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A priori lithium dosage regimen using population characteristics of pharmacokinetic parameters.

The important problem of initiation of long-term lithium treatment is tackled by means of the selection of an a priori dosage regimen based on the presumed efficacy of lithium and absence of toxicity. The pharmacokinetics of Li+ ion is represented by a four-compartment open model including the supposed first-order processes for the release of the active compound from the dosage form and its absorption. Experimental protocols for measurements of serum concentrations and of urinary amounts after single and multiple dosing to healthy volunteers were derived with several oral dosage forms. Estimation of the pharmacokinetic parameters for each subject made it possible to validate the model for the various dosage forms. The interindividual variability of these parameters is taken into account by estimating the characteristics of the statistical distribution for the whole population. A dosage regimen is considered optimum when serum concentration profiles at steady state range from the threshold of efficacy (0.8 mmol/liter) to the threshold of toxicity (2.0 mmol/liter). When the number of daily intakes is fixed, the search for the optimum dose for the whole population is effected by minimizing the expected value of the random variable which characterizes the risks of excursion out of the therapeutic range. By this means universal dosages are shown to be unsatisfactory. However, certain dosage regimens individualized with respect to the renal clearance value of lithium and based on two or three daily intakes can give excellent results even when conventional dosage forms are used.

Adolescent

Population characteristics and the distribution of general medical practitioners.

By applying the logic of the Resource Allocation Working Party to the analysis of the distribution of general medical practitioners, the relevant Family Practitioner Committee (FPC) populations were weighted according to known patterns of use related to specific characteristics--namely, age, sex, marital state, and socioeconomic group. Comparative weightings were also calculated using standardised mortality ratios. Adjusting the populations to take account of differential use has relatively little impact on national variations in list sizes but an appreciable effect on particular FPCs, notably East and West Sussex, Dorset, and the Isle of Wight. Inequalities in the distribution of general practitioners are increased considerably, however, if figures taking account of the inflation of list sizes and cross-boundary flows are used. To formulate and monitor policy about the distribution of general practitioners more sensitive measures of population and its likely demand for services must be developed.

Adolescent

Biology of the human myeloma cell population. I.Macromolecular characteristics.

Several human myeloma cell populations were studied using a combination of cytochemical (Unna-Pappenheim and naphthol yellow staining, Feulgen reaction) and autoradiographical (uridine, leucine, thymidine uptake and actinomycin binding) techniques. Progressive differentiation of the myeloma population was associated with: 1. a loss of proliferative activity, 2. decreased transcriptional capacity, 3. decreased RNA and protein synthesis, 4. increased RNA and protein concentrations, 5. greater stability of the protein synthesis template. The existence of a pre-myelomatous compartment is suggested in the light of these results and those of previous kinetic studies in vivo.

Cell Cycle

The factorial structure of the Personal Health Survey in normals and schizophrenics.

Administered the Personal Health Survey to five different groups: 74 incarcerated felons, 47 hospitalized alcoholics, 172 unmarried mothers, 51 college students, and 386 hospitalized chronic schizophrenics. On 191 of 200 items, the schizophrenics had higher base rates than any other group. Although some groups did not have large enough Ns for statistically adequate factor analyses, factorial studies also were done on the four control groups. Every group studied gave different factor patterns, with different orders of emergence of factors, different item loadings and heterogeneous composition of items. It is concluded that subgroups should be factored independently across time to determine population characteristics because overall population patterns do not make possible more than general predictions about subgroups. Individuals cannot be predicted from either overall or subgroup factorial characteristics.

Affective Symptoms

The characteristics and mortality of outpatient-acquired pneumonia.

One-hundred fifty-four cases of pneumonia occurring over a 6-month period were analyzed. Population characteristics, admission diagnoses, causative pathogens, frequency of associated illnesses, antibiotic usage and mortality were evaluated. Despite population characteristics known to predispose to a poor clinical outcome, the mortality was low, probably because of rapid institution of a single, appropriate antibiotic.

Adult

Growth characteristics of populations of Tibetan origin in Nepal.

Previous growth studies of highland-dwelling populations in the ecologically diverse areas of Peru and Ethiopia have yielded highly varied results: the retarded growth of the Peruvian sample was attributed to the effects of hypoxia, while the increased height and weight of the highland Ethiopian sample could be traced to better health conditions in the highland village than in the lowland village studied. In an attempt to provide a basis for evaluating studies of growth at high altitude, the present study compared Sherpa children living in the Everest region of Nepal with Tibetan children living in Kathmandu. It was found that: (1) the growth of Sherpa and Tibetan children is considerably retarded compared to other high altitude populations; (2) despite conditions favorable for optimum growth among the Tibetans, their growth resembled that of the Sherpas and (3) increased chest circumference, which seems to reflect a developmental acclimatization to hypoxia among Peruvian high-altitude natives, was not seen among the Sherpas.

Adolescent

The MMPI and chronic pain: the diagnosis of psychogenic pain.

This study investigates the capacity of the MMPI to discriminate among groups of patients with different types of pain. When multivariate analysis of variance is used, the standard set of MMPI scales discriminates between acute pain and chronic pain but not between chronic pain of two different etiologies (surgical-iatrogenic vs. unknown). The three scales that discriminate acute from chronic pain patients are those in the "neurotic triad," Hs, D, and Hy. The possibility that the unknown pain etiology group could be broken down into psychogenic pain and undetected somatogenic pathology subgroups was explored using cluster analysis. This procedure did not yield any group of patients who could be identified as having chronic pain of psychogenic origin. These results suggest that the MMPI is not a reliable tool for the differential diagnosis of chronic pain. It appears, however, that patterns of findings are partly contingent on population characteristics. Researchers should be cautious about generalizing to populations other than those from which samples are drawn.

Diagnosis, Differential

A Digital Tool for Clinical Evidence-Driven Guideline Development by Studying Properties of Trial Eligible and Ineligible Populations: Development and Usability Study.

BACKGROUND: Clinical guideline development preferentially relies on evidence from randomized controlled trials (RCTs). RCTs are gold-standard methods to evaluate the efficacy of treatments with the highest internal validity but limited external validity, in the sense that their findings may not always be applicable to or generalizable to clinical populations or population characteristics. The external validity of RCTs for the clinical population is constrained by the lack of tailored epidemiological data analysis designed for this purpose due to data governance, consistency of disease or condition definitions, and reduplicated effort in analysis code. OBJECTIVE: This study aims to develop a digital tool that characterizes the overall population and differences between clinical trial eligible and ineligible populations from the clinical populations of a disease or condition regarding demography (eg, age, gender, ethnicity), comorbidity, coprescription, hospitalization, and mortality. Currently, the process is complex, onerous, and time-consuming, whereas a real-time tool may be used to rapidly inform a guideline developer's judgment about the applicability of evidence. METHODS: The National Institute for Health and Care Excellence-particularly the gout guideline development group-and the Scottish Intercollegiate Guidelines Network guideline developers were consulted to gather their requirements and evidential data needs when developing guidelines. An R Shiny (R Foundation for Statistical Computing) tool was designed and developed using electronic primary health care data linked with hospitalization and mortality data built upon an optimized data architecture. Disclosure control mechanisms were built into the tool to ensure data confidentiality. The tool was deployed within a Trusted Research Environment, allowing only trusted preapproved researchers to conduct analysis. RESULTS: The tool supports 128 chronic health conditions as index conditions and 161 conditions as comorbidities (33 in addition to the 128 index conditions). It enables 2 types of analyses via the graphic interface: overall population and stratified by user-defined eligibility criteria. The analyses produce an overview of statistical tables (eg, age, gender) of the index condition population and, within the overview groupings, produce details on, for example, electronic frailty index, comorbidities, and coprescriptions. The disclosure control mechanism is integral to the tool, limiting tabular counts to meet local governance needs. An exemplary result for gout as an index condition is presented to demonstrate the tool's functionality. Guideline developers from the National Institute for Health and Care Excellence and the Scottish Intercollegiate Guidelines Network provided positive feedback on the tool. CONCLUSIONS: The tool is a proof-of-concept, and the user feedback has demonstrated that this is a step toward computer-interpretable guideline development. Using the digital tool can potentially improve evidence-driven guideline development through the availability of real-world data in real time.

Humans

Population-level genomic surveillance of human norovirus using wastewater-based whole-genome sequencing.

Wastewater-based surveillance has garnered increasing attention as a valuable approach for capturing community-level infection dynamics that are often difficult to detect through clinical reporting systems alone. In this study, we analyzed human norovirus genotype distributions and whole-genome-level variations in wastewater samples collected in Gwangju, Korea. These results were interpreted in conjunction with a documented foodborne outbreak to evaluate the epidemiological relevance of wastewater-based monitoring. Human norovirus concentrations were quantified using TaqMan Array Card-based RT-qPCR, and whole-genome next-generation sequencing (NGS) was performed to obtain viral read counts and reads per kilobase per million filtered reads values. Overall, strong correlations were observed between RT-qPCR-based concentrations and NGS-derived metrics. Genotype dynamics varied among wastewater treatment plants, reflecting differences in catchment size and local population characteristics. In particular, the relative abundance of GII.17[P17] increased during epidemiological week 50, temporally coinciding with a documented local foodborne outbreak. Variant analysis revealed that wastewater samples exhibited mixed nucleotide patterns, with multiple alleles coexisting at varying relative frequencies rather than fixed substitutions. Notably, some nonsynonymous variants detected in clinical samples were also observed in wastewater samples collected surrounding the outbreak period. Together, these findings demonstrate that wastewater-based whole-genome surveillance can capture both genotype-level shifts and nucleotide-level dynamics at the population scale, highlighting its potential as a complementary tool for monitoring community-level norovirus circulation and outbreak-associated genotype dynamics.IMPORTANCEWastewater-based surveillance is increasingly recognized as a promising approach for capturing community-level infection dynamics that are often missed by clinical surveillance. In this study, we applied whole-genome sequencing to wastewater samples collected in Gwangju, South Korea, to comprehensively characterize human norovirus genotype distributions and genetic variation. Distinct genotype patterns were observed across wastewater treatment plants, reflecting differences in catchment population size and local characteristics. Notably, an increase in the GII.17[P17] genotype detected in wastewater coincided with a foodborne outbreak investigated in Gwangju, demonstrating the potential of wastewater surveillance to reflect ongoing community transmission and emerging outbreak-associated genotypes. In addition, wastewater samples contained diverse and coexisting genetic variants, capturing population-level viral diversity and evolutionary dynamics that are not readily detected through clinical surveillance alone. These findings highlight the value of wastewater-based whole-genome surveillance for monitoring community-level viral circulation and support its integration as a complementary strategy to existing clinical surveillance systems.

genotype dynamics

Genetic Research on Cardiac Channelopathies in African and African-Descent Populations: A Scoping Review.

Cardiac channelopathies are inherited arrhythmias that can lead to sudden cardiac death. Despite Africa's extensive genomic diversity, African and African-descent populations remain underrepresented in genetic research, creating gaps in variant interpretation and clinical care. This scoping review aims to map the extent, range, and nature of genetic research on cardiac channelopathies in these populations and to identify key geographic, thematic, and methodological gaps. Using the Joanna Briggs Institute scoping review methodology and the Population-Concept-Context framework, systematic searches in PubMed, Embase, and Web of Science identified original human studies on cardiac channelopathies with genetic data. Extracted variables included study characteristics, populations, types of channelopathies, and reported genes and variants. Forty-four studies met the inclusion criteria. Most studies originated from the United States and South Africa, while West, Central, and East Africa were largely underrepresented. US Black individuals and South African individuals of continental African or African-descended ancestry (excluding populations of European descent such as Cape Afrikaner people) were the most studied groups, with other continental African groups rarely included. Long QT syndrome was the predominant focus, and SCN5A, KCNQ1, and KCNH2 were the most frequently analyzed genes. Many of the genetic variants discussed remained of uncertain significance due to limited functional validation and the underrepresentation of African genomes in reference databases. Genetic research on cardiac channelopathies in populations of African ancestry is limited, restricting variant interpretation, counseling, and risk prediction. Broader African inclusion, expanded gene screening, and functional studies are essential to improve diagnostics and promote equity in genomic medicine.

Humans