Citations

AbstractBackgroundIntegrating shared decision making between patients and physicians and incorporating their values and preferences in the development of clinical practice guidelines (CPGs) is of critical importance to optimize CPG implementation and treatment adherence. This applies to many debilitating diseases, including hypercalcemia of malignancy (HCM).ObjectiveEvaluate patient and physician values, preferences, and attitudes to better inform CPGs to treat HCM in adults.MethodsWe followed a mixed-methods approach. We conducted a systematic review using 5 databases to identify studies reporting on patient and physician values, costs and resources, feasibility, acceptability, and equity regarding HCM treatment. We also gathered data from different countries on the cost of multiple treatment modalities. We collected data on outcome prioritization from the CPG Working Group. Similarly, we collected data from patients with HCM regarding outcome prioritization and administered a questionnaire to evaluate their attitudes and perceptions toward treatment as well as treatment acceptability and feasibility.ResultsIn the systematic review, we included 2 cross-sectional surveys conducted on the same population of physicians who agreed that treating HCM alleviates symptoms and improves quality of life; however, harms and benefits should be thoroughly considered when deciding on the duration of treatment. We also included 2 studies on cost showing that intravenous (IV) bisphosphonate is more cost-effective than a combination of IV bisphosphonate and calcitonin and administration of IV zoledronic acid at home is more cost-effective than other IV bisphosphonates. The cost of zoledronic acid, denosumab, and cinacalcet varied widely among countries and types (brand vs generic). Both the CPG Working Group and patients with HCM agreed that the most important outcomes when deciding on treatment were survival and resolution of HCM, but there was some variability in the ratings for other outcomes.ConclusionUsing mixed methods, CPG developers can obtain meaningful information regarding evidence to decision criteria. In the case of HCM CPGs, this approach has provided the required contextual information and supported the development of evidence-based recommendations.

Introduction Hypercalcaemia of malignancy (HCM) is the second most common cause of hypercalcaemia and is associated with significant morbidity and mortality. Several treatment options are available including pharmacological therapy with bisphosphonates, denosumab, glucocorticoids and calcimimetics, as well as conventional therapy with hydration and possibly calcitonin. While guidelines have previously considered treatment effects, no guideline has yet considered a range of contextual factors impacting recommendations for the management. The aim of this study was to summarise the available evidence on important decisional factors for the development of guidelines for the treatment of HCM. These include patient’s values and preferences, cost, acceptability, feasibility and equity. Methods and analysis This protocol is registered in PROSPERO (registration number: CRD42021264371). This is a systematic review of observational studies, case series, trials, reviews and qualitative studies involving treatment of adult patients with HCM. We will develop and execute two independent search strategies using five databases: PubMed, Medline (OVID), Embase.com, CINAHL (EBSCO) and Cochrane, and review their combined output. Two reviewers will screen titles and abstracts and full texts and will implement data abstraction from relevant studies independently and in duplicate. The outcomes of interest are the decisional factors that influence drug selection, with possible subgroup summaries by drug class or aetiology of HCM. We will present the data collected in a narrative and thematic approach. Ethics and dissemination Ethical approval is not applicable for our study, since we will only collect data from available literature. This systematic review will be submitted to a peer-reviewed journal when completed.

Abstract Context Guidelines for the dosage of vitamin D supplementation vary widely globally. Objective To investigate the impact of 2 vitamin D doses, bracketed between the IOM recommended dietary allowance (RDA) and the upper tolerable limit, on vitamin D nutritional status in elderly individuals. Methods This post hoc analysis of data collected from a 12-month, double-blind, randomized control trial included 221 ambulatory participants (≥ 65 years) with a mean BMI of 30.2 kg/m2 and a mean baseline serum 25-hydroxyvitamin D [25(OH)D] level of 20.4 ± 7.4 ng/mL, who were recruited from 3 outpatient centers in Lebanon. All participants received 1000 mg of elemental calcium daily from calcium citrate plus the daily equivalent of either 600 IU or 3750 IU of vitamin D3. Results Mean 25(OH)D level at 12 months was 26.0 ng/mL with low dose and 36.0 ng/mL with high dose vitamin D3. The proportion of participants reaching a value ≥ 20 ng/mL was 86% in the low dose, and 99% in the high dose arms, with no gender differences. The increment of 25(OH)D per 100 IU/day was 1 ng/mL with the low dose, and 0.41 ng/mL with the high dose. Serum 25(OH)D levels at 1 year were highly variable in both treatment arms. Baseline 25(OH)D level and vitamin D dose—but not age, BMI, gender, or season—were significant predictors of serum 25(OH)D level post-intervention. Conclusion The IOM Recommended Dietary Allowance (RDA) of 600 IU/day does not bring 97.5% of ambulatory elderly individuals above the desirable threshold of 20 ng/mL. Country-specific RDAs are best derived taking into account the observed variability and predictors of achieved 25(OH)D levels.

Abstract Background: Hypercalcemia of malignancy is the second most common cause of hypercalcemia and is associated with significant morbidity and mortality. Several treatment options are available including pharmacological therapy with bisphosphonates, denosumab, glucocorticoids, and calcimimetics, as well as conventional therapy with hydration and possibly calcitonin. While guidelines have previously considered treatment effects, no guideline has yet considered a range of contextual factors impacting recommendations for the management. Objective: The aim of this study is to summarize the available evidence on important decisional factors for the development of guidelines for the treatment of hypercalcemia of malignancy. These include patient’s values and preferences, cost, acceptability, feasibility, and equity. Methods/Design: This is a systematic review of observational studies, case series, trials, reviews and qualitative studies involving treatment of adult patients with hypercalcemia of malignancy. We developed and executed two independent search strategies using five databases: Pubmed, Medline (OVID), Embase.com, CINAHL (EBSCO) and Cochrane, and reviewed their combined output. Two reviewers screened titles and abstracts and full texts and will implement data abstraction from relevant studies independently and in duplicate. The outcomes of interest are the decisional factors that influence drug selection, with possible subgroup analyses by drug class or etiology of hypercalcemia of malignancy. We will present the data collected in a narrative and thematic approach. Discussion: This systematic review will identify important treatment decisional factors, and will assist guidelines panels, physicians and patients to decide on therapeutic options based on the current evidence.

Abstract Context Questions regarding the superiority of free and bioavailable 25-hydroxyvitamin D [25(OH)D] in predicting health outcomes remain unresolved. Objective This study investigates the impact of vitamin D variables—total, bioavailable, or free 25(OH)D—on indices of bone and mineral metabolism, at baseline and in response to 2 vitamin D doses. Design Our objectives are implemented as exploratory analyses on data collected in a 1-year, double-blind, randomized controlled trial completed in July 2014. Setting Participants were recruited from 3 major hospitals in an ambulatory setting. Participants Participants were >65 years of age, overweight, and had a baseline serum 25(OH)D between 10 and 30 ng/mL. A total of 221 participants completed the study. Intervention Subjects were randomized to receive calcium and oral vitamin D3 (600 IU/day or 3750 IU/day) supplementation. Results Participants who received the higher vitamin D dose had levels that were 1.3- to 1.4-fold higher than those taking the lower dose, for all variables (P value < 0.001). Serum values of bioavailable and free 25(OH)D were associated with total 25(OH)D, with r values of 0.942 and 0.943, respectively (P value < 0.001). Parathyroid hormone (PTH) was negatively associated with all vitamin D variables, with correlation coefficients ranging from −0.22 to −0.25, while calcium and bone turnover markers (carboxy-terminal collagen crosslinks and osteocalcin) did not. Only total 25(OH)D had a positive relationship with % change bone mineral density (BMD) at the femoral neck at 12 months, while only free and bioavailable 25(OH) had a positive relationship with % change total body BMD at 12 months. Conclusion Calculated free and bioavailable 25(OH)D do not appear to be superior to total 25(OH)D in predicting indices of bone health in an elderly population.

Abstract Background Hypercalcemia of malignancy is the second most common cause of hypercalcemia and is associated with significant morbidity and mortality. Several treatment options are available including pharmacological therapy with bisphosphonates, denosumab, glucocorticoids, and calcimimetics, as well as conventional therapy with hydration and possibly calcitonin. While guidelines have previously considered treatment effects, no guideline has yet considered a range of contextual factors impacting recommendations for the management. Objective The aim of this study is to summarize the available evidence on important decisional factors for the development of guidelines for the treatment of hypercalcemia of malignancy. These include patient’s values and preferences, cost, acceptability, feasibility, and equity. Methods/Design: This is a systematic review of observational studies, case series, trials, reviews and qualitative studies involving treatment of adult patients with hypercalcemia of malignancy. We developed and executed two independent search strategies using five databases: Pubmed, Medline (OVID), Embase.com, CINAHL (EBSCO) and Cochrane, and reviewed their combined output. Two reviewers screened titles and abstracts and full texts and will implement data abstraction from relevant studies independently and in duplicate. The outcomes of interest are the decisional factors that influence drug selection, with possible subgroup analyses by drug class or etiology of hypercalcemia of malignancy. We will present the data collected in a narrative and thematic approach. Discussion This systematic review will identify important treatment decisional factors, and will assist guidelines panels, physicians and patients to decide on therapeutic options based on the current evidence.