Correction: The Effect of an App-Based Home Exercise Program on Self-reported Pain Intensity in Unspecific and Degenerative Back Pain: Pragmatic Open-label Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/41899.].

The Effect of an App-Based Home Exercise Program on Self-reported Pain Intensity in Unspecific and Degenerative Back Pain: Pragmatic Open-label Randomized Controlled Trial.

BACKGROUND: The recommended first-line treatment for unspecific and degenerative back pain consists of movement exercises and patient education. OBJECTIVE: Using a pragmatic, randomized controlled trial, we evaluated the effectiveness of a digital home exercise program on self-reported pain intensity compared with the standard of care for physiotherapy. METHODS: Participant recruitment was based on newspaper advertisements and a consecutive on-site assessment for eligibility and enrollment. Participants with unspecific and degenerative back pain aged ≥18 years were randomly assigned in a 1:1 ratio to receive a 12-week stand-alone digital home exercise program or physiotherapy. The digital home exercise program included 4 exercises daily, while physiotherapy included 6 to 12 sessions, depending on the severity of symptoms. The primary outcome was pain, which was assessed using a verbal numerical rating scale. The clinical relevance of pain reduction was assessed using the following thresholds: improvement of at least 1.4 points on the verbal numerical rating scale and a pain reduction of at least 30%. RESULTS: During the study period, 108 participants were assigned to the intervention group and 105 participants to the control group. The mean difference in pain scores between the 2 groups at 12 weeks was -2.44 (95% CI -2.92 to -1.95; P<.01) in favor of the intervention group. The group receiving the digital therapeutic achieved a clinically relevant reduction in pain over the course of the study (baseline vs 12 weeks), with a mean change of -3.35 (SD 2.05) score points or -53.1% (SD 29.5). By contrast, this change did not reach clinical relevance in the control group (mean -0.91, SD 1.5; -14.6%, SD 25.3). Retention rates of 89.9% in the intervention group and 97.3% in the control group were maintained throughout the study. CONCLUSIONS: The use of the app-based home exercise program led to a significant and clinically relevant reduction in pain intensity throughout the 12-week duration of the program. The intervention studied showed superior improvement in self-reported pain intensity when compared with the standard of care. Given the great demand for standard physiotherapy for unspecific and degenerative back pain, digital therapeutics are evolving into a suitable therapeutic option that can overcome the limitations of access and availability of conventional modes of health care delivery into this spectrum of indications. However, further independent evaluations are required to support the growing body of evidence on the effectiveness of digital therapeutics in real-world care settings. TRIAL REGISTRATION: German Clinical Trials Register DRKS00022781; https://tinyurl.com/hpdraa89.

Genetic, Environmental, and Disease-Associated Correlates of Vitamin D Status in Children with CKD.

BACKGROUND AND OBJECTIVES: Vitamin D deficiency is endemic in children with CKD. We sought to investigate the association of genetic disposition, environmental factors, vitamin D supplementation, and renal function on vitamin D status in children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Serum 25-hydroxy-vitamin D, 1,25-dihydroxy-vitamin D, and 24,25-dihydroxy-vitamin D concentrations were measured cross-sectionally in 500 children from 12 European countries with CKD stages 3-5. All patients were participants of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease Study, had CKD stage 3-5, and were age 6-18 years old. Patients were genotyped for single-nucleotide polymorphisms in the genes encoding 25-hydroxylase, vitamin D binding protein, 7-dehydrocholesterol reductase, and 24-hydroxylase. Associations of genetic status, season, local solar radiation, oral vitamin D supplementation, and disease-associated factors with vitamin D status were assessed. RESULTS: Two thirds of patients were vitamin D deficient (25-hydroxy-vitamin D <16 ng/ml). 25-Hydroxy-vitamin D concentrations varied with season and were twofold higher in vitamin D-supplemented patients (21.6 [14.1] versus 10.4 [10.1] ng/ml; P<0.001). Glomerulopathy, albuminuria, and girls were associated with lower 25-hydroxy-vitamin D levels. 24,25-dihydroxy-vitamin D levels were closely correlated with 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D (r=0.87 and r=0.55; both P<0.001). 24,25-dihydroxy-vitamin D concentrations were higher with higher c-terminal fibroblast growth factor 23 and inversely correlated with intact parathyroid hormone. Whereas 25-hydroxy-vitamin D levels were independent of renal function, 24,25-dihydroxy-vitamin D levels were lower with lower eGFR. Vitamin D deficiency was more prevalent in Turkey than in other European regions independent of supplementation status and disease-related factors. Single-nucleotide polymorphisms in the vitamin D binding protein gene were independently associated with lower 25-hydroxy-vitamin D and higher 24,25-dihydroxy-vitamin D. CONCLUSIONS: Disease-related factors and vitamin D supplementation are the main correlates of vitamin D status in children with CKD. Variants in the vitamin D binding protein showed weak associations with the vitamin D status.

Impact of Increasing Dietary Calcium Levels on Calcium Excretion and Vitamin D Metabolites in the Blood of Healthy Adult Cats.

BACKGROUND: Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken. RESULTS: Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D2 and 25(OH)D3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001). CONCLUSIONS: In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P.

Effect of vitamin A supplementation on the urinary retinol excretion in very low birth weight infants.

UNLABELLED: Despite high-dose vitamin A supplementation of very low birth weight infants (VLBW, <1500 g), their vitamin A status does not improve substantially. Unknown is the impact of urinary retinol excretion on the serum retinol concentration in these infants. Therefore, the effect of high-dose vitamin A supplementation on the urinary vitamin A excretion in VLBW infants was investigated. Sixty-three VLBW infants were treated with vitamin A (5000 IU intramuscular, 3 times/week for 4 weeks); 38 untreated infants were classified as control group. On days 3 and 28 of life, retinol, retinol-binding protein 4 (RBP4), glomerular filtration rate, proteinuria, and Tamm-Horsfall protein were quantified in urine. On day 3 of life, substantial retinol and RBP4 losses were found in both groups, which significantly decreased until day 28. Notwithstanding, the retinol excretion was higher (P < 0.01) under vitamin A supplementation as compared to infants of the control group. On day 28 of life, the urinary retinol concentrations were predictive for serum retinol concentrations in the vitamin A treated (P < 0.01), but not in the control group (P = 0.570). CONCLUSION: High urinary retinol excretion may limit the vitamin A supplementation efficacy in VLBW infants. Advanced age and thus postnatal kidney maturation seems to be an important contributor in the prevention of urinary retinol losses.

The relative dose response test based on retinol-binding protein 4 is not suitable to assess vitamin A status in very low birth weight infants.

BACKGROUND: The relative dose response (RDR) test, which quantifies the increase in serum retinol after vitamin A administration, is a qualitative measure of liver vitamin A stores. Particularly in preterm infants, the feasibility of the RDR test involving blood is critically dependent on small sample volumes. OBJECTIVES: This study aimed to assess whether the RDR calculated with retinol-binding protein 4 (RBP4) might be a substitute for the classical retinol-based RDR test for assessing vitamin A status in very preterm infants. METHODS: This study included preterm infants with a birth weight below 1,500 g (n = 63, median birth weight 985 g, median gestational age 27.4 weeks) who were treated with 5,000 IU retinyl palmitate intramuscularly 3 times a week for 4 weeks. On day 3 (first vitamin A injection) and day 28 of life (last vitamin A injection), the RDR was calculated and compared using serum retinol and RBP4 concentrations. RESULTS: The concentrations of retinol (p < 0.001) and RBP4 (p < 0.01) increased significantly from day 3 to day 28. On day 3, the median (IQR) retinol-RDR was 27% (8.4-42.5) and the median RBP4-RDR was 8.4% (-3.4 to 27.9), compared to 7.5% (-10.6 to 20.8) and -0.61% (-19.7 to 15.3) on day 28. The results for retinol-RDR and RBP4-RDR revealed no significant correlation. The agreement between retinol-RDR and RBP4-RDR was poor (day 3: Cohen's κ = 0.12; day 28: Cohen's κ = 0.18). CONCLUSION: The RDR test based on circulating RBP4 is unlikely to reflect the hepatic vitamin A status in preterm infants.