Location of active transmission sites of Schistosoma japonicum in lake and marshland regions in China.

Schistosomiasis control in China has, in general, been very successful during the past several decades. However, the rebounding of the epidemic situation in some areas in recent years raises concerns about a sustainable control strategy of which locating active transmission sites (ATS) is a necessary first step. This study presents a systematic approach for locating schistosomiasis ATS by combining the approaches of identifying high risk regions for schisotosmiasis and extracting snail habitats. Environmental, topographical, and human behavioural factors were included in the model. Four significant high-risk regions were detected and 6 ATS were located. We used the normalized difference water index (NDWI) combined with the normalized difference vegetation index (NDVI) to extract snail habitats, and the pointwise 'P-value surface' approach to test statistical significance of predicted disease risk. We found complicated non-linear relationships between predictors and schistosomiasis risk, which might result in serious biases if data were not properly treated. We also found that the associations were related to spatial scales, indicating that a well-designed series of studies were needed to relate the disease risk with predictors across various study scales. Our approach provides a useful tool, especially in the field of vector-borne or environment-related diseases.

Generalized negative binomial distribution: a promising statistical distribution for Oncomelania hupensis in the lake- and marsh-land regions of China.

A new generalization of the negative binomial distribution (GNBD) is introduced and fitted to counts of Oncomelania hupensis, the intermediate host of Schistosoma japonicum, made, in areas of Chinese lakeland and marshland, early in the winter of 2005 and late in the spring of 2006. The GNBD was found to fit the snail data better than the standard negative binomial distribution (NBD) that has previously been widely used to model the distribution of O. hupensis. With two more parameters than the NBD, the GNBD can integrate many discrete distributions and is more flexible than the NBD in modelling O. hupensis. It also provides a better theoretical distribution for the quantitative study of O. hupensis, especially in building an accurate prediction model of snail density. The justification for adopting the GNBD is discussed. The GNBD allows researchers to broaden the field in the quantitative study not only of O. hupensis and schistosomiasis japonica but also of other environment-related helminthiases and family-clustered diseases that have, traditionally, been modelled using the NBD.

An evaluation of osteoporosis screening tools for the osteoporotic fractures in men (MrOS) study.

UNLABELLED: No large-scale evaluations of osteoporosis screening tools have been done in men. OST and MOST were examined among 4658 US Caucasian and 1914 Hong Kong Chinese men. Both tools have high negative predictive values, accurately screening out men with low risk, and saving a third of DXA tests. INTRODUCTION: Prior investigations have studied the performance of osteoporosis screening tools in women, but no large-scale evaluations have been done in men. METHODS: This study examines the performance of the Osteoporosis Self-assessment Tool (OST), the Male Osteoporosis Screening Tool (MOST), quantitative ultrasound index (QUI), and body weight as screening tools. Osteoporosis was defined by a dual-energy X-ray absorptiometry (DXA) measured bone mineral density (BMD) T-score < or =-2.5. Four thousand six hundred and fifty-eight US Caucasian and 1914 Hong Kong Chinese men, aged > or =65 years and community-dwelling, were included in the analysis. Receiver operating characteristic (ROC) analysis was used to compare the area under the ROC curve (AUC) between different screening tools. RESULTS: MOST had a significantly larger AUC (> or =0.8) than OST, QUI, and body weight in detecting osteoporosis. Using the second tertile as cutoff, OST and MOST yielded sensitivities of around 90% and negative predictive values (NPVs) of >97%, accurately screening out Caucasian and Chinese men with low risk of osteoporosis. CONCLUSIONS: OST and MOST can effectively rule out osteoporosis for both Caucasian and Chinese men, and compared to referring men 65 years and older for BMD DXA testing, they save a third of DXA resources.

Hepatitis C virus infection and neurocognitive function.

Hepatitis C virus (HCV) infection may be associated with neurocognitive deficits. The Hemophilia Growth and Development Study enrolled HIV-infected and HIV-uninfected patients and a group of nonhemophiliac siblings. After controlling for multiple factors, HCV monoinfection was not associated with deficits in adaptive behavior, intelligence, or attention/concentration.

Bone mineral density reference norms for Hong Kong Chinese.

The aim of this study was to establish bone mineral density (BMD) reference norms for Hong Kong Chinese using Hologic QDR 2000 and 4500 densitometers, and to estimate the prevalence of osteoporosis in the population. Altogether, 4,274 subjects (2,415 females and 1,859 males), aged 9-94 years old, were recruited using a combination of private solicitation and public advertising from schools, community centers, nursing homes, housing estates, and the general community in Hong Kong. Among females, BMD increased by 20% at the total hip and 48% at the lumbar spine between ages 10 and 20 but remained essentially constant between ages 20 and 40. Between ages 40 and 70, BMD declined by 17% at the total hip and 23% at the spine. Total hip BMD continued to drop after age 70 but little change in spine BMD was observed. Among males, BMD increased by 45% at the total hip and 77% at the spine between age 10 and 30. Between ages 30 and 80, total hip BMD decreased by 20%. Lumbar spine BMD decrease was milder, showing a loss of 4% between ages 30 to 50 and remaining relatively constant afterwards. The prevalence of osteoporosis was consistently overestimated when using Hologic-supplied Caucasian cutoffs as compared with local Chinese cutoffs. The prevalence of osteoporosis among Chinese women 50 years or older was 37% and 16% at the spine and total hip, respectively, while that among Chinese men 50 years or older was 7% and 6% at the spine and total hip, respectively. Prior studies have been limited by size or restricted to women. This study represents the largest sample of Hong Kong Chinese amassed to date, provides continuous BMD reference values from ages 10 to 85 for both women and men, and yields more reliable estimates of the prevalence of osteoporosis for the population.

An osteoporosis screening tool for Chinese men.

Several osteoporosis risk instruments have been proposed to select women for bone densitometry, but no validated instruments are currently available for men. This study aims to address this deficiency by developing and validating a Male Osteoporosis Screening Tool (MOST) for Chinese men. Two thousand ambulatory men, aged 65 and above, were recruited from the general community in Hong Kong, and a cohort of 1,970 men with valid total hip and lumbar spine dual-energy X-ray absorptiometry (DXA) measurements was included in the current analysis. A 60% random sample was selected as the training sample for developing the screening tool, and the remaining 40% constituted the validation sample. Logistic regression and receiver operating characteristic (ROC) analysis were used to identify the simplest combination of risk factors to be included in the screening tool for predicting osteoporosis at the femoral neck, total hip, or lumbar spine. Body weight and quantitative ultrasound index (QUI) were found to contribute significantly to the area under the ROC curve (AUC), yielding an AUC of 0.823 in the training sample. The resulting MOST had a sensitivity of 94% and a specificity of 46% when using a cutoff score of 3. MOST had an AUC of 0.839 in the validation sample. The risk of osteoporosis was 1% among those with MOST scores < or = 2, but 72% among those with MOST scores > 7. Using a cutoff of 3, the negative predictive value was 97.5% which suggests that the 42% with MOST scores < or = 3 may be accurately screened out as being without osteoporosis, thus saving two fifths of our DXA resources. The positive predictive value was 72% when using a cutoff of 7, implying that MOST cannot replace DXA for case-finding purposes. Nevertheless, for resource allocation and patient satisfaction, it is prudent and economical to offer DXA screening first to the 6% with MOST scores > 7.

Is dietary counselling effective in increasing dietary calcium, protein and energy intake in patients with osteoporotic fractures? A randomized controlled clinical trial.

To determine the feasibility of increasing the calcium, protein and calorie intake of osteoporotic fracture patients by repeated dietary counselling delivered by a dietitian, a randomized controlled trial was conducted. Among 189 patients presenting with osteoporotic fractures to an Orthopaedics and Traumatology Department of a large regional hospital, 98 patients were randomized to the intervention group and 91 were randomized to the control group (with usual care). Intervention group received three sessions of dietary counselling with tailored made recommendations over a period of 4 months, while the control group only received dietary assessment and pamphlets on the prevention of osteoporosis. Almost all subjects in both intervention and control groups had calcium intake below the recommended level of 1000 mg at baseline. Half and 60% of subjects in both groups had total energy and protein intake below recommended levels respectively. The mean weights of control and intervention groups at baseline were 51.5 and 50.9 kg respectively, while the body mass index (BMI) were 22.6 (kg m(-2)) and 22.6 (kg m(-2)) respectively. After dietary intervention, significant increase of intake was seen in calcium intake (P = 0.0095 by t-test) in the intervention group. No significant increase was seen in protein or calorie intake. No significant change was observed in the body weight or BMI although there was a positive trend in the intervention group for all these parameters. We concluded that there was general malnutrition in Chinese elderly who presented with osteoporotic fractures. Dietary calcium could be increased by repeated professional dietary counselling. Future studies with longer duration and more objective clinical outcomes will be helpful to further demonstrate the long-term effects of dietary intervention on osteoporosis and other chronic diseases.

Defining the impact of hemophilia: the Academic Achievement in Children with Hemophilia Study.

OBJECTIVES: We characterized a population-based cohort of school-aged children with severe hemophilia with respect to type of treatment, on-demand versus prophylaxis, and frequency of bleeding episodes in the year before enrollment. We also investigated the association between hemophilia-related morbidity, measured by number of bleeding episodes in the year before enrollment, and academic performance after adjustment for other factors known to have an effect on achievement. Finally, we explored the mechanisms for the association between bleeding episodes and academic achievement. STUDY DESIGN: This study was a multicenter investigation of boys 6 to 12 years old with severe factor VIII deficiency (clotting factor level <2%) receiving care in US hemophilia treatment centers. Children with a history of inhibitor, severe developmental disorder, significant psychiatric disorder, or insufficient fluency in English were excluded from the study. On-demand treatment was defined as administration of clotting factor on the occurrence of a bleeding episode. Prophylactic therapy was defined as a course of regular infusions for >2 months with a goal of preventing bleeding episodes. Academic achievement was measured by the Wechsler Individual Achievement Test. Quality of life was measured by the Child Health Questionnaire. Of particular interest was the Physical Summary (PhS) measure of the Child Health Questionnaire. The type of information captured by the PhS includes limitations in physical activity, limitations in the kind or amount of schoolwork or social activities the child engaged in, and presence of pain or discomfort. RESULTS: One hundred thirty-one children were enrolled, a median center recruitment rate of 77%. The mean age of the participants was 9.6 years, and approximately half of the participants had completed less than the fourth grade at the time of enrollment. Sixty-two percent of the children were on prophylaxis at enrollment, and 9% had previously been on prophylaxis but were currently on on-demand therapy. Two groups were defined: ever treated with prophylaxis and never treated with prophylaxis. For those ever treated, treatment duration ranged from 2.7 months to 7.7 years, with one half of the children treated with prophylaxis for >40% of their lifetimes; 29% had always been on on-demand therapy. Children in both treatment groups were similar with respect to age, clotting factor level, parents' education, and IQ. The median number of bleeding episodes experienced in the year before enrollment for the cohort as a whole was 12. The median number of bleeding episodes in children on prophylaxis at enrollment was significantly lower than in children on on-demand therapy (6 vs 25.5). The mean achievement scores were within the average range of academic performance: reading, 100.4; mathematics, 101.6; language, 108.1; writing, 95.4; and total achievement, 102.5. When children were categorized as above or below the study group median by number of bleeding episodes, those who had a low number of bleeding episodes (< or =11) had better total achievement (104.4 vs 100.6) and mathematics (103.6 vs 99.6) than children in the higher bleeding episode category (> or =12) after adjusting for child's IQ and parents' education. Treatment with prophylaxis per se was not associated with better test scores, but children who had been treated on a regimen of long-term prophylaxis (>40% of lifetime) and reported < or =11 bleeding episodes in the year before enrollment had significantly higher scores in total achievement (104.9 vs 100.6), mathematics (105.2 vs 99.6), and reading (104.0 vs 98.6) than all other children reporting > or =12 bleeding episodes in the same time period. Increased school absenteeism and hemophilia-related limitations in physical functioning among children with greater frequency of bleeding episodes were proposed as the mechanisms for lower scores. The number of bleeding episodes was positively correlated with school absenteeism (Spearman correlation = 0.23), and children with more school absences had lower scores in mathematics, reading, and total achievement, even after adjusting for the child's IQ and parents' education. Children with fewer bleeding episodes also had better PhS scores than children in the high bleeding episode category (48.4 vs 41.3). The mean PhS for children in the low bleeding episode group (48.4) was similar to that of the general US population (50), but the mean PhS for children in the higher bleeding episode group was almost a full standard deviation lower than the mean for the general US population. PhS scores were positively related to reading and total achievement scores after adjusting for IQ and parents' education. Of interest and concern was a group of children who were reportedly being treated with prophylaxis during the year before enrollment (N = 18) but whose bleeding events were not optimally suppressed. These children were 3 times as likely (33.3% vs 11.1%) to be receiving < or =2 infusions per week as children on prophylaxis who reported < or =11 bleeding episodes during the same period. A review of the sites of bleeding reported for the 18 children revealed that 12 (66.6%) experienced > or =25% of their bleeding episodes in the same joint. CONCLUSIONS: Each child should have the opportunity to achieve his or her potential. Control of a chronic disorder must include this important goal as well as the more commonly identified medical outcomes. This study has identified an important association between the number of bleeding episodes experienced and academic achievement in a cohort of school-aged children with severe hemophilia. The data support the assertion that therapeutic care programs in this population must not be evaluated only in terms of financial cost to achieve adequate musculoskeletal outcomes. Also significant are the individual and societal benefits of increased academic accomplishments if adequate suppression of hemorrhagic events can be attained. The number of bleeding episodes experienced, regardless of treatment regimen, should be followed to optimize the child's academic outcome.

The effect of plasma human immunodeficiency virus RNA and CD4(+) T lymphocytes on growth measurements of hemophilic boys and adolescents.

OBJECTIVE: The investigation examined the associations of plasma human immunodeficiency virus (HIV) RNA and CD4(+) T lymphocytes with height, weight, skeletal maturation, testosterone levels, and height velocity for hemophilic children and adolescents with HIV infection in the Hemophilia Growth and Development Study. STUDY DESIGN: Two hundred seven participants were evaluated over 7 years. RESULTS: A threefold increment in baseline plasma HIV RNA was associated with a 0.98-cm decrease in height and a 1.67-kg decrease in weight; 100-cells/microL decrements in baseline CD4(+) were associated with a 2.51-cm decrease in height and a 3.83-kg decrease in weight. Participants with high plasma HIV RNA (>3125 copies/mL) experienced significant delay in achieving maximum height velocity and lower maximum velocity compared with those with low viral load. The high CD4(+) (>243)/low plasma HIV RNA group had earlier age at maximum height velocity compared with the other 3 groups and higher maximum height velocity compared with the low CD4(+)/high plasma HIV RNA and low CD4(+)/low plasma HIV RNA groups. Decrements in CD4(+) were associated with decreases in bone age and testosterone level. CONCLUSIONS: CD4(+) and HIV RNA were important in predicting growth outcomes.

Maximum likelihood inference for left-censored HIV RNA data.

Left-censored data are characteristic of many bioassays due to inherent limit of detection and limit of quantitation (LOQ) in the assays. This paper examines how the left-censoring of plasma HIV RNA measurements, collected for the Hemophilia Growth and Development Study, affects the quantification of viral load and the assessment of its association with a continuous or dichotomous outcome. Data analyses using maximum likelihood estimation are compared to analyses where the LOQ or LOQ/2 value is substituted for the left-censored observations, and also to other methods like multiple imputation. A Gaussian distribution is assumed for the log-transformed plasma HIV RNA data, and simulations are used to explore the sensitivity of the results to changes in the model parameters. The robustness of the estimators is also investigated when the data are generated from a mixture of two Gaussian distributions. Maximum likelihood is in general the least biased method. However, multiple imputation assuming a censored Gaussian imputation model and substituting the censored values with the expectation of its conditional predictive distribution are also competitive to maximum likelihood, and may be appealing because of their simpler computational algorithms.

Incidence of focal white matter lesions in a population of hemophiliac children and their normal siblings. Hemophilia Growth and Development Study.

OBJECTIVE: This analysis was undertaken to evaluate the etiology and sequelae of 2- to 5-mm focal white matter hyperintensities on T2-weighted MR images of some participants enrolled in the Hemophilia Growth and Development Study (HGDS). MATERIALS AND METHODS: The HGDS is a multicenter study of the growth and development, neurological, neuropsychological, and immune functioning of a cohort of children and adolescents, 62% of whom were infected with HIV through the use of clotting factor concentrates, and their non-hemophiliac, non-HIV infected male siblings. The current investigation was conducted with all three groups of HGDS participants: HIV-positive hemophiliacs (n = 207), HIV-negative hemophiliacs (n = 126), and their siblings (n = 47). Magnetic resonance imaging was performed at each center, with a variety of 0.3 to 1.5 T instruments. Standard examinations included 5-mm-thick T1-weighted sagittal and axial images, intermediate, and T2-weighted axial images. A study of abnormalities of the coagulation system known to be associated with thrombotic events was conducted among a subgroup of participants (n = 51) from eight centers. RESULTS: Lesions were not associated with hemophilia-related factors, immune function, hematologic, or neurologic factors. There were no associations between the presence of white matter lesions and defects of coagulation in any of the assays completed. CONCLUSION: The 2- to 5-mm focal white matter hyperintensities on T2-weighted MR images of the brain were incidental findings in our study population.

When does it pay to break the matches for analysis of a matched-pairs design?

Two methods of analysis are compared to estimate the treatment effect of a comparative study where each treated individual is matched with a single control at the design stage. The usual matched-pairs analysis accounts for the pairing directly in its model, whereas regression adjustment ignores the matching but instead models the pairing using a set of covariates. For a normal linear model, the estimated treatment effect from the matched-pairs analysis (paired t-test) is more efficient. For a Bernoulli logistic model, matched-pairs analysis performs better when the sample size is small, but is inferior to logistic regression for large sample sizes.

Ten-year follow-up of HIV-infected homosexual men with lymphadenopathy syndrome: evidence for continuing risk of developing AIDS.

Seventy-five homosexual men with lymphadenopathy syndrome (LAS), subsequently shown to be seropositive for the human immunodeficiency virus (HIV), were enrolled in a prospective study in Atlanta in 1982 and 1983. Subjects have been followed up at 3- to 6-month intervals with clinical and immunologic evaluations, including analysis of T-cell subsets. As of February 28, 1991, AIDS had developed in 36 (48%) of the 75 men. The AIDS cases continued to occur through the 10th year after onset of LAS; the 10-year cumulative incidence of AIDS was 56.6% (Kaplan-Meier survival analysis). Six-year incidence rates following the first observation of a T-helper cell count greater than or equal to 500/mm3, 400-499/mm3, 300-399/mm3, 200-299/mm3, and less than 200/mm3 were 29, 35, 50, 58, and 88%, respectively. Among individual symptoms and signs, only thrush conferred a poorer prognosis (odds ratio = 5.80; 95% confidence interval, 2.93, 11.39, p less than 0.001, Mantel-Byar analysis). The risk of AIDS persists 10 years after the onset of LAS. The AIDS incidence is related directly to T-helper cell depletion; with the exception of thrush, the presence or absence of symptoms and signs appears to be of lesser prognostic significance.