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Phenotype of frailty: characterization in the women's health and aging studies.

BACKGROUND: "Frailty" is an adverse, primarily gerontologic, health condition regarded as frequent with aging and having severe consequences. Although clinicians claim that the extremes of frailty can be easily recognized, a standardized definition of frailty has proved elusive until recently. This article evaluates the cross-validity, criterion validity, and internal validity in the Women's Health and Aging Studies (WHAS) of a discrete measure of frailty recently validated in the Cardiovascular Health Study (CHS). METHODS: The frailty measure developed in CHS was delineated in the WHAS data sets. Using latent class analysis, we evaluated whether criteria composing the measure aggregate into a syndrome. We verified the criterion validity of the measure by testing whether participants defined as frail were more likely than others to develop adverse geriatric outcomes or to die. RESULTS: The distributions of frailty in the WHAS and CHS were comparable. In latent class analyses, the measures demonstrated strong internal validity vis à vis stated theory characterizing frailty as a medical syndrome. In proportional hazards models, frail women had a higher risk of developing activities of daily living (ADL) and/or instrumental ADL disability, institutionalization, and death, independently of multiple potentially confounding factors. CONCLUSIONS: The findings of this study are consistent with the widely held theory that conceptualizes frailty as a syndrome. The frailty definition developed in the CHS is applicable across diverse population samples and identifies a profile of high risk of multiple adverse outcomes.

Aged↗

Validation of psychoanalytic theories: towards a conceptualization of references.

The authors discuss criteria for the validation of psychoanalytic theories and develop a heuristic and normative model of the references needed for this. Their core question in this paper is: can psychoanalytic theories be validated exclusively from within psychoanalytic theory (internal validation), or are references to sources of knowledge other than psychoanalysis also necessary (external validation)? They discuss aspects of the classic truth criteria correspondence and coherence, both from the point of view of contemporary psychoanalysis and of contemporary philosophy of science. The authors present arguments for both external and internal validation. Internal validation has to deal with the problems of subjectivity of observations and circularity of reasoning, external validation with the problem of relevance. They recommend a critical attitude towards psychoanalytic theories, which, by carefully scrutinizing weak points and invalidating observations in the theories, reduces the risk of wishful thinking. The authors conclude by sketching a heuristic model of validation. This model combines correspondence and coherence with internal and external validation into a four-leaf model for references for the process of validating psychoanalytic theories.

Humans↗

The Color-A-Person Body Dissatisfaction Test: stability, internal consistency, validity, and factor structure.

Stability, internal consistency, validity, and factor structure of the Color-A-Person Body Dissatisfaction Test (CAPT) were assessed. Two- and 4-week test-retest correlations for college students and alpha coefficients for students and eating-disorder patients ranged from .70 to .89. Factor structure was unaffected by gender and clinical status. Correlations were mostly between -.40 and -.60 with Rosenberg's (1965) Self-Esteem Scale and Secord and Jourard's (1953) Body Cathexis Scale (BCS). Men higher on Body Mass Index (BMI) liked upper body parts; women higher on BMI disliked lower body parts. Treatment for bulimia affected both body image tests comparably.

Adult↗

Improved validation of the Inflammatory Bowel Disease Questionnaire and development of a short form in Greek patients.

OBJECTIVES: The Inflammatory Bowel Disease Questionnaire (IBDQ) is a disease-specific questionnaire for assessing health-related quality of life. The main objective of this study is to assess three main areas of the validation of the Greek IBDQ: internal validity, designating items to dimensions, and selecting items for a short form. An additional aim is to present alternative validation methods for improved and robust results. METHODS: A total of 134 patients with IBD, including 74 with ulcerative colitis (UC) and 60 with Crohn's disease (CD), completed the Greek IBDQ. Internal validity was assessed by using standard methods and multiple correlation analysis. Factor analysis of the 32 items of the questionnaire was carried out to identify the underlying dimensions, using principal factor analysis and maximal likelihood. For selecting items for a short form, three methods of linear regression analysis were used. RESULTS: All items had adequate convergent validity (except item 11 in the CD group) and acceptable discriminant validity (except item 11 for both groups). Factor analysis yielded five factors (emotional function, social function, systemic symptoms, bowel symptoms, and abdominal symptoms). The combination of three regression techniques and their internal validity yielded two similar but distinct short forms, one for UC and one for CD. Both forms had high correlation with the total IBDQ score (R(2) = 0.949 and 0.977, respectively). CONCLUSIONS: The Greek IBDQ had good internal validity. The original designation in four dimensions and the original short form could be improved with only slight modifications.

Adolescent↗

Randomized placebo-controlled trials of antibiotics for acute bronchitis: a critical review of the literature.

BACKGROUND: Acute bronchitis is a common clinical problem that causes considerable morbidity and presents both diagnostic and treatment dilemmas for the physician. An evaluation of all published randomized controlled trials of antibiotics in the treatment of acute bronchitis was conducted to (1) quantitatively assess methodologic rigor, (2) determine if effectiveness of antimicrobial therapy is known, and (3) analyze strengths and weaknesses of randomized controlled trials in family practice settings. METHODS: A scoring system for the evaluation of randomized controlled trials was adapted for this study. Four raters, who were blinded to which journals published the studies and the type of antibiotic used in each study, assessed the six-randomized clinical trials for treatment of bronchitis identified through a literature search. The trials were rated according to criteria that measured internal validity. RESULTS: Scores for internal validity ranged from 65.5 to 102.5 points with a maximum possible score of 120 points (54.6% to 85.4%). The two trials with the highest scores assessed doxycycline and showed no benefit from use of this antibiotic. Single trials that studied erythromycin and trimethoprim-sulfamethoxazole showed improvement in outcome from use of these drugs; however, of the six trials, these two studies ranked fourth and fifth for internal validity. Low scores resulted from small sample size, possible contamination with other treatment measures, and poor assessment of subjects' compliance with antibiotic regimen. CONCLUSIONS: An evaluation of the current literature does not support antibiotic treatment for acute bronchitis. Further studies of this common illness are indicated. It is hoped that this critical review of randomized control trials will prove useful in the planning of future studies, in placing greater emphasis on methodologic rigor, and in giving greater consideration to the practical constraints of research in the family practice setting.

Acute Disease↗

Quantification of communication processes, is it possible?

The PAS system (Problem-Analysis-Solution-system) is developed to quantify oral communication processes during counselling in pharmacy practice. The pharmacist translates the patient's drug-related questions into a P-code, the analysis of the question into an A-code and finally the given solution upon the question into a S-code. The PAS system has been developed for two goals. First, for the registation of drug-related questions from patients which gives the pharmacist insight in the most common issues addressed by patients. Second, it might help the pharmacist to structure the communication with the patient during the consultation. Forty-one pharmacists participated in the evaluation of the PAS system. The validation of the PAS system consisted of two phases: the external validation and the internal validation. Kappa values were calculated as a measure of agreement in the coding by the pharmacists. The kappa-value of the external validation for the P-, A- and S-codes for the total set of questions indicate a moderate to poor agreement. This means that pharmacists categorize drug-related questions from patients in a different way. Therefore we conclude that the PAS system is less reliable for research purpose. The kappa-value of the internal validation for the P-code varies from 0.42 to 0.91. For the A-code it varies from 0.07 to 0.35 and for the S-code from zero to 0.68. Internal reproducibility is good for P-code but not for the A-code and S-code. This implies that the pharmacist can use the P-codes for registration of patients' questions in his own pharmacy. Moreover, the usage of the PAS system during counselling in pharmacy practice can structure the consultation.

Communication↗

External validity, generalizability, and knowledge utilization.

PURPOSE: To examine the concepts of external validity and generalizability, and explore strategies to strengthen generalizability of research findings, because of increasing demands for knowledge utilization in an evidence-based practice environment. FRAMEWORK: The concepts of external validity and generalizability are examined, considering theoretical aspects of external validity and conflicting demands for internal validity in research designs. Methodological approaches for controlling threats to external validity and strategies to enhance external validity and generalizability of findings are discussed. CONCLUSIONS: Generalizability of findings is not assured even if internal validity of a research study is addressed effectively through design. Strict controls to ensure internal validity can compromise generalizability. Researchers can and should use a variety of strategies to address issues of external validity and enhance generalizability of findings. Enhanced external validity and assessment of generalizability of findings can facilitate more appropriate use of research findings.

Data Collection↗

[Clinical usefulness of oligoclonal bands].

The presence of oligoclonal bands (OCB) of immunoglobulin G (IgG) is in our days the most useful finding in the study of the CSF for the diagnosis of multiple sclerosis (MS). The most sensitive method for the detection of OCB is the isoelectric focusing followed by immunoblotting. The prevalence of OCB changes in different populations with a rank of results from 60 to 95 97%. We have determined the prevalence of OCB in our population and the sensitivity and the specificity of the technique used in our laboratory. We have included 391 patients in whom we analysed the presence of OCB, subdivided in; Group 0: Diagnosed of MS, group 1: First episode of demyelinating process, group 2: Neurological disorders considered noninflammatory or nonautoimmune (NINA),group 3: Neurological disorders considered inflammatory, infectious or autoimmune (IIA). The presence of OCB was searched in CSF and serum simultaneously using isoelectric focusing and immunoblotting. In order to standardize the technique we achieved and internal and external validation. Internal validation: sensitivity and specificity (using as a control group first the group NINA and after the group IA). External validation: we choose 10 pairs of CSF/serum from patients with different diagnostics and sent to a reference laboratory ( Karolinska Institute Medical School) that was blind of our results and of the diagnostics. The prevalence of OCB in each group has been: group 0 (MS): 87.7%, group 1: 54.8%, group 2 (NINA): 17.5%, group 3(IIA): 52.7%. Sensitivity: 97.7%, specificity using group NINA as control 82.5% and using group IIA 45.7%. Concordance with the reference laboratory in 9/10 determinations. We conclude that in our population the prevalence of OCB, in patients with MS, is lower than in Northern Europe. The OCB appear in may inflammatory, autoimmune diseases, their specificity for the diagnostic of MS is low.

Autoimmune Diseases↗

The Strain of Care for Delirium Index: a new instrument to assess nurses' strain in caring for patients with delirium.

This study evaluated content validity, internal consistency and construct validity of the Strain of Care for Delirium Index (SCDI), a newly constructed instrument to measure the strain nurses experience in caring for patients with delirium. Content validity, evaluated by eight experts, reduced the initial pool of items from 38 to 28. Using a convenience sample of 190 nurses, Cronbach's alpha for the 28-item version was 0.88. Using non-linear principal components analysis another eight items were eliminated and a four-factor structure was identified. The proportion of variance explained by the remaining 20 items was 61.51%. Preliminary psychometric evaluation of the SCDI supported content validity, internal consistency and construct validity; however additional psychometric evaluation is warranted.

Adult↗

Development of a multidimensional labour satisfaction questionnaire: dimensions, validity, and internal reliability.

BACKGROUND: No published quantitative instrument exists to measure maternal satisfaction with the quality of different models of labour care in the UK. METHODS: A quantitative psychometric multidimensional maternal satisfaction questionnaire, the Women's Views of Birth Labour Satisfaction Questionnaire (WOMBLSQ), was developed using principal components analysis with varimax rotation of successive versions. Internal reliability and content and construct validity were assessed. RESULTS: Of 300 women sent the first version (WOMBLSQ1), 120 (40%) replied; of 300 sent WOMBLSQ2, 188 (62.7%) replied; of 500 women sent WOMBLSQ3, 319 (63.8%) replied; and of 2400 women sent WOMBLSQ4, 1683 (70.1%) replied. The latter two versions consisted of 10 dimensions in addition to general satisfaction. These were (Cronbach's alpha): professional support in labour (0.91), expectations of labour (0.90), home assessment in early labour (0.90), holding the baby (0.87), support from husband/partner (0.83), pain relief in labour (0.83), pain relief immediately after labour (0.65), knowing labour carers (0.82), labour environment (0.80), and control in labour (0.62). There were moderate correlations (range 0.16-0.73) between individual dimensions and the general satisfaction scale (0.75). Scores on individual dimensions were significantly related to a range of clinical and demographic variables. CONCLUSION: This multidimensional labour satisfaction instrument has good validity and internal reliability. It could be used to assess care in labour across different models of maternity care, or as a prelude to in depth exploration of specific areas of concern. Its external reliability and transferability to care outside the South West region needs further evaluation, particularly in terms of ethnicity and social class.

Female↗

Prognostic modeling of overall survival in metastatic pancreatic cancer: an inflammation-based tool validated in PANTHEIA-SEOM cohort.

PURPOSE: To develop and internally validate the PANTHEIA-SIRI prognostic model, which integrates log-transformed systemic inflammation response index (SIRI) with clinical predictors, to estimate overall survival (OS) in metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with first-line chemotherapy. METHODS: We used data from the multicenter PANTHEIA-SEOM registry. OS was defined from chemotherapy start. The model was fitted as a Weibull accelerated failure time model in the survival-analysis population with multiple imputation. Predictors were log-transformed baseline SIRI, modeled with restricted cubic splines, ECOG, tumor burden, chemotherapy regimen, and anorexia-cachexia syndrome. Internal validation used a separate, non-overlapping cohort from the same registry; the centers contributing to each cohort are listed in a supplementary annex. TRIPOD was followed. Discrimination was assessed with Harrell´s C-index and calibration with IPCW Brier scores and IPA. RESULTS: The derivation cohort comprised 672 patients with SIRI data (593 analyzed for survival) across 22 Spanish hospitals (2015-2025); 80.1% had died after a median OS of 9.9 months. The imputation-pooled derivation C-index was 0.654 (95% CI, 0.627-0.681); optimism-corrected, 0.629. Internal validation used 62 separate patients from the same registry; 96.8% had died after a median OS of 9.2 months. The validation C-index was 0.603 (95% CI, 0.518-0.687). Calibration was adequate at 6 and 12 months. CONCLUSIONS: The PANTHEIA-SIRI model provides individualized OS estimates in mPDAC with routine clinical predictors. Its open-access calculator ( https://pantheia-siri.shinyapps.io/calc/ ) may support prognostic communication, treatment-intensity selection, and supportive-care planning. Routine clinical implementation will require further validation in larger, fully independent cohorts.

Cachexia↗

Validation of the embryonic stem cell test in the international ECVAM validation study on three in vitro embryotoxicity tests.

A detailed report is presented on the performance of the embryonic stem cell test (EST) in a European Centre for the Validation of Alternative Methods (ECVAM)-sponsored formal validation study on three in vitro tests for embryotoxicity. Twenty coded test chemicals, classified as non-embryotoxic, weakly embryotoxic or strongly embryotoxic on the basis of their in vivo effects in animals and/or humans, were tested in four laboratories. The outcome showed that the EST can be considered to be a scientifically validated test, which is ready for consideration for use in assessing the embryotoxic potentials of chemicals for regulatory purposes.

Animal Testing Alternatives↗

Technical note: validation of internal control genes for gene expression analysis in bovine polymorphonuclear leukocytes.

Analysis of gene expression is becoming more important in all areas of biological research to evaluate gene expression during physiological and pathological conditions (e.g., mastitis), not the least in the field of animal research. Presently, real-time gene expression analysis is considered to be the method of choice for accurate and sensitive quantification of mRNA transcripts. Because comparison of gene expression levels is frequently the aim of these experiments, there is a critical need to validate internal control genes. When studying gene expression in bovine polymorphonuclear leukocytes, special attention should be paid to this validation, because polymorphonuclear leukocytes are subjected to numerous physiological influences, depending on the stage of lactation. In this study, 8 commonly used reference genes (ACT, GAPD, H2A, TBP, HPRT1, SDHA, YWHAZ, and 18S rRNA) were evaluated in bovine polymorphonuclear leukocytes. The transcription levels of 6 reference genes were determined using real-time PCR. By geometrically averaging the expression levels of these genes, SDHA, YWHAZ, and 18S rRNA were selected as being the most stable genes for accurate normalization of real-time results of bovine polymorphonuclear leukocytes.

Animals↗

Validation of the rat limb bud micromass test in the international ECVAM validation study on three in vitro embryotoxicity tests.

A detailed report is presented on the performance of the rat limb bud micromass (MM) test in a European Centre for the Evaluation of Alternative Methods (ECVAM)-sponsored formal validation study on three in vitro tests for embryotoxicity. Twenty coded test chemicals, classified as non-embryotoxic, weakly embryotoxic or strongly embryotoxic on the basis of their in vivo effects on animals and/or humans, were tested in four laboratories. The outcome showed that the MM test is an experimentally validated test, which holds promise for use for identifying strongly embryotoxic chemicals, but which needs to be improved before it can be recommended for use for regulatory purposes.

Animal Testing Alternatives↗

Uncertainty-based internal quality control. Harmonization considerations.

Three main quality aspects for analytical laboratories are internal method validation, internal quality control (IQC), and sample result uncertainty. Unfortunately, in the past they have been used in a nonharmonized way. The most universal IQC tool is the mean chart, but some criteria used to fix their control limits do not fit the real nature of analytical results. A new approach for fixing these limits is proposed (the u-approach). The key is the combined uncertainty, u, obtained from the method validation information, also used for estimating the sample result uncertainty. A comparative study on "in-control" simulated, bibliographic, and real laboratory data suggests that the u-approach is more reliable than other well-established criteria. In addition, the u-approach mean chart emerges as an IQC tool, consistent with chemical assays, which harmonizes the validation-control-uncertainty process.

Journal Article↗

A probabilistic model of intensive designs.

Without internal validity, experimental data are uninterpretable. With intensive designs, most methods presented to quantify a design's internal validity have been subject to criticism. A probabilistic model of intensive designs is presented that demonstrates the high degree of internal validity of these designs without relying on adaptations from traditional inferential statistics. Where the experimenter is able to conform to the restrictions of the model, the equations provide an estimation of internal validity for either reversal or multiple-baseline designs. More importantly, the model provides mathematical bases for some of the common recommendations and design considerations in intensive research (such as the desirability of within-subject replications and of four or more multiple baselines).

Journal Article↗

Validation of the Omron HEM-907 device for blood pressure measurement.

BACKGROUND: The aim of this study was to validate the Omron HEM-907 blood pressure (BP) measuring device according to the international validation protocol. DESIGN: The international validation protocol is divided into two phases: the first phase is performed on 15 selected subjects and if the device passes this phase, 18 more subjects are selected making a total number of 33 subjects on which the final validation is performed. METHODS: For each subject, BP measurements were performed simultaneously by two trained observers using mercury sphygmomanometers alternately with the Omron HEM-907 device. In all, 99 measurements were obtained for comparison. The difference between the BP value given by the device and that obtained by the two observers (mean of the two observers) was calculated for each measure. RESULTS: The difference between the two observers was -1 +/- 2 mmHg for the systolic BP (SBP) and for the diastolic BP (DBP). The Omron HEM-907 passed the first phase of the validation process. For the second phase, the average differences between the device and mercury sphygmomanometer readings were -1 +/- 7 and -5 +/- 6 mmHg for SBP and DBP respectively. Readings for the HEM-907 device differed by less than 5 mmHg for 61 of the systolic readings and 52 of the diastolic readings; by less than 10 mmHg for 85 of the systolic readings and 85 of the diastolic readings; and by less than 15 mmHg for 94 of the systolic readings and 96 of the diastolic readings. CONCLUSIONS: The Omron HEM-907 device passes the two phases of the international validation protocol.

Adult↗

Using discrete choice modelling in priority setting: an application to clinical service developments.

Limited resources for health care means that techniques are required to aid the process of priority setting. This paper represents one of the first attempts to use discrete choice modelling (DCM) within the area of priority setting. It is shown how the technique can be used to estimate cost per unit of benefit ratios for competing clinical service developments. Integer programming is proposed as a method to be used, alongside DCM, to help policy makers select the optimal combination of clinical service developments within a given budget. The technique is also shown to be internally valid and internally consistent. It is argued that DCM is a potentially useful technique to be used within the area of priority setting more generally. However, further work is required to address methodological issues around the technique.

Adult↗