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Does long-term GH replacement therapy in hypopituitary adults with GH deficiency normalise quality of life?

OBJECTIVE: To determine whether impaired quality of life (QoL) in adults with GH deficiency (GHD) is reversible with long-term GH therapy and whether the responses in QoL dimensions differ from each other. METHODS: QoL was measured by the Quality of Life-Assessment for Growth Hormone Deficiency in Adults (QoL-AGHDA) in general population samples in England & Wales, The Netherlands, Spain and Sweden (n = 892, 1038, 868 and 1682 respectively) and compared with corresponding patients' data from KIMS (Pfizer International Metabolic Database) (n = 758, 247, 197 and 484 respectively) for 4-6 years a follow-up. The subsets of patients from England and Wales, and Sweden with longitudinal data for 5 years' follow-up were also analysed. The change of the total QoL-AGHDA scores and responses within dimensions were evaluated. Subanalyses were performed to identify any specificity in response pattern for gender, age, disease-onset and aetiology. RESULTS: Irrespective of the degree of impairment, overall QoL improved dramatically in the first 12 months, with steady progress thereafter towards the country-specific population mean. Problems with memory and tiredness were the most serious burden for untreated patients, followed by tenseness, self-confidence and problems with socialising. With treatment, these improved in the reverse order, normalising for the latter three. CONCLUSIONS: Long-term GH replacement results in sustained improvements towards the normative country-specific values in overall QoL and in most impaired dimensions. The lasting improvement and almost identical pattern of response in each patient subgroup and independent of the level of QoL impairment support the hypothesis that GHD may cause these patients' psychological problems.

Adult↗

Statistical concepts in the interpretation of serial bone densitometry.

The precision of a measurement can be expressed as the variance of multiple measurements. The coefficient of variation is a dimensionless expression of precision that is prevalent in the radiology literature. However, the coefficient of variation has important limitations. The question whether measured change is significant arises whenever any quantitative clinical parameter is followed over time. When serial bone mineral density measurements are made, change is commonly estimated as the slope of a line fitted to the serial data by linear regression. Confidence intervals for change based on this method usually assume that the precision error in measurement remains constant over time and that change is truly linear. Estimates of long-term precision may be elusive, and if constant, may vary for different individuals. If separate measurement precisions are known or are indeed constant, one can assess the level of statistical agreement of longitudinal data to linear, or other theoretical, models.

Absorptiometry, Photon↗

Cognitive functioning in young "social drinkers": is there impairment to detect?

Literature on the cognitive effects of nonexcessive alcohol use suggests that relatively high-quantity-per-occasion use may be related to subsequent decreases in sober-state abstracting skills in adults, but provides no clear prediction for youth. The need to identify persistent alcohol-intake effects on cognition is particularly acute for the period of adolescence and young adulthood because even slight damage may impair developmentally significant skills. We examine the relation between multiple measures of neuropsychological status and both continuous and categorical measures of alcohol-use patterns in an age- and sex-stratified sample of 1,308 18-, 21-, and 24-year-olds. The results of correlational and hierarchial regression analyses suggest that cognitive performance bears little direct relation to drinking behaviors in young nonclinical males and females. Although the data provide no strong support for the hypothesis of a causal relationship between alcohol use and cognitive functioning, there is a slight suggestion that frequent high-quantity consumption may become a salient parameter of use as subjects age. Prospective longitudinal data are needed to explore the directional causality of effects.

Adolescent↗

Quantitative description of the shape of the mandible.

The purpose of this study was to provide quantitative data on the shape of the mandible at the period around the pubertal growth spurt and to test the hypothesis that early mandibular shape may influence the amount and direction of subsequent mandibular growth. Longitudinal data from lateral cephalograms of 55 white female and 39 white male subjects were used. The mandibular outline from articulare to gnathion was analyzed into cosine curves, according to the Fourier equation. The resulting Fourier coefficients, representing mandibular outline shape, were analyzed statistically in relation to age, sex, craniofacial pattern, and mandibular growth rotation. Statistically significant growth changes of the Fourier coefficients were observed, especially during the postpubertal period, indicating a decrease in the gonial angle with age. Sex-related differences in shape were observed at all ages, male subjects showing a more rounded shape of the mandible than female subjects. Mandibular shape, as represented by the Fourier coefficients, was correlated to cephalometric variables, indicating mandibular inclination, but only poorly to cephalometric variables, indicating anteroposterior jaw relation. Total rotation of the mandible during growth could not be predicted by mandibular shape.

Cephalometry↗

Illness episodes, physician visits, and depressive symptoms.

Although there is a large literature examining the effects of distress on the demand for medical care, the data on which this literature is based are equivocal. Nonetheless, this literature is cited frequently by those who advocate a national mental health policy designed to produce a cost-effective "medical offset effect." In this study, longitudinal data on illness episodes, physician visits, and depressive symptoms were collected from 940 Medicare recipients enrolled in a health maintenance organization (HMO) under a Tax Equity and Fiscal Responsibility Act (TEFRA) contract. Seven waves of interviews were conducted over a period of 1 year. This article presents two sets of analyses. In the first, controlling for chronic conditions and demographics reported at baseline, the relationships between depressive symptoms reported at baseline, and all illness episodes and physician visits that occurred over the subsequent year are examined. In the second, controlling for depressive symptoms and demographics reported at baseline, the relationships between illness episodes and physician visits over the study year, and depressive symptoms recorded at the final interview are examined. The data indicate that, whereas depressive symptoms at baseline are virtually unrelated to subsequent illness episodes and physician visits, illness episodes and physician visits are related to subsequent depressive symptoms. These data indicate, therefore, that policies aimed at diverting the distressed from seeking medical care may result in further inequities in the receipt of needed care.

Aged↗

Contributions of vertebral fractures to stature loss among elderly Japanese-American women in Hawaii.

Loss of stature is a typical feature of osteoporosis and associated vertebral fractures. However, there have been few prospective population-based studies to estimate the magnitude of this association. Further, the separate contributions of different types of vertebral fractures to stature loss have not been evaluated using prospective data. In this study we investigated the extent to which stature loss could be explained by the number of different types of vertebral fractures (wedge, endplate, and crush fractures) after adjusting for other covariates. Longitudinal data on stature loss and vertebral fractures were collected among 504 postmenopausal Japanese-American women living in Hawaii with mean age 73.4 (SD 4.9) years. During an average of 7.7 years of follow-up, women with at least one incident vertebral fracture had an average of 2.1 cm of stature loss while the average stature loss among those without incident fractures was only 0.4 cm. The mean rate of stature loss was very slight (< 1 mm/year) for those without incident vertebral fractures even after age 80. Our analyses suggest that both the number of wedge and the number of crush fractures are strong predictors of stature loss. After adjusting for age and total height loss in the anterior dimension over T3-L5, the estimated stature loss resulting from each wedge and crush fracture was 0.86 and 1.08 cm, respectively. Endplate fractures did not show significant contributions to stature loss.

Adult↗

A discrete-state discrete-time model using indirect observation.

This research was motivated by a desire to model the progression of a chronic disease through various disease stages when data are not available to directly estimate all the transition parameters in the model. This is a common occurrence when time and expense make it unfeasible to follow a single cohort to estimate all the transition parameters. One difficulty of developing a model of chronic disease progression from such data is that the available studies often do not include the transitions of interest. For example, in our model of diabetic nephropathy, many clinical studies did not differentiate between patients without nephropathy and those who had microalbuminuria (a pre-clinical stage of nephropathy). Another difficulty was a lack of data to directly estimate parameters of interest. We consider models which can accommodate such difficulties. In this paper we consider the problem of estimating parameters of a discrete-time Markov process when longitudinal data describing the entire process are not available. First, we present a likelihood approach to estimate parameters of a discrete-time Markov model. Next, we use simulation to investigate the finite-sample behaviour of our approach. Finally, we present two examples: a model of diabetic nephropathy and a model of cardiovascular disease in diabetes.

Albuminuria↗

Change in household composition of the elderly: a preliminary investigation.

Selected environmental and life-cycle determinants of change in household composition were examined using longitudinal data. Although cross-sectional analysis would suggest that 12% of a random sample of 276 older community residents had experienced a change in type of household composition over a 30-month period, longitudinal analysis showed that 18% experienced a change in major type of household composition, some types of households being more stable than others. Longlinear analysis showed that these changes were best accounted for by earlier life cycle events that were largely beyond the individual's present control (i.e., by change in marital status, typically death of spouse, and by extent of help available from family and friends). The importance of such family life cycle events in explaining change in household composition was emphasized.

Aged↗

Lower urinary tract symptoms suggestive of benign prostatic obstruction--Triumph: the role of general practice databases.

The Triumph project aims to document the current management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in general practice and to assess the effectiveness of the initial treatment options used. The first phase of the project will consider existing data sources in primary care. A patient's medical record will contain most, if not all, clinically relevant information, and databases combining the records from a network of computerised general practices can provide longitudinal data for complete populations, linking prescribing records to clinical information on disease progression and outcomes for individual patients. Database research can provide rapid information and offers the ability to conduct studies on a scale that would previously have been prohibited by both time and expense. Within the Triumph project, the THALES, General Practice Research Database (GPRD) and Integrated Primary Care Information (IPCI) databases are, or will be, used to examine the current management of LUTS/BPH in France, the UK and the Netherlands respectively. Preliminary results from the UK General Practice Research Database (GPRD) showed that LUTS/BPH incidence increased linearly from the ages of 45 to 85 years (r(2) = 0.992) and prevalence increased from 3.5% to 35% for men in their late 40s and 80s respectively. With treatment failure defined as a change to another medical therapy, catheterisation or prostatic surgery, and accounting for age and year variation, patients receiving the older alpha(1)-blockers (indoramin and prazosin) appeared to fail significantly earlier than those receiving finasteride. There was no significant difference between finasteride and the newer alpha(1)-blockers (tamsulosin, alfuzosin, terazosin and doxazosin). Patterns of changes between products from the THALES database in France were broadly similar to those seen in the UK.

Databases, Factual↗

Assessing biological age: practicality?

There are many problems in measuring "biological" age rather than chronological age, not least the necessity of demonstrating that this measure has validity in terms of better predicting mortality or morbidity. This review considers nine problems in measuring biological age and attempts to provide a full or partial solution to these difficulties. The problems presented include the fact that different organs age at different rates; biological age depends on the parameters studied; 'regression dilution bias' may produce misleading results; the validity of the measurement has to be established; the age range for measures has to be agreed; persons affected by accident or disease may or may not be excluded; accidental deaths may have to be excluded from a study of validation; individuals age at different rates at different times, and the fact that longitudinal data are necessary. The solutions suggested include both the presentation of aging profiles including several systems and the provision of summary statistics; adjusting for 'regression dilution bias', and calculating rate of aging from longitudinal studies over different age ranges and in the two sexes separately. It is argued that in this field of research it is well worth confronting the difficulties and extending our body of knowledge by further careful studies.

Aging↗

Beyond Morphology: Reframing Lymph-Node Metastasis Prediction Through Clonal Ecology-Decades-Long Genomic Instability and Polyclonal-to-Monoclonal Transitions as the Missing Dimension in Cancer.

Recent whole-genome, lineage-tracing, single-cell, and spatial studies have reshaped our understanding of tumor evolution, revealing that cancers can arise from polyclonal populations, undergo decades-long genomic instability before clinical detection, and progress through dynamic changes in subclonal composition, cellular state, and ecological organization. These findings challenge the assumption underlying morphology-based prediction models that metastatic risk can be inferred from static histological features alone. Here, we revisit lymph-node metastasis prediction in colorectal cancer through clonal ecology, integrating computational pathology with evolutionary oncology. Drawing on the subclonal switchboard model proposed in 2012 and subsequent artificial intelligence (AI)-enabled approaches for tracking dominant and dormant subclones, we synthesize evidence that metastatic potential reflects clonal ancestry, evolutionary timing, spatial niche architecture, cellular plasticity, intercellular interactions, dormancy, and treatment-driven shifts in subclonal fitness. We define five complementary methodological pillars for operationalizing clonal ecology: single-cell transcriptomics for resolving rare subclones, evolutionary trajectories, and adaptive cell states; lineage tracing and phylogenetics for reconstructing clonal ancestry and divergence; spatial transcriptomics and genomics for mapping subclonal geography and tumor-stromal-immune interactions; longitudinal liquid biopsy surveillance for monitoring residual disease, clonal turnover, and emerging resistance; and AI-enabled multimodal integration for connecting histopathology, genomics, spatial biology, and longitudinal data into predictive ecological-state models. Multiple-instance learning and pathology foundation models provide scalable computational foundations for evolution-aware prediction. Translationally, dormant subclones represent actionable reservoirs of recurrence. A longitudinal clinical and experimental study of KMT2A-rearranged acute myeloid leukemia further supports central predictions of the subclonal switchboard framework by demonstrating treatment-associated shifts in subclonal dominance, persistence of cryptic adaptive programs, and ecological rewiring during resistance and relapse. We propose clonal ecology as a measurable dimension for extending morphology-driven prediction toward integrative models that anticipate evolutionary transitions, identify therapeutic windows, and proactively constrain adaptive tumor ecosystems before resistant or metastatic subclones achieve clinical dominance.

Humans↗

I can use a condom, i just don't: the importance of motivation to prevent HIV in adolescent seeking psychiatric care.

Youth continue to show high HIV infection rates, and adolescents with mental health problems are especially at risk. We used longitudinal data to test a cognitive-behavioral model of risky sexual behavior among 175, ethnically diverse urban adolescents seeking mental health services. Path analyses of the cross-sectional data revealed that Motivation was a strong predictor of Behavioral Skills and Sexual Risk Taking. The model explained 42% of the variance in Sexual Risk Taking with age included-29% without age. In the longitudinal path analyses, Motivation had a significant negative effect on levels of Sexual Risk Taking 6 months later, controlling for Information, Behavioral Skills, age, and baseline levels of Sexual Risk Taking. These longitudinal effects explained 60% of the variance in Sexual Risk Taking. These results underscore the need to address motivational factors in HIV prevention programs designed for adolescents with mental health problems.

Adolescent↗

Increases in depressive symptomatology in the rural elderly: results from a cross-sectional and longitudinal study.

Depressive symptomatology was examined in a large sample of noninstitutionalized older adults using the Center for Epidemiological Studies-Depression scale (CES-D). Both cross-sectional and longitudinal data showed age-related increases in mean CES-D scores and increases in the percentage of respondents scoring at or above the cutoff score of 16. Variables collected at baseline in the longitudinal study from 2,032 participants 65 years of age and older were significant predictors of depressive symptomatology 3 and 6 years later. Baseline CES-D scores accounted for the largest proportion of the variance.

Activities of Daily Living↗

Parental substance use disorder and the risk of adolescent drug abuse: an event history analysis.

A common observation in the research literature is that children of drug-dependent parents are at significantly heightened risk of adolescent drug use, abuse, and dependence. Recent research indicates that several psychological and interpersonal factors may affect the association between parents' psychoactive substance use disorder (PSUD) and drug use risks among adolescents, yet studies have failed to examine explicitly whether these factors moderate the association between PSUD and adolescent substance abuse. This paper explores these potential relationships using longitudinal data from a study that has followed three cohorts of adolescents and their families over a 7-year period. The cohorts are defined by parental diagnoses of PSUD, affective disorders, or no diagnosable disorder. The results indicate that PSUD is positively associated with adolescent drug abuse, yet this association is attenuated by strong family cohesion. Affective disorders among parents are associated with a higher risk of alcohol, but not drug, abuse. The associations are stronger in the presence of lower stress and higher self-esteem. PSUD is also associated more strongly with offspring drug and alcohol abuse when levels of use are lower. Hence, some unobserved mechanism that may involve physiological sensitivities to drugs and alcohol appears to put children of parents with drug problems at particular risk of drug and alcohol abuse. Limitations of the data and analysis are discussed.

Adolescent↗

Changes in cohort wealth over a generation.

Empirical computation of expected wealth is hampered by two problems: mortality risks vary in the population and over time; and observation of net estates for most cohorts is truncated, as some individuals in a cohort survive the calendar date on which observation is terminated. These two problems are solved in estimating cohort wealth for a sample of Wisconsin taxpayers. Hazard rate models of differential occupational mortality risks were estimated from the occupational information on the tax records. Values of net estate are simulated for individuals in each birth cohort who survived. Survivors have characteristics that imply greater wealth holdings than the deceased in every birth year covered by the study (1890-1924). Because of this, estimates of wealth-age relationships produced by the estate multiplier method for any given year will have a serious downward bias. Longitudinal data imply that dissaving does not occur after age 65.

Actuarial Analysis↗

Metabolic control, quality of life, and negative life events: a longitudinal study of well-controlled and poorly regulated patients with type 1 diabetes after changeover to insulin pen treatment.

In a previous study of a group of 74 patients with Type I diabetes, quality of life was found to be consistently enhanced a year after transition to multiple injection therapy with the insulin pen, whereas metabolic control (HbA1C) only improved moderately. The aim of the present investigation was to examine quality of life, recent life events, and metabolic control longitudinally in this original study group over a 5-year period beginning 1 year after transition to the insulin pen. Multiple analysis of variance with a repeated-measures design was used to analyze the data longitudinally and compare metabolic control in subgroups of well-controlled and poorly regulated patients during the study period. For the group as a whole, quality of life was found to change only moderately, whereas metabolic control deteriorated significantly across time following transition to the insulin pen. The two subgroups exhibited distinct differences, however, in quality of life, recent life events, and metabolic control patterns. These findings are discussed in terms of the clinical suitability of a multiple injection regimen.

Aged↗

Clinical value of soluble IgG Fc receptor type III in plasma from patients with chronic idiopathic neutropenia.

Previous studies have shown that the plasma level of soluble IgG Fc receptor type III (sFcgammaRIII) is a measure of the total body neutrophil mass. The aim of this study was to determine whether the plasma level sFcgammaRIII is associated with the risk of contracting bacterial infections in patients with neutropenia. We collected blood from 66 patients suffering from acquired idiopathic neutropenia, whose blood was sent to our laboratory for diagnostic evaluation of neutropenia (neutrophil count <1,500 cells/microL). Soluble FcgammaRIII levels were measured in plasma. Genotype distibutions of FcgammaR polymorphisms were determined. Clinical data were obtained from the patient files. Patients were assessed as to whether or not they had suffered from a bacterial infection 3 months before to 3 months after a single sFcgammaRIII measurement. In addition, longitudinal data were obtained from 21 patients. Of the 66 neutropenic patients who were included, 15 had suffered from a bacterial infection in the period 3 months before to 3 months after sFcgammaRIII measurement. The age and sex distribution was equal among the groups with and without infections, as were the genotype frequencies of neutrophil FcgammaR polymorphisms. Both neutrophil count and plasma level sFcgammaRIII were significantly lower in the patient group with infections, compared with the noninfected group (P = .03 and P < .0001, respectively). No infections were reported for patients who had plasma sFcgammaRIII levels above 100 arbitrary units (AU; normal value, 30 to 200). After matching each infected patient with two noninfected patients having the same neutrophil count, sFcgammaRIII plasma levels remained significantly lower in the group with infections (P = . 0001). For the patients who were followed in time, no infections were reported when sFcgammaRIII levels were above 100 AU. In conclusion, our population of patients with chronic idiopathic neutropenia with plasma sFcgammaRIII levels above 100 AU did not show an increased risk of contracting bacterial infections.

Adolescent↗

Validity of the longitudinal, expert, all data procedure for psychiatric diagnosis in patients with psychoactive substance use disorders.

The longitudinal, expert, all data (LEAD) procedure has been employed as a criterion for the assessment of the procedural validity of diagnostic instruments. This study evaluated the procedure's concurrent, discriminant and predictive validity. Interview and questionnaire data obtained from 100 individuals in a substance abuse treatment program were used to assess current and lifetime substance use disorders and common comorbid disorders. An experienced, doctoral-level clinician formulated LEAD diagnoses for each patient, based on an initial interview, ongoing clinical contact and the results of the research assessment and all available clinical records. LEAD-derived substance use diagnoses showed good concurrent, discriminant and predictive validity. The validity of comorbid diagnoses obtained using the LEAD procedure was generally fair to good. Comparison with diagnoses based only on the clinician's unstructured initial interview showed that the availability of additional data enhanced diagnostic validity. Diagnoses derived by a research technician using the Structured Clinical Interview for DSM-III-R showed validity comparable to that of LEAD diagnoses. To enhance its diagnostic validity, applications of the LEAD standard should include a structured interview. Other variations in the application of the LEAD standard, including a longer evaluation period, may also enhance its performance as a diagnostic criterion measure.

Adult↗