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A randomized clinical trial of hospital-based, comprehensive cardiac rehabilitation versus usual care for patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease (the DANREHAB trial)--design, intervention, and population.

BACKGROUND: Current guidelines broadly recommend comprehensive cardiac rehabilitation (CR), although evidence for this is still limited. It is not known whether evidence from before 1995 is still valid. STUDY DESIGN: The DANish Cardiac ReHABilitation (DANREHAB) trial was designed as a centrally randomized clinical trial to clarify whether hospital-based comprehensive CR is superior to usual care for patients with congestive heart failure, ischemic heart disease, or high risk for ischemic heart disease. A combined primary outcome measure included total mortality, myocardial infarction, or readmissions due to heart disease based on linkage to public registries. The CR was an individually tailored, multidisciplinary program (6 weeks of intensive CR and 12 months of follow-up) including patient education, exercise training, dietary counseling, smoking cessation, psychosocial support, risk factor management, and clinical assessment. STUDY POPULATION: Of 5060 discharged patients, 1614 (32%) were eligible for the trial and 770 patients were randomized (47% of those eligible). Participants were younger (P < .001) and had less comorbidity than nonparticipants (P < .03). CONCLUSION: Our trial shows that a large-scale, centrally randomized clinical trial on comprehensive CR can be conducted among a broadly defined patient group, but reaching the stipulated number of 1800 patients was difficult. Although the study included relatively many women and older people, elderly patients and patients with high comorbidity were underrepresented, which may influence the external validity.

Adult↗

The validity of DSM-III-R hypochondriasis.

BACKGROUND: Because of the uncertainty about the status of hypochondriasis, the disorder is rarely diagnosed. To address this problem we examined the validity of DSM-III-R hypochondriasis as identified by structured interview. METHODS: Patients in a general medicine clinic were screened for hypochondriacal attitudes and symptoms. Those patients who scored above an established cutoff had a structured diagnostic interview, and 50 patients who met DSM-III-R criteria for hypochondriasis and 50 age- and sex-matched controls were thus identified. Information was obtained from both groups on health perceptions, health care utilization, and level of functioning using self-report and physician-rated measures. Additional information on diagnoses and treatment recommendations was obtained from record audits. RESULTS: Clinic physicians rated hypochondriacal subjects as having more unrealistic fear of illness (hypochondriasis) and diagnosed psychiatric and functional somatic syndromes more frequently in hypochondriacal than in control subjects. Hypochondriacal subjects viewed their health as worse, had more health worries, and had more severe psychiatric symptoms than control subjects. They also reported poorer physical functioning and work performance, greater health care utilization, poorer response to medical treatment, and less satisfaction with the care received than controls. CONCLUSIONS: Results show that, although the diagnosis of hypochondriasis is rarely made, physician recognition is high. They also show that several indicators of internal and external validity of this diagnostic category exist. Findings suggest that if physicians are to reduce the functional impairment and nonproductive health care utilization of these patients, they will need to make the diagnosis of hypochondriasis and intervene appropriately. However, for this to occur, research demonstrating predictive validity and treatment responsiveness of the disorder will be required.

Adult↗

Effectiveness of self-management training in type 2 diabetes: a systematic review of randomized controlled trials.

OBJECTIVE: To systematically review the effectiveness of self-management training in type 2 diabetes. RESEARCH DESIGN AND METHODS: MEDLINE, Educational Resources Information Center (ERIC), and Nursing and Allied Health databases were searched for English-language articles published between 1980 and 1999. Studies were original articles reporting the results of randomized controlled trials of the effectiveness of self-management training in people with type 2 diabetes. Relevant data on study design, population demographics, interventions, outcomes, methodological quality, and external validity were tabulated. Interventions were categorized based on educational focus (information, lifestyle behaviors, mechanical skills, and coping skills), and outcomes were classified as knowledge, attitudes, and self-care skills; lifestyle behaviors, psychological outcomes, and quality of life; glycemic control; cardiovascular disease risk factors; and economic measures and health service utilization. RESULTS: A total of 72 studies described in 84 articles were identified for this review. Positive effects of self-management training on knowledge, frequency and accuracy of self-monitoring of blood glucose, self-reported dietary habits, and glycemic control were demonstrated in studies with short follow-up (<6 months). Effects of interventions on lipids, physical activity, weight, and blood pressure were variable. With longer follow-up, interventions that used regular reinforcement throughout follow-up were sometimes effective in improving glycemic control. Educational interventions that involved patient collaboration may be more effective than didactic interventions in improving glycemic control, weight, and lipid profiles. No studies demonstrated the effectiveness of self-management training on cardiovascular disease-related events or mortality; no economic analyses included indirect costs; few studies examined health-care utilization. Performance, selection, attrition, and detection bias were common in studies reviewed, and external generalizability was often limited. CONCLUSIONS: Evidence supports the effectiveness of self-management training in type 2 diabetes, particularly in the short term. Further research is needed to assess the effectiveness of self-management interventions on sustained glycemic control, cardiovascular disease risk factors, and ultimately, microvascular and cardiovascular disease and quality of life.

Adaptation, Psychological↗

Development and validation of stroke risk equation for Hong Kong Chinese patients with type 2 diabetes: the Hong Kong Diabetes Registry.

OBJECTIVE: We sought to develop stroke risk equations for Chinese patients with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS: A total of 7,209 Hong Kong Chinese type 2 diabetic patients without a history of stroke at baseline were analyzed. The data were randomly and evenly divided into the training subsample and the test subsample. In the training subsample, stepwise Cox models were used to develop the risk equation. Validation of the U.K. Prospective Diabetes Study (UKPDS) stroke risk engine and the current stroke equation was performed in the test dataset. The life-table method was used to check calibration, and the area under the receiver operating characteristic curve (aROC) was used to check discrimination. RESULTS: A total of 372 patients developed incident stroke during a median of 5.37 years (interquartile range 2.88-7.78) of follow-up. Age, A1C, spot urine albumin-to-creatinine ratio (ACR), and history of coronary heart disease (CHD) were independent predictors. The performance of the UKPDS stroke engine was suboptimal in our cohort. The newly developed risk equation defined by these four predictors had adequate performance in the test subsample. The predicted stroke-free probability by the current equation was within the 95% CI of the observed probability. The aROC was 0.77 for predicting stroke within 5 years. The risk score was computed as follows: 0.0634 x age (years) + 0.0897 x A1C + 0.5314 x log(10) (ACR) (mg/mmol) + 0.5636 x history of CHD (1 if yes). The 5-year stroke probability can be calculated by: 1 - 0.9707(EXP (Risk Score - 4.5674)). CONCLUSIONS: Although the risk equation performed reasonably well in Chinese type 2 diabetic patients, external validation is required in other populations.

Asian People↗

The tissue-specific effects of glucose-lowering drug targets on aging mediated through DNA methylation: a multi-omics genetic study.

BACKGROUND: DNA methylation plays a key role in mediating the anti-aging effects of glucose-lowering drugs. This study aims to systematically explore the potential anti-aging effects of target genes of FDA-approved glucose-lowering drugs and the underlying epigenetic mediators. METHODS: We conducted a two-sample Mendelian randomization (MR) study to investigate the putative causal relationships between the gene expression levels of glucose-lowering drug targets and 10 aging-related phenotypes, followed by a two-step MR to estimate the mediation effect of DNA methylation. Drug candidates were selected according to the latest review of clinical drug use for type 2 diabetes, and their target genes were obtained from the DGIdb. Tissue-specific cis-expression quantitative trait loci (eQTLs) from GTEx Consortium were selected as genetic instruments to proxy the expression level of drug-target genes. Glycemic phenotypes were used as positive controls to validate the instruments. The cis- and trans-methylation QTLs of Cytosine-phosphate-Guanine sites near the drug target genes were obtained from GoDMC Consortium. Additionally, we performed enrichment analyses focused on tissue specificity and aging pathways to further corroborate our findings. RESULTS: We obtained 194 target genes interacting with 36 FDA-approved anti-diabetic drugs, of which the tissue-specific eQTLs were used to proxy the drug target effects. MR showed strong evidence that nine interacting genes of six glucose-lowering drugs showed anti-aging potential on one or more aging-related phenotypes mediated by DNA methylation: EHMT2, HSPA4, IGF2BP2, IRS1, LPL, NDUFAF1, NDUFS3, SLC22A3, and TCF7L2. These genes were distributed in 17 tissues, especially in the central nervous system, suggesting a potential neural component in their anti-aging effects. For instance, expression of EHMT2 in several brain basal ganglia regions, where the gene interacted with Tolazamide, showed a protective effect on frailty (odds ratio (OR) in caudate&#x2009;=&#x2009;1.02, 95%CI&#x2009;=&#x2009;1.01-1.04, FDR adjusted P&#x2009;=&#x2009;1.69&#x2009;&#xd7;&#x2009;10-2; OR in putamen&#x2009;=&#x2009;1.02, 95% CI&#x2009;=&#x2009;1.01-1.03, PFDR&#x2009;=&#x2009;3.37&#x2009;&#xd7;&#x2009;10-2, OR in nucleus accumbens&#x2009;=&#x2009;1.02, 95% CI&#x2009;=&#x2009;1.01-1.04, PFDR&#x2009;=&#x2009;3.37&#x2009;&#xd7;&#x2009;10-2). These associations were externally validated by searching literature evidence in existing EWAS and TWAS studies, as well as evidence from enrichment analyses. CONCLUSIONS: This study prioritizes nine glucose-lowering genes as anti-aging drug targets in specific tissues and prioritizes their epigenetic regulation through DNA methylation for future drug development.

DNA Methylation↗

Clinical trials for drugs against diabetic neuropathy: can we combine scientific needs with clinical practicalities?

Diabetic neuropathy is a chronic progressive disease accounting for considerable morbidity and reduced quality of life among patients with diabetes. Accumulating evidence suggests that the clinical and neurophysiological markers used to assess neuropathy not only predict the development of neuropathic foot ulceration, one of the most common causes for hospital admission and lower limb amputations, but are also predictors of increased mortality in diabetic patients. In addition to metabolic control, drug treatment of both incipient and clinically manifest diabetic neuropathy will be necessary for the years to come. Because 1-2% of the whole population in western societies may be affected, the search for effective drug treatment is not only a very important goal for the patient suffering from diabetic neuropathy and for the practicing physician, but also an economic task for both the health care systems and pharmaceutical companies. The validity of inferences about the clinical consequences of the use of any given agent to induce a specific pharmacologic effect will depend not only on the extent to which it affects the targeted biological phenomenon, but also on the extent to which all of the actions of the agent have been defined and the extent to which all affect the entire organism, alone and in concert. The ultimate test of the usefulness of a drug or device depends on the determination of outcomes, ideally in randomized clinical trials (RCTs) of sufficient scope and duration. The efficacy and safety of a variety of drugs based on the different pathogenetic hypotheses proposed have been evaluated in RCTs since the 1970s. However, the quality of RCTs published between 1981 and 1992 that evaluated the effects of medical treatment in diabetic polneuropathy was poor. Adequate designs for RCTs in diabetic neuropathy must consider the following criteria: type and stage of neuropathy, homogeneity of the study population, outcome measures (neurophysiological markers, intermediate clinical end points, ultimate clinical outcomes, quality of life), natural history, sample size, study duration, reproducibility of neurophysiological and intermediate end points, nonspecific effects of treatment, measures of treatment effect, the extent to which the overall trail result applies to individual patients (external validity), and the reporting of the RCTs. Trials focusing preferentially on patients with mild or moderate early stages of neuropathy over long periods of 3-5 years aimed at slowing or prevention, rather than reversal, using end point measures that have clinical and prognostic significance are most likely to produce meaningful results.

Animals↗

Derivation of clinical prediction rules to identify children with fractures after twisting injuries of the ankle.

OBJECTIVE: The authors sought to derive maximally sensitive prediction rules for identifying children with significant fractures after acute twisting injuries to the ankle. METHODS: The authors prospectively enrolled a convenience sample of patients younger than 18 years of age who presented to the pediatric emergency department of an urban, tertiary care center after sustaining acute twisting injuries of the ankle. The ankle was defined in two regions: the malleolar zone and the midfoot zone. Clinical findings were documented on standardized data collection sheets by faculty physicians before completion of ankle and/or foot radiograph series. Significant fracture was defined a priori as any fracture other than an avulsion < or =3 mm. The authors conducted binary recursive partitioning with cross-validation to develop models to predict fracture. RESULTS: Data from 717 enrolled patients with a median age of 12.9 years were analyzed. Significant malleolar zone and midfoot zone fractures were diagnosed in 81 of 682 (11.9%) and 10 of 173 (5.8%) patients for whom ankle and foot radiographs were obtained. Recursive partitioning identified patients at low risk for malleolar zone fracture if 1) they had no bone tenderness at either malleolus or the region just proximal to the fibula malleolus or 2) they had bone tenderness at either malleolus but were able to walk four steps in the emergency department and had no swelling at either malleolus. The two-part malleolar zone rule had a sensitivity of 100% and specificity of 19.1% on the learning data and 95.1% (95% confidence interval [95% CI] = 87.8% to 98.6%) and 20.0% (95% CI = 16.8% to 23.4%) on the test data. Tenderness either at the proximal fifth metatarsal or cuboid identified midfoot zone fractures with a sensitivity of 100% and specificity of 31.9% on the learning data and 90.0% (95% CI = 55.4% to 99.7%) and 35.0% (95% CI = 27.7% to 42.8%) on the test sample. CONCLUSIONS: A set of sensitive prediction rules was developed to identify children with significant fractures after twisting injuries to the ankle. External validation and refinement of the rules will be needed before recommendation of widespread use.

Adolescent↗

Validating the soft bipolar spectrum in the French National EPIDEP Study: the prominence of BP-II 1/2.

BACKGROUND: Much of the current literature on bipolar disorder is focused on bipolar I (BP-I), and to a much lesser extent on bipolar II (BP-II). The French multi-center national EPIDEP study has, among its objectives, the feasibility of validating a broader spectrum of bipolarity (the so-called "soft spectrum") by practicing clinicians. In this report we test aspects of a bipolar schema proposed earlier by Akiskal and Pinto [Akiskal, H.S., Pinto, O., 1999. The evolving bipolar spectrum: Prototypes I, II, III, IV. Psychiatr. Clin. North Am. 22: 517-534.]. METHODS: EPIDEP was scheduled in three phases: Phase 1 to recruit DSM-IV major depressives; Phase 2 to assess hypomania and affective temperaments; and Phase 3 to obtain history on course of illness, family history, and comorbidity. Comparative analyses are presented between affective subgroups constructed on a hierarchical basis: spontaneous hypomania (BP-II), cyclothymic temperament (BP-II 1/2), antidepressant-associated hypomania (BP-III), hyperthymic temperament (BP-IV), versus "strict unipolar" (UP). RESULTS: We present data on 490 patients for whom we obtained full assessment during all three phases of the study, classified as BP-II 1/2 (N=164), II (N=61), III (N=28), IV (N=22), as well as UP (N=174) as the reference nonbipolar group. Systematic inter-group comparison among the soft spectrum showed significant differences along clinical, descriptive, course, pharmacologic response and familial affective disorder patterns, which confirm the heterogeneity of the soft bipolar spectrum, with special characteristics for each of the subgroups. In terms of external validation, familial bipolar loading characterized all soft bipolar subgroups except type IV. LIMITATION: Data collection conducted in a practice setting, clinicians cannot be entirely held "blind" to all measures. This is an exploratory attempt, with many variables examined, to help characterize the clinical terrain of soft bipolarity. CONCLUSION: This is nonetheless the first systematic clinical attempt to validate the bipolar spectrum beyond mania (BP-I). BP-II 1/2, BP-III and BP-IV appeared distinct from BP-II and strict UP -- along most of the variables examined. BP-II 1/2 -- with early onset complex temperament structure, and high mood instability, rapid switching, irritable ("dark") hypomania and suicidality -- emerged as the most prevalent and severe expression of the bipolar spectrum, and accounting for 33% of all MDE. These results, which are of great public health relevance, testify to the cyclic nature of bipolarity in its softest expressions. The soft phenotypes are also of interest for genetic investigations of bipolar disorder.

Bipolar Disorder↗

Validity of a population-based cancer register in Sweden--an assessment of data reproducibility in the South-East Region Prostate Cancer Register.

BACKGROUND: With a population-based setting, high coverage and accurately recorded data, the validity of a register is guaranteed. The South-East Region Prostate Cancer relies on the National Cancer Register as a basic source of data, thereby ensuring a high coverage of the corresponding geographic area. To assess the reproducibility of the data recorded a random sample of the cases were reviewed a second time and compared to the original recording. MATERIAL AND METHODS: The South-East Region Prostate Cancer Register was started in 1987. In addition to the basic data acquired from the Swedish National Register, it also includes tumour stage, grade, treatment and, since 1992, PSA. In the first stage of quality assessment 10 cases for each of the years 1987-1996 from Linköping University Hospital were randomly selected for two independent recodings according to the same protocol as the original registration. In the second step 10 cases each for the same years from the remaining 8 hospitals in the region were selected for a single recoding. RESULTS: No systematic deviations were seen between the two independent recodings from Linköping, a single recoding was therefore considered sufficient for assessing the reproducibility of the data from the remaining hospitals in the region. The Kappa values for agreement between the original registration and the single recoding ranged from 0.589 to 0.869. CONCLUSION: The population-based setting and high coverage guarantees the external validity of the register. The internal validity is ensured by the high reproducibility shown in the present study.

Humans↗

Mortality in Emergency Department Sepsis (MEDS) score predicts 1-year mortality.

OBJECTIVE: To assess the predictive performance for 1-yr mortality of the previously derived and validated Mortality in Emergency Department Sepsis (MEDS) score. DESIGN: Prospective cohort study. PATIENTS: Consecutive adult (aged > or =18 yrs) emergency department patients presenting to an urban, tertiary care, university hospital were eligible if they had a clinically suspected infection as indicated by the decision to obtain a blood culture. The enrollment period was between February 1, 2000, and February 1, 2001. Of 3,926 eligible patient visits, 3,762 (96%) were enrolled and 3,102 unique first visits were analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 667 patients (21.5%) died within 1 yr. The unadjusted 1-yr mortality rates for the MEDS risk groups were: very low risk, 7%; low risk, 20%; moderate risk, 37%; high risk, 64%; very high risk, 80%. Using a Cox proportional hazard model that controlled for age, sex, and Charlson co-morbidity index, the 1-yr hazard ratios compared with the baseline very low-risk group were: low risk, 2.2 (1.7-2.9); moderate risk, 3.5 (2.7-4.6); high risk, 6.7 (4.9-9.3); and very high risk, 10.5 (7.2-15.4). The groups were significantly different (p < .0001). CONCLUSIONS: Although the score was initially derived for 28-day in-hospital mortality, our results indicate that the MEDS score also predicts patient survival at 1 yr after index hospital visit with suspected infection. The score needs external validation before widespread use.

Adult↗

Large-scale multi-omics enhance risk prediction for type 2 diabetes.

BACKGROUND: Polygenic risk scores (PRS), metabolomics, and proteomics have each shown promise in improving type 2 diabetes risk prediction, but their combined utility beyond established clinical models remains unclear. We aimed to evaluate whether integrating multi-omics biomarkers enhances 10-year type 2 diabetes risk prediction beyond single-omics extensions and the clinical Cambridge Diabetes Risk Score (CDRS), which includes HbA1c measurements. METHODS: We analysed data from 42,840 UK Biobank participants without diagnosed diabetes at baseline. The study population was split into a derivation set (Phase 1 metabolomics release, N&#x2009;=&#x2009;23,108) to fit models and an independent validation set (Phase 2 release, N&#x2009;=&#x2009;19,732) to evaluate performance. Data for a PRS for type 2 diabetes, 11 metabolites, and 15 proteins were added to the CDRS to develop multi-omics prediction models. Model performance was evaluated using Harrell's C-index and the net reclassification index (NRI). RESULTS: During 10 years of follow-up, 1090 participants developed incident type 2 diabetes. Among individual omics layers, proteomics contributed the greatest improvement in predictive performance, increasing the C-index from 0.862 (clinical CDRS) to 0.884 (&#x394;C-index; + 0.022; P&#x2009;<&#x2009;0.001), with a continuous NRI of 42.0%. The full multi-omics model further significantly increased the C-index compared to a model combining the clinical CDRS with proteomics data (C-index, 0.891; &#x394;C-index; + 0.007; P&#x2009;<&#x2009;0.001). CONCLUSION: Integrating proteomics, metabolomics, and a diabetes-PRS into a clinical model substantially improves type 2 diabetes risk prediction beyond single-omics extensions. Several of the selected proteins and metabolites are on cardiovascular disease pathways, highlighting the link between diabetes and cardiovascular risk. However, the C-index difference between the proteomics extended and full multi-omics extended models is small, and the clinical models extended with proteomics data would be easier to translate into routine care because it needs only the measurement of 15 proteins. External validation and cost-effectiveness analyses are needed to support clinical adoption.

Humans↗

A fetal alcohol syndrome screening tool.

The purpose of this study was to derive a multivariate, quantitative case definition of the fetal alcohol syndrome (FAS) facial phenotype from a dysmorphologist-derived gold standard and use it to develop an effective screening tool for identification of children at risk for FAS. The facial and physical features of a racially mixed group of children (0.2-10.0 years of age), evaluated by a single dysmorphologist in the University of Washington FAS Clinic, were used to determine which feature or set of features best differentiated between children with and without a diagnosis of FAS. The study population was divided into two groups balanced on gender, age at examination, race, diagnosis, and date of examination. Group 1 was used to identify the most differentiating feature(s), and group 2 was used to validate the differentiating capability of the feature(s). Group 1 included 97 children (20 with FAS and 77 without FAS). Group 2 included 97 children (19 with FAS and 78 without FAS). Discriminant analysis identified smooth philtrum, thin upper lip, and short palpebral fissures as the cluster of features that best differentiated children with and without FAS based on the discriminant function [D = 1.7953086 + 0.8116083 (thin upper lip) + 2.6411562 (smooth philtrum)-3.4073780 (% predicted right palpebral fissure length)]. Patients with a D-score > or = 1.5 were classified as at-risk for FAS (screen positive). Using this cut-off value for the D-score, children in group 1 were classified with 100% sensitivity (20 of 20 true positives) and 90.0% specificity (70 of 77 true negatives). The children in group 2 were classified with 100% sensitivity (19 of 19 true positives) and 87.3% specificity (68 of 78 true negatives). Across all 194 patients, sensitivity was 100% [95% confidence interval (97-100)] and specificity was 89% [95% confidence interval (85 to 93)]. Seventy-one percent (n = 12) of the 17 false-positives had a true classification of possible fetal alcohol effects. Sensitivity and specificity were unaffected by race, gender, and age through 10 years. The screening tool is effective at differentiating children with and without FAS as diagnosed by a single dysmorphologist (S.K.C) at the University of Washington FAS Clinic. Assessment of diagnostic interrater agreement between trained dysmorphologists and testing in other clinic populations will be needed to assess the tool's external validity.

Anthropometry↗

Evaluation and cultural adaptation of a German version of the AIMS2-SF questionnaire (German AIMS2-SF).

OBJECTIVES: The aim of the study was to examine the validity of a translated and culturally adapted version of the Arthritis Impact Measurement Scales 2, Short Form (AIMS2-SF) in patients suffering from osteoarthritis (OA) in primary care. METHODS: A structured procedure was used for the translation and cultural adaptation of the AIMS2-SF into German. The questionnaire was administered to 220 primary care patients with OA of the knee or hip. Test-retest reliability was tested in 35 randomly selected patients, who received the questionnaire a second time after 1 week. The physical scale of the original AIMS2-SF was divided into an 'upper body limitations' scale and a 'lower body limitations' scale. RESULTS: With values ranging from 0.52 to 0.97 for Pearson's r, item-scale correlations were reasonably good. The discriminative power of separate scales was also good, reflected in low values for correlation between different scales, indicating little redundancy. Only two items (13 and 15) referring to the symptom scale showed item-scale correlation of r = 0.72 and r = 0.67, respectively with the lower body limitation scale. The assessment of internal consistency reliability also revealed satisfactory values: Cronbach's alpha was > or =0.83 for all scales, except for the social interaction scale (0.66). The test-retest reliability, estimated as the intraclass correlation coefficient (ICC), exceeded 0.85 except for the affect scale (0.72). Substantial floor effects occurred in the upper limb scale (33.8%). Principal factor analysis confirmed the postulated three-factor structure with physical, physiological and social dimensions, explaining 49.8, 14.1 and 6.4% of the variation, respectively. The assessment of external validity revealed satisfactory correlations with the corresponding WOMAC (Western Ontario and McMaster Universities Arthrosis Index) scales. As expected, correlations with radiological grading were moderate to low. The correlation with the physician's assessment was high in the scales that were dominated by physical factors, but rather low in the areas of health, which were found to be dominated by psychological or social factors. CONCLUSION: The German AIMS2-SF is a reliable and valid instrument to assess the quality of life in primary care patients suffering from OA. When addressing the different impacts of OA, the physical scale should be divided into an upper body scale and a lower body scale. The floor and ceiling effects revealed are in accordance with the disease characteristics of the study sample and do not limit the significance of the questionnaire.

Adult↗

Identifying diagnostic studies in MEDLINE: reducing the number needed to read.

OBJECTIVES: The search filters in PubMed have become a cornerstone in information retrieval in evidence-based practice. However, the filter for diagnostic studies is not fully satisfactory, because sensitive searches have low precision. The objective of this study was to construct and validate better search strategies to identify diagnostic articles recorded on MEDLINE with special emphasis on precision. DESIGN: A comparative, retrospective analysis was conducted. Four medical journals were hand-searched for diagnostic studies published in 1989 and 1994. Four other journals were hand-searched for 1999. The three sets of studies identified were used as gold standards. A new search strategy was constructed and tested using the 1989-subset of studies and validated in both the 1994 and 1999 subsets. We identified candidate text words for search strategies using a word frequency analysis of the abstracts. According to the frequency of identified terms, searches were run for each term independently. The sensitivity, precision, and number needed to read (1/precision) of every candidate term were calculated. Terms with the highest sensitivity x precision product were used as free text terms in combination with the MeSH term "SENSITIVITY AND SPECIFICITY" using the Boolean operator OR. In the 1994 and 1999 subsets, we performed head-to-head comparisons of the currently available PubMed filter with the one we developed. MEASUREMENTS: The sensitivity, precision and the number needed to read (1/precision) were measured for different search filters. RESULTS: The most frequently occurring three truncated terms (diagnos*; predict* and accura*) in combination with the MeSH term "SENSITIVITY AND SPECIFICITY" produced a sensitivity of 98.1 percent (95% confidence interval: 89.9-99.9%) and a number needed to read of 8.3 (95% confidence interval: 6.7-11.3%). In direct comparisons of the new filter with the currently available one in PubMed using the 1994 and 1999 subsets, the new filter achieved better precision (12.0% versus 8.2% in 1994 and 5.0% versus 4.3% in 1999. The 95% confidence intervals for the differences range from 0.05% to 7.5% (p = 0.041) and -1.0% to 2.3% (p = 0.45), respectively). The new filter achieved slightly better sensitivities than the currently available one in both subsets, namely 98.1 and 96.1% (p = 0.32) versus 95.1 and 88.8% (p = 0.125). CONCLUSIONS: The quoted performance of the currently available filter for diagnostic studies in PubMed may be overstated. It appears that even single external validation may lead to over optimistic views of a filter's performance. Precision appears to be more unstable than sensitivity. In terms of sensitivity, our filter for diagnostic studies performed slightly better than the currently available one and it performed better with regards to precision in the 1994 subset. Additional research is required to determine whether these improvements are beneficial to searches in practice.

Diagnosis↗

Childhood maltreatment, posttraumatic stress symptomatology, and adolescent dating violence: considering the value of adolescent perceptions of abuse and a trauma mediational model.

The present study, utilizing both a child protective services and high school sample of midadolescents, examined the issue of self-report of maltreatment as it relates to issues of external validity (i.e., concordance with social worker ratings). reliability (i.e.. overlap with an alternate child maltreatment self-report inventory; association of a self-labeling item as "abused" with their subscale item counterparts), and construct validity (i.e., the association of maltreatment with posttraumatic stress symptomatology and dating violence). Relevant theoretical work in attachment, trauma, and relationship violence points to a mediational model, whereby the relationship between childhood maltreatment and adolescent dating violence would be expected to be accounted for by posttraumatic stress symptomatology. In the high school sample, 1329 adolescents and, in the CPS sample, 224 youth on the active caseloads completed comparable questionnaires in the three domains of interest. For females only, results supported a mediational model in the prediction of dating violence in both samples. For males, child maltreatment and trauma symptomatology added unique contributions to predicting dating violence. with no consistent pattern emerging across samples. When considering the issue of self-labeling as abused. CPS females who self-labeled had higher posttraumatic stress symptomatology and dating violence victimization scores than did their nonlabeling, maltreated counterparts for emotional maltreatment. These results point to the need for ongoing work in understanding the process of disclosure and how maltreatment experiences are consciously conceptualized.

Adolescent↗

Two rules for early prediction of bacteremia: testing in a university and a community hospital.

BACKGROUND: Two rules (model 1 and model 2) were previously derived and prospectively validated at the same institution to predict the likelihood of bacteremia. The objective of the present study was to test and compare the performance of the rules in patients admitted to two sites of inpatient care: a university hospital and a community hospital. METHODS: Clinical and laboratory data (including the variables contained in the two models) were collected within 24 hours in all patients admitted to the Department of Medicine of the Beilinson Medical Center, a university hospital in central Israel, and Emek Hospital, a community hospital in northern Israel, because of an acute infectious disease. The scores of the models were compared with the results of blood cultures. RESULTS: The percentage of bacteremia was 15% in the university and 18.5% in the community hospital. The area under the receiver-operating characteristic curve was 0.56 + or - 0.04 SE for model 1, and 0.67 + or - 0.04 SE for model 2 in the university hospital; and 0.59 + or - 0.05 SE versus 0.63 + or - 0.04 SE, respectively, in the community hospital. At the best calibration, model 1 defined low-risk groups of 205 patients in the university hospital, and 66 patients in the community hospital, with prevalences of bacteremia of 13% and 15%. The high-risk groups defined by model 1 had prevalences of 30% and 32%. Model 2 defined low-risk groups with prevalences of bacteremia of 7% (8 of 114) and 8% (6 of 76); and high-risk groups with percentages of 29% and 38%. CONCLUSIONS: The overall accuracy of the two models deteriorated significantly. Both models defined groups at high risk of bacteremia, but the percentages of bacteremia and of death in the low-risk groups do not encourage withholding blood cultures in these patients. The failure of the two models points toward the need for external validation, and for monitoring performance of prediction models over time.

Adolescent↗

Machine learning-based prediction of unplanned readmission and construction of an online calculator for elderly patients with mild ischemic stroke.

OBJECTIVE: To screen for independent risk factors for unplanned readmission in elderly patients with mild ischemic stroke, and to construct and validate an online risk prediction calculator based on an interpretable machine learning model, thereby providing a promising practical tool for accurate clinical assessment of 30&#x2011;day all&#x2011;cause unplanned readmission risk in this population. METHODS: A prospective cohort study was conducted, including 1050 patients aged&#xa0;&#x2265;&#xa0;60&#xa0;years with mild ischemic stroke admitted between August 2023 and September 2024. Participants were randomly divided into a training set (840 cases) and a test set (210 cases) at a ratio of 8:2. Risk factors were screened by univariate analysis and multivariable Logistic regression. Four machine learning models, namely LightGBM, XGBoost, Random Forest, and K&#x2011;Nearest Neighbors (KNN), were developed and their performance was evaluated using AUC, accuracy, sensitivity, and specificity as metrics. The SHAP framework was used for interpretability analysis, and an online calculator was subsequently developed based on the optimal model. RESULTS: Univariate analysis showed significant differences (P&#xa0;<&#xa0;0.05) in 13 factors including age, smoking, AIP, TyG index, HALP score, etc. Multivariable Logistic regression identified age (OR&#xa0;=&#xa0;9.752), smoking (OR&#xa0;=&#xa0;5.171), AIP (OR&#xa0;=&#xa0;6.691), TyG index (OR&#xa0;=&#xa0;4.393), HALP score (OR&#xa0;=&#xa0;2.831), and&#xa0;&#x2265;&#xa0;2 comorbidities (OR&#xa0;=&#xa0;3.664) as independent risk factors. All four machine learning models demonstrated good predictive performance. Based on a comprehensive evaluation of multiple metrics and computational efficiency, the LightGBM model exhibited the best predictive performance (AUC&#xa0;=&#xa0;0.884, accuracy&#xa0;=&#xa0;0.829, sensitivity&#xa0;=&#xa0;0.812, specificity&#xa0;=&#xa0;0.875). SHAP analysis showed that age, AIP, TyG index, smoking, and HALP score were key predictors. An online calculator developed based on this model enables individualized risk predictions. CONCLUSION: Key risk factors associated with 30&#x2011;day unplanned readmission in elderly patients with mild ischemic stroke were identified. The LightGBM model demonstrated high predictive accuracy, and together with the interpretability analysis and online calculator, offers a practical tool to support clinical risk assessment. However, this tool requires future external validation.

Humans↗

Memory evaluation in Alzheimer's disease. Caregivers' appraisals and objective testing.

OBJECTIVES: To evaluate if caregivers are reliable informants concerning memory deficits in patients with Alzheimer's disease (AD). DESIGN: Responses of caregivers of patients with probable AD and responses of healthy control subjects on a standardized memory questionnaire were compared with objective measures of cognition (Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery) and with clinical estimates of activities of daily living, depression, and psychopathology (Consortium to Establish a Registry for Alzheimer's Disease [CERAD] clinical assessment battery) using the Self-report Memory Questionnaire. SETTING: A federally funded AD research center. SUBJECTS: The referred sample included 117 patients with probable AD, their informants, and 41 healthy control subjects age-matched to the patients. Patients and control subjects were between the ages of 58 and 85 years, had between 9 and 19 years of education, and were in good health. EXCLUSIONS: Patients who did not meet NINCDS-ADRDA criteria of probable AD. MAIN OUTCOME MEASURE: The optimal number of questionnaire items yielding the best combination of sensitivity and specificity. RESULTS: An abbreviated version of the scale, renamed the Short-Memory Questionnaire, had excellent specificity and sensitivity for identifying dementia. Positive and negative predictive values were 63.5% and near 100%, respectively. The Short-Memory Questionnaire showed good reliability, internal consistency, and external validity. Caregiver appraisals of memory deficits significantly correlated with objective measures of memory and also with generalized cognitive dysfunction. CONCLUSIONS: Caregivers of patients with AD are reliable informants of their relatives' deficits. The Short-Memory Questionnaire is an easily administered, informant-based scale that may be useful in clinical settings or epidemiologic studies to screen out persons with memory difficulties.

Aged↗