Quality and Outcomes of Treatment of Hypercalcemia of Malignancy.
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ABSTRACT:
SUBMITTER: Wright JD
PROVIDER: S-EPMC4666677 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Project description:Hypercalcemia of malignancy (HCM), caused primarily by tumor-induced bone resorption, may lead to renal failure, coma, and death. Although HCM can be treated with intravenous bisphosphonates, patients may not respond or may relapse on therapy. Denosumab binds the bone resorption mediator RANKL. In this single-arm, open-label, proof-of-concept study, HCM patients with albumin-corrected serum calcium (CSC) levels greater than 12.5mg/dL (Common Terminology Criteria for Adverse Events grade ≥ 3) despite recent intravenous bisphosphonate treatment received subcutaneous denosumab on days 1, 8, 15, and 29, and then every 4 weeks. The primary endpoint was the proportion of patients with CSC 11.5mg/dL or less (grade ≤ 1) within 10 days of denosumab initiation. In a prespecified interim analysis, 15 patients received denosumab (median CSC = 13.6 mg/dL). Time to response and response duration were analyzed with Kaplan-Meier methods. All statistical tests were two-sided. By day 10, 12 patients (80%; 95% exact confidence interval [CI] = 52% to 96%) responded (CSC ≤ 11.5mg/dL); median response duration was 26 days. Ten patients (67%; 95% exact CI = 38% to 88%) had complete responses (CSC ≤ 10.8 mg/dL) by day 10. Denosumab may offer a new treatment option for HCM. Clinicaltrials.gov identifier: NCT00896454.
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Project description:Hypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.
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Project description:To obtain utilities (a unit of measure of a person's relative preferences for different health states compared with death or worst possible outcome) for uterine fibroids before and after treatment and to measure short-term utilities for the following uterine fibroid treatments: abdominal hysterectomy, magnetic resonance (MR) imaging-guided focused ultrasound surgery, and uterine artery embolization (UAE).This retrospective study was approved by the institutional review board and was HIPAA compliant. The waiting trade-off (WTO) method, a variation on the time trade-off (TTO) method, is used to obtain utilities for diagnostic procedures on the basis of the fact that people wait longer to avoid noxious tests and/or procedures. The WTO method provides short-term quality of life tolls in terms of quality-adjusted life-weeks by scaling wait times with pre- and posttreatment utilities. Utilities for uterine fibroids before and after treatment were obtained with the TTO method and a visual analog scale (VAS) by using a questionnaire administered by means of a phone interview. WTO wait times were adjusted for quality of life with VAS and TTO utilities and a transformation of VAS. Wait times were compared by using nonparametric tests. The study participants included 62 patients who had undergone abdominal hysterectomy, 74 who had undergone UAE, and 61 who had undergone MR imaging-guided focused ultrasound surgery.Quality of life increased with all treatments. The median WTO wait time was higher for hysterectomy (21.6 weeks) than for UAE or MR imaging-guided focused ultrasound surgery (14.1 weeks for both) (P < .05). Quality-adjusted life-week tolls were smaller when scaled according to TTO than when scaled according to VAS or transformation of VAS.Quality of life increased after all fibroid treatments. WTO is feasible for assessing the quality-adjusted morbidity of treatment procedures.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11100704/-/DC1.
| S-EPMC3099045 | biostudies-other
Project description:Hemophagocytic lymphohistiocytosis is an overwhelming systemic inflammatory process that is life-threatening if not treated appropriately. We analyzed prognostic factors in patients with secondary hemophagocytic lymphohistiocytosis excluding malignancy. In this retrospective study, we analyzed 126 adult cases between 2001 and 2017. Treatment was based on dexamethasone with or without etoposide and cyclosporine. Patients who achieved a complete response by 4 weeks were defined as early stable responders, those who failed to achieve a complete response but showed continuous improvement until 8 weeks were defined as late responders, and those whose conditions waxed and waned until 8 weeks were defined as unstable responders. Patients with hemophagocytic lymphohistiocytosis caused by Epstein-Barr virus had a worse 5-year overall survival compared to those whose disease was secondary to autoimmune disease, other infections, or unknown causes (25.1% versus 82.4%, 78.7% and 55.5%, respectively; P<0.001). We observed that the overall response rate at 4 weeks was similar, but decreased at 8 weeks in the Epstein-Barr virus subgroup from 75.5% to 51.0%, and finally decreased to 30.6%. Multivariate analysis revealed that 8-week treatment response was the most relevant factor for overall survival. Excluding 8-week response, the presence of Epstein-Barr virus, old age, hyperferritinemia, and thrombocytopenia were associated with poor survival. We established a prognostic model with the parameters: low-risk (score 0-1), intermediate-risk (score 2), and high-risk (score ≥3). These groups had 5-year overall survival rates of 92.1%, 36.8%, and 18.0%, respectively (P<0.001). We found that 8-week treatment response was a good predictor for overall survival, and that Epstein-Barr virus, old age, thrombocytopenia, and hyperferritinemia were associated with poor survival outcomes. Physicians should take care to identify high-risk patients for appropriate treatment strategies.
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Project description:Children with osteogenesis imperfecta (OI) type VI often have high fracture rates despite the current standard treatment with bisphosphonates. Subcutaneous injections of denosumab have been proposed as an alternative treatment approach, but safety data on denosumab in children are limited. Here we describe fluctuations in bone and mineral metabolism during denosumab treatment in four children with OI type VI who started denosumab (basic protocol: 1 mg per kg body mass every 3 months) between 1.9 and 9.0 years of age, after having received intravenous bisphosphonates previously. All four children developed hypercalciuria during active denosumab therapy. In two children aged 3.9 and 4.6 years, episodes of hypercalcemia were observed between 7 and 12 weeks after the preceding denosumab injection. During times when the interval between denosumab injections was increased to 6 months for clinical reasons, lumbar spine bone mineral density z-scores decreased rapidly. It appears that the duration of action of denosumab is short and variable in children with OI type VI. These observations call into question the concept that denosumab can be used as a stand-alone alternative to bisphosphonates to treat children with OI.
| S-EPMC5881132 | biostudies-literature
Project description:Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin disorder. Although the patients are at risk for cutaneous squamous cell carcinoma (SCC), no case of cutaneous SCC derived from RDEB with humoral hypercalcemia of malignancy (HHM) has been reported. We present the first case report of a male patient with HHM with leukocytosis caused by cutaneous SCC resulting from RDEB. A 20-yr-old Japanese male patient with RDEB; the diagnosis was confirmed by electron microscopic examination, suffered an intractable skin ulcer and hypercalcemia and leukocytosis. PTH-rP, SCC antigen and Granulocyte colony-stimulating factor (G-CSF) levels were elevated. The histological diagnosis of the skin lesion was made well-differentiated SCC. Immunohistochemical staining showed the expression of PTH-rP in atypical tumor cells. For the control of hypercalcemia before an amputation, we used zoledronate safely and could control the serum Ca concentration in the normal range. After the amputation of his right leg including SCC, leukocytosis improved immediately and PTH-rP in blood decreased to the normal range. One month after the amputation, local recurrence of cutaneous SCC and multiple lung metastases were observed. PTH-rP increased gradually associated with hypercalcemia. Although the patient reached an unfortunate turning point about 4 mo after the amputation, we propose that zoledronate is an effective and safe treatment for HHM with cardiorenal complications.
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Project description: Not available
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Project description:BACKGROUND:Surgical and medical treatments for emphysema may affect both quality and quantity of life. The purpose of this article is to report outcomes from the National Emphysema Treatment Trial (NETT) using an index that combines quality and quantity of life. METHODS:This was a prospective randomized clinical trial. Following pulmonary rehabilitation, 1,218 patients with severe emphysema were randomly assigned to maximal medical therapy or to lung volume reduction surgery (LVRS). A generic quality-of-life measure, known as the Quality of Well-being Scale (QWB), was administered at baseline and again at 6, 12, 24, 36, 48, 60, and 72 months following treatment assignment. RESULTS:At baseline, QWB scores were comparable for the Medical and LVRS groups. For both groups, scores significantly improved following the rehabilitation program. The QWB scores before death for patients in the LVRS group improved up to the year 2 visit, whereas scores for the Medical group dropped significantly following the baseline visit. Imputing zeros (0) for death, QWB scores decreased significantly for both groups. With or without scoring death as 0, the LVRS group achieved better outcomes, and the significant differences were maintained until the sixth year. Over 6 years of follow-up, LVRS produced an average of 0.30 quality-adjusted life years (QALYs), or the equivalent of about 3.6 months of well life. CONCLUSIONS:Compared with maximal medical therapy alone, patients undergoing maximal medical therapy plus LVRS experienced improved health-related quality of life and gained more QALYs. TRIAL REGISTRY:ClinicalTrials.gov; No.: NCT00000606; URL: www.clinicaltrials.gov.
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Project description:BackgroundLandmark clinical trials have led to optimal treatment recommendations for patients with diabetes. Whether optimal treatment is actually delivered in practice is even more important than the efficacy of the drugs tested in trials. To this end, treatment quality indicators have been developed and tested against intermediate outcomes. No studies have tested whether these treatment quality indicators also predict hard patient outcomes.MethodsA cohort study was conducted using data collected from >10.000 diabetes patients in the Groningen Initiative to Analyze Type 2 Treatment (GIANTT) database and Dutch Hospital Data register. Included quality indicators measured glucose-, lipid-, blood pressure- and albuminuria-lowering treatment status and treatment intensification. Hard patient outcome was the composite of cardiovascular events and all-cause death. Associations were tested using Cox regression adjusting for confounding, reporting hazard ratios (HR) with 95% confidence intervals.ResultsLipid and albuminuria treatment status, but not blood pressure lowering treatment status, were associated with the composite outcome (HR?=?0.77, 0.67-0.88; HR?=?0.75, 0.59-0.94). Glucose lowering treatment status was associated with the composite outcome only in patients with an elevated HbA1c level (HR?=?0.72, 0.56-0.93). Treatment intensification with glucose-lowering but not with lipid-, blood pressure- and albuminuria-lowering drugs was associated with the outcome (HR?=?0.73, 0.60-0.89).ConclusionTreatment quality indicators measuring lipid- and albuminuria-lowering treatment status are valid quality measures, since they predict a lower risk of cardiovascular events and mortality in patients with diabetes. The quality indicators for glucose-lowering treatment should only be used for restricted populations with elevated HbA1c levels. Intriguingly, the tested indicators for blood pressure-lowering treatment did not predict patient outcomes. These results question whether all treatment indicators are valid measures to judge quality of health care and its economics.
| S-EPMC3813585 | biostudies-literature
Project description:IntroductionRetroperitoneal fibrosis (RPF) is characterized by a highly fibrotic retroperitoneal mass and encompasses the idiopathic form and secondary to malignancies. Because we have limited knowledge whether RPF is associated with malignancy, we aimed to investigate the relationship between RPF and malignancy and to compare the characteristics and prognosis of cancers among patients with RPF.MethodsMedical records of 111 patients diagnosed as having RPF were reviewed and 38 cases of cancer, confirmed by biopsy, were identified. Standardized incidence ratios (SIRs) were calculated for cancers and stratified according to cancer type and RPF-cancer diagnosis interval. Cancer characteristics and outcomes were compared between RPF-cancer diagnosis intervals.ResultsThe average age at RPF diagnosis was 59.2 ± 15.0 years, and 69.4% of the patients were male. The cancer SIRs in patients with RPF relative to age- and sex-matched individuals in the general population was 2.2 (1.6-3.1). SIRs of renal pelvis cancer and multiple myeloma were significantly higher than in the general population. When stratified by RPF-cancer intervals, the SIR for cancer was 9.9 within 1 year of RPF diagnosis, while no significant increase in the SIR was found after 1 year from RPF diagnosis. Cancer stage was more advanced at the time of diagnosis in patients within a 1-year interval for RPF than those with cancer within a >5-year interval, with a correspondingly increased mortality in the former patients.ConclusionsRPF was significantly associated with malignancy, particularly those diagnosed within 1 year of RPF diagnosis. Cancer stages at diagnosis were more advanced and the mortality rate was higher in patients within a 1-year interval between RPF and cancer diagnosis than in those with a >5-year interval between diagnoses.
| S-EPMC8474894 | biostudies-literature