reducing the bias in the estimation of the parameters under all types of compliance distributions. The MSEs, however, are larger under some of the compliance distribution considered. Finally, the results of this simulation study show that the adjustments for the high dose case are successful in achieving both a reduction in bias as well as a reduction in MSE, hence the overall efficiency of the estimation is improved.