Using automated extraction of hepatitis B tests for surveillance: evidence of decreasing incidence of acute hepatitis B in England.

Surveillance of acute hepatitis B in England is necessary to estimate incidence, determine routes of transmission and inform public health actions. Here we describe an automated process to extract information on testing for markers of hepatitis B infection in English sentinel laboratories between 2002 and 2008. The resulting data were used to identify individuals with acute infections, describe their characteristics and estimate the incidence of infection. Two-thirds of acute infections were in males. Heterosexual exposure and injecting drug use were the main risks reported. Annual incidence was estimated at 1.3/100 000 person-years overall (1.7 and 0.6 for males and females, respectively) and declined each year. Automated extraction of hepatitis B markers, including quantitative results where available, can help to classify HBV status more accurately for surveillance. HBV incidence in England is at its lowest level in recent years.

A re-evaluation of the risk of transfusion-transmitted HIV prevented by the exclusion of men who have sex with men from blood donation in England and Wales, 2005-2007.

BACKGROUND AND OBJECTIVES One component of the rationale for lifetime exclusion of men who have sex with men (MSM) from blood donation in the UK is the probable reduction in the risk of transfusion-transmitted HIV; this exclusion has recently been questioned. MATERIALS AND METHODS Data about HIV in blood donors and MSM were analysed to estimate the risk of infectious donations entering the blood supply under different scenarios of donor selection criteria (and donor compliance) for MSM and a heterosexual group with increased risk of HIV. RESULTS In 2005-2007, a change from lifetime exclusion of MSM to 5-year deferral or no deferral increased the point estimate of HIV risk by between 0·4% and 7·4% depending on compliance with the deferral (range -4% to 15%) and 26·5% (range 18% to 43%) respectively. A change from a 12-month deferral of the high-risk heterosexual group to lifetime exclusion reduced the estimated risk by about 7·2% (range 6% to 9%). Each point estimate was within the probable range of risk under the current criteria. CONCLUSION If prevalence is the only factor affected by a reduced deferral, then the increased risk of HIV is probably negligible. However, the impact of a change depends on compliance; if this stays the same or worsens, the risk is expected to increase because of more incident infections in MSM who donate blood. The risk of transfusion-transmitted HIV could probably be reduced further by improving compliance with any exclusion, particularly after recent risk behaviours.

Recruiting individuals into the HTLV cohort study in the United Kingdom: clinical findings and challenges in the first six years, 2003 to 2009.

Human T-lymphotropic virus (HTLV) infection is rare in the United Kingdom (UK) and few studies are available worldwide. Following introduction of blood donation testing in 2002, a cohort of individuals could be identified and prospectively recruited to describe progression and onset of disease. Here we describe baseline characteristics of participants, and evaluate recruitment into the UK HTLV National Register over the first six years, from July 2003 to June 2009. A multicentre cohort study recruited participants from the UK blood services (recipients and donors) and specialist HTLV clinics. Almost half of the 148 participants recruited were blood donors, nine were blood transfusion recipients, 40 contacts and 29 clinic attendees (nine asymptomatic and 20 symptomatic). Most participants were HTLV-1 positive (n=115); 11 had HTLV-2 and 22 were HTLV-negative. Baseline self-completion questionnaires were received for 83%. The most commonly reported condition was a past operation/serious illness (69%). Twenty-six participants reported four or more possible signs/symptoms of HTLV-1-associated myelopathy/tropical spastic paraparesis. Recruitment into a study of a rare, long-term infection is challenging. This cohort will enable descriptions of HTLV-associated disease progression amongst people recruited from varying sources; it is the first prospective study of its kind in Europe.

Time-dependent association of total serum cholesterol and cancer incidence in a cohort of 172,210 men and women: a prospective 19-year follow-up study.

BACKGROUND: The relationship between serum cholesterol and cancer incidence remains controversial. PATIENTS AND METHODS: We investigated the association of total serum cholesterol (TSC) with subsequent cancer incidence in a population-based cohort of 172 210 Austrian adults prospectively followed up for a median of 13.0 years. Cox regression, allowing for time-dependent effects, was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the association of TSC with cancer. RESULTS: We observed pronounced short-term associations of TSC and overall cancer incidence in both men and women. For malignancies diagnosed shortly (<5 months) after baseline TSC measurement, the highest TSC tertile (>235.0 mg/dl in men and >229.0 in women) compared with the lowest tertile (<194.0 mg/dl in men and <190.0 in women) was associated with a significantly lower overall cancer risk [HR = 0.58 (95% CI 0.43-0.78, P(trend) = 0.0001) in men, HR = 0.69 (95% CI 0.49-0.99, P(trend) = 0.03) in women]. However, after roughly 5 months from baseline measurement, overall cancer risk was not significantly associated with TSC. The short-term inverse association of TSC with cancer was mainly driven by malignancies of the digestive organs and lymphoid and hematopoietic tissue. CONCLUSION: The short-term decrease of cancer risk seen for high levels of TSC may largely capture preclinical effects of cancer on TSC.

The problem with using computer programmes to assign ethnicity: immigration decreases sensitivity.

OBJECTIVES: It is recognized that ethnic group is important in describing differences in infection and disease, but is often not routinely available to surveillance systems. Computerized programmes, such as NamPehchan, can assign ethnicity according to name; however, sensitivity and positive predictive value (PPV) can vary. The aim of this study was to assess whether the sensitivity and PPV of NamPehchan had changed, after an observation that surnames previously associated with South Asians were increasingly reported as Black. STUDY DESIGN: Cross-sectional. METHODS: NamPehchan was used to classify women as South Asian using name, and compared with the gold standard (midwife-reported ethnicity). Sensitivity and PPV were calculated overall and by year. Frequency of infection by ethnic group was estimated. RESULTS: A total of 627 women positive for hepatitis B surface antigen were identified. The majority were from minority ethnic groups, particularly Asian. The overall sensitivity of NamPehchan was 74.5% and PPV was 68.5%. Almost 50% of Black African women were classified as South Asian by NamPehchan. CONCLUSIONS: Immigration from African countries has reduced the sensitivity of NamPehchan in this group. Care is needed when using NamPehchan for groups which include Africans from Muslim areas, as misclassification is likely to occur.

Where are people being tested for anti-HCV in England? Results from sentinel laboratory surveillance.

SUMMARY: Many people infected with hepatitis C virus (HCV) are unaware of their infection and are, therefore. potentially infectious to others. To enable effective case-finding policies to be developed, an understanding of where people, and injecting drug users (IDUs) in particular, are accessing HCV antibody testing is needed. HCV antibody testing data were collected electronically from 21 sentinel laboratories in England between 2002 and 2006 in this cross-sectional study. Service types of the physician requesting the HCV test were identified and classified. Differences in people being tested in each service type and over time were investigated. Over half a million people were tested in 5 years. Whilst most testing took place in hospital, a large proportion of people were tested in community care, particularly in general practice surgeries and genito-urinary medicine clinics. Younger people were more likely to be tested in community care, and there was evidence that testing differed according to ethnic status. IDUs were tested in all parts of the health services, although the highest proportion positive were from prisons and specialist services for drug users. Testing increased between 2002 and 2005 whilst the proportion of people testing positive declined. Routine laboratory data can provide valuable information on where people are being tested for HCV. Risk exposures should be investigated and testing targeted to people at higher risk for infection. Local laboratories should review data on testing locations and proportion positive to inform local initiatives to improve testing and yield.

Diagnosis of acute hepatitis C virus infection and estimated incidence in low- and high-risk English populations.

The diagnosis of acute hepatitis C virus (HCV) infection is not straightforward; few people exhibit clinical symptoms and genome/antigen detection techniques do not indicate when infection had occurred. Here, a strategy to detect HCV RNA in the absence of antibody ('window-period') for diagnosis of acute infection is assessed. The sentinel surveillance of hepatitis testing study was used to retrospectively identify anti-HCV negative samples from high-risk individuals (2002-2003), for testing singly for HCV RNA. Additional samples were identified prospectively (2005) and tested in pools for HCV RNA. Positive samples were genotyped. Incidence and costs of adopting the pooling strategy were estimated. In the retrospective study, 8/390 (2.1%) samples were confirmed HCV RNA positive, anti-HCV negative. Prospectively, 3237 samples were tested in 325 pools. Five positive pools identified four confirmed HCV RNA positive patients (one false positive). Estimated incidence was 12.9 per 100 person-years in injecting drug users (IDUs) (retrospective study) and 3.7 per 100 person-years among drug/alcohol services and prison attendees (prospective study). Estimated costs were pound 850 per positive sample, in areas of higher risk. The yield from a window-period strategy depends upon the population tested. Pooled HCV RNA testing of anti-HCV negative samples from the current IDUs is realistic and relatively inexpensive to identify recently infected individuals.

Infections detected in English surgical bone and deceased donors (2001-2006) and estimated risk of undetected hepatitis B and hepatitis C virus.

BACKGROUND AND OBJECTIVES: Infections can be transmitted through donated tissue products, such as femoral heads. Here we describe infections detected through microbiological testing of English surgical bone and deceased donors (2001-2006) and estimate the residual risk of infection. MATERIALS AND METHODS: Data on infected tissue donors identified by NHS Blood and Transplant (NHSBT) were collected through the NBS/Health Protection Agency Infection Surveillance programme. The blood donor model for estimating risk was adapted for tissue donors. Incidence among surgical bone donors was derived from new blood donor data and estimates of residual risk presented for surgical bone donors only. RESULTS: Fifty-seven surgical bone and four deceased donors were identified with 60 and five infections, respectively, during the 6 years. Syphilis was the most common infection detected, with no human T-lymphotropic virus infections and one HIV infection in a deceased donor. Hepatitis B virus, hepatitis C virus and syphilis prevalence was higher among surgical bone and deceased donors than new blood donors for the same period. The overall estimated risk of undetected hepatitis B and hepatitis C virus among surgical bone donors (2001-2006) on initial screening was 0.426 and 0.048 per 100 000 donors, respectively. Testing a follow-up sample made these risks almost negligible. CONCLUSION: The prevalence of infections was low among English tissue donors. Risk estimates were higher for surgical bone donors on first screening than among new blood donors. However, the probability of an infectious donation entering the tissue supply became negligible after obtaining a follow-up sample 6 months post-donation and were well below that of new blood donors.

Setting up an enhanced surveillance of newly acquired hepatitis C infection in men who have sex with men: a pilot in London and South East region of England.

Preliminary findings suggest ongoing HCV transmission among MSM infected with human immunodeficiency virus (HIV) and that enhanced surveillance for newly acquired HCV in MSM is feasible.

Estimation of prostatic growth using serial prostate-specific antigen measurements in men with and without prostate disease.

Prostate growth curves were estimated from serial prostate-specific antigen (PSA) measurements on frozen sera in three groups of men: (a) 16 men with no prostatic disease by urological history and examination; (b) 20 men with a histological diagnosis of benign prostatic hyperplasia (BPH) who had undergone simple prostatectomy; and (c) 18 men with a histological diagnosis of prostate cancer. The median number of repeated PSA measurements over an 8- to 26-yr period prior to histological diagnosis or exclusion of prostate disease was eight and 11 for noncancer and cancer subjects, respectively. Predicted rates of change in PSA (PSA velocity) were linear and curvilinear for control and BPH subjects, respectively. Subjects with cancer demonstrated both a linear and an exponential phase of PSA velocity. Based on time to double PSA, we estimated the epithelial doubling time for men without prostate disease to range from 54 +/- 13 yr at age 40 to 84 +/- 13 yr at age 70. For men with BPH, doubling times ranged from 2 +/- 13 yr at age 40 to 17 +/- 5 yr at age 85. Subjects with local/regional and advanced/metastatic cancer had similar PSA doubling times of 2.4 +/- 0.6 yr and 1.8 +/- 0.2 yr, respectively. These data are consistent with what is known about prostatic growth with age in men without prostate disease and BPH, and the kinetics of prostate cancer growth. Estimates of prostatic growth rate from changes in PSA may be useful clinically in management of men with prostate disease.

Growth and hematological changes in the Eskimo children of Wainwright, Alaska: 1968 to 1977.

The growth and hematological status of all 152 Eskimo children of Wainwright, AK observed in 1977 are reported and compared with the respective status of the children living there in 1968. Fifty-two children (34%) in the 1977 study were also in the 1968 study. Comparison of height data observed in 1977 with those observed in 1968 reveals that male children less than 11 yr of age and female children ages 3 to 9 yr showed a significant improvement in stature (p less than 0.05). At the same time, an improvement in nutrition was observed among the children in 1977 as evidenced by the marked decrease in anemia for children under 6 yr (p less than 0.001). These changes in growth and hematological status have occurred during a time in which health services were improved, a supplemental nutrition program was instituted, and subsistence food gathering remained high. These changes underscore the contribution of environmental factors rather than of genetic variability to the growth potential of these children.

Is the apoE4 allele an independent predictor of coronary events?

PURPOSE: Although the apolipoprotein E genotype epsilon4 (apoE4) has been associated with high cholesterol levels, whether it is an independent predictor of coronary events is not certain. SUBJECTS AND METHODS: We measured apoE genotypes in 730 participants in the Baltimore Longitudinal Study of Aging (421 men and 309 women, mean [+/- SD] age of 52+/-17 years) who were free of preexisting coronary heart disease. A proportional hazards regression model was used to study the association between risk factors and the occurrence of coronary events, defined as angina pectoris, documented myocardial infarction by history or major Q waves on the electrocardiogram (Minnesota Code 1:1 or 1:2), or coronary death, adjusted for other risk factors, including total plasma cholesterol level. RESULTS: The apoE4 allele was observed in 200 subjects (27%), including 183 heterozygotes and 17 homozygotes. Coronary risk factor profiles were similar in those with and without apoE4. Coronary events developed in 104 (14%) of the 730 subjects, including 77 (18%) of the 421 men during a mean follow-up of 20 years and 27 (9%) of the 309 women during a mean follow-up of 13 years. Coronary events occurred significantly more frequently in subjects with apoE4 (n = 40, 20%) than in those without this allele (64, 12%, P <0.05). In a multivariate model, apoE4 was an independent predictor of coronary events in men (risk ratio [RR]= 2.9, 95% confidence interval [CI]: 1.8 to 4.5, P<0.0001) but not in women (RR = 0.9, 95% CI: 0.4 to 1.9, P = 0.62). CONCLUSION: The apoE4 genotype is a strong independent risk factor for coronary events in men, but not women. The association does not appear to be mediated by differences in total cholesterol levels.

Factors affecting attrition in the Baltimore Longitudinal Study of Aging.

In a longitudinal study of aging, the influence on attrition of age, marital status, education, occupation, distance between a subject's residence and study center, self-health and financial assessment, and method of recruitment was examined. Prospective, follow-up information on the subsequent active/dropout and alive/dead status on the 1088 subjects, who joined the Baltimore Longitudinal Study of Aging during the first twenty years (1958-1977), were studied using a proportional hazards model. Three analyses, each controlling for death in a different manner, produced similar results. The analysis indicates that age, education and distance have the strongest association with attrition (p less than 0.001), while self-health assessment has a lesser association (p less than 0.05). The lowest risk in age, for example, occurs in 40-49.9 year olds with subjects less than 30 having an increased risk of 91% and subjects 70 or older having an increased risk of 189%. Examination of attrition probabilities show that subjects living 500 or more miles from study center, ages 70 and older, with less than bachelors degree, and perceiving their health as average or below have the greatest probability of dropping out-approximately 3-fold greater than the average subject's probability.

Physical restraint use and cognitive decline among nursing home residents.

OBJECTIVE: This study investigated the association between physical restraint use and decline in cognition. DESIGN: Cohort analytic study describing changes in resident characteristics. SETTING: Eight nursing homes, both urban and suburban, operated by a proprietary corporation in a large metropolitan area. PARTICIPANTS: 437 nursing home admissions, with 201 remaining at 1 year. MAIN OUTCOME MEASURES: Cognitive status was measured by geropsychiatrists, using the Folstein Mini-Mental State Exam, during a psychiatric evaluation of the resident. Daily restraint use was documented from nursing orders. Observations were made at 2 weeks, 10 weeks, and 1 year. RESULTS: Restraint use alone and in combination with neuroleptic use was associated with poor cognition. Other variables associated with poor cognitive scores were: ADL impairment, poor adaptive behavior, and longer time in the nursing home. The use of neuroleptics alone was not significant. Variables which were associated with good cognitive status were: being non-ambulatory but without dementia and having strong social support. CONCLUSIONS: These findings raise the possibility that restraint use may contribute to cognitive impairment, specifically among residents who have moderate to no cognitive impairment at admission; however, the findings do not exclude an alternative explanation that residents undergoing cognitive decline are more likely to be put in restraints. Further research is needed to understand whether factors which can be manipulated contribute to cognitive decline.

Age-associated changes in blood pressure in a longitudinal study of healthy men and women.

BACKGROUND: Current knowledge of age-associated increases in blood pressure is based primarily on unscreened population studies that may not be representative of healthy men and women. We examined longitudinal patterns of change in blood pressure in healthy male and female volunteers from the Baltimore Longitudinal Study of Aging (BLSA). METHODS: Longitudinal mixed-effects regression models are used to estimate the age-associated changes in blood pressure in 1307 men (age 17-97) and 333 women (age 18-93) who have been followed for up to 32 years (mean: 8.4 years for men and 3.4 years for women) and who have been screened for health problems or medications that affect blood pressure. RESULTS: On average, systolic pressure is relatively stable in men and women until approximately age 45, increases at 5-8 mm Hg per decade in middle age, then accelerates in men and stabilizes in women. Diastolic pressure increases at 1 mm Hg per decade at all ages in men, whereas in women the rate of change in diastolic pressure increases in middle age and then plateaus and may decline after age 70. Additional findings include: (a) BLSA cross-sectional and longitudinal findings are more similar than has been observed in studies of unscreened samples; (b) there is no evidence of a gender cross-over in this group of healthy men and women; and (c) compared to previous studies of unscreened samples, healthy BLSA men and women show a weaker association between baseline blood pressure and subsequent rate of blood pressure change. CONCLUSIONS: These findings suggest that several previously described age-associated patterns of blood pressure change partially reflect the effects of hypertension and its treatment, rather than intrinsic age changes in the blood pressure of healthy individuals.

Longitudinal changes in smell identification.

BACKGROUND: Cross-sectional studies have demonstrated that olfactory function diminishes with increasing age, which may impact on the safety and quality of life of older persons. To date, however, there have been no published longitudinal studies on olfaction. The purpose of this study was to examine the influence of age and gender on smell identification over a 3-year period in a group of generally healthy men and women. METHODS: Males (n = 85) and females (n = 76) between the ages of 19 and 95 years were administered the University of Pennsylvania Smell Identification Test (SIT) over a 3-year span as part of the oral physiology component of the Baltimore Longitudinal Study of Aging. A linear mixed-effects regression model was used to determine how longitudinal changes in SIT scores differ with respect to gender, history of medical problems, and use of prescription medications. RESULTS: Over the 3-year period, SIT scores diminished progressively with increased age. Women and men in the eighth decade of life experienced a decline of greater than one SIT point per year. Females consistently performed better than males in smell identification. Similar results were obtained regardless of medical problems or medication usage. CONCLUSIONS: These results extend the conclusions of previous cross-sectional olfactory studies and indicate that smell identification deteriorates progressively with greater age. Furthermore, age-related declines in olfaction occur even in the absence of overt medical problems.

The effect of gestational parity on FEV1 in a group of healthy volunteer women.

In the past, studies utilizing within-subject comparisons of small groups of pregnant women showed that forced expiratory volume in 1 s (FEV1) remained essentially unchanged during pregnancy. However, one of the findings from an epidemiological study was that women with greater number of children experienced a faster decline of FEV1. The aim of this study was to examine the effect of parity on FEV1 in a group of healthy volunteer women. To this end, cross-sectional multiple regression analyses of data from 397 healthy women participants in the Baltimore Longitudinal Study of Aging (BLSA) with a mean (range) age of 47.7 (18-92) years were performed. Similar analyses were done using the younger (50 years or less) and the older (> 50 years) subgroups. After controlling for age, height, weight, and smoking, parity as a dichotomous variable was associated with a higher FEV1 in women of child-bearing age (0.139 1; P = 0.02) but not in the older women. There was a modest link with the number of children (P = 0.05), with the first child possibly having the greatest effect on FEV1. We could not account for the effect of parity on FEV1 by the educational level, occupation, health status of the women, or by the presence of a cohort effect. Thus the nulliparous state is associated with lower FEV1 in this group of healthy adult women of child-bearing age.

Basal DNA damage in individual human lymphocytes with age.

A role for DNA damage is central to many theories of aging, but attempts to show an increase in DNA damage with age have yielded contradictory results. However, previous experiments have been of limited sensitivity, only able to examine induced (not basal) damage or pooled (not individual) cells. In this report, we apply a novel technique (Singh et al., 1988) to directly measure basal levels of DNA single-strand breaks and alkali-labile sites in individual human peripheral blood lymphocytes (PBL) obtained from young (less than 60 years) and old (more than 60 years) male donors. This approach shows that while average changes with age are small, changes in certain individuals and in certain cells may be large: the mean increase in damage was only 12%, but the increase in a subpopulation of highly damaged lymphocytes was 5-fold. However, most of this increase was contributed by just 3 of 17 older subjects. Further characterization of these individuals may shed light on the relationship between DNA damage and aging.

The role of mental morbidity in the nursing home experience.

The history of a newly admitted cohort to eight nursing homes (N = 454) was studied prospectively over the first year of residence. Data were gathered at admission, 2 months, and 1 year, and included full psychiatric examination and staff reports of behavior. Chart reviews collected additional data on preadmission and postdischarge information. At admission, 80% of the population had mental illnesses, 60% of which were dementia, and about half of demented patients had other complicating mental illnesses. Use of mixed-effects linear model analysis revealed significant associations of mental morbidity, restraints, and psychotropic medication with behaviors indicative of noncoping and nonadaptation to the nursing home settings.