Population-based Reference Values Research Articles

Telemedicine-assisted exercise program (TAEP) for coronary heart disease

Introduction & Purpose Cardiovascular diseases (CVD) are a common cause of declining physical performance and quality of life. Despite the recommendation of physical activity as class 1A in the American Heart Association’s guidelines for cardiac rehabilitation (Pelliccia et al., 2021) and the clear need for innovative rehabilitation programs, no tele-medical exercise program has been adopted into standard care (Scherrenberg et al., 2021; Snoswell et al., 2020). Classic CVD exercise therapy typically includes group ergometer and strength training. The primary aim of this project was to integrate exercise as a pillar of therapy in the HerzMobil Tirol project, leading to the implementation of a telemedicine-assisted exercise program. Methods Patients enrolled in the CHD project had the opportunity to participate in TAEP. The initial and final therapeutic examinations included a medical history interview, the 1-minute sit-to-stand test (STS; Strassmann et al., 2013) and standardized EQ-5D-5L to assess the quality of life. Based on the guidelines and the classic CVD therapy the TAEP participants completed a twelve-week home-based exercise program. It included endurance training (5 days/week for 30 minutes) and video-guided strength, mobility and coordination training (2-3 times/week), where the focus was on strength training. The program was analysed and adapted individually by an exercise therapist. The intensity was controlled using the Borg scale and the talk test (Bok et al., 2022). Results 22 patients completed the TAEP, 77% (n = 17) were male and 23% (n = 5) were female and the median age was 61 (53-71) years. During the twelve weeks, the patients completed a median of 257 (213-351) minutes per week of endurance-oriented exercise training (e.g. walking or cycling) and performed video-guided home-based strength training with a median of twice (1-2) per week. 95% of patients fulfilled the recommendations for endurance training and 64% for strength training. The TAEP participants showed a significant (p < 0.001) increase in STS with a median of 37% (18-24). There was a significant improvement in quality of life according to the EQ-5D-5L health scale with a median from 70 (60-85) to 83 (79-95; p < 0.001). Discussion The current literature on cardiovascular diseases and exercise as therapy continues to underline the importance of physical activity for the prevention and treatment of these conditions. Studies indicate that regular exercise can reduce the risk of cardiovascular diseases and serves as an effective complement to pharmacological therapy. The results of the present project show that the integration of exercise therapy into a telemedical care program is feasible and effective. However, the lack of a control group and the small sample size made it difficult to compare the results directly and if the observed changes are actually attributable to the TAEP. Conclusion In our programme, we have learned that (1) a doctor’s recommendation for exercise therapy and (2) personal contact between the exercise therapist and the patient are key to patients’ adherence to exercise therapy. The TAEP was well received by the patients and feasible irrespective of the patients’ age. In the age of digitalisation, telemedicine-supported training therapy is an option in cardiac rehabilitation, even for people in remote catchment areas. References Bok, D., Rakovac, M., & Foster, C. (2022). An examination and critique of subjective methods to determine exercise intensity: The talk test, feeling scale, and rating of perceived exertion. Sports Medicine, 52(9), 2085–2109. https://doi.org/10.1007/s40279-022-01690-3 Pelliccia, A., Sharma, S., Gati, S., Bäck, M., Börjesson, M., Caselli, S., Collet, J.-P., Corrado, D., Drezner, J. A., Halle, M., Hansen, D., Heidbuchel, H., Myers, J., Niebauer, J., Papadakis, M., Piepoli, M. F., Prescott, E., Roos-Hesselink, J. W., Graham Stuart, A., … Rakhit, D. (2021). 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. European Heart Journal, 42(1), 17–96. https://doi.org/10.1093/eurheartj/ehaa605 Scherrenberg, M., Wilhelm, M., Hansen, D., Völler, H., Cornelissen, V., Frederix, I., Kemps, H., & Dendale, P. (2021). The future is now: A call for action for cardiac telerehabilitation in the COVID-19 pandemic from the secondary prevention and rehabilitation section of the European Association of Preventive Cardiology. European Journal of Preventive Cardiology, 28(5), 524–540. https://doi.org/10.1177/2047487320939671 Strassmann, A., Steurer-Stey, C., Lana, K. D., Zoller, M., Turk, A. J., Suter, P., & Puhan, M. (2013). Population-based reference values for the 1-min sit-to-stand test. International Journal of Public Health, 58(6), 949–953. https://doi.org/10.1007/s00038-013-0504-z Snoswell, C. L., Taylor, M. L., Comans, T. A., Smith, A. C., Gray, L. C., & Caffery, L. J. (2020). Determining if telehealth can reduce health system costs: Scoping review. Journal of Medical Internet Research, 22(10), Article e17298. https://doi.org/10.2196/17298

Population-based reference values for kidney function and kidney function decline in 25- to 95-year-old Germans without and with diabetes

Understanding normal aging of kidney function is pivotal to help distinguish individuals at particular risk for chronic kidney disease. Glomerular filtration rate (GFR) is typically estimated via serum creatinine (eGFRcrea) or cystatin C (eGFRcys). Since population-based age-group-specific reference values for eGFR and eGFR-decline are scarce, we aimed to provide such reference values from population-based data of a wide age range. In four German population-based cohorts (KORA-3, KORA-4, AugUR, DIACORE), participants underwent medical exams, interview, and blood draw up to five times within up to 25 years. We analyzed eGFRcrea and eGFRcys cross-sectionally and longitudinally (12,000 individuals, age 25-95 years). Cross-sectionally, we found age-group-specific eGFRcrea to decrease approximately linearly across the full age range, for eGFRcys up to the age of 60 years. Within age-groups, there was little difference by sex or diabetes status. Longitudinally, linear mixed models estimated an annual eGFRcrea decline of -0.80 [95% confidence interval -0.82, -0.77], -0.79 [-0.83, -0.76], and -1.20 mL/min/1.73m2 [-1.33, -1.08] for the general population, “healthy” individuals, or individuals with diabetes, respectively. Reference values for eGFR using cross-sectional data were shown as percentile curves for “healthy” individuals and for individuals with diabetes. Reference values for eGFR-decline using longitudinal data were presented as 95% prediction intervals for “healthy” individuals and for individuals with diabetes, obesity, and/or albuminuria. Thus, our results can help clinicians to judge eGFR values in individuals seen in clinical practice according to their age and to understand the expected range of annual eGFR-decline based on their risk profile.

Outcomes >30 Years After Initial Nonoperative Treatment of Anterior Cruciate Ligament Injuries

Background: It is unclear how anterior cruciate ligament (ACL) reconstruction (ACLR) affects the development of osteoarthritis (OA). This uncertainty is partly caused by the lack of long-term studies on ACL injuries treated primarily without reconstruction and the underreporting of symptomatic OA. Purpose: To determine (1) the knee function, symptoms, and activity level, as well as the presence of radiographic and symptomatic OA; (2) how these clinical outcomes have changed over time; and (3) the frequency of subsequent knee surgeries after the index ACL injury in a cohort of patients with ACL injuries treated primarily without reconstruction. Study Design: Case series; Level of evidence, 4. Methods: A total of 100 patients underwent initial nonoperative treatment >30 years ago (mean, 33.2 ± 1.4 years). Of these, 81 patients (mean age, 59 ± 8 years) completed the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Scoring Scale, and Tegner Activity Scale. Seventy-three patients underwent radiography to evaluate tibiofemoral and patellofemoral OA in the ACL-injured knee. Patients only underwent late ACLR if they experienced insufficient knee stability. Results: At 33 years after the ACL injury, the KOOS Activities of Daily Living subscore was better than population-based reference values, but scores were similar for the remaining KOOS subscales. Furthermore, 65% of patients had a good or excellent Lysholm score (≥84 points). The Tegner score decreased 4 points from before the injury to 33-year follow-up (P < .001). Most patients (75%) had evidence of radiographic tibiofemoral and/or patellofemoral OA, but only 38% were classified as having symptomatic OA (defined as radiographic OA in combination with a symptomatic knee according to cutoffs on the KOOS). Approximately 50% underwent meniscal surgery, and 29% subsequently underwent ACLR for recurrent instability. There were 2 patients who underwent total knee replacement. Conclusion: Despite a high prevalence of radiographic OA, patients achieved acceptable subjective knee function and had a relatively low prevalence of symptomatic OA at >30 years after an ACL injury when an initial nonoperative treatment strategy was employed.

Plasma lipids in Pseudoxanthoma Elasticum (PXE) patients: A comparative study with population-based reference values and Non-PXE controls

Background and aims– Pseudoxanthoma elasticum (PXE) is a rare genetic disease caused by pathogenic mutations in the ABCC6 gene, resulting in low values of inorganic pyrophosphate (PPi). While low PPi is thought to contribute to arterial calcification, it remains unclear whether this fully explains premature calcification in PXE. It has been hypothesized that the ABCC6 gene could be related to dyslipidemia, which could contribute to vascular calcification seen in PXE. The aim of this study is to evaluate the relation between PXE and plasma lipid concentrations in a large cohort of PXE patients compared with reference values for the general population and compared with non-PXE controls. Methods– The plasma concentrations of total cholesterol, HDL-cholesterol, tiglycerides, and LDL-cholesterol of 312 PXE patients were compared to age- and sex-matched modeled data of the general Dutch population. Differences in median lipid levels were compared with Mann-Whitney-U test. Secondly, plasma lipid concentrations of 44 PXE patients were compared to 44 not-genetically related relatives (spouses or friends), with linear models adjusted for age, sex and BMI. Results– Total cholesterol in PXE patients was 5.6 [IQR 4.6–6.4] mmol/L versus 5.3 [IQR 4.7–6.0] mmol/L (p < 0.01) in the general population; triglycerides were 1.1 [IQR 0.9–1.7] mmol/L versus 1.0 [0.7–1.4] mmol/L (p < 0.01); HDL-c was 1.4 [IQR 1.2–1.7] mmol/L versus 1.5 [IQR 1.2–1.8] mmol/L (p = 0.03) and LDL-c was 3.3 [IQR 2.7–4.1] mmol/L versus 3.2 [IQR 2.7–3.8] mmol/L (p = 0.01). In the patient control analysis with 44 pairs and age, sex and BMI adjusted, comparison with the non-PXE controls only triglycerides were significantly different (mean difference: 0.38 (0.13–0.63)). Conclusion–The lipid profiles of PXE patients are marginally different from the general population or compared to a matched control group, but the differences are unlikely to be clinically relevant. It is therefore unlikely that plasma lipids contribute to the premature vascular calcifications in PXE patients.

Heart rate-corrected systolic ejection time: population-based reference values and differential prognostic utility in acute heart failure.

Systolic ejection time (SET) is discussed as a treatment target in patients with heart failure (HF) and a reduced left ventricular (LV) ejection fraction (EF). We derived reference values for SET correcting for its dependence on heart rate (SETc), and explored its prognostic utility in patients admitted with decompensated HF. SETc was derived in 4836 participants of the population-based STAAB study (mean age 55 ± 12 years, 52% women). There, mean SETc was 328 ± 18 ms, increased with age (+4.7 ms per decade), was shorter in men than women (-14.9 ms), and correlated with arterial elastance (r = 0.30; all P < 0.001). In 134 patients hospitalized with acute HF, SETc at admission was shorter when compared with the general population and differed between patients with HF with reduced EF (HFrEF; LVEF ≤40%; 269 ± 35 ms), HF with mildly reduced EF (HFmrEF; LVEF 41-49%; 294 ± 27 ms), and HF with preserved EF (HFpEF; LVEF ≥50%; 317 ± 35 ms; P < 0.001). In proportional hazard regression, an in-hospital increase in SETc was associated with an age- and sex-adjusted hazard ratio of 0.38 (95% confidence interval 0.18-0.79) in patients with HFrEF, but a hazard ratio of 2.39 (95% confidence interval 1.24-4.64) in patients with HFpEF. In the general population, SETc increased with age and an elevated afterload. SETc was mildly reduced in patients hospitalized with HFpEF, but markedly reduced in patients with HFrEF. In-hospital prolongation of SETc predicted a favourable outcome in HFrEF, but an adverse outcome in HFpEF. Our results support the concept of a U-shaped relationship between cardiac systolic function and risk, providing a rationale for a more individualized treatment approach in patients with HF.

A revised concept for deriving reference values for internal exposures to chemical substances and its application to population-representative biomonitoring data in German children and adolescents 2014–2017 (GerES V)

HBM reference values, in contrast to toxicologically derived values, are statistically derived values that provide information on the exposure of the population. The exceedance frequency (if applicable for individual population groups) is often a first assessment standard for the local exposure situation for municipalities. More than 25 years have passed since the German Human Biomonitoring Commission (HBMC) formulated the first recommendations for the derivation of population-based reference values (HBM reference values, RV95) for substance concentrations based on HBM studies. A fundamental revision is timely, for several reasons. There have been considerable advances in relevant statistical methods, which meant that previously time-consuming and inaccessible procedures and calculations are now widely available. Furthermore, not all steps for the derivation of HBM reference values were clearly elaborated in the first recommendations. With this revision we intended to achieve a rigorous standardization of the entire process of deriving HBM reference values, also to realise a higher degree of transparency.In accordance with established international practice, it is recommended to use the 95th percentile of the reference distribution as the HBM reference value. To this end, the empirical 95th percentile of a suitable sample should be rounded, ensuring that the rounded value is within the two-sided 95% confidence interval of the percentile. All estimates should be based on distribution-free methods, and the confidence interval should be estimated using a bootstrap approach, if possible, according to the BCa (“bias-corrected and accelerated bootstrap”). A minimum sample size of 80 observations is considered necessary. The entire procedure ensures that the derived HBM reference value is robust against at least two extreme values and can also be used for underlying mixed distributions.If it is known in advance that certain subgroups (different age groups, smokers, etc.) show differing internal exposures, it is recommended that group-specific HBM reference values should be derived. Especially when the sample sizes for individual subgroups are too small, individual datasets with potential outliers can be excluded in advance to homogenize the reference value population.In the second part, new HBM reference values based on data of the German Environmental Survey for Children and Adolescents (GerES V, 2014–2017) were derived in accordance with the revised recommendations. The GerES V is the most recent population-representative monitoring of human exposure to pollutants in Germany on children and adolescents aged 3–17 years (N = 2294). RV95 for GerES V are reported for four subgroups (males/females and 3–11/12-17 years) for 108 different substances including phthalates and alternative plasticisers, metals, organochlorine pesticides, polychlorinated biphenyls (PCB), per- and polyfluoroalkyl substances (PFAS), parabens, aprotic solvents, chlorophenols, polycyclic aromatic hydrocarbons (PAH) and UV filter, in total 135 biomarkers. Algorithms implemented in R were used for the statistics and the determination of the HBM reference values. To facilitate a quality control of the study data, the corresponding R source code is given, together with graphical representations of results.The HBM reference values listed in this article replace earlier RV95 values derived by the HBMC for children and adolescents from data of precedent GerES studies (e.g. published in Apel et al., 2017).

National population-based reference data for the Hip Disability and Osteoarthritis Outcome Score (HOOS).

Interpretation of patient-reported outcome scores such as the Hip Disability and Osteoarthritis Outcome Score (HOOS) can be improved with use of reference values. The aim of the study was to establish population-based reference values for the HOOS' five subscales and its short-form HOOS-12. A representative sample of 9997 Danish citizens 18years and older were identified. The population record-based sample was based on seven predefined age groups and an equal sex distribution within each age group. A national secure electronic system was used to send the HOOS questionnaire and one supplementary question regarding previous hip complaints to all participants. 2277 participants completed the HOOS, 947 women (42%) and 1330 men (58%). The mean HOOS subscale scores were: pain 86.9 (95% CI 86.1-87.7), symptoms 83.7 (95% CI 82.9-84.5), ADL 88.2 (95% CI 87.5-89.0), sport and recreation function 83.1 (95% CI 82.0-84.1), QOL 82.7 (95% CI 81.8-83.6). The youngest age group reported better mean scores in four subscales compared to the oldest age group (pain 91.7 vs. 84.5, mean difference 7.2 95% CI 0.4-14.0), (ADL 94.6 points vs. 83.2, mean difference 11.4 95% CI 4.9-17.8), (sport and recreation function 91.5 points vs. 73.8 points, mean difference 17.7 95% CI 9.0-26.4), (QOL 88.9 points vs. 78.8, mean difference 10.1 points 95% CI 2.0-18.2). Participants with a self-reported hip complaint had worse HOOS scores across all subscales (mean difference range 22.1-34.6). Super obese patients (BMI > 40) had > 12.5 points worse scores across the five HOOS subscales. Results were similar for the HOOS-12. This study provides reference values for the HOOS and its short form HOOS-12. Results show that older patients and patients with a BMI over 40 have worse HOOS and HOOS-12 scores that may be of clinical importance in the interpretation of scores both when evaluating potential for improvement and post-treatment results.

Role of the Inspiratory Muscles on Functional Performance From Critical Care to Hospital Discharge and Beyond in Patients With COVID-19.

The role of inspiratory muscle performance in functional performance in patients with coronavirus disease 2019 (COVID-19) is poorly understood. The purpose of this study was to perform a longitudinal examination of inspiratory and functional performance from intensive care unit (ICU) discharge (ICUD) to hospital discharge (HD) and symptoms at HD and 1month after HD in patients with COVID-19. Thirty patients (19 men, 11 women) with COVID-19 were included. Examination of inspiratory muscle performance at ICUD and HD was performed with an electronic manometer, which provided the maximal inspiratory pressure (MIP) and several other inspiratory measures. Examination of dyspnea and functional performance was performed at ICUD and HD with the Modified Borg Dyspnea Scale and the 1-minute sit-to-stand test (1MSST), respectively. The mean age was 71 (SD = 11) years, the mean length of ICU stay was 9 (SD = 6) days, and the mean length of hospital stay was 26 (SD = 16) days. Most of the patients were diagnosed with severe COVID-19 (76.7%) and had a mean Charlson Comorbidity Index of 4.4 (SD = 1.9), reflecting high comorbidity. The mean MIP of the entire cohort increased minimally from ICUD to HD (from 36 [SD = 21] to 40 [SD = 20] cm H2O), reflecting predicted values for men and women at ICUD and HD of 46 (25%) to 51 (23%) and 37 (24%) to 37 (20%), respectively. The 1MSTS score increased significantly from ICUD to HD (9.9 [SD = 7.1] vs 17.7 [SD = 11.1]) for the entire cohort but remained far below population-based reference values (2.5th percentile) for the majority of patients at ICUD and HD. At ICUD, MIP was found to be a significant predictor of a favorable change in 1MSTS performance (β = 0.308; odds ratio = 1.36) at HD. A significant reduction in inspiratory and functional performance exists in patients with COVID-19 at both ICUD and HD, with a greater MIP at ICUD being a significant predictor of a greater 1MSTS score at HD. This study shows that inspiratory muscle training may be an important adjunct after COVID-19.

Generation of de novo reference values for the thyroid hormones TT4, fT4 and TSH in healthy pet rabbits (Oryctolagus cuniculus) and healthy pet guinea pigs (Cavia porcellus) in conjunction with a TRH-stimulation test

In rabbits and guinea pigs, total thyroxine (TT4) and free thyroxine (fT4) reference values have been previously published. However, most studies have been performed on laboratory animals with small sample sizes. A reference value for thyroid-stimulating hormone (TSH) measurement has not yet been established for either species. With the increasing popularity of pet guinea pigs and rabbits in veterinary practice, established reference values are needed to make a diagnosis and promptly initiate appropriate treatment. Plasma samples from a healthy and defined animal population of 41 pet rabbits (n = 41 TT4, fT4, TSH) and 73 pet guinea pigs (n = 73 TT4 and fT4; n = 51 TSH) were evaluated using chemiluminescence assay (CLIA; for TT4, fT4) and enzyme-linked immunosorbent assay (ELISA; for TSH) to establish reference values. A thyrotropin teleasing hormone (TRH)-stimulation test (n = 4; for each species) was conducted to validate the TSH ELISA test kits. Range, mean, median, standard deviation, interquartile range, 95% reference interval, and 90% confidence intervals for lower and upper reference limits of TT4, fT4, and TSH in healthy pet guinea pigs and healthy pet rabbits were assessed. In addition, the influence of age, sex, and housing on TT4, fT4, and TSH levels was investigated. In this study, TSH reference values were established in pet rabbits and guinea pigs for the first time. Reference values for both TT4 and fT4 were also established de novo for both species. Only with evidence- and population-based reference values can thyroid diseases be precisely and correctly diagnosed to prevent inadequate treatment.

Population-based reference values for 4D flow MRI derived aortic blood flow parameters

Objective. This study assesses age-related differences of thoracic aorta blood flow profiles and provides age- and sex-specific reference values using 4D flow cardiovascular magnetic resonance (CMR) data. Approach. 126 volunteers (age 20–80 years, female 51%) underwent 4D flow CMR and 12 perpendicular analysis planes in the thoracic aorta were specified. For these planes the following parameters were evaluated: body surface area-adjusted aortic area (A′), normalized flow displacement (NFD), the degree of wall parallelism (WPD), the minimal relative cross-sectional area through which 80% of the volume flow passes (A80) and the angle between flow direction and centerline (α). Main results. Age-related differences in blood flow parameters were seen in the ascending aorta with higher values for NFD and angle and lower values for WPD and A80 in older subjects. All parameters describing blood flow patterns correlated with the cross-sectional area in the ascending aorta. No relevant sex-differences regarding blood flow profiles were found. Significance. These age- and sex-specific reference values for quantitative parameters describing blood flow within the aorta might help to study the clinical relevance of flow profiles in the future.

Population-based reference values for tongue pressure in Japanese older adults: A pooled analysis of over 5,000 participants.

To establish age- and sex-specific population reference values for tongue pressure (TP) in community-dwelling Japanese older adults. For this analysis, we pooled four population-based studies on community-dwelling adults aged ≥65 years that measured TP using a JMS tongue pressure measuring device. We calculated the means and deciles of TP per 5-year age group for each sex. We also estimated age trends in TP for men and women. In total, 5,083 individuals (2,150 men and 2,933 women, with a mean [standard deviation] age of 75.2 [6.5] years) were included in the present analysis. In male participants, the mean (standard deviation) TPs for ages 65-69, 70-74, 75-79, 80-84, and ≥85 years were 34.0 (8.4), 32.2 (8.1), 30.8 (8.3), 28.4 (8.9), and 24.4 (8.2) kPa, respectively. In female participants, the corresponding values were 31.5 (7.1), 30.5 (7.5), 29.6 (7.3), 28.4 (8.0), and 26.4 (7.6) kPa, respectively. For both sexes, there were significant declining trends in TP with advanced age. In addition, the interaction between age and sex had a significant effect on TP (regression coefficient [95% confidence interval] = -0.18 [-0.25 to -0.11] when age was modeled as a continuous variable and sex was modeled as a categorical variable [coded as 0=women, 1=men]). This study determined age- and sex-specific reference values for TP, presented as means and deciles, in community-dwelling Japanese older adults aged ≥65 years. This study also demonstrated sex differences in age-related declines in TP.

Carotid intima media thickness (CIMT) in adults in the AWI-Gen Nairobi site study: Profiles and predictors

BackgroundCarotid intima media thickness (CIMT) is used as a marker of subclinical and asymptomatic atherosclerotic vascular disease. Increased CIMT is associated with future cerebrovascular and cardiovascular events. There is limited data on the profile and correlates of CIMT in Africa. The aim of this study was to describe the profile and correlates of CIMT in apparently normal younger-age adults in an urban setting in Kenya. MethodsThis study used population-based data collected from 2003 adults between the ages of 40 and 60 years in two slums of Nairobi as part of a genetic study. CIMT was measured using LOGIQ e (GE Healthcare, CT, USA) ultrasound on both left and right carotid arteries, whereby maximum, mean, and minimum values were recorded. Age- and sex-specific CIMT measurements were calculated and their association with basic sociodemographic, behavioral and body composition indicators were investigated. ResultsThe median (IQR) CIMT were 0.58 (0.51, 0.66) and 0.59 (0.53, 0.66) in men and women, respectively. About 16% of the study population had CIMT greater than 0.7mm, the cut off for higher CIMT. Nearly 60% had CIMT values ≥75th percentile. Age, current use of alcohol, systolic blood pressure, subcutaneous fat thickness, pulse rate and pulse pressure were found to be the main predictors of CIMT in our study population. ConclusionThis study provided population-based reference values and predictors for CIMT for an adult population living in urban poor settings in Kenya. Future studies need to consider biochemical and genetic predictors of CIMT in this population.

Selenium Associates With Response to Erythropoiesis-Stimulating Agents in Hemodialysis Patients

IntroductionImpaired response to erythropoiesis-stimulating agents (ESAs) is associated with increased mortality in patients with end-stage kidney disease. However, the underlying mechanisms are not fully elucidated. Accumulating data reveal that selenium (Se), a trace element, plays a key role in stress erythropoiesis and erythrocyte homeostasis. We evaluated the relationship between serum Se levels and the response to ESAs in hemodialysis patients.MethodsIn this cross-sectional study, we determined serum Se levels in 173 hemodialysis patients. We analyzed the association of serum Se with ESA responsiveness, as defined by ESA resistance index.ResultsOf the study participants, 50% had lower Se levels than the population-based reference values. We found that serum Se levels were significantly and inversely correlated with erythropoiesis resistance index (ERI) but not transferrin saturation (TSAT) or ferritin levels. Multiple regression analyses confirmed the association between Se levels and ESA hyporesponsiveness, independently of other known factors, such as iron status, being female, and dialysis vintage (β = −0.11, P < 0.001). When patients were divided according to Se levels and iron status, both low serum Se (<10.5 μg/dl) and iron deficiency significantly affected the response to ESA. Conversely, serum Se levels were significantly different among groups when patients were divided according to ERI quartiles. The association of low serum Se with ESA hyporesponsiveness persisted after adjustment of confounding variables.ConclusionSerum Se levels are associated with the response to ESAs and can predict ESA resistance independently of iron status in Japanese hemodialysis patients. These data open the possibility to test whether Se supplementation reduces ESA demand.

Use of infrared thermography in medical diagnostics: a scoping review protocol

IntroductionThermography offers a non-invasive radiation-free methodology for diagnostic imaging and temperature measurement, but the extent of the current application is unclear, as is the level of evidence for each use...

Can numerical rating scales of disease impact be used as targets for patient-centred management in rheumatoid arthritis?

Patient centred care is an increasingly important paradigm. Applying a treat-to-target strategy to the impact of the disease in patients' lives seems a very promising tool to serve this purpose. We aimed to evaluate if maximum acceptable impact scores (target-values) defined at the population level provide an appropriate representation for most individual patients. To determine if the individually established target values of impact are consistent enough to be used in a treat-to-target strategy. Consecutive patients with rheumatoid arthritis were asked to indicate, in two consecutive visits, the maximum severity of impact they considered acceptable to live with for the rest of their lives, in the seven domains of Rheumatoid Arthritis Impact of Disease score. The individual adequacy of population-based reference values was assessed by measures of dispersion. Stability of individual target-values were evaluated through intraclass correlation coefficient. Socio-demographic, clinical and psychological features were tested as co-factors of stability. 299 patients were included. The dispersion of targets was wide (CV>0.68), thus limiting the use of any population-based single values as targets for the individual patients. Although the mean target values were very similar in both visits for all domains, reliability was poor in all cases (ICCs: 0.37-0.47). Only 25-30% of the patients selected the same target value in the 2 visits. No explanatory factors for (non-)stability were identified. Quantified impact targets defined at population level are not appropriate for individual patient care. Research on alternative tools to support patient-centred, target-oriented management strategies is warranted.

Low health-related quality of life in adult individuals with multiple limb deficiencies compared with population-based reference values.

Knowledge on health-related quality of life (HRQoL) in multiple limb deficiencies (LDs) is limited. To investigate self-reported HRQoL in multiple LDs, assess differences between congenital LD and acquired LD and sex, and to evaluate associations between the types of LDs, demographic variables, and HRQoL. Cross-sectional cohort study. A total of 106 individuals with multiple limb deficiencies treated at the EX-Center were invited by mail to fill out the Short Form-36 survey. Responses from 62 participants, mean age ± SD 49.5 ± 14.2, showed that 43 had congenital LD and 19 had acquired LD. Responders reported reduced HRQoL in all Short Form-36 domains except Role-Emotional, compared with reference values (P < 0.05-<0.001). Individuals with a congenital LD reported worse Bodily Pain than acquired LD (P < 0.05), and women reported lower Physical Function than men (P < 0.05). Sick leave was negatively associated with physical composite score. Living in a rural area was positively associated with Mental Health (P < 0.01), and congenital LD was negatively associated with Vitality (P < 0.05). Individuals with multiple LDs in Sweden have lower HRQoL compared with reference values. There are significant associations between sick leave and physical function, rural living and mental health, and the type of LD and vitality.

Applicability of Thermography in Dentistry-Scoping Review

Introduction: Thermography offers a non-invasive radiation-free methodology for diagnostic imaging and temperature measurement, but the extent of the current application is unclear, as is the level of evidence for each use case. Moreover, population-based thermographic reference values for diagnostic purposes are nearly unknown. The present scoping review aims to assess the extent of literature and available evidence regarding the application of infrared thermography in dentistry to establish indications and further scope of its utility. Material and Methods: PubMed, Cochrane Database of Systematic Reviews and CENTRAL and Web of Science searches were done in July 2022 with specific keywords. Wide eligibility criteria were used to capture all relevant studies, published in English, and addressing thermal imaging in dentistry. The literature found was selected regarding the eligibility criteria. Relevant data was extracted from the included references into a collection chart in a synthesized narrative format and classified under the Levels of Evidence and Grades of Recommendation (Oxford Centre for Evidence-based Medicine, March 2009). Results: 13 studies were selected, 6 in vitro, 5 clinical trial and 1 case study and 1 systematic review. Four studies related the temperature variation of dental pieces with pulpal diagnosis. Three evaluated the effectiveness of thermography in the diagnosis of temporomandibular disorders. Five were used in surgery to measure inflammatory responses resulting from surgical procedures and temperatures reached when cutting hard tissues. One study evaluated, from an ergonomic point of view, the impact of bad working positions of oral health professionals. Conclusion: Within the limitations of this review, studies suggest that thermography has the potential to become an important tool in dental medicine, either as an auxiliary means of diagnosis in endodontics and temporomandibular disorders or as a complementary element in cutting procedures capable of producing heat with implications for the viability of the underlying structures. In addition, this scoping review can rouse new research foci regarding thermography.

Population-based pediatric reference values for serum parathyroid hormone, vitamin D, calcium, and phosphate in Danish/North-European white children and adolescents

IntroductionParathyroid hormone (PTH) and vitamin D are essential hormones in bone metabolism, especially during pediatric growth. Vitamin D insufficiency is often asymptomatic and is prevalent in high-latitude countries. MethodsIn a Danish population-based cohort of 2211 6–18-year-olds, sex- and age-specific pediatric reference values for fasting concentrations of intact serum PTH, vitamin D (25-hydroxycholecalciferol, 25-OH-D), total calcium, and phosphate were generated in accordance with Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines. The effect of season on these biomarkers of bone metabolism was evaluated. ResultsIn boys, PTH concentrations increased with age, while the vitamin D and phosphate concentrations decreased (all p < .001). In girls, a peak in PTH concentrations and a nadir in vitamin D concentrations were observed in the 10–14-year-olds (both p < .001). Calcium and phosphate decreased with age for both sexes (girls: both p < .001; boys calcium: p < .05, boys phosphate: p < .001). Vitamin D was 20% lower in winter than summer for both sexes (both p < .001). Individuals with vitamin D sufficiency (25-OH-D > 50 nmol/L) exhibited a 5% lower level of PTH compared to the whole sample population (p < .001). ConclusionThe concentrations of PTH, vitamin D, calcium, and phosphate vary during childhood and adolescence, and is dependent on sex and season. These factors should be considered when screening for and treating imbalances in bone metabolism.

Health-related quality of life in diabetes mellitus patients in primary health care

ObjectiveTo analyse the relationship between health-related quality of life (HRQoL) and sociodemographic and clinical factors in patients with diabetes mellitus, also comparing with Spanish population-based reference values. MethodCross-sectional descriptive-analytical observational study through nonprobability sampling on diabetic patients from San Roque Primary Health Centre (Badajoz, Spain), using a questionnaire regarding sociodemographic and diabetes care data, SF-36 and Duke-UNC questionnaires, and clinical history data. ResultsSixty patients (55% women) fundamentally with type 2 diabetes and a mean age of 68.67 ± 11.09 years were studied. Women older than 75 presented poorer HRQoL than their reference group. Women showed worse HRQoL than men. Age, evolution of diabetes, presence of acute and chronic complications, and comorbidities, pharmacological treatment, and glycaemic control affect HRQoL in these patients. Living alone, having a low socioeconomic status, and needing help with diabetes-related self-care can negatively affect quality of life. ConclusionsHRQoL assessment allows us to detect alterations in the different domains and perform an early intervention. This way, we can incorporate these aspects into the nursing evaluation and interventions in the nursing care plan; allowing us to develop individualized care strategies and diabetes education programmes that contribute to improving HRQoL in patients with diabetes.

Transthoracic echocardiographic reference values of the aortic root: results from the Hamburg City Health Study

Here we generate up-to-date reference values of transthoracic echocardiographic aortic root dimensions matched by sex, age, and body surface area (BSA) derived from the population-based Hamburg City Health Study (HCHS) cohort. In 1687 healthy subjects (mean age 57.1 ± 7.7, 681 male and 1006 female), derived from the first prospectively-recruited 10,000 HCHS participants, dimensions of the aortic root were measured in systole and diastole using state-of-the-art 2-dimensional transthoracic echocardiography. Diameters were assessed at four levels: aortic annulus, Sinus of Valsalva, sinotubular junction, and ascending aorta. Female sex was associated with significantly smaller absolute aortic root dimensions, while indexing for BSA resulted in a reverse effect at all levels. There was a strong age dependency of all aortic root diameters as well as aortic annulus/sinotubular junction ratio for both sexes. Multivariate analysis revealed age, sex, weight, height, and BSA to be significant determinants of aortic root size. Finally, formulas were generated for the calculation of individual aortic root reference values considering age, sex, weight, and height. We provide population-based reference values of aortic root diameters based on a standardized transthoracic echocardiographic protocol of the population-based HCHS which may support the diagnosis, monitoring, and treatment of aortic root disease.