Implementing an Application Programming Interface for PROMIS Measures at Three Medical Centers.

BACKGROUND: There is an increasing body of literature advocating for the collection of patient-reported outcomes (PROs) in clinical care. Unfortunately, there are many barriers to integrating PRO measures, particularly computer adaptive tests (CATs), within electronic health records (EHRs), thereby limiting access to advances in PRO measures in clinical care settings. OBJECTIVE: To address this obstacle, we created and evaluated a software integration of an Application Programming Interface (API) service for administering and scoring Patient-Reported Outcomes Measurement Information System (PROMIS) measures with the EHR system. METHODS: We created a RESTful API and evaluated the technical feasibility and impact on clinical workflow at three academic medical centers. RESULTS: Collaborative teams (i.e., clinical, information technology [IT] and administrative staff) performed these integration efforts addressing issues such as software integration as well as impact on clinical workflow. All centers considered their implementation successful based on the high rate of completed PROMIS assessments (between January 2016 and January 2021) and minimal workflow disruptions. CONCLUSION: These case studies demonstrate not only the feasibility but also the pathway for the integration of PROMIS CATs into the EHR and routine clinical care. All sites utilized diverse teams with support and commitment from institutional leadership, initial implementation in a single clinic, a process for monitoring and optimization, and use of custom software to minimize staff burden and error.

Combined Cubital and Carpal Tunnel Release Results in Symptom Resolution Outside of the Median or Ulnar Nerve Distributions.

BACKGROUND: Resolution of symptoms including pain, numbness, and tingling outside of the median nerve distribution has been shown to occur following carpal tunnel release. We hypothesized that a similar effect would be found after combined release of the ulnar nerve at the elbow with simultaneous release of the median nerve at the carpal tunnel. METHODS: 20 patients with combined cubital and carpal tunnel syndrome were prospectively enrolled. The upper extremity was divided into six zones and the location of pain, numbness, tingling, or strange sensations was recorded pre-operatively. Two-point discrimination, Semmes-Weinstein monofilament testing, and validated questionnaires were collected pre-operatively and at six-week follow-up. RESULTS: Probability of resolution was greater in the median nerve distribution than the ulnar nerve for numbness (71% vs. 43%), tingling (86% vs. 75%). Seventy percent of the cohort reported at least one extra-anatomic symptom pre-operatively, and greater than 80% of these resolved at early follow-up. There was a decrease in pain as measured by validated questionnaires. CONCLUSION: This study documents resolution of symptoms in both extra-ulnar and extra-median distributions after combined cubital and carpal tunnel release. Pre-operative patient counseling may therefore include the likelihood of symptomatic improvement in a non-expected nerve distribution after this procedure, assuming no other concomitant pathology which may cause persistent symptoms. Future studies could be directed at correlating pre-operative disease severity with probability of symptom resolution using a larger population.

Prospective cohort study of symptom resolution outside of the ulnar nerve distribution following cubital tunnel release.

BACKGROUND: Resolution of symptoms including pain, numbness, and tingling outside of the median nerve distribution has been shown to occur following carpal tunnel release. We hypothesized that a similar effect would be found after release of the ulnar nerve at the elbow. METHODS: Twenty patients with isolated cubital tunnel syndrome were prospectively enrolled. The upper extremity was divided into six zones, and the location of pain, numbness, tingling, or strange sensations was recorded pre-operatively. Two-point discrimination, Semmes-Weinstein monofilament testing, and validated questionnaires were collected. The same data were collected at 6-week follow-up. Paired t tests or non-parametric Wilcoxon Signed-Rank tests were used where appropriate to examine for significant (p ≤ 0.05) changes between pre- and post-operative scores. RESULTS: Probability of resolution was greater outside of the ulnar nerve distribution than within at early follow-up. There was a decrease in pain, numbness, and tingling symptoms both within and outside the ulnar distribution after cubital tunnel release. There was a decrease in pain as measured by several validated questionnaires. CONCLUSION: This study documents resolution of symptoms in an extra-ulnar distribution after cubital tunnel release. Improvement in pain and function after cubital tunnel release may be associated with an improvement in symptoms both within and outside the ulnar nerve distribution. Future studies could be directed at correlating pre-operative disease severity with probability of extra-territorial symptom resolution using a larger sample population.

Placental vitamin D receptor (VDR) expression is related to neonatal vitamin D status, placental calcium transfer, and fetal bone length in pregnant adolescents.

The purpose of the study was to identify determinants of placental vitamin D receptor (VDR) expression and placental calcium (Ca) transfer among pregnant adolescents. Placental tissue was obtained in 94 adolescents (≤18 yr) at term. In 12 of these teens, stable Ca isotopes were given intravenously ((42)Ca) and orally ((44)Ca) early in labor. Placental VDR expression was assessed via Western blot and validated by RT-PCR. Maternal-to-fetal Ca transfer was calculated as the enrichment in cord blood at delivery relative to maternal serum enrichment 2 h postdosing. Isotopic study outcomes were examined in relation to fetal long bone length, placental VDR, serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and parathyroid hormone (PTH) in maternal circulation and cord blood at delivery. Placental VDR expression was inversely associated with neonatal 25(OH)D (P=0.012) and positively with neonatal 1,25(OH)2D (P=0.006). Placental VDR was a positive predictor of fetal femur length Z score (P=0.018; R(2)=0.06) and was positively correlated with maternal-to-fetal transfer of intravenous (42)Ca (P=0.004; R(2)=0.62). The fetus may regulate placental VDR expression given the significant associations with neonatal vitamin D metabolites. The association between placental VDR and fetal long bone length may indicate a role for VDR in fetal bone development, potentially by mediating transplacental Ca transfer.

Maternal vitamin D status and calcium intake interact to affect fetal skeletal growth in utero in pregnant adolescents.

BACKGROUND: Maternal calcium intake and vitamin D status may affect fetal bone development. OBJECTIVE: This study was designed to examine relations between maternal calcium intake, 25-hydroxyvitamin D [25(OH)D] status, and fetal bone growth across pregnancy. DESIGN: This was a prospective longitudinal design. Maternal 25(OH)D, parathyroid hormone, and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were determined at midgestation (∼26 wk) and at delivery in 171 adolescents (≤ 18 y). Dietary recalls and fetal sonograms were performed up to 3 times across gestation, and fetal femur and humerus z scores were generated. RESULTS: Fetal femur and humerus z scores and neonatal birth length were significantly greater (P < 0.03) in adolescents consuming ≥ 1050 mg than in those consuming <1050 mg Ca/d. Maternal 25(OH)D > 50 nmol/L was significantly positively associated with fetal femur and humerus z scores (P < 0.01). When maternal smoking, height, race, weight gain, and gestational age were controlled for, these relations remained significant. Interactions between calcium intake and 25(OH)D were evident. Calcium intake was associated with fetal femur z scores and birth length only when maternal 25(OH)D was ≤ 50 nmol/L (P < 0.05). Similarly, maternal 25(OH)D was associated with fetal femur and humerus z scores only when maternal calcium intake was <1050 mg/d (P < 0.03). CONCLUSIONS: Optimal calcium intake and adequate maternal vitamin D status are both needed to maximize fetal bone growth. Interactions between these nutrients were evident when either calcium or vitamin D status was limited. Improving maternal calcium intake and/or vitamin D status during pregnancy may have a positive effect on fetal skeletal development in pregnant adolescents.

Vitamin D insufficiency is prevalent and vitamin D is inversely associated with parathyroid hormone and calcitriol in pregnant adolescents.

Few large studies have assessed changes in calcitropic hormones and maternal 25-hydroxyvitamin D (25(OH)D) status across pregnancy, and how this may impact maternal bone turnover and neonatal hormone status. We aimed to identify determinants of 25(OH)D, parathyroid hormone (PTH), and calcitriol across pregnancy in a longitudinal study of 168 pregnant adolescents (≤18 years of age). Maternal 25(OH)D, PTH, and calcitriol were assessed at mid-gestation (∼26 weeks), delivery, and in cord blood. Data were related to measures of maternal anthropometrics, dietary intake, physical activity, and bone turnover markers. Approximately 50% of teens and their infants had serum 25(OH)D ≤ 20 ng/mL; 25(OH)D was lower in African Americans versus whites (p < 0.001). PTH increased across gestation (p < 0.001). Elevated PTH (≥60 pg/mL) was detected in 25% of adolescents at delivery, and was associated with increased concentrations of serum N-telopeptide (NTX) (p = 0.028). PTH and calcitriol did not significantly differ across the range of Ca intake consumed (257-3220 mg/d). In the group as a whole, PTH was inversely associated with 25(OH)D in maternal circulation at mid-gestation (p = 0.023) and at delivery (p = 0.019). However, when the cohort was partitioned by 25(OH)D status, this relationship was only present in those with 25(OH)D ≤ 20 ng/mL, suggestive of a threshold below which 25(OH)D impacts PTH during pregnancy. Mid-gestation 25(OH)D was inversely associated with calcitriol at delivery (p = 0.023), irrespective of Ca intake. Neonatal PTH and calcitriol were significantly lower than (p < 0.001), but unrelated to maternal concentrations. These findings indicate that maternal 25(OH)D status plays a role in calcitropic hormone regulation in pregnant adolescents.

Maternal hepcidin is associated with placental transfer of iron derived from dietary heme and nonheme sources.

The determinants of placental transport of dietary iron remain largely uncharacterized. The objective of this research was to elucidate determinants of fetal Fe transfer from maternally ingested dietary heme and non-heme Fe. The study was undertaken in 19 pregnant females (16-32 y) who ingested intrinsically labeled (58)Fe-heme and a nonheme Fe source ((57)FeSO(4)) during the third trimester of pregnancy. At delivery, maternal and cord blood was obtained to assess neonatal (57)Fe and (58)Fe enrichment as a function of maternal/neonatal Fe status [serum ferritin (SF), transferrin receptor, hemoglobin (Hb), total body Fe, and hepcidin]. There was a greater percentage of maternally absorbed (58)Fe tracer present in the neonates compared to the (57)Fe tracer (5.4 ± 2.4 vs. 4.0 ± 1.6; P < 0.0001). Net dietary nonheme Fe (mg) and heme Fe (mg) transferred to the fetus were both inversely correlated with measures of maternal serum hepcidin (P = 0.002, r(2) = 0.43; P = 0.004, r(2) = 0.39) and SF (P = 0.0008, r(2) = 0.49; P = 0.003, r(2) = 0.41) and directly associated with neonatal Hb (P = 0.004, r(2) = 0.39; P = 0.008, r(2) = 0.35). The results of this study suggest that during pregnancy there appears to be preferential fetal use of maternally ingested Fe derived from a dietary, animal-based heme source compared to Fe ingested as ferrous sulfate. Maternal serum hepcidin and maternal/neonatal Fe status may play a role in placental uptake of dietary heme and nonheme Fe.

Placental expression of the heme transporter, feline leukemia virus subgroup C receptor, is related to maternal iron status in pregnant adolescents.

Little is known about the expression of heme transporters in human placenta and possible associations between these transporters and maternal or neonatal iron status. To address this area of research, relative protein expression of 2 heme transporters, Feline Leukemia Virus, Subgroup C, Receptor 1 (FLVCR1) and Breast Cancer Resistance Protein (BCRP), was assessed using Western-blot analysis in human placental tissue in relation to maternal/neonatal iron status and placental iron concentration. Placental FLVCR1 (n = 71) and BCRP (n = 83) expression were assessed at term (36.6-41.7 wk gestation) in a cohort of pregnant adolescents (13-18 y of age) at high-risk of iron deficiency. Both FLVCR1 and BCRP were detected in all placental samples assayed. Placental FLVCR1 expression was positively related to placental BCRP expression (n = 69; R(2) = 0.104; P < 0.05). Adolescents that were anemic at delivery had lower placental FLVCR1 expression (n = 49; P < 0.05). Placental FLVCR1 expression was positively associated with placental iron concentration at delivery (n = 61; R(2) = 0.064; P < 0.05). In contrast, placental BCRP expression was not significantly associated with maternal iron status or placental iron content. Both FLVCR1 and BCRP are highly expressed in human placental tissue, but only FLVCR1 was significantly inversely associated with maternal iron status and placental iron concentration. Further analysis is needed to explore potential functional roles of FLVCR1 in human placental iron transport.

Utilization of iron from an animal-based iron source is greater than that of ferrous sulfate in pregnant and nonpregnant women.

Heme iron absorption during pregnancy and the role of hepcidin in regulating dietary heme iron absorption remains largely unexplored. The objective of this research was to examine relative differences in heme (animal based) and nonheme (ferrous sulfate) iron utilization. This study was undertaken in 18 pregnant (ages 16-32 y; wk 32-35 of gestation) and 11 nonpregnant women (ages 18-27 y). Women were randomly assigned to receive both an animal-based heme meal (intrinsically labeled (58)Fe pork) and labeled ferrous sulfate ((57)Fe) fed on alternate days. Blood samples obtained 2 wk postdosing were used to assess iron status indicators and serum hepcidin and iron utilization based on RBC incorporation of iron isotopes. Heme iron utilization was significantly greater than nonheme iron utilization in the pregnant (47.7 ± 14.4 vs. 40.4 ± 13.2%) and nonpregnant women (50.1 ± 14.8 vs. 15.3 ± 9.7%). Among pregnant women, utilization of nonheme iron was associated with iron status, as assessed by the serum transferrin receptor concentration (P = 0.003; r(2) = 0.43). In contrast, heme iron utilization was not influenced by maternal iron status. In the group as a whole, women with undetectable serum hepcidin had greater nonheme iron utilization compared with women with detectable serum hepcidin (P = 0.02; n = 29); however, there were no significant differences in heme iron utilization. Our study suggests that iron utilization from an animal-based food provides a highly bioavailable source of dietary iron for pregnant and nonpregnant women that is not as sensitive to hepcidin concentrations or iron stores compared with ferrous sulfate.