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Referral bias among health workers in studies using hospitalization as a proxy measure of the underlying incidence rate.

Contacts with health services like hospitals or general practitioners are usually the only available proxy measure of incidence of disease in studies based on secondary data and differential referrals or care-seeking behavior often bias such proxy measures. In former analyses based on the Occupational Hospitalization Register in Denmark assisting nurses had high Standardized Hospitalization Ratios for many diseases. It was, however, suspected that it fully or partly was due to a referral bias or self-selection to hospital treatment rather than exposures to occupational hazards. The aim of the present study is to evaluate the referral bias hypothesis by comparing hospitalization and mortality data for health workers for a disease category with a high mortality. Cohorts of all gainfully employed 20- to 59-year-old Danes were formed in order to compare Standardized Mortality Ratios and Standardized Hospitalization Ratios of ischemic heart disease (IHD) in occupational groups. The follow-up period was 10 years. For most of the investigated occupational groups a similar disease pattern was found whether hospitalization or death was used as the outcome measure. In "nurse assistants" a statistically significant higher risk was, however, found using hospitalization due to IHD as the end point rather than mortality. Additional analysis did not support the hypothesis that the finding could be explained by differentiated hospitalization due to social factors. The true incidence rates of the disease need not be equally well described by proxy measures such as hospitalization diagnosis or death diagnosis in all occupational groups. Differential access to medical treatment in some groups may lead to bias when hospital data are used as proxy measures for the underlying incidence rates.

Bias↗

A comparison of proxy measures of abdominal obesity in Chinese, European and South Asian adults.

AIMS: To assess whether four proxy measures of abdominal obesity (waist circumference; waist-to-hip ratio (WHR); waist-to-height ratio and C index, a measure of body shape) were uniformly associated with features of the metabolic syndrome (triglycerides, high density lipoprotein (HDL) cholesterol, 2-h glucose) in three ethnic groups. METHODS: Anthropometric and biochemical data were collected in 629 Europeans (320 men, 309 women), 380 Chinese (183 men, 197 women) and 597 South Asians (275 men, 322 women) aged 25-64 years in Newcastle upon Tyne, UK. Linear regression models were used to determine whether relationships differed between ethnic groups. RESULTS: Linear regression analysis showed that most proxy measures of abdominal obesity were associated with features of the metabolic syndrome. There were significant interactions between WHR and ethnicity and C index and ethnicity in the relationship with log triglycerides when comparing European and Chinese women. Interactions existed between all proxy measures and ethnicity in the relationship with log triglycerides and HDL cholesterol when comparing European and South Asian women. In men, interactions between ethnicity and waist circumference, WHR and C index when comparing Europeans and South Asians, and between ethnicity and WHR and C index when comparing South Asian and Chinese for log 2-h glucose were significant (P < 0.001). All interactions remained significant when differences in smoking, alcohol and physical activity were taken into account. CONCLUSIONS: Not all the proxy measures of abdominal obesity were consistently related to features of the metabolic syndrome across the ethnic groups studied. However, waist circumference and waist to height ratio were the most consistent and WHR the least when comparing across the ethnic groups.

Abdomen↗

Effects of agricultural work and other proxy-derived case-control data on Parkinson's disease risk estimates.

This study examined the effects on Parkinson's disease risk estimates of exposure misclassification in proxy-derived data on agricultural work, pesticide use, rural living, well water drinking, head trauma, smoking, and family history of Parkinson's disease or essential tremor. The data were collected in 1989 as part of a population-based case-control study of Parkinson's disease in Calgary, Canada. Nondemented cases (n = 130) were selected from a case register of Calgary residents with neurologist-confirmed Parkinson's disease. For each case, two matched (sex and age +/- 2.5 years) community controls were selected by random digit dialing. Forty cases and 77 controls were randomly selected as index respondents. The cases, controls, and one proxy respondent (spouse or offspring) for each index respondent were interviewed using a structured questionnaire. The data were analyzed using conditional logistic regression. Incorporation of proxy-derived data for 30% of the cases or controls, or both, resulted in considerable misclassification of exposure for some variables and, in most cases, attenuation of the odds ratio. The results indicate that pooling dichotomously classified data derived in part from self- and proxy respondents may result in biased estimates of Parkinson's disease risk associated with agricultural, family history, and head trauma factors.

Agriculture↗

Patient- and proxy-reported utility in Alzheimer disease using the EuroQoL.

This study aims to compare patient- and proxy-rated utilities and health-related quality of life from individuals in different stages of Alzheimer disease (AD). Two hundred seventy-two patients and their primary caregivers were enrolled in a prospective observational study and underwent three consecutive interviews, 6 months apart. Average Mini-Mental State Examination (MMSE) scores were 19.3, 18.0, and 16.4 at the three interviews; scores ranged from 0 to 30. Using the EuroQoL EQ-5D instrument, patient-rated health utilities were on average 0.833 with little variation across MMSE-based severity levels. Proxy-rated health utilities were 0.69 (MMSE >25), 0.64 (MMSE 21-25), 0.50 (MMSE 15-20), 0.49 (MMSE 10-14), and 0.33 (MMSE <10). Proxy-rated utilities, as well as changes in utilities over time, were significantly related to MMSE scores and inversely related to scores on a brief version of the neuropsychiatric inventory (NPI) and institutionalization. Utilities were highly correlated with the disease-specific quality of life instrument QoL-AD. The study shows that the EuroQoL can be used to rate utilities in Alzheimer disease, but there are important differences between patient- and proxy-ratings.

Activities of Daily Living↗

Genetically Proxied Leukocyte Telomere Length and Epigenetic Age Acceleration in Relation to Healthspan: A Mendelian Randomization Study.

BACKGROUND: Leukocyte telomere length (LTL) and epigenetic age acceleration (EAA) are widely studied biomarkers of biological aging, but their potential roles in healthspan remain unclear. We evaluated whether genetically proxied LTL and EAA show evidence of potential effects on healthspan. METHODS: We conducted a two-sample Mendelian randomization study. Genetic instruments for LTL and four EAA biomarkers were obtained from published genome-wide association studies, including up to 472,174 individuals for LTL and approximately 35,000 individuals for each EAA biomarker. Summary statistics for healthspan, defined as age at first diagnosis of any of eight major chronic conditions or death, were derived from 300,447 unrelated European-ancestry participants in the UK Biobank. We used inverse-variance-weighted (IVW) models for the main analysis, with complementary MR estimators and sensitivity analyses to evaluate consistency, pleiotropy, instrument heterogeneity, and robustness. RESULTS: Genetically proxied longer LTL was associated with extended healthspan (IVW &#x3b2; = 0.106; 95% CI: 0.054-0.158; p = 6.9&#xa0;&#xd7;&#xa0;10-5). The association was robust across multiple sensitivity analyses. In contrast, the four genetically proxied EAA biomarkers did not show consistent MR evidence of an association with healthspan. CONCLUSIONS: These findings provide genetic evidence consistent with a potential role of LTL in healthspan, while providing little support for comparable associations involving the genetically proxied components of the evaluated EAA biomarkers. The findings do not exclude potential associations with environmentally or physiologically acquired EAA.

Mendelian randomization↗

Elder-proxy agreement concerning the functional status and medical history of the older person: the impact of caregiver burden and depressive symptomatology.

OBJECTIVES: To examine the influence of caregiver burden and depressive symptomatology on elder-proxy response concordance regarding the older person's functional status and medical history. DESIGN: Cross-sectional study via telephone interviews. SETTING: Community-dwelling older people and caregivers in North Carolina. PARTICIPANTS: 340 matched pairs of frail persons aged 65 and older and their respective caregivers. MEASUREMENTS: Multidimensional Functional Assessment: The OARS methodology RESULTS: Percent agreement on the ADL items ranged from 97.6% on personal hygiene to 99.7% for toileting, with moderate kappa coefficients. IADL percent agreement ranged from 71.5 to 93.7%, with fair to moderate kappa coefficients. Agreement among the medical history items ranged from 76.3 to 98.5% (kappa = .138-.831). Response bias for the IADL composite measure is influenced marginally by caregiver burden (F[259] = 1.751, P = .098). Five of the individual IADL bias items are influenced significantly by burden, such that an increase in burden results in a greater likelihood that the caregiver will overstate disability compared with the rating by the older person. Response bias on the ADL scale was increased among persons who experienced more caregiver burden (OR = 1.096, 95% CI = 1.000, 1.192) and those who spent more hours providing care (OR = 1.012, 95% CI = 1.001, 1.024). Additionally, black caregivers were more likely than white caregivers to disagree with the older people on the ADL scale (OR = 2.73, 95% CI = 1.642, 3.809). A composite of the medical history items is influenced by the relationship of the caregiver to the older person; bias is more likely among adult children ((F[227] = 1.56, P = .081). CONCLUSION: Elder-proxy concordance is highest among ADL items, followed by medical history items and IADL items. Caregiver depressive symptomotology had no significant impact on elder-proxy response concordance on any of the three outcomes of interest: IADL and medical history bias and ADL disagreement. However, caregiver burden was marginally predictive of bias on the total ADL and IADL scales. Additionally, increased burden was significantly predictive of bias on five of the seven individual items of the IADL scale, suggesting that the more burden a caregiver feels, the greater likelihood that s/he will overstate the older person's disability compared with self-report. These findings suggest that clinicians and researchers who use proxy reports to determine treatment regimens and complete data collection efforts may do so with confidence on ADL individual items and medical history items when the older person's frailty is marginal. However, caregiver burden may result in misleading representation of the older person's functional status, specifically in regard to IADL items.

Activities of Daily Living↗

Genetically Proxied Inhibition of Cholesterol-Lowering Drug Targets and Survival in HPV-Positive and Non-HPV-Driven Head and Neck Cancer: A Multicentre MR Study.

BACKGROUND: Cholesterol pathways may influence head and neck squamous cell carcinoma (HNSCC) progression, but evidence on prognosis is inconsistent. We used Mendelian randomization (MR) to test whether genetically proxied inhibition of major low-density lipoprotein cholesterol (LDL-C)-lowering drug targets and circulating lipid traits affects overall survival (OS) in HPV-positive and non-HPV-driven HNSCCs. METHODS: We proxied lifelong LDL-C lowering using 55 cis-acting single-nucleotide polymorphisms in HMGCR, NPC1L1, PCSK9, and LDL-receptor (LDLR) from the updated 2021 Global Lipids Genetics Consortium and instrumented circulating lipid traits. Two-sample MR estimated effects on OS in 4,869 multicentre HNSCC cases (1,291 HPV-positive; 3,578 non-HPV-driven) using minimally adjusted Cox models. Sensitivity analyses additionally adjusted for tumor stage and treatment, assessed collider bias using an external HNSCC incidence genome-wide association study, and examined between-center heterogeneity and colocalization. RESULTS: Using the updated Global Lipids Genetic Consortium 2021 instruments, genetically proxied HMGCR inhibition showed a directionally protective but nonsignificant association with OS in HPV-positive oropharyngeal HNSCC in the primary analysis [inverse variance weighted (IVW) HR = 0.19; 95% confidence interval (CI), 0.03-1.18; P = 0.08], with directionally concordant weighted median results. No corresponding protective association was observed for HMGCR in non-HPV-driven disease (IVW HR = 1.68; 95% CI, 0.78-3.63; P = 0.19). No clear evidence of association was observed for NPC1L1, PCSK9, LDLR, or circulating lipid traits in either HPV stratum. Colocalization did not support a shared causal variant. CONCLUSIONS: These analyses provide suggestive evidence that genetically proxied HMGCR inhibition may influence survival in HPV-positive oropharyngeal HNSCC. IMPACT: HMGCR-related pathways may be relevant to prognosis in HPV-positive oropharyngeal HNSCC, whereas clear survival effects of other cholesterol-lowering targets were not supported.

Humans↗

Do proxy evaluations of health status predict mortality?

The ability of self-evaluations of health to predict mortality remains despite efforts to explain their contribution. To further the understanding of global evaluations, this study investigated whether proxy evaluations of health status also predict mortality. Data from the Longitudinal Study of Aging were used. For men and women, the unadjusted odds ratios for proxy evaluations exhibited a monotone relationship to 3-year and 7-year mortality rates and were predictive of 7-year mortality. This monotone relationship remained even after controlling for other factors when predicting 7-year mortality rates. However, only the fair and poor evaluations were significant, and only for men. The adjusted relationship when predicting 3-year mortality was not completely monotone, although good and poor proxy evaluations were significant. This suggests that proxy evaluations are useful, and that there are aspects of health status that are currently unmeasured but that should lend themselves to being quantified.

Activities of Daily Living↗

Response comparability of family and staff proxies for nursing home residents.

Response comparability on a wide variety of factual and judgmental information regarding nursing home residents was assessed for two proxy groups: family and staff. Family proxies had the most information. Family and staff proxies are not interchangeable. A general lack of response comparability suggests that proxies for nursing home residents should be selected in relation to the type of data needed and the time period of interest.

Activities of Daily Living↗

Using aggregate geographic data to proxy individual socioeconomic status: does size matter?

OBJECTIVES: This study assessed whether aggregate-level measures of socioeconomic status (SES) are less biased as proxies for individual-level measures if the unit of geographic aggregation is small in size and population. METHODS: National Health Interview Survey and census data were used to replicate analyses that identified the degree to which aggregate proxies of individual SES bias interpretations of the effects of SES on health. RESULTS: Ordinary least squares regressions on self-perceived health showed that the coefficients for income and education measured at the tract and block group levels were larger than those at the individual level but smaller than those estimated by Geronimus et al. at the zip code level. CONCLUSIONS: Researchers should be cautious about use of proxy measurement of individual SES even if proxies are calculated from small geographic units.

Data Collection↗

[Religiosity and mood in the last week of life: an explorative approach based on after-death proxy-interviews].

The current contribution focuses on the role of religiousness on aspects of mood in the last week of life. After-death interviews with proxy respondents of deceased participants of the Longitudinal Aging Study Amsterdam provided information on depressive mood and anxiety in the last week of life, as well as on a sense of peace with the approaching end of life. Furthermore, the proxy respondents were asked about serious physical symptoms in the last week of life, cognitive decline, salience of religion, and whether the deceased respondent had talked about religion. Other characteristics were derived from the last interviews with the respondents when still alive: depressive symptoms, religious affiliation, church-attendance, orthodoxy, salience of religion, and cosmic transcendence. None of the characteristics of religiousness were significantly associated with depressive mood or anxiety as estimated by the proxy-respondent. A sense of peace, however, was predicted by higher church-attendance, Protestant affiliation (as compared to no affiliation), and the proxy's estimate of the salience of religion. It is concluded that religiousness does not affect depressive mood or anxiety in the last week of life in the current sample. Possibly, religiousness supports a sense of peace, which may be a more existential facet of mood, and which is discussed as relevant in the last phase of life and in palliative care.

Adaptation, Psychological↗

Münchausen syndrome by proxy and sleep disorders medicine.

Münchausen syndrome by proxy is a factitious disorder of childhood in which a parent fabricates medical history or produces signs of illness in a child to keep the child in a sick role. Since approximately half of all cases of Münchausen syndrome by proxy are presentations of central nervous system illness, such as excessive daytime sleepiness and near-miss sudden infant death syndrome, sleep disorders centers are likely diagnostic consultants for the evaluation of children involved in this disorder. We review characteristics that may suggest that a particular case has an increased likelihood of Münchausen syndrome by proxy. The recent presentations of two cases of Münchausen syndrome by proxy to sleep disorders centers are discussed as examples.

Child Abuse↗

Use of proxies to measure health and functional outcomes in effectiveness research in persons with Alzheimer disease and related disorders.

As the focus in the study of Alzheimer disease moves from the laboratory and research-oriented care setting to the broader array of community settings where effectiveness research takes place, it becomes necessary to rely less on medical records and reports of health care professionals experienced in following research protocols and more on observers who are not trained to interpret and report their observations in a standardized way. The present paper targets the use of proxy interviews to obtain information about health and functional outcomes for effectiveness research. Included are indications of the type of information that may be obtained from proxies, a discussion of issues surrounding the use of proxies in research on older persons with cognitive impairment, a summary of the current state of knowledge in this area, identification of practical strategies researchers may employ when using proxies, and recommended directions for further research.

Aged↗

Validity of self-reports and reliability of spousal proxy reports on the smoking behavior of Chinese parents with young children.

This study aims to examine the validity of self-reports and reliability of spousal proxy reports of smoking behavior among Chinese parents with young children. Agreement of self-reported smoking status with expired CO concentration among parents in the intake interview was significant with kappa at 0.70. Agreement of the mothers' and fathers' proxy reports on their spouses' smoking status and cigarette consumption by ICC were 1.0 and 0.58, and 0.82 and 0.33, respectively. Self-report and proxy reports of smoking status are considered valid and reliable to assess smoking behavior of parents with young children in Hong Kong.

Adult↗

Symptom distress and quality-of-life assessment at the end of life: the role of proxy response.

This study sought to advance understanding of the relationships among proxy and patient reports of symptom distress and quality of life (QOL). English-speaking adults (n=86), their nurses (n=86), and family caregivers (n=49) from 11 hospice/palliative care organizations completed the Memorial Symptom Assessment Scale (MSAS) and McGill Quality of Life Questionnaire (MQOL) at hospice/palliative care enrollment, at 1 week, 2 weeks, then monthly until death or discharge. Patients and proxies provided similar average reports of symptom distress, both physical and psychological, but MSAS correlations were generally poor. MQOL correlations were higher for nurse-patient than for patient-caregiver dyads. Based on small differences between ratings but only moderate levels of correlation, proxy response appears to be a fair substitute for patient response, suggesting that symptom and QOL reports should be obtained from all available respondents throughout the course of clinical care or research in the hospice/palliative care setting.

Caregivers↗

Munchausen Syndrome by Proxy: medical diagnostic criteria.

Medical diagnostic criteria for Munchausen Syndrome by Proxy are presented. The strength of the known facts may vary from case to case, and thus there may be different degrees of diagnostic conviction. Therefore, diagnostic criteria for a definitive diagnosis, and a possible diagnosis of Munchausen Syndrome by Proxy are provided. Because the gathering of evidence in a case may, ultimately, diminish or exclude the diagnosis of Munchausen Syndrome by Proxy, diagnostic criteria for the inconclusive determination and the definitely excluded diagnosis are also enunciated.

Child↗

Measuring agreement between patient and proxy responses to multidimensional health-related quality-of-life measures in clinical trials. An application of psychometric profile analysis.

When patients cannot provide responses to health-related quality-of-life (HRQOL) measures in clinical trials, family or friends may be asked to respond. We present a simple, comprehensive method for assessing agreement between patients with head injury and their proxy responders. In contrast to more traditional approaches, this method defines agreement separately for each patient-proxy pair, and compares HRQOL profiles along three dimensions-level, or the average of the ratings; scatter, or the variability in the ratings; and shape, or the ranks of the ratings. We demonstrate this method in the context of a clinical trial of a treatment for traumatic head injury and compare the results to those obtained using traditional analyses. Options for incorporating proxy responses into clinical trial analyses are discussed.

Activities of Daily Living↗

Munchausen syndrome by proxy unmasked by nasal signs.

The protean manifestations of child abuse continue to cause diagnostic difficulty. Recent observations of the high mortality in victims of Munchausen syndrome by proxy, and their siblings, reinforce the need for early diagnosis and appropriate intervention. We report the nasal manifestations which unmasked Munchausen syndrome by proxy in an infant who presented with intestinal and peri-orifical signs masquerading as Crohn's disease. The possibility of Munchausen syndrome by proxy should be considered in an infant with persistent nasal excoriation presenting as part of an undiagnosed illness.

Adult↗