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PubMed2005

A prospective cohort analysis of adjacent vertebral body bone mineral density in lumbar surgery patients with or without instrumented posterolateral fusion: a 9- to 12-year follow-up.

STUDY DESIGN: A prospective, cohort study of 11 patients who underwent either a posterior lumbar spinal fusion with instrumentation (n = 7) or a lumbar laminotomy and discectomy alone (n = 4) and who were evaluated by dual energy radiograph absorptiometry (DEXA) to determine bone mineral density (BMD) at the adjacent three cephalad vertebral levels. OBJECTIVES: To determine long-term BMD changes that occur at the adjacent three levels above an instrumented posterolateral lumbar fusion or an isolated laminotomy and lumbar discectomy. SUMMARY OF BACKGROUND DATA: No long-term prospective study has evaluated the affects of instrumented lumbar fusions on bone remodeling at adjacent vertebral levels. Several studies in animals and humans have reported a decrease in BMD at the adjacent level during the first 6 months after spinal fusion with a return to baseline at 1-year follow-up in up to 60% of patients. METHODS: DEXA was performed initially at a mean postoperative follow-up of 4 years (range, 2.3-5.5 years) and again at a mean of 10.8 years (range, 9.1-2.4 years). Eleven patients were divided into two groups: laminotomy and discectomy (n = 4) and instrumented posterior spinal fusion (n = 7). All patients underwent surgical procedures at the L4-L5 or L5-S1 levels with DEXA analysis being performed on the adjacent three cephalad levels. The discectomy group (mean age, 57.8 years) underwent lumbar hemilaminotomy without fusion whereas the other group (mean age, 60 years) underwent pedicle-screw instrumentation and posterolateral lumbar fusion. Peripheral sites, including the femoral neck, were included in the DEXA analysis to normalize for individual differences in bone mineral metabolism. RESULTS: At the mean 10.8-year follow-up, the fusion group was noted to have at the adjacent level, two levels cephalad, and three levels cephalad normalized BMDs of 1.47, 1.39, and 1.27, respectively. A 14.8%, 10.8%, and 9.5% increase respectively in normalized BMD was observed when compared with the mean 4-year fusion values (P < 0.05). This increase was also noted on comparative T-score, Z-score, and absolute BMD values (P < 0.05). The discectomy group when evaluated revealed no statistically significant change from the mean 4 to 10.8-year follow-up (BMD, normalized BMD, T-score, Z-score). No statistically significant difference was noted in hip BMD at the mean 4-year and 10.8-year follow-up (1.05 versus 1.03), suggesting that the effects were local. CONCLUSIONS: The local BMD adjacent to an instrumented lumbar fusion is increased at a mean of 10.8-years after surgery. There is a gradual decrease in BMD changes with increasing distance from the fusion level. Alterations in fusion site biomechanics and modulus mismatch between the host bone and the spinal instrumentation most likely result in chronic, localized bone remodeling with an increased BMD that decreases the greater the distance from the fusion mass.

Bone Density↗
PubMedDate not supplied

Age-period-cohort analysis of lung cancer mortality in Taiwan, 1966-1990.

The specific aim of this study was to examine the effects of age, calender period of death, and birth cohort in lung cancer mortality in Taiwan over the period 1966-1990. A log-linear model modified from the method of Osmond and Gardner was used. Age is the most important predictor of lung cancer mortality according to the model. The oldest age group of 75-79 years old had a lung cancer mortality 185.3 and 79.2 times those for the youngest age group of 30-34 for males and females, respectively. There was also a significant cohort effect. The birth cohorts at the highest risk of lung cancer death were those born around 1931 for males and 1921 for females. A leveled off or declined trend of lung cancer mortality was observed for more recent cohorts. Parameters of the period factor showed an increasing lung cancer mortality from 1966 to 1990. In addition to the adverse effect of cigarette smoking, dietary and environmental factors should be taken into consideration in interpreting the results.

Adult↗
PubMed1997

Age-period-cohort analysis of cervical cancer mortality in Taiwan, 1974-1992.

OBJECTIVES: To develop a hypothesis about the carcinogenesis of cervical cancer from a descriptive analysis. METHODS: The mortality data of cervical cancer were analyzed over the period from 1974 to 1992 among Taiwanese women using a log-linear Poisson model modified from the method of Osmond and Gardner to examine the effects of age, calendar period of death, and birth cohort on cervical cancer mortality. RESULTS: This age-period-cohort model provides a summary guide for interpretation of cancer mortality trends. According to this model, age was found to be the strongest factor predicting cervical cancer mortality. Women in 50-54 age group have 89.3-fold risk of cervical cancer compared to those in the 30-34 age group. The cohort effect is also of particular interest because the generation at greatest risk for cervical cancer is the one born between 1893 and 1938, and a dramatically declining trend is observed thereafter for 1938-1963 birth cohort. Interest has emerged about the increasing trend in recent cohorts (after 1963 birth cohort). However calendar time only has a slight effect in the APC analysis. The model also identified a possible role of female sex hormones as the age effect, promiscuous sexual activity as the period effect (promoter) and the change in reproductive behavior as the cohort effect (initiator). CONCLUSIONS: These results may help to develop a hypothesis of carcinogenesis of cervical cancer in Taiwan.

Adult↗
PubMed2004

Cohort analysis of a single nucleotide polymorphism on DNA chips.

A method has been developed to determine SNPs on DNA chips by applying a flow-through bioscanner. As a practical application we demonstrated the fast and simple SNP analysis of 24 genotypes in an array of 96 spots with a single hybridisation and dissociation experiment. The main advantage of this methodical concept is the parallel and fast analysis without any need of enzymatic digestion. Additionally, the DNA chip format used is appropriate for parallel analysis up to 400 spots. The polymorphism in the gene of the human phenol sulfotransferase SULT1A1 was studied as a model SNP. Biotinylated PCR products containing the SNP (The SNP summary web site: ) (mutant) and those containing no mutation (wild-type) were brought onto the chips coated with NeutrAvidin using non-contact spotting. This was followed by an analysis which was carried out in a flow-through biochip scanner while constantly rinsing with buffer. After removing the non-biotinylated strand a fluorescent probe was hybridised, which is complementary to the wild-type sequence. If this probe binds to a mutant sequence, then one single base is not fully matching. Thereby, the mismatched hybrid (mutant) is less stable than the full-matched hybrid (wild-type). The final step after hybridisation on the chip involves rinsing with a buffer to start dissociation of the fluorescent probe from the immobilised DNA strand. The online measurement of the fluorescence intensity by the biochip scanner provides the possibility to follow the kinetics of the hybridisation and dissociation processes. According to the different stability of the full-match and the mismatch, either visual discrimination or kinetic analysis is possible to distinguish SNP-containing sequence from the wild-type sequence.

Arylsulfotransferase↗
PubMed2003

Influence of follow-up bias on PSA failure after external beam radiotherapy for localized prostate cancer: results from a 10-year cohort analysis.

PURPOSE: To estimate the biases inherent in prostate cancer outcome that arise from different failure end points and variations in follow-up time and intensity using a cohort of men with long follow-up. METHODS AND MATERIALS: The study cohort consisted of 205 men with T1-T2N0-Nx prostate cancer treated with conventional radiotherapy between 1991 and 1993. The median follow-up was 103 months. Outcome was assessed using different definitions of biochemical failure, including the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria and the "nadir plus two" criteria (any rise of 2 ng/mL greater than the current nadir). Patient subgroups were created according to where patients had received their last 2 years of follow-up. Patients were also stratified according to whether they were initially present in the departmental database (under regular surveillance) or were uncovered after more vigorous investigation (previously "lost to follow-up"). RESULTS: In this series with maximized follow-up, the 10-year biochemical disease-free survival rate did not change significantly with varying definitions of failure, 49% and 45% for ASTRO and "nadir plus two" criteria, respectively. Patients followed by outside physicians (n = 99) were faring better at 10 years than those followed at the treating institution by either their radiation oncologist (n = 50) or their medical oncologist or urologist (n = 52). This was by all measures of outcome, including overall survival, and metastasis-free survival. Patients previously lost to follow-up (n = 43) who were tracked down also appeared to be doing better than those on our database for whom information had been readily available (n = 161). This, however, may have been an artifact of the ASTRO criteria, which underestimates failure when insufficient prostate-specific antigen values are available. CONCLUSION: The ASTRO definition of failure underestimates late failure. This bias may be compensated for by the use of cohorts with long follow-up or the use of the "nadir plus two" definition of failure. The use of institutional prostate cancer databases may overestimate failure rates because patients followed outside of the treating institution fared better with respect to both survival and biochemical recurrence. Vigorous attempts to obtain follow-up beyond the hospital walls may correct this bias.

Aged↗
PubMed2001

Age-period-cohort analysis of lung cancer mortality in Japan, 1960-1995.

The mortality data on lung cancer in Japan from 1960 to 1995 was analysed based on an age-period-cohort (APC) model. Though the APC model has an 'identifiable problem' caused by the relationship of age, period and cohort parameters, non-linear components of them revealed their original (separated) effects. They were: (1) non-linear age effects had a peak in 55-59 and 60-64 years old in males and 50-54 in females, (2) non-linear period effects were very small in both genders, (3) non-linear age and period effects were small enough to neglect compared with their linear effects, and (4) there were five parts of trends in Japanese lung cancer mortality in both genders in the non-linear birth cohort effects. The 1961-65 birth cohort effect seemed to increase differently from previous birth years. This trend should be monitored carefully.

Adult↗
PubMedDate not supplied

The transition in Korean family planning behavior, 1935-1976: a retrospective cohort analysis.

This study traces the diffusion of family planning behavior-the use of abortion, contraception, and/or sterilization-in Korea between 1935 and 1976. Within- and cross-cohort examinations were made of the levels of ever-use of family planning, method of initiation of family planning, and patterns of family planning behavior. Ever-use of any of the three modes was very low for all cohorts prior to the introduction of the National Family Planning Program in 1962; afterwards, family planning diffused at a rapid rate. A major determinant of ever-use levels attained by cohorts married before 1962 was the length of time between the introduction of the program and menopause.

Abortion, Induced↗
PubMed2004

Satisfaction of the uncertainty principle in cancer clinical trials: retrospective cohort analysis.

OBJECTIVE: To assess whether publicly funded adult cancer trials satisfy the uncertainty principle, which states that physicians should enroll a patient in a trial only if they are substantially uncertain which of the treatments in the trial is most appropriate for the patient. This principle is violated if trials systematically favour either the experimental or the standard treatment. DESIGN: Retrospective cohort study of completed cancer trials, with randomisation as the unit of analysis. SETTING: Two cooperative research groups in the United States. STUDIES INCLUDED: 93 phase III randomised trials (103 randomisations) that completed recruitment of patients between 1981 and 1995. MAIN OUTCOME MEASURES: Whether the randomisation favoured the experimental treatment, the standard treatment, or neither treatment; effect size (outcome of the experimental treatment compared with outcome of the standard treatment) for each randomisation. RESULTS: Three randomisations (3%) favoured the standard treatment, 70 (68%) found no significant difference between treatments, and 30 (29%) favoured the experimental treatment. The average effect size was 1.20 (95% confidence interval 1.13 to 1.28), reflecting a slight advantage for the experimental treatment. CONCLUSIONS: In cooperative group trials in adults with cancer, there is a measurable average improvement in disease control associated with assignment to the experimental rather than the standard arm. However, the heterogeneity of outcomes and the small magnitude of the advantage suggest that, as a group, these trials satisfy the uncertainty principle.

Clinical Trials, Phase III as Topic↗
PubMed1998

A birth cohort analysis of AIDS in Europe: high incidence among young persons at risk.

OBJECTIVES: To study trends in AIDS incidence in Europe by age and year of birth. DESIGN: Age-period-cohort analyses were adopted to distinguish the different time factors of calendar year, age and year of birth. METHODS: Non-aggregate AIDS incidence data from 12 European countries (1978-1994) were adjusted for reporting delay and expressed per unit of population (per 100000 persons or 100000 person-years). Age-specific incidence patterns (absolute level and rate of increase) were compared between 5-year birth cohorts for homo-/bisexual men, injecting drug users (IDU) and heterosexual contact cases. RESULTS: Mean age at diagnosis increased strongly amongst IDU, but less so among homo-/bisexual men and heterosexual contact cases. Of a total 110646 reported cases (116311 after adjustment for reporting delay), 87167 (78.8%) were among people born in 1950-1974 [91951 (79.1%) after adjustment for reporting delay]. The relative impact on specific birth cohorts differed strongly by exposure group. Incidences at age ranges of 20-24 and 25-29 years among cohorts born in 1965 and after were about the same level (homo-/bisexual men, IDU) or higher (heterosexual contact cases) than older birth cohorts when these were in the same age range; rates of increase were less among homo-/bisexual men and IDU, but higher among heterosexuals. There were large differences between counties. CONCLUSIONS: Overall, AIDS incidence among cohorts born in 1965 and after is about the same level (homo-/bisexual men, IDU) or higher (heterosexual contact cases) than older cohorts when these were in the same age range. Rates of increase of AIDS incidence curves suggest reduced HIV transmission amongst the most recent cohorts of homo-/bisexual men and IDU, but among young heterosexuals the epidemic is still expanding.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Insight into the infection dynamics of the AIDS epidemic: a birth cohort analysis of New York City AIDS mortality.

The authors analyzed the secular trends of New York City acquired immunodeficiency syndrome (AIDS) mortality from 1980 through the first quarter of 1991 using birth cohort techniques to provide insight into reasons for temporal changes in growth of the epidemic. By disaggregating AIDS mortality data into composite birth cohorts, the authors determined that the slowing in the growth of the epidemic is a result of a leveling or decline in AIDS deaths in male birth cohorts born before 1950 and a continued growth in younger male and all female birth cohorts. This phenomenon is believed to largely reflect earlier human immunodeficiency virus type 1 (HIV-1) infection patterns associated with age-related risk behaviors; however, to some lesser extent, it could also reflect age-related host factors or therapies that may influence the time from HIV-1 infection to death. The findings support the hypothesis that the early infection dynamics of the epidemic were differentially related to age and sex, which resulted in a diffusion of infection from older to younger cohorts and from males to females over time. The future growth of the epidemic will largely depend upon the infection patterns of younger birth cohorts. This method of analyzing AIDS incidence or mortality data may contribute to a better understanding of earlier patterns of HIV-1 infection within a defined population, which will be useful for targeting prevention efforts and improving AIDS forecasting methods.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Incidence rates of acute nerve function impairment in leprosy: a prospective cohort analysis after 24 months (The Bangladesh Acute Nerve Damage Study).

In this paper, the incidence rates and cumulative incidence of nerve function impairment (NFI) and leprosy reactions over 24 months follow-up of the prospective cohort of 2664 new leprosy cases are presented. Graphs showing the cumulative incidence of NFI relative to time since registration are presented. Hazard ratios (HRs) for the development of NFI for four variables are given. The majority of patients who developed NFI after registration did so in the first year (67% of multibacillary (MB) patients, and 91% of paucibacillary (PB) patients who developed NFI). Thirty-three percent of all MB patients who developed NFI after registration did so in the second year of follow-up. No PB patients developed NFI for the first time in the last 6 months of follow-up. However, seven NFI events occurred amongst PB patients in that period, amongst those who had already had one NFI event. The incidence rate (IR) of NFI amongst MB patients was 24/100 person-years at risk (PYAR), and amongst PB patients was 1.3/100 PYAR. The HR for the development of NFI amongst MB patients compared with PB patients was 16 using univariate analysis. Amongst patients who had long-standing NFI present at registration, the IR was 27/100 PYAR compared with 1.7/100 PYAR amongst those who did not have long-standing NFI. The HR for developing acute NFI amongst those with long-standing NFI present at registration compared with those without was 14 using univariate analysis. When multivariate regression analysis is applied, the apparently significant univariate HRs for sex and age disappeared. The resultant multivariate HR for leprosy group is 8.8, and 6.1 for the presence/absence of long-standing NFI at registration. In all, 142/166 (86%) of all new NFI events were silent, underlining the need for regular nerve function testing. IRs are presented for the four 6-month periods of the 24-month follow-up. They show a clear stepwise reduction over the total period. The IRs amongst MB patients and those with long-standing NFI present at registration are very high at 34 and 41/100 PYAR, respectively, for the first 6 months of follow-up. Even during the final 6-month period, the IR is maintained at a moderately high level (18 and 15/100 PYAR, respectively).

Adult↗
PubMed2004

Age-period-cohort analysis of breast cancer mortality rates in Andalucia (Spain).

BACKGROUND: The aim of this paper is to analyse breast cancer mortality in Andalucia (Spain) between 1975 and 1999 based on age-period-cohort. PATIENTS AND METHODS: Mortality data were obtained from the Mortality Registry of Andalucia. Deaths and population were divided into 13 age groups and five 5-year periods. From this, age-specific mortality rates for 17 birth cohorts were computed. These were plotted and fitted to Poisson regression models to assess age, period and cohort effects. RESULTS: The best fit was found for the complete model, which simultaneously considered the effects of age-period-cohort. Cohort effects were found to be more important than period effects in terms of model fit. CONCLUSION: These effects were manifest as a seemingly consistent increase in the relative risk of breast cancer mortality with a three-fold increase in women born in the 1950s relative to those born in the 1890s.

Adult↗
PubMed1981

Prenatal care and pregnancy outcome in an HMO and general population: a multivariate cohort analysis.

We studied the use of prenatal care and pregnancy outcome in 4,148 deliveries among members of a well-established health maintenance organization (HMO) and 19,116 births among the 1973-1974 White birth cohort in the Portland, Oregon area. Mothers in the HMO were almost one year older on the average, slightly better educated, and less frequently unmarried, but had virtually identical past pregnancy histories when compared with the general population cohort. HMO members began prenatal care one month later and had three fewer visits than the general population (p less than .01); 78 per cent of the general population and only 64 per cent of HMO members began prenatal care in the first trimester (p less than .01). With maternal risk held constant, low birthweight, neonatal mortality, and infant mortality were 1.5 to 5 times greater with late, less frequent prenatal care than with early, frequent care. Multivariate analysis demonstrated a positive relationship between prenatal care and birthweight. Although this relationship was independent of risk factors recorded on birth certificates, it is not necessarily a causal relationship. Unadjusted prematurity, neonatal and infant mortality rates did not differ between the HMO and general populations. Multivariate analyses indicated that, independent of all maternal risk factors, HMO membership was associated with an increase of 30 grams in the predicted birthweight (P less than .01), but had no effect on mortality. The data suggest that, in Portland, Oregon, pregnancy outcome for HMO members is comparable to that of the general population.

Adult↗
PubMed2000

The reliability of case register diagnoses: a birth cohort analysis.

BACKGROUND: Few studies assess the reliability of case register diagnoses, despite their widespread use in psychiatric research. This study investigates case register diagnostic reliability in comparison to casenote derived diagnoses in a birth cohort. METHODS: Diagnostic information from the case register and casenotes of 449 individuals was extracted. The incident and lifetime register diagnoses were compared with those derived from the casenotes. RESULTS: Inter-rater reliability was good (kappa = 0.71). Agreement between casenote and incident register diagnosis was moderate (kappa = 0.52), as was agreement between casenote and register lifetime diagnosis (kappa = 0.58). Case register diagnoses were insufficiently accurate to stand alone. Case register diagnoses for organic disorder, schizophrenia, alcoholism, learning disability, personality disorder and transient or no psychiatric disorder were reliable enough for the case register to act as a useful screening instrument. The case register was not acceptable, even as a screening instrument, for the diagnoses of neurotic or affective disorders. CONCLUSIONS: Studies relying only on case register diagnoses may be flawed if diagnoses are not independently verified. National statistics derived from case register data, especially for neurosis and affective disorder, may be unreliable.

Cohort Studies↗
PubMed2006

Is there an association between SV40 contaminated polio vaccine and lymphoproliferative disorders? An age-period-cohort analysis on Norwegian data from 1953 to 1997.

Between 1955 and 1963, an estimated number of 150 million people in various parts of the world, including Norway, received poliomyelitis vaccine possibly contaminated with infectious simian virus 40 (SV40). Human studies have investigated the hypothesised association between SV40 and various cancers, but the results have so far been contradicting. The aim of the present study was to examine Norwegian cancer incidence data to assess a possible association between birth cohorts assumed to have been subjected to the vaccine and the incidence rate of lymphoproliferative disorders (excluding Hodgkin's lymphoma), further subdivided into non-Hodgkin's lymphoma (NHL), lymphocytic leukemia and plasma cell neoplasms. Between 1953 and 1997, the incidence rate of lymphoproliferative diseases combined increased about 3-fold in both males and females. Subgroup analysis showed that this increase was largely attributable to NHL. Age-period-cohort modelling of the subgroups, as well as of all groups combined, showed that the cohort effect was more prominent than the period effect. However, the variations in incidence patterns across the birth cohorts did not fit with the trends that would be expected if a SV40 contaminated vaccine did play a causative role. Thus, our data do not support the hypothesis of an association between the vaccine and any subgroup of lymphoproliferative diseases.

Adult↗
PubMed2006

Age-period-cohort analysis of cervical cancer incidence in Hong Kong from 1972 to 2001 using maximum likelihood and Bayesian methods.

OBJECTIVE: To examine the secular effects of opportunistic screening for cervical cancer in a rich, developed community where most other such populations have long adopted organised screening. DESIGN, SETTING, AND PARTICIPANTS: The analysis was based on 15 140 cases of invasive cervical cancer from 1972 to 2001. The effects of chronological age, time period, and birth cohort were decomposed using both maximum likelihood and Bayesian methods. RESULTS: The overall age adjusted incidence decreased from 24.9 in 1972-74 to 9.5 per 100,000 in 1999-2001, in a log-linear fashion, yielding an average annual reduction of 4.0% (p<0.001) during the 30 year period. There were two second order and thus identifiable changes: (1) around the mid-1920s cohort curve representing an age-period interaction masquerading as a cohort change that denotes the first availability of Pap testing during the 1960s concentrated among women in their 40s; (2) a hook around the calendar years 1982-83 when cervical cytology became a standard screening test for pregnant women. CONCLUSIONS: Hong Kong's cervical cancer rates have declined since Pap tests first became available in the 1960s, most probably because of increasing population coverage over time and in successive generations in a haphazard fashion and punctuated by the systematic introduction of routine cytology as part of antenatal care in the 1980s.

Adult↗
PubMed1998

Significance of cytomegalovirus for long-term survival after orthotopic liver transplantation: a prospective derivation and validation cohort analysis.

BACKGROUND: Cytomegalovirus (CMV) infection and disease has been found to be associated with decreased graft and patient survival among heart transplant recipients. We sought to explore the effect of CMV infection and disease on long-term survival in orthotopic liver transplant (OLT) recipients using a derivation and validation cohort. METHODS: For derivation-validation modeling, we used data collected from two prospectively followed cohorts as the basis for multivariate analyses: 167 OLT recipients from the Boston Center for Liver Transplantation (the derivation set; median follow-up: 5.5 years, mortality: 40%) and an independent cohort of 294 OLT recipients from the Mayo Clinic (the validation set; median follow-up: 4.8 years, mortality: 27%). RESULTS: Underlying liver disease other than primary biliary cirrhosis or sclerosing cholangitis, number of units of red blood cells administered during transplantation, and donor CMV seropositivity were the pre- and intratransplant variables independently associated (P<0.01) with decreased long-term survival in the derivation cohort. For variables collected up to 1 year after transplantation, the need for retransplan. tation, CMV pneumonia, invasive fungal disease, and underlying liver disease other than primary biliary cirrhosis or sclerosing cholangitis were independently associated (P<0.01) with decreased long-term survival in the derivation cohort. The magnitude of the relationship of each pre-, intra-, and posttransplant factor with survival, as measured by the relative risk, did not significantly differ between the derivation and validation cohorts. The derivation model, incorporating pre-, intra-, and posttransplant factors, had receiver operating characteristic areas of 73% and 74% for 5-year mortality in the derivation and validation cohorts, respectively. CONCLUSIONS: Data from a derivation and an independent validation cohort demonstrate that CMV factors (reflected by either donor CMV seropositivity at transplantation, CMV pneumonia, or CMV disease within the first posttransplant year) are independently associated with decreased long-term survival in OLT recipients.

Adolescent↗