Understanding the associations between receipt of, and interest in, advice from a healthcare professional and quality of life in individuals with a stoma from colorectal cancer: a latent profile analysis.

PURPOSE: To explore whether profiles derived from self-reported quality of life were associated with receipt of, and interest in, advice from a healthcare professional in people with a stoma. METHODS: Secondary analysis of cross-sectional national survey data from England of 4487 people with a stoma from colorectal cancer. The survey assessed quality of life using various scales, receipt and interest in various forms of advice, and physical activity. A three-step latent profile analysis was conducted to determine the optimum number of profiles. Multinomial regression explored factors associated with profile membership. A series of logistic regression models examined whether profile membership was associated with interest in advice. RESULTS: Five profiles were identified; 'consistently good quality of life', 'functional issues', 'functional and financial issues', 'low quality of life' and 'supported but struggling'. Individuals in the 'functional and financial issues' and 'low quality of life' profiles were more likely to have received financial advice compared to the 'consistently good quality of life' profile. When compared to the 'consistently good quality of life' profile, all other profiles were more likely to report wanting advice across a range of areas, with the strongest associations in the 'low quality of life' profile. CONCLUSION: Findings indicate that people with a stoma are not a homogenous group in terms of quality of life. Participants in profiles with quality of life concerns report wanting more advice across various categories but findings suggest there is scope to explore how this can be tailored or adapted to specific groups.

"I have to get up and exercise because that's how I'm going to get over this": a qualitative exploration of exercise identity and behavior in early cancer survivorship.

PURPOSE: Exercise is beneficial for people living with and beyond cancer (LWBC); however, many people LWBC fail to meet the exercise guidelines. Having an identity related to exercise, a component of one's self-concept, correlates with exercising more frequently in general adult populations. Understanding how exercise identity influences exercise behaviors in people LWBC is warranted due to the many barriers people LWBC face in relation to physical activity. The purpose of this study was to explore the perceived impact of an exercise identity of the exercise behaviors and motivations among people LWBC. METHODS: Thirteen participants of mixed diagnoses (Mage = 60.8 ± 10.8 years) in the early survivorship period (i.e., within five years of primary treatment completion or diagnosis) participated in semi-structured interviews to identify influences of exercise identity on exercise behavior. Interviews were transcribed verbatim and analyzed using thematic analysis. RESULTS: Findings demonstrated that people LWBC with a strong exercise identity engage in high and varied exercise behaviors. Despite barriers such as changes in motivations and ability to engage in exercise, participants maintained exercise throughout cancer by constant adaptation of their outlook and behaviors related to exercise. These results demonstrate a maintenance of physical activity in relation to a strong exercise identity. IMPLICATIONS FOR CANCER SURVIVORS: Results of this study have implications for the design and implementation of exercise behavior change programs for people LWBC as it provides insights into predictors of sustained exercise behavior during and following cancer treatment.

Hernia Active Living Trial (HALT): an exercise intervention in people with a parastomal hernia or bulge.

BACKGROUND: Parastomal hernias are a common consequence of stoma surgery and can occur in up to 50% of patients. They are mangaged either conservatively, through support hosiery, or surgically. A patient feasibility study called the Hernia Active Living Trial (HALT) was designed to examine if a clinical pilates-based exercise programme offers an alternative approach to managing a parastomal hernia or bulge. METHOD: Adults with an ileostomy or colostomy who perceived they had a bulge around their stoma were included in the study. The intervention included up to 12 online sessions of an exercise booklet and videos with an exercise specialist. Interviews were conducted to explore participants' experiences of the intervention. The interview data were analysed systematically and thematically. Participants were also asked to complete patient diaries every week. RESULTS: Twelve of the 13 participants who completed the intervention agreed to be interviewed. Following analysis, three main themes emerged including managing a hernia/bulge, benefits and barriers. Participants talked about the benefits of this programme including: reduction of the size of their hernia, increased abdominal control, body confidence and posture, as well as increased physical activity levels. The barriers described were generally overcome allowing participants to engage in what was perceived to be a positive and potentially life-changing experience. CONCLUSIONS: A clinical pilates-based exercise programme for people with a parastomal hernia can bring both direct and indirect improvements to a patient's hernia management, sense of wellbeing and day-to-day life. Individuals with a hernia should be informed about the need for, and value of, exercise to strengthen core muscles, as part of their non-surgical options for self-management.

Development and initial qualitative evaluation of a novel school-based nutrition intervention - COOKKIT (Cooking Kit for Kids).

BACKGROUND: Excess weight and an unhealthy diet are risk factors for many cancers, and in high income countries, both are more prevalent among low income families. Dietary interventions targeting primary-school aged children (under 11) can improve healthy eating behaviours, but most are not designed to support the translation of skills learnt in the classroom to the home setting. This paper assessed attitudes and approaches to cooking and eating at home, and the potential to enhance engagement in healthy eating through the COOKKIT intervention. METHODS: COOKKIT is an intervention to deliver weekly cooking classes and supportive materials for low-income families to maintain healthy eating at home. Preliminary qualitative interviews were conducted with teachers and parent-child dyads from a range of primary schools in the UK to explore attitudes, barriers and facilitators for healthy eating and inform the development of COOKKIT. Following implementation, ten children (8-9 y/o) participated in post-intervention focus groups, alongside interviews with teaching staff and parents. RESULTS: Thematic analysis identified five themes under which to discuss the children's experience of food, cooking and the impact of COOKKIT: Involving children in planning and buying food for the family; Engaging children in preparing meals at home; Trying to eat healthy meals together in the midst of busy lives; Role-modelling; and Balancing practicalities, information and engagement when delivering cooking classes. CONCLUSIONS: Results suggest COOKKIT provides engaging and easy to follow in-school resources for children and school staff with take-home kits facilitating continued engagement and reinforcing lessons learned in the home environment. Importantly, participants highlighted the combination of healthy eating information, applied practical skills and low costs could support families to continue following the COOKKIT advice beyond the intervention, suggesting further evaluation of COOKKIT is warranted.

Impact of exercise and/or dietary interventions, and their behaviour change techniques, on quality of life in middle-aged and older women following treatment for cancer: A systematic review.

Many middle-aged or older women are treated for cancer and their quality of life can be significantly impaired following treatment. Exercise and dietary interventions could address this. The aim of this review was to determine whether exercise and/or dietary interventions which are scaffolded by behaviour change theories and techniques are associated with improved quality of life in middle-aged and older women following cancer treatment. Secondary outcomes included self-efficacy, distress, waist circumference, and food variety. A search of CINAHL (EBSCOhost), Embase, MEDLINE (EBSCOhost), PsycINFO, PubMed and Scopus databases up to 17th November 2022 was conducted. A narrative summary was provided. Twenty articles discussing 18 independent randomised controlled trials/interventions were included, with a total of 1754 participants. No studies reported the outcomes of distress or food variety. Exercise and/or dietary interventions had mixed effects on quality of life, self-efficacy and waist circumference (positive effect: n = 4/14; n = 3/5; n = 4/7, respectively). Two-thirds of the interventions (exercise-only, n = 2; exercise and diet, n = 2) that demonstrated an improvement in quality-of-life scores were based upon Social Cognitive Theory. All studies that reported improvements in waist circumference employed combined exercise and dietary interventions, with individualised aspects for the dietary components. Exercise and/or dietary interventions could potentially enhance quality of life and self-efficacy, and reduce waist circumference, in middle-aged and older women treated for cancer. Although findings are currently mixed, avenues for the development of interventions include ensuring there is a theoretical underpinning and incorporating more behaviour change techniques in exercise and/or dietary interventions in this population.

The Extent of Engagement With Telehealth Approaches by Patients With Advanced Cancer: Systematic Review.

BACKGROUND: Telehealth approaches are increasingly being used to support patients with advanced diseases, including cancer. Evidence suggests that telehealth is acceptable to most patients; however, the extent of and factors influencing patient engagement remain unclear. OBJECTIVE: The aim of this review is to characterize the extent of engagement with telehealth interventions in patients with advanced, incurable cancer reported in the international literature. METHODS: This systematic review was registered with PROSPERO (International Prospective Register of Systematic Reviews) and is reported in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. A comprehensive search of databases was undertaken for telehealth interventions (communication between a patient with advanced cancer and their health professional via telehealth technologies), including MEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Sociological Abstracts, and Web of Science, from the inception of each electronic database up until December 31, 2020. A narrative synthesis was conducted to outline the design, population, and context of the studies. A conceptual framework of digital engagement comprising quantitative behavioral measures (frequency, amount, duration, and depth of use) framed the analysis of engagement with telehealth approaches. Frequency data were transformed to a percentage (actual patient engagement as a proportion of intended engagement), and the interventions were characterized by intensity (high, medium, and low intended engagement) and mode of delivery for standardized comparisons across studies. RESULTS: Of the 19,676 identified papers, 40 (0.2%) papers covering 39 different studies were eligible for inclusion, dominated by US studies (22/39, 56%), with most being research studies (26/39, 67%). The most commonly reported measure of engagement was frequency (36/39, 92%), with substantial heterogeneity in the way in which it was measured. A standardized percentage of actual patient engagement was derived from 17 studies (17/39, 44%; n=1255), ranging from 51% to 100% with a weighted average of 75.4% (SD 15.8%). A directly proportional relationship was found between intervention intensity and actual patient engagement. Higher engagement occurred when a tablet, computer, or smartphone app was the mode of delivery. CONCLUSIONS: Understanding engagement for people with advanced cancer can guide the development of telehealth approaches from their design to monitoring as part of routine care. With increasing telehealth use, the development of meaningful and context- and condition-appropriate measures of telehealth engagement is needed to address the current heterogeneity in reporting while improving the understanding of optimal implementation of telehealth for oncology and palliative care. TRIAL REGISTRATION: PROSPERO (International Prospective Register of Systematic Reviews) CRD42018117232; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018117232.

Calcimimetic use in US hemodialysis facilities in first 2 years after the launch of etelcalcetide: A descriptive analysis of real-world clinical practice and outcomes.

INTRODUCTION: This study described control of parathyroid hormone (PTH), phosphorus, and corrected calcium in adults initiating calcimimetics in small dialysis organizations after the introduction of etelcalcetide. METHODS: This retrospective study using Visonex Clarity electronic health records between October 1, 2017, and December 31, 2019, identified adults ≥ 18 years of age receiving in-center hemodialysis as either a cinacalcet or etelcalcetide initiator based on their first calcimimetic use in 2018 (index date) with no prior calcimimetic use in the 3 months preindex date. Patients were stratified by PTH at index date and were followed for 15 months. Subcohorts of patients who were persistent on a single calcimimetic for 15 months and of patients who had their calcimimetic changed from cinacalcet to etelcalcetide were also analyzed. FINDINGS: A total of 677 patients initiated cinacalcet and 711 initiated etelcalcetide. Mean PTH (pg/ml), phosphorus, and corrected calcium (mg/dl) at baseline were 864, 5.9, and 9.3 for cinacalcet and 804, 5.9, and 9.4 for etelcalcetide, respectively. During follow-up, the proportion of initiators considered in-target (monthly average PTH < 600) increased from 48% to 62% with cinacalcet and from 56% to 86% with etelcalcetide in the baseline PTH 600 to < 800 subgroup; increased from 30% to 64% with cinacalcet and 31% to 59% with etelcalcetide among those with baseline PTH 800 to < 1000; and increased from 14% to 41% with cinacalcet and 12% to 58% with etelcalcetide among those with baseline PTH ≥1000. A similar pattern was observed for persistent users (n = 646). For patients changed from cinacalcet to etelcalcetide (n = 183), the proportion of patients considered in-target increased from 22% in the month prior to the treatment change to 51% in Month 6 postchange. DISCUSSION: Patients initiating calcimimetics at lower baseline PTH had better biochemical control than patients starting at higher PTH. Patients changed from cinacalcet to etelcalcetide had improvements in PTH control postchange.

Activation of the Calcium Receptor by Calcimimetic Agents Is Preserved Despite Modest Attenuating Effects of Hyperphosphatemia.

BACKGROUND: Phosphorus levels in the range seen clinically among patients undergoing dialysis have been reported to attenuate calcium receptor activation and modify parathyroid hormone (PTH) release from isolated parathyroid glands in vitro. Some clinicians and providers of dialysis thus have suggested that calcimimetic agents are ineffective and should not be used to manage secondary hyperparathyroidism among those undergoing dialysis when serum phosphorus concentrations exceed certain threshold levels. METHODS: To determine whether hyperphosphatemia diminishes the therapeutic response to calcimimetic agents, we used data from large clinical trials to analyze the effects of etelcalcetide and cinacalcet to lower plasma PTH levels in individuals on hemodialysis who had secondary hyperparathyroidism and varying degrees of hyperphosphatemia. RESULTS: Plasma PTH levels declined progressively during 26 weeks of treatment with either etelcalcetide or cinacalcet without regard to the degree of hyperphosphatemia at baseline. However, with each calcimimetic agent, the decreases in PTH from baseline were less at each interval of follow-up during the trials among participants with serum phosphorus levels above one of three prespecified threshold values compared with those with serum phosphorus levels below these thresholds. CONCLUSIONS: These in vivo findings are the first in humans to support the idea that hyperphosphatemia attenuates calcium receptor activation by calcium ions and by calcimimetic agents. The effect of hyperphosphatemia on the responsiveness to calcimimetic agents appears relatively modest, however, and unlikely to be significant therapeutically. The efficacy of treatment with calcimimetic agents for lowering plasma PTH levels among those with secondary hyperparathyroidism remains robust despite substantial elevations in serum phosphorus.

A physical activity intervention to improve the quality of life of patients with a stoma: a feasibility study protocol.

BACKGROUND: Physical activity (PA) is positively associated with quality of life. People with a stoma are less likely to engage in PA than those without a stoma. METHODS: In this feasibility intervention study, we will perform the following: (1) Develop a PA intervention for people with a stoma. An Expert Working Group of behavioural scientists, exercise scientists, clinicians and a Patient Advisory Group of people with a bowel stoma will meet with the research team to inform the development of a PA intervention for people with a stoma. A manual of the intervention will be the main output. (2) Explore PA instructors' experiences of delivering the PA intervention. PA instructors will record on paper the number of PA consultations with each patient and a researcher will interview the PA instructors about their experiences of delivering the intervention. (3) Assess the level of patient (bowel cancer or inflammatory bowel disease (IBD) patients with a stoma between 6 weeks and 24 months post-surgery) engagement with the PA intervention and their views on intervention acceptability and usefulness. Patients will keep a PA diary to record daily pedometer recorded step count and type and duration of activities. A researcher will interview patients about their experiences of the PA intervention. (4) Assess screening, eligibility, consent, data completion, loss to follow up, and missing data rates, representativeness of participants and potential treatment effects. A researcher will record on paper all study procedure parameters. Quality of life (stoma-quality of life; Functional Assessment of Cancer Therapy, Short IBD questionnaire), fatigue (FACIT fatigue scale) and PA (accelerometer) will be measured pre- and post-intervention in patients. For IBD patients only, blood will be taken to measure systemic inflammation. DISCUSSION: We hypothesise that a PA intervention will be an effective means of improving the quality of life of people with a stoma. Before embarking on a full randomised controlled trial to test this hypothesis, a PA intervention needs to be developed and a feasibility study of the proposed PA intervention conducted. TRIAL REGISTRATION: ISRCTN58613962, Protocol version: 0.1. 14 September 2017.

Etelcalcetide, A Novel Calcimimetic, Prevents Vascular Calcification in A Rat Model of Renal Insufficiency with Secondary Hyperparathyroidism.

Etelcalcetide, a novel peptide agonist of the calcium-sensing receptor, prevents vascular calcification in a rat model of renal insufficiency with secondary hyperparathyroidism. Vascular calcification occurs frequently in patients with chronic kidney disease (CKD) and is a consequence of impaired mineral homeostasis and secondary hyperparathyroidism (SHPT). Etelcalcetide substantially lowers parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) levels in SHPT patients on hemodialysis. This study compared the effects of etelcalcetide and paricalcitol on vascular calcification in rats with adenine-induced CKD and SHPT. Uremia and SHPT were induced in male Wistar rats fed a diet supplemented with 0.75% adenine for 4 weeks. Rats were injected with vehicle, etelcalcetide, or paricalcitol for 4 weeks from the beginning of adenine diet. Rats fed an adenine-free diet were included as nonuremic controls. Similar reductions in plasma PTH and parathyroid chief cell proliferation were observed in both etelcalcetide- and paricalcitol-treated rats. Serum calcium and phosphorus were significantly lower in etelcalcetide-treated uremic rats and was unchanged in paricalcitol-treated rats. Both serum FGF23 and aortic calcium content were significantly lower in etelcalcetide-treated uremic rats compared with either vehicle- or paricalcitol-treated uremic rats. The degree of aortic calcium content for etelcalcetide-treated rats was similar to that in nonuremic controls and corroborated findings of lack of histologic aortic mineralization in those groups. In conclusion, etelcalcetide and paricalcitol similarly attenuated progression of SHPT in an adenine rat model of CKD. However, etelcalcetide differentially prevented vascular calcification, at least in part, due to reductions in serum FGF23, calcium, and phosphorus levels.

Determination of Etelcalcetide Biotransformation and Hemodialysis Kinetics to Guide the Timing of Its Dosing.

INTRODUCTION: Etelcalcetide, a novel calcimimetic agonist of the calcium-sensing receptor for treatment of secondary hyperparathyroidism in chronic kidney disease patients on hemodialysis, is a d-amino acid linear heptapeptide with a d-cysteine that is linked to an l-cysteine by a disulfide bond. In addition to binding to the calcium-sensing receptor, etelcalcetide is biotransformed by disulfide exchange in whole blood to predominantly form a covalent serum albumin peptide conjugate (SAPC). Key factors anticipated to affect the pharmacokinetics and disposition of etelcalcetide in chronic kidney disease patients on hemodialysis are the drug's intrinsic dialytic properties and biotransformation kinetics. METHODS: These factors were investigated using in vitro methods, and the findings were modeled to derive corresponding kinetic rate constants. RESULTS: Biotransformation was reversible after incubation of etelcalcetide or SAPC in human whole blood. The rate of SAPC formation from etelcalcetide was 18-fold faster than the reverse process. Clearance of etelcalcetide by hemodialysis was rapid in the absence of blood and when hemodialysis was initiated immediately after addition of etelcalcetide to blood. Preincubation of etelcalcetide in blood for 3 hours before hemodialysis resulted in formation of SAPC and decreased its clearance due to the slow rate of etelcalcetide formation from SAPC. Etelcalcetide hemodialysis clearance was >16-fold faster than its biotransformation. DISCUSSION: These results indicate that etelcalcetide should be administered after hemodialysis to avoid elimination of a significant fraction of the dose.

The Use of Calcimimetics for the Treatment of Secondary Hyperparathyroidism: A 10 Year Evidence Review.

Until the discovery of calcimimetics, the management of secondary hyperparathyroidism (SHPT) relied exclusively on treatment with phosphate binders, vitamin D derivatives or surgical parathyroidectomy with limited success. The therapeutic use of calcimimetic agents, together with a better understanding of the pivotal role of the calcium-sensing receptor (CaSR) in the physiological regulation of parathyroid gland function, substantially advanced the management of hyperparathyroidism in dialysis practice. Calcimimetics bind selectively to the CaSR receptor in parathyroid tissue and enhance the inhibitory effect of extracellular calcium ions on parathyroid hormone (PTH) secretion, thereby reducing PTH levels even when serum calcium concentrations are normal or low. The availability of calcimimetic agents for clinical use has opened a new era in the management of patients with SHPT. Indeed, calcimimetic compounds have been shown to reduce PTH levels and to lower serum calcium concentrations in all forms of hyperparathyroidism, including primary hyperparathyroidism (PHPT) and parathyroid carcinoma. Such findings underscore the critical importance of the CaSR as a therapeutic target in this family of clinical disorders. New calcimimetic agents are being developed that have the potential to offer improved efficacy and safety compared with currently available calcimimetic compounds.

Bone histomorphometry before and after long-term treatment with cinacalcet in dialysis patients with secondary hyperparathyroidism.

The multicenter, single-arm BONAFIDE study characterized the skeletal response to cinacalcet in adult dialysis patients with plasma parathyroid hormone (PTH) levels of 300 pg/ml or more, serum calcium of 8.4 mg/dl or more, bone-specific alkaline phosphatase over 20.9 ng/ml and biopsy-proven high-turnover bone disease. Of 110 enrolled patients, 77 underwent a second bone biopsy with quantitative histomorphometry after 6-12 months of cinacalcet treatment. The median PTH decreased from 985 pg/ml at baseline to 480 pg/ml at the end of study (weeks 44-52). Bone formation rate/tissue area decreased from 728 to 336 µm(2)/mm(2)/day, osteoblast perimeter/osteoid perimeter decreased from 17.4 to 13.9%, and eroded perimeter/bone perimeter decreased from 12.7 to 8.3%. The number of patients with normal bone histology increased from none at baseline to 20 at 12 months. Two patients had adynamic bone at the end of study with a PTH under 150 pg/ml, and one patient with overt hypophosphatemia at baseline that reoccurred during follow-up developed osteomalacia. Thus, long-term treatment with cinacalcet substantially reduced PTH, diminished the elevated bone formation rate/tissue area, lowered several biochemical markers of high-turnover bone disease toward normal, and generally improved bone histology. Twenty patients had normal bone histology at follow-up, whereas most had mild hyperparathyroidism or mixed uremic osteodystrophy.

Presence of valvular calcification predicts the response to cinacalcet: data from the ADVANCE study.

BACKGROUND AND AIM OF THE STUDY: Cardiac valve calcification (CVC) and coronary artery calcification (CAC) appear to be linked pathogenetically, and both are associated with a poor prognosis among patients with chronic kidney disease on dialysis (CKD-5D). Little is known, however, about factors that affect the progression of CVC and CAC. METHODS: A post-hoc analysis was performed of the ADVANCE study to assess whether patients with CVC are more prone to CAC progression, and whether CVC predicts the response to different treatments for secondary hyperparathyroidism. RESULTS: Subjects were randomized to treatment with either cinacalcet and low doses of vitamin D analogs or larger, varying doses of vitamin D. Among 235 subjects, aortic valve or mitral valve calcification was detected in 108 (46%) and 118 (50%), respectively; 69 subjects (29%) had calcification of both valves. CVC was associated both with baseline CAC and CAC progression (p < 0.05). Subjects with aortic valve calcification who were treated with cinacalcet and low doses of vitamin D experienced less progression of CAC than subjects given larger, varying doses of vitamin D (adjusted OR: 0.26; 95% CI: 0.10, 0.64). This effect was greater in subjects with larger CAC burden at baseline. CONCLUSION: The study findings suggest that CVC is a predictor of CAC progression and, potentially, of greater cardiovascular vulnerability. Treatment with cinacalcet combined with low doses of vitamin D slowed the progression of CAC compared to therapy using larger, varying doses of vitamin D.

The clinical course of treated hyperparathyroidism among patients receiving hemodialysis and the effect of cinacalcet: the EVOLVE trial.

CONTEXT: The clinical course of secondary hyperparathyroidism (sHPT) in patients on hemodialysis is not well described, and the effect of the calcimimetic cinacalcet on disease progression is uncertain. OBJECTIVE: Our objective was to describe 1) the clinical course of sHPT in patients treated with phosphate binders and/or vitamin D sterols and 2) the impact of cinacalcet on the occurrence of severe unremitting HPT, defined by the persistence of markedly elevated PTH concentrations together with hypercalcemia or parathyroidectomy (PTX). DESIGN AND SETTING: This was a randomized, double-blind, placebo-controlled, global, multicenter clinical trial. PATIENTS: Of 5755 patients screened with moderate to severe sHPT, 3883 patients on hemodialysis were included in the trial. MAIN OUTCOME MEASURES: Outcomes included PTX; severe, unremitting HPT; and use of commercial cinacalcet (a protocol violation). INTERVENTION: Intervention was cinacalcet (30-180 mg daily) or placebo for up to 64 months. RESULTS: In the 1935 patients randomized to placebo, 278 patients (14%) underwent PTX (median PTH 1872 pg/mL within the previous 12 weeks from surgery). Age, sex, geographic region, co-morbidity, calcium-containing phosphate binder use, and baseline serum calcium, phosphorus, and PTH concentrations were associated with PTX. Commercial cinacalcet was started in 443 (23%) patients (median PTH 1108 pg/mL before treatment began). Severe unremitting HPT developed in 470 patients (24%). In a multivariable Cox model, the relative hazard (comparing patients randomized to cinacalcet versus placebo) of severe unremitting HPT was 0.31 (95% confidence interval = 0.26-0.37). The relative hazard differed little when adjusted by baseline clinical characteristics. CONCLUSIONS: Severe unremitting HPT develops frequently in patients on hemodialysis despite conventional therapy, and cinacalcet substantially reduces its occurrence.

The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis.

BACKGROUND: This prospective, randomized, controlled trial compared the progression of vascular and cardiac valve calcification in 360 prevalent adult hemodialysis patients with secondary hyperparathyroidism treated with either cinacalcet plus low-dose vitamin D sterols or flexible doses of vitamin D sterols alone. METHODS: Eligible subjects were on hemodialysis for ≥ 3 months with parathyroid hormone (PTH) > 300 pg/mL or PTH 150-300 pg/mL with calcium-phosphorus product > 50 mg(2)/dL(2) while receiving vitamin D. All subjects received calcium-based phosphate binders. Coronary artery calcification (CAC) and aorta and cardiac valve calcium scores were determined both by Agatston and volume scoring using multi-detector computed tomography. Subjects with Agatston CAC scores ≥ 30 were randomized to cinacalcet (30- 180 mg/day) plus low-dose calcitriol or vitamin D analog (≤ 2 µg paricalcitol equivalent/dialysis), or flexible vitamin D therapy. The primary end point was percentage change in Agatston CAC score from baseline to Week 52. RESULTS: Median (P10, P90) Agatston CAC scores increased 24% (-22%, 119%) in the cinacalcet group and 31% (-9%, 179%) in the flexible vitamin D group (P = 0.073). Corresponding changes in volume CAC scores were 22% (-12%, 105%) and 30% (-6%, 133%; P = 0.009). Increases in calcification scores were consistently less in the aorta, aortic valve and mitral valve among subjects treated with cinacalcet plus low-dose vitamin D sterols, and the differences between groups were significant at the aortic valve. CONCLUSIONS: In hemodialysis patients with moderate to severe secondary hyperparathyroidism, cinacalcet plus low-dose vitamin D sterols may attenuate vascular and cardiac valve calcification.

Study design and subject baseline characteristics in the ADVANCE Study: effects of cinacalcet on vascular calcification in haemodialysis patients.

BACKGROUND: The ADVANCE (A Randomized Study to Evaluate the Effects of Cinacalcet plus Low-Dose Vitamin D on Vascular Calcification in Subjects with Chronic Kidney Disease Receiving Haemodialysis) Study objective is to assess the effect of cinacalcet plus low-dose active vitamin D versus flexible dosing of active vitamin D on progression of coronary artery calcification (CAC) in haemodialysis patients. We report the ADVANCE Study design and baseline subject characteristics. METHODS: ADVANCE is a multinational, multicentre, randomized, open-label study. Adult haemodialysis patients with moderate to severe secondary hyperparathyroidism (intact parathyroid hormone [iPTH] >300 pg/mL or bio-intact PTH >160 pg/mL) and baseline CAC score >or=30 were stratified by CAC score (>or=30-399, >or=400-999, >or=1000) and randomized in a 1:1 ratio to cinacalcet (30-180 mg/day) plus low-dose active vitamin D (cinacalcet group) or flexible dosing of active vitamin D alone (control). The study had three phases: screening, 20-week dose titration and 32-week follow-up. CAC scores obtained by cardiac computed tomography were determined at screening and weeks 28 and 52. The primary end point was percentage change in CAC score from baseline to Week 52. RESULTS: Subjects (n = 360) were randomized to cinacalcet or control. Mean age was 61.5 years, 43% were women, and median dialysis vintage was 36.7 months (range, 2.7-351.5 months). The baseline geometric mean CAC score by the Agatston method was 548.7 (95% confidence interval, 480.5-626.6). Baseline CAC score was independently associated with age, sex, dialysis vintage, diabetes and iPTH. Subjects also had extensive aortic and valvular calcification at baseline. CONCLUSIONS: Subjects enrolled in ADVANCE have extensive CAC at baseline. The ADVANCE Study should help determine whether cinacalcet attenuates progression of vascular calcification.

Update on clinical trials with cinacalcet in secondary hyperparathyroidism due to chronic kidney disease / Atualização sobre os Ensaios clínicos com cinacalcete no hiperparatireoidismo secundário associado à doença renal crônica

Data from several recent clinical trials reaffirm the efficacy of treatment with cinacalcet for controlling plasma PTH levels among dialysis patients with established secondary HPT. In contrast to results reported previously from studies where cinacalcet was used together with relatively large but constant doses of vitamin D sterols, plasma PTH levels can be reduced effectively during treatment with cinacalcet among patients receiving lower doses of vitamin Dsterols. Compared to conventional treatment with vitamin D sterols, serum calcium and phosphorus levels are better controlled with this therapeuticapproach, and a larger proportion of patients are able to achieve serum calcium and phosphorus concentrations and values for Ca x P with the ranges recommended in current practice guidelines. Additional prospective clinical trials are needed, however, to determine whether the use of cinacalcet among dialysis patients with secondary HPT affects other important and clinically relevant outcomes such bone morphology, bone mass and/or bone density, skeletal fracture rates, and the need for parathyroidectomy.

Dados de vários ensaios clínicos recentes reafirmam a eficácia do tratamento com cinacalcete para controlar o nível plasmático do PTH em pacientes em diálise com hiperparatireoidismo secundário estabelecido. Em contraste com resultados previamente relatados, derivados de estudos onde cinacalcete era usado junto com doses relativamente altas porém constantes de vitamina D ou derivados, os níveis plasmáticos de PTH podem ser efetivamente reduzidospor cinacalcet em pacientes recebendo doses mais baixas de esteróides da vitamina D. Em comparação ao tratamento convencional com esteróides da vitamina D, os níveis séricos de cálcio e fósforo são melhor controlados com esta abordagem terapêutica e uma maior proporção de pacientes podealcançar concentrações séricas de cálcio e fósforo e valores do produto Ca x P dentro das faixas recomendadas pelas diretrizes atuais. Entretanto, ensaiosclínicos prospectivos adicionais são necessários para determinar se o uso de cinacalcete em pacientes em diálise com hiperparatireoidismo secundárioafeta outras variáveis importantes e clinicamente relevantes como, por exemplo, a morfologia do osso, a massa e/ou a densidade óssea, a taxa de fraturas, e a necessidade de paratireoidectomia.

Adherence to K/DOQI practice guidelines for bone metabolism and disease.

OBJECTIVE: To determine adherence to Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines for frequency of testing and control of parathyroid hormone (PTH), calcium, and phosphorus levels among patients with chronic kidney disease (CKD). STUDY DESIGN: Retrospective cohort. METHODS: The analysis was performed with administrative claims data from large US managed care plans. Patients with CKD were identified based on claims and laboratory data. Patients were excluded if they were <18 years or >or=65 years old, had fewer than 18 months of continuous eligibility, or had renal cancer. RESULTS: A total of 793 patients were identified with CKD stages 3, 4, or 5 (n = 424, n = 212, and n = 157, respectively). Serum calcium testing was conducted according to guidelines (once a year) in a high percentage of patients with stage 3 CKD (91%); however, the percentage dropped among patients with stage 4 CKD (64%), for whom the guidelines recommend testing 4 times a year. Plasma PTH and serum phosphorus levels were tested infrequently. Among those tested, a high percentage of both stage 3 and 4 CKD patients were in K/DOQI target ranges for calcium and phosphorus. However, fewer than half of the patients tested had PTH values within the target ranges. CONCLUSION: There remains substantial opportunity to improve the quality of care with respect to bone and mineral metabolism in patients with CKD.

Case report on PWC of a competitive cyclist before and after heart transplant.

INTRODUCTION: It has been well documented that for heart transplant recipients (HTR), posttransplantation physical work capacity (PWC) normally does not exceed 60% of the value for healthy age-matched controls. Few, if any, studies have undertaken posttransplantation PWC measurements of well-conditioned individuals (i.e., PWC>300 W). CASE SUMMARY: A 37-yr-old professionally trained male cyclist suffered an acute myocardial infarction (AMI) immediately after a road race and received a heart transplant (HT) 4 months after the AMI. The participant resumed training 1 month after surgery and underwent a maximal exercise test 6 months after surgery. Peak PWC (33.8 mL.kg(-1).min(-1), 250 W) was 92% of the age-predicted maximum, and peak heart rate (165 bpm) was 96% of his known maximum. These results were similar to the participants in a study who had been training regularly for 36+/-24 months before testing, and PWC evaluations occurred 43+/-12 months after HT. CONCLUSION: Results suggest that 1) lifestyle before HT may positively affect posttransplantation PWC, 2) exercise capacity was not limited by chronotropic incompetence, and 3) a more aggressive approach to HT recovery could be applied to HTR with similar activity histories.