Patient and Physician Decisional Factors Regarding Hypercalcemia of Malignancy Treatment: A Novel Mixed-Methods Study.

BACKGROUND: Integrating 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). OBJECTIVE: Evaluate patient and physician values, preferences, and attitudes to better inform CPGs to treat HCM in adults. METHODS: We 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. RESULTS: In 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. CONCLUSION: Using 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.

Effect of antiresorptive therapy on aromatase inhibitor induced bone loss in postmenopausal women with early-stage breast cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Aromatase inhibitors (AIs) are routinely used to treat postmenopausal women with early-stage breast cancer. Although AIs improve breast cancer outcomes, they increase the risk of osteoporosis and fractures. This systematic review and meta-analysis assesses the effect of antiresorptive drugs on AI induced bone loss in postmenopausal women with non-metastatic breast cancer. METHODS: We searched four databases until November 4th 2020. We included Randomized controlled trials (RCTs) of antiresorptive drugs in postmenopausal women with breast cancer treated with AI. Two authors screened studies, extracted data and assessed the risk of bias independently and in duplicate. RESULTS: We identified 14 RCTs: 7 on zoledronic acid, 6 on oral bisphosphonates and 1 on denosumab. The mean difference in bone mineral density (BMD) was 5% at the lumbar spine and 4% at the total hip, at 12 months, favoring zoledronic acid compared to control. The certainty of the evidence was low for lumbar spine and moderate for total hip BMD. Similarly, the mean difference was 3% at the lumbar spine and 2% at the total hip, favoring oral bisphosphonates with moderate certainty. The mean difference was 6% at the lumbar spine, and 4% at the total hip BMD favoring denosumab compared to placebo. In addition, zoledronic acid resulted in a mean difference in bone turnover marker levels of -35-41%, and the relarive risk for morphometric vertebral fractures was 0.7 [0.3-1.4], compared to control. Denosumab reduced fracture incidence by 50% compared to placebo. CONCLUSION: Evidence suggests a protective effect of antiresorptive drugs on BMD and bone turnover markers in postmenopausal women with non-metastatic breast cancer on AI. However, data on fracture risk reduction remains unclear.

Values and other decisional factors regarding treatment of hypercalcaemia of malignancy: a systematic review protocol.

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.

Vitamin D supplementation in obesity and during weight loss: A review of randomized controlled trials.

Vitamin D deficiency is common in obese individuals and during weight loss. The recommended vitamin D doses in this specific population are higher than for healthy adults. We reviewed vitamin D supplementation trials in obesity, and during medical or surgical weight loss, and report the effects on 25-hydroxyvitamin D [25(OH)D] concentrations and other relevant outcomes. We conducted a systematic search in PubMed, Medline, Embase and the Cochrane library for relevant randomized controlled trials (RCTs) of oral vitamin D supplementation for at least 3 months in obese individuals without weight loss (OB), and those on medical weight loss (MWL) (2010-2018), and following bariatric surgery (Bar S) (without time restriction). Two reviewers screened the identified citations in duplicate and independently and performed full text screening. One reviewer completed data extraction. We identified 13 RCTs in OB, 6 in MWL and 7 in Bar S. Mean baseline 25(OH)D concentrations ranged between 7 and 27 ng/ml in OB, 15-29 ng/ml in MWL and 15-24 ng/ml in Bar S. In OB (Total N 2036 participants), vitamin D doses of 1600-4000 IU/d increased mean 25(OH)D concentrations to ≥30 ng/ml. Based on three trials during MWL (Total N 359 participants), vitamin D doses of 1200-4600 IU/d for 12 months increased 25(OH)D concentration to ≥30 ng/ml. In Bar S (Total N 615 participants), doses ≥2000 IU/d were needed to reach 30 ng/ml. The change in 25(OH)D concentration was inversely proportional to the administered dose, and to BMI and baseline level with doses of 600-3000 IU/day. With these doses, the change in 25(OH)D concentration [Δ25(OH)D] per 100 IU/d was 0.5-1.2 ng/ml. Three trials assessed bone mineral density as a primary outcome, but only one of them showed a protective effect of vitamin D against bone loss at all sites post-Bar S. There was no effect of vitamin D on weight loss. Data on extra-skeletal parameters, namely glycemic and vascular indices were mostly identified in OB, and findings were inconsistent. In conclusion, Vitamin D doses ≥1600-2000 IU/d may be needed to reach a 25(OH)D concentration of 30 ng/ml in obese individuals and following bariatric surgery. The optimal concentration in this population is unknown, and whether the above doses protect against weight loss induced bone loss and fractures still needs to be confirmed. There is no clear evidence for a beneficial effect of vitamin D supplementation on cardio-metabolic parameters in obese individuals, and data on such parameters with weight loss are very scarce. Well-designed long term RCTs assessing the effect of vitamin D supplementation during weight loss on patient important outcomes are needed.