HealthyRHearts - reducing cholesterol in rural adults via telehealth-based medical nutrition therapy: protocol for a cluster randomised controlled trial.

BACKGROUND: Few randomised controlled trials specifically focus on prevention in rural populations. Cardiovascular disease (CVD) contributes to approximately one quarter of deaths in Australia. Nutrition is a key component affecting many risk factors associated with CVD, including hypercholesterolaemia. However, access to medical nutrition therapy (MNT) is limited for people living in rural areas, potentially exacerbating inequities related to health outcomes. Telehealth services present an opportunity to improve MNT access and address healthcare disparities for rural populations. The present study aims to evaluate feasibility, acceptability, and cost-effectiveness of a telehealth MNT CVD intervention program in lowering CVD risk over 12-months in regional and rural primary health care settings. METHODS/DESIGN: A cluster randomised controlled trial set in rural and regional general practices in NSW, Australia, and their consenting patients (n = 300 participants). Practices will be randomised to either control (usual care from their General Practitioner (GP) + low level individualised dietetic feedback) or intervention groups (usual care from their GP + low level individualised dietetic feedback + telehealth MNT intervention). Telehealth consultations will be delivered by an Accredited Practising Dietitian (APD), with each intervention participant scheduled to receive five consultations over a 6-month period. System-generated generic personalised nutrition feedback reports are provided based on completion of the Australian Eating Survey - Heart version (AES-Heart), a food frequency questionnaire. Eligible participants must be assessed by their GP as at moderate (≥ 10%) to high (> 15%) risk of a CVD event within the next five years using the CVD Check calculator and reside in a regional or rural area within the Hunter New England Central Coast Primary Health Network (HNECC PHN) to be eligible for inclusion. Outcome measures are assessed at baseline, 3, 6 and 12 months. The primary outcome is reduction in total serum cholesterol. Evaluation of the intervention feasibility, acceptability and cost-effective will incorporate quantitative, economic and qualitative methodologies. DISCUSSION: Research outcomes will provide knowledge on effectiveness of MNT provision in reducing serum cholesterol, and feasibility, acceptability, and cost-effectiveness of delivering MNT via telehealth to address CVD risk in rural regions. Results will inform translation to health policy and practice for improving access to clinical care in rural Australia. TRIAL REGISTRATION: This trial is registered at anzctr.org.au under the acronym HealthyRHearts (Healthy Rural Hearts), registration number ACTRN12621001495819.

Decentralized vitamin C & D dual biosensor chip: Toward personalized immune system support.

Combating the ongoing COVID-19 pandemic has put the spotlight on nutritional support of the immune system through consumption of vitamins C and D. Accordingly, there are urgent demands for an effective on-the-spot multi-vitamin self-testing platform that monitors the levels of these immune-supporting micronutrients for guiding precision nutrition recommendations. Herein, we present a compact bioelectronic dual sensor chip aimed at frequent on-the-spot simultaneous monitoring of the salivary vitamin C and D dynamics. The new bioelectronic chip combines a new electrocatalytic vitamin C amperometric assay along with competitive vitamin D immunoassay on neighboring electrodes, to perform selective and cross-talk free detection of both vitamins in a 10-µL saliva sample within 25 min. The distinct vitamin C or D temporal profiles obtained for different individuals after vitamin supplementation indicate the potential of the new bioelectronic chip strategy for enhancing personalized nutrition towards guiding dietary interventions to meet individual nutrition needs and promote immune system health.

Vitamin B6 deficiency with normal plasma levels of pyridoxal 5'-phosphate in perinatal hypophosphatasia.

Pyridoxal 5'-phosphate (PLP), the principal circulating form of vitamin B6 (B6), is elevated in the plasma of individuals with hypophosphatasia (HPP). HPP is the inborn-error-of-metabolism caused by loss-of-function mutation(s) of ALPL, the gene that encodes the "tissue-nonspecific" isoenzyme of alkaline phosphatase (TNSALP). PLP accumulates extracellularly in HPP because it is a natural substrate of this cell-surface phosphomonoester phosphohydrolase. Even individuals mildly affected by HPP manifest this biochemical hallmark, which is used for diagnosis. Herein, an exclusively breast-fed newborn boy with life-threatening perinatal HPP had uniquely normal instead of markedly elevated plasma PLP levels before beginning asfotase alfa (AA) TNSALP-replacement therapy. These abnormal PLP levels were explained by B6 deficiency, confirmed by his low plasma level of 4-pyridoxic acid (PA), the B6 degradation product. His mother, a presumed carrier of one of his two ALPL missense mutations, had serum ALP activity of 50 U/L (Nl 40-130) while her plasma PLP level was 9 µg/L (Nl 5-50) and PA was 3 µg/L (Nl 3-30). Her dietary history and breast milk pyridoxal (PL) level indicated she too was B6 deficient. With B6 supplementation using a breast milk fortifier, the patient's plasma PA level corrected, while his PLP level remained in the normal range but now in keeping with AA treatment. Our experience reveals that elevated levels of PLP in the circulation in HPP require some degree of B6 sufficiency, and that anticipated increases in HPP can be negated by hypovitaminosis B6.

Dialectical behavior therapy as treatment for borderline personality disorder.

Dialectical behavior therapy (DBT) is a structured outpatient treatment developed by Dr Marsha Linehan for the treatment of borderline personality disorder (BPD). Dialectical behavior therapy is based on cognitive-behavioral principles and is currently the only empirically supported treatment for BPD. Randomized controlled trials have shown the efficacy of DBT not only in BPD but also in other psychiatric disorders, such as substance use disorders, mood disorders, posttraumatic stress disorder, and eating disorders. Traditional DBT is structured into 4 components, including skills training group, individual psychotherapy, telephone consultation, and therapist consultation team. These components work together to teach behavioral skills that target common symptoms of BPD, including an unstable sense of self, chaotic relationships, fear of abandonment, emotional lability, and impulsivity such as self-injurious behaviors. The skills include mindfulness, interpersonal effectiveness, emotion regulation, and distress tolerance. Given the often comorbid psychiatric symptoms with BPD in patients participating in DBT, psychopharmacologic interventions are oftentimes considered appropriate adjunctive care. This article aims to outline the basic principles of DBT as well as comment on the role of pharmacotherapy as adjunctive treatment for the symptoms of BPD.

Autologous protein solution prepared from the blood of osteoarthritic patients contains an enhanced profile of anti-inflammatory cytokines and anabolic growth factors.

The objective of this clinical study was to test if blood from osteoarthritis (OA) patients (n = 105) could be processed by a device system to form an autologous protein solution (APS) with preferentially increased concentrations of anti-inflammatory cytokines compared to inflammatory cytokines. To address this objective, APS was prepared from patients exhibiting radiographic evidence of knee OA. Patient metrics were collected including: demographic information, medical history, medication records, and Knee Injury and Osteoarthritis Outcome Score (KOOS) surveys. Cytokine and growth factor concentrations in whole blood and APS were measured using enzyme-linked immunosorbent assays. Statistical analyses were used to identify relationships between OA patient metrics and cytokines. The results of this study indicated that anti-inflammatory cytokines were preferentially increased compared to inflammatory cytokines in APS from 98% of OA patients. APS contained high concentrations of anti-inflammatory proteins including 39,000 ± 20,000 pg/ml IL-1ra, 21,000 ± 5,000 pg/ml sIL-1RII, 2,100 ± 570 pg/ml sTNF-RI, and 4,200 ± 1,500 pg/ml sTNF-RII. Analysis of the 82 patient metrics indicated that no single patient metric was strongly correlated (R(2) > 0.7) with the key cytokine concentrations in APS. Therefore, APS can be prepared from a broad range of OA patients.

Pralatrexate with vitamin supplementation in patients with previously treated, advanced non-small cell lung cancer: safety and efficacy in a phase 1 trial.

INTRODUCTION: Pralatrexate is an antifolate designed for preferential tumor cell uptake and accumulation and received accelerated Food and Drug Administration approval in relapsed/refractory peripheral T-cell lymphoma. Pralatrexate 135 to 150 mg/m(2) every 2 weeks without vitamin supplementation was active in non-small cell lung cancer (NSCLC) although mucositis was dose limiting. This phase 1 study evaluated the safety of higher pralatrexate doses with vitamin supplementation to minimize toxicities. METHODS: Patients with stage IIIB/IV NSCLC received pralatrexate 150 to 325 mg/m(2) every 2 weeks with folic acid and vitamin B12 supplementation. Outcomes measured included adverse events (AEs), pharmacokinetics, and radiologic response. RESULTS: Thirty-nine patients were treated for a median of two cycles (range 1-16+). Common treatment-related grade 3 and 4 AEs by dose (≤190 mg/m(2) and >190 mg/m(2)) included mucositis (33 and 40%) and fatigue (11 and 17%). Treatment-related serious AE (SAE) rates for doses ≤190 and >190 mg/m(2) were 0 and 20%, respectively. The response rate was 10% (95% confidence interval: 1-20%), including two patients with complete response (26+ and 32+ months) and two with partial response. Serum pralatrexate concentrations increased dose dependently up to 230 mg/m(2). CONCLUSIONS: Pralatrexate with vitamin supplementation was safely administered to patients with previously treated NSCLC, and durable responses were observed. The recommended starting dose for phase 2 is 190 mg/m(2). A similar safety profile was observed in patients treated at 230 mg/m(2), although a higher serious AE rate was evident. Mucositis remains the dose-limiting toxicity of pralatrexate, and this study failed to demonstrate that vitamin supplementation prevents mucositis and failed to identify clinical predictors of mucositis. Individualized dose-modification strategies and prospective mucositis management will be necessary in future trials.

The effect of thrombin activation of platelet-rich plasma on demineralized bone matrix osteoinductivity.

BACKGROUND: Demineralized bone matrix is an osteoinductive and osteoconductive material that is often used in orthopaedic surgery to induce bone formation. Autologous platelet-rich plasma, which contains proliferative and chemoattractant growth factors, has been used as a demineralized bone matrix adjuvant with mixed results. One variable during clinical use appears to be whether the platelet-rich plasma is activated with thrombin or is implanted in a liquid form with intact platelets. The objective of the present study was to determine if platelet-rich plasma can increase the osteoinductivity of demineralized bone matrix when used without thrombin activation. METHODS: The bioactivity of the demineralized bone matrix was evaluated in vitro by determining alkaline phosphatase production by C2C12 myoblast cells. The effect of thrombin activation on platelet-rich plasma was studied in vitro by evaluating osteosarcoma and bone marrow stromal cells for cell number and transforming growth factor-beta1 activation. Demineralized bone matrices supplemented with platelet-rich plasma, with or without thrombin activation, were implanted intramuscularly in athymic rats and were examined at fourteen, twenty-eight, and fifty-six days. Histological samples were analyzed for osteogenesis and chondrogenesis. Osteogenesis was further characterized on the basis of alkaline phosphatase activity. RESULTS: In vitro, thrombin triggered an immediate release of growth factors from the platelet-rich plasma, and the platelet-rich plasma increased the number of both osteosarcoma and stromal cells in a dose-dependent manner. Thrombin activation of the platelet-rich plasma eliminated such stimulatory effects. In vivo, the platelet-rich plasma stimulated chondrogenesis on Day 14 and osteogenesis on Days 28 and 56, whereas thrombin-activated platelet-rich plasma acted as an inhibitor of such events. In addition, inflammatory cells were detected in demineralized bone matrix samples that were mixed with thrombin-activated platelet-rich plasma. These cells were not present in matrix mixed with platelet-rich plasma alone. CONCLUSIONS: Platelet-rich plasma significantly increased in vivo demineralized bone matrix osteoinductivity only when used without thrombin activation.

Demineralized bone matrix graft: a scientific and clinical case study assessment.

Osteoinductive demineralized bone matrix results from bone demineralization and is attributed to matrix-associated bone morphogenetic proteins. The osteoinductive potential can vary with donor. Many bioassay methods are available to screen donors, each with its own interpretation, so performance of more than one may be of value. Furthermore, little is known about the relationship between bioassay results and clinical outcomes. A study designed to meaningfully explore these issues would require assay of a large number of donors as well as clinical utilization in a large patient population. A preliminary study was undertaken to gain initial perspective. Using demineralized bone matrix derived from one 33-year-old female donor, 2 methods of bioassay and a clinical case study were performed. The levels of bone morphogenetic proteins 2, 4, and 7 in lyophilized demineralized bone matrix powder were measured (19.65 +/- 0.30 ng/g, 2.49 +/- 0.19 ng/g, and 82.03 +/- 6.89 ng/g, respectively). Also, putty (Osteostim DBM Putty), prepared from powder, was intramuscularly implanted in athymic rats and de novo bone formation quantified (6.7% +/- 3.5% new bone formation with 49% +/- 17% of the implant area associated with new bone formation). The putty, in conjunction with internal fixation, was used in the revision of a medial malleolar nonunion of an obese, 76-year-old woman. Radiographic union with excellent graft incorporation was achieved by 12 weeks postoperatively, with maintenance of an acceptable clinical result during the 14-month follow-up period. These results are interpreted in the broader context of demineralized bone grafting, in general, and an outline for further study is presented.