Assessment of Bone Health Awareness and Education in Breast Cancer Patients with Bone Metastasis in the USA.

Bone metastases are common in advanced breast cancer (BC) patients and increase the risk for skeletal-related events (SREs), which present a significant health and economic burden. Bone targeting agents (BTAs) can improve health-related quality of life by delaying or preventing SREs; nevertheless, a significant portion of eligible BC patients are not receiving this therapy. A bone health education needs assessment survey was conducted to examine cancer-related bone health awareness and to identify opportunities to improve bone health education. Direct-to-patient outreach was used to recruit adult BC patients in the USA self-reporting a diagnosis of bone metastasis within the past 3 years. Of the 200 patients, 59% experienced at least one SRE prior to survey participation (44% radiation to bone, 29% bone fracture, 17% spinal cord compression, 15% surgery to bone), and 83% were currently receiving a BTA. Awareness of general cancer bone health, protection strategies against SREs, and screening tests were low to moderate. Patients currently not receiving a BTA were least knowledgeable about cancer bone health, with only 40% aware of BTAs as a protective strategy, and only 26% were very or extremely satisfied with the information received from healthcare providers. Sixty-two percent of patients wanted to receive information by more than one mode of communication. Notable gaps in bone health education were observed in bone metastatic BC patients at risk for SREs, suggesting the need for earlier and more effective communication and education strategies to promote appropriate BTA use and better health outcomes.

Osteonecrosis of the jaw among patients with cancer treated with denosumab or zoledronic acid: Results of a regulator-mandated cohort postauthorization safety study in Denmark, Norway, and Sweden.

BACKGROUND: Osteonecrosis of the jaw (ONJ) is an adverse effect of antiresorptive treatment. This study estimated incidence proportions and incidence rates of ONJ in cancer patients with bone metastases from solid tumors treated for the prevention of skeletal-related events in routine clinical practice. METHODS: This cohort study in Denmark, Norway, and Sweden in 2011-2018 included 3 treatment cohorts: a denosumab inception cohort (DEIC), a zoledronic acid inception cohort (ZAIC), and a denosumab-switch cohort (DESC). The authors estimated 1- to 5-year incidence proportions and incidence rates of ONJ overall, by cancer site (breast, prostate, or other solid tumor), and by country. ONJ diagnoses were confirmed by adjudication. RESULTS: There were 1340 patients in the DEIC, 1352 in the ZAIC, and 408 in the DESC. The median ages of the 3 cohorts were 70, 69, and 70 years, respectively; the proportions of men were 72.6%, 53.8%, and 48.3%, respectively; and the median follow-up was 19.8, 12.9, and 13.3 months, respectively. The 5-year incidence proportions of ONJ were 5.7% (95% confidence interval [CI], 4.4%-7.3%) in the DEIC, 1.4% (95% CI, 0.8%-2.3%) in the ZAIC, and 6.6% (95% CI, 4.2%-10.0%) in the DESC. The corresponding ONJ incidence rates per 100 person-years were 3.0 (95% CI, 2.3-3.7), 1.0 (95% CI, 0.6-1.5), and 4.3 (95% CI, 2.8-6.3). Incidence proportions and incidence rates were highest in patients with prostate cancer and in Denmark. CONCLUSIONS: This study provides estimates of the risk of medically confirmed ONJ among patients initiating denosumab or zoledronic acid in routine clinical practice in 3 Scandinavian countries. The results varied by cancer site and by country. LAY SUMMARY: Denosumab and zoledronic acid reduce the risk of bone fractures, pain, and surgery in patients with advanced cancers involving bone. Osteonecrosis of the jaw (ONJ)-death of a jawbone-is a known side effect of treatment with denosumab or zoledronic acid. The authors examined almost 2900 denosumab- or zoledronic acid-treated patients with cancer in Denmark, Norway, and Sweden. Over the course of 5 years, ONJ developed in 5.7% of the patients whose initial treatment was denosumab, in 1.4% of the patients whose initial treatment was zoledronic acid, and in 6.6% of the patients who switched from zoledronic acid to denosumab.

Assessment of Bone Health Education in US Multiple Myeloma and Solid Tumor Patients at Risk for Skeletal-Related Events.

PURPOSE: Cancer patients with bone metastasis (BM) from solid tumors or multiple myeloma (MM) have an increased risk of painful skeletal-related events (SREs), which can decrease quality of life and increase mortality. Bone targeting agents (BTAs) can help delay or prevent SREs; however, a significant portion of eligible patients are not receiving BTA therapy. This study was conducted to understand patient awareness of cancer-related bone health and to identify opportunities to improve bone health education in cancer patients at risk of SREs. METHODS: The online BonE heAlth eduCatiOn Needs assessment (BEACON) survey included questions about patient demographics, cancer diagnosis and treatments (including BTA usage), and extent and satisfaction with bone health education received. Direct-to-patient outreach was used to recruit patients. Eligible patients were US adults with a diagnosis of self-reported MM or BM from a solid tumor (breast, lung, or prostate cancer) within the past three years. RESULTS: Of 125 patients, 71% were diagnosed with solid tumors with BM and 29% with MM. At least one prior SRE was experienced by 57% of patients (38% radiation to bone, 32% bone fracture, 22% spinal cord compression, and 19% surgery to bone), and 74% were currently receiving BTA therapy. Awareness of cancer bone health, protection strategies, and screening tests was low to moderate; patients were least informed of the impact of lifestyle changes (38%) and specific cancer treatments (≤35%) on bone health. Sixty-two percent of patients were not completely satisfied with the bone health education received. Patients generally wanted more information (58%) and to receive information by more than one mode of communication. CONCLUSION: Notable gaps in bone health education were observed in cancer patients at risk for SREs indicating an important need for improved communication and education strategies to promote better health outcomes.

Navigating metastatic colorectal treatment options in the USA: a survey of patient acceptance of skin toxicities associated with Vectibix.

PURPOSE: To understand the extent to which metastatic colorectal cancer (mCRC) patients receive education on the prevention and management associated with skin rash following Vectibix treatment. Furthermore, to investigate how this adverse event affects a patient's quality of life (QoL) and influences their treatment decisions. METHODS: A cross-sectional survey was administered to 200 mCRC patients (100 Vectibix users and 100 Vectibix non-users). After excluding respondents who had used cetuximab, 61 Vectibix users and 56 Vectibix non-users remained. RESULTS: Most Vectibix users (79%) experienced a skin rash in response to treatment of which 65% considered the rash moderate, 27% mild, and 8% severe. Vectibix users generally felt they were adequately informed about the rash (83%), with the most common messages received related to sun protection. However, sunscreen was used by only 42% of patients prior to rash and 60% of patients following the appearance of rash. The use of oral antibiotics was low prior to rash (21%) and following rash (46%). Among patients experiencing a rash within the past week (n=16), 75% reported the rash had a large negative impact on their QoL based on the Dermatology Life Quality Index. CONCLUSION: There was a disconnect between patients feeling they were adequately informed and use of prevention and management strategies such as sun protection. This suggests a gap in patient education and adoption currently exists on management strategies both prior to and following the appearance of rash. Given the negative impact that skin toxicity has on the patient's quality of life, it is essential that patients receive and subsequently utilize all information that can minimize rash severity.

An evaluation of RAS testing among metastatic colorectal cancer patients in the USA.

Background: Data on RAS testing practices prior to metastatic colorectal cancer (mCRC) treatment initiation are lacking in the USA. Materials & methods: Flatiron data were utilized for patients diagnosed with mCRC between 2011 and 2017. Flatiron is a longitudinal, demographically and geographically diverse database representing data from over 1.5 million active US patients treated at 255 community and hospital-affiliated oncology clinics. Results: Among 17,387 mCRC patients 69% were RAS tested and 31% were never tested. Timing of RAS testing was as follows: 23% were tested at the time of their initial CRC diagnosis, 60% following mCRC diagnosis but prior to first line of treatment, 3% prior to third line, the remaining 14% were tested following third line. Conclusion: A third (31%) of patients failed to receive RAS testing, therefore all treatment options were unavailable to them. These data highlight how universal testing has not been achieved.

Biomarker testing and mutation prevalence in metastatic colorectal cancer patients in five European countries using a large oncology database.

Background: The literature on biomarker testing for metastatic colorectal cancer (mCRC) in Europe is scarce. This study aimed to estimate the percentage of mCRC patients from five European countries tested for biomarkers over time. Materials & methods: An oncology database was retrospectively analyzed; evaluated biomarkers were RAS, BRAF and microsatellite instability (MSI). The patients were drug treated during 2018 and tested for relevant biomarkers in 2013-2018. Results: RAS testing was conducted in >90% of mCRC patients from 2014 onwards. BRAF testing increased from 31% of mCRC patients in 2013 to 67% in 2018. MSI testing increased from 10 to 41%. There was no notable trend over time for RAS and BRAF mutation or MSI-high prevalence. Conclusion: Biomarker testing among patients diagnosed with mCRC was increased over time. This study demonstrates the quick uptake of biomarker testing in clinical practice. These findings are significant as biomarker-based drugs are becoming more common.

Lay abstract Each patient's cancer is unique. To find the best medicine for each patient, doctors perform tests to look at the cancer's genes. It is unknown how often and how well these tests are done. We tried to find this out for patients with cancer of the bowel or rectum that has spread to other organs. We found that an important genetic test called RAS is done in most patients. Other tests, called BRAF and microsatellite instability, are also conducted increasingly frequently. This is important because the results of such tests allow doctors to decide which drug(s) should be the most effective depending on the patient's cancer genes.

Impact of biomarkers and primary tumor location on the metastatic colorectal cancer first-line treatment landscape in five European countries.

Background: Advances in therapies for patients with metastatic colorectal cancer (mCRC) and improved understanding of prognostic and predictive factors have impacted treatment decisions. Materials & methods: This study used a large oncology database to investigate patterns of monoclonal antibody (mAb) plus chemotherapy treatment in France, Germany, Italy, Spain and the UK in mCRC patients treated in first line in 2018. Results: Anti-EGFR mAbs were most often administered to patients with RAS wild-type mCRC and those with left-sided tumors, while anti-VEGF mAbs were preferred in RAS mutant and right-sided tumors. Adopted treatment strategies differed between countries, largely due to reimbursement. Conclusion: Biomarker status and primary tumor location steered treatment decisions in first line. Adopted treatment strategies differed between participating countries.

Lay abstract Each patient's cancer is unique. For example, colon cancer on the left side is different from colon cancer on the right side. Colon cancer is different from cancer of the rectum. Cancers also have changes in their genes, which means some treatments should work, while others may not. Doctors can select among different medicines to find the drug that works best for each patient. We looked at patients with cancer of the colon or rectum that has spread to other organs. We tried to find out how doctors in Europe select drugs for their patients after performing tests called RAS or BRAF. We found that doctors make different choices in different countries.

Discharge status and post-discharge healthcare costs after skeletal-related event hospitalizations among medicare patients with bone metastatic solid tumors or multiple myeloma.

BACKGROUND: Previous studies have quantified direct inpatient costs of skeletal-related events (SREs); however, costs associated with subsequent post-SRE care have not been examined. METHODS: We identified two study cohorts using 2011-2015 Medicare 20% sample data: patients diagnosed with 1) bone metastases from solid tumors or 2) multiple myeloma (MM), both with SRE-related hospitalization discharge dates January 1, 2011-September 30, 2015. We assessed discharge status and costs from discharge to the earliest of death, end of Medicare enrollment, or December 31, 2015. Discharge status was defined as: skilled nursing facility (SNF), rehabilitation facility, hospice, home health agency (HHA), long-term care (LTC) nursing home, LTC hospital, or rehospitalization within or after 30 days. Percentage, stay duration, and Medicare costs were calculated for each setting. All analyses were descriptive. RESULTS: We identified 7988 bone metastases patients and 4277 MM patients discharged from index SRE-related hospitalizations; corresponding mean ages were 76.9 and 76.6 years. The largest proportion of bone metastases patients were discharged to SNF (32.9%), then HHA (13.7%), hospice (13.5%), and LTC (11.3%); the pattern was similar for MM patients (SNF, 35.9%; HHA, 18.2%; hospice, 7.2%; LTC, 1.5%). Almost 10% of patients in both cohorts were re-hospitalized within 30 days. Mean Medicare cost per patient per facility stay was < $10,000 for hospice, and from $15,517 for LTC nursing home to $49,729 for LTC hospital for MM patients. CONCLUSION: Most elderly cancer patients (>75%) require healthcare facility support after SRE-related hospitalization, with substantial associated costs. Post-discharge management is clinically and economically important.

Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta-analysis.

Studies have shown that the prevalence of RAS and BRAF mutations may differ by tumor sidedness among metastatic colorectal cancer (mCRC) patients. Both mutation status and tumor sidedness may impact survival and disease progression and RAS mutation status has been shown to predict response to anti-epidermal growth factor receptor (EGFR) therapy. A systematic literature review and meta-analysis were conducted to estimate the pooled prevalence of RAS and BRAF mutations by tumor sidedness in studies of mCRC patients. Forty-four studies comprising 15 981 mCRC patients tested for RAS and/or BRAF mutations were included in the meta-analyses. The prevalence of RAS mutations differed significantly by tumor side (32.4% among left-sided tumors, 41.3% among right-sided tumors; P = .017), as did the prevalence of KRAS mutations (35.8% among left-sided tumors, 46.3% among right-sided tumors; P < .0001) and BRAF mutations (4.3% among left-sided tumors, 16.3% among right-sided tumors; P < .0001). Among right-sided tumors, the prevalence of RAS and KRAS mutations varied significantly by study design, with higher prevalence among observational studies than clinical trials, and there was significant variation by study location for the prevalence of KRAS mutations in left-sided tumors and the prevalence of BRAF mutations in right-sided tumors. These results help to better characterize the mCRC population to better inform clinicians and researchers. Few of the included studies reported overall or progression-free survival (PFS) by both tumor sidedness and mutation status. As both of these factors may have prognostic impact, future studies should consider evaluating survival by these variables.

A National Survey of Medical Oncologist's Opinions and Perceptions for Managing Rash Among mCRC Patients Treated with Panitumumab.

INTRODUCTION: This study aimed to describe medical oncologist's opinions and perceptions regarding the management of dermatologic toxicities among metastatic colorectal cancer (mCRC) patients who were treated with panitumumab in the USA and assess if there were differences across demographic and clinical characteristics. METHODS: We developed a survey based on the current literature and expert opinions regarding the management of dermatologic toxicities. The survey was implemented online in September 2016. Eligible oncologists were board certified and had treated at least five new or continuing patients with mCRC in the last 3 months, among whom at least three patients had received or were currently receiving panitumumab. RESULTS: A total of 250 oncologists completed the survey. The data suggest that approximately 82% of patients received recommendations for moisturizer, 88% for sunscreen and 67% for ultraviolet (UV)-protective garments prior to or at the time of initiation of panitumumab therapy. There were minor differences in how dermatologic toxicities were managed across specific demographic or clinical groups. The data also suggest that the management associated with panitumumab use among mCRC patients can be greatly improved. CONCLUSIONS: Our results highlight the urgent need for heightened education regarding dermatologic toxicity management among oncologists who treated mCRC patients with panitumumab. Easily implemented strategies, such as moisturizer, sunscreen, and UV-protective garments should be recommended to all patients. FUNDING: Amgen, Inc. Plain language summary available for this article.

Dermatologic Toxicities: A Chart Review of Clinical Management Among Patients With Metastatic Colorectal Cancer Treated With Panitumumab.

BACKGROUND: At least 90% of patients with metastatic colorectal cancer (mCRC) who are treated with an anti-EGFR will develop a dermatologic toxicity. Preemptive management strategies have been shown to reduce the severity of rash. OBJECTIVES: This article aims to describe treatment modalities used for the management of dermatologic toxicity among patients with mCRC who were treated with panitumumab and to assess the proportion of patients who were recommended preemptive versus reactive management strategies. METHODS: This retrospective chart review evaluated different treatment modalities and routes of administration. The modalities were categorized as prescription or over-the-counter. The timing in relation to the first dose of panitumumab was used to define preemptive versus reactive treatments. FINDINGS: In a sample of 330 patients, only 10% of patients were recommended to begin treatment for rash preemptively. The two most common treatment modalities for preemptively and reactively treated patients were prescription oral antibiotics and prescription topical antibiotics.

Racial and Ethnic Variability in the Prevalence and Incidence of Comorbidities Associated with Gastric Cancer in the United States.

PURPOSE: Comorbidities are known to impact quality of life, treatment choices, and survival. Our objectives were to characterize comorbid conditions in a cohort of elderly gastric cancer patients and to determine if there is variability in the prevalence or incidence of the comorbid conditions across racial/ethnic groups. METHODS: A total of 12,612 individuals, ≥66 years of age, diagnosed with gastric cancer between 2000 and 2007, and an equal number of gender- and region-matched cancer-free individuals, were identified using the National Cancer Institute's Surveillance, Epidemiology, and End Results registry linked to Medicare claims in the United States. The prevalence (%) in the year before diagnosis and the 12-month incidence rates after diagnosis were estimated for 32 chronic and ten acute comorbid conditions for the entire cohort and by race/ethnicity (Asian, Black, Hispanic, White, and other) and Asian subgroups (e.g., Chinese, Filipino, Japanese, Pacific Islander). RESULTS: White and Black cases exhibited the highest prevalence of most comorbid conditions. Asian and Pacific Islander cases exhibited the lowest. There was substantial variability in the 12-month incidence of the comorbidities across the racial/ethnic groups. Electrolyte disorder was the most common incident condition among Whites and Blacks. With the exception of Whites, anemia was the most common incident condition in all racial and ethnic groups 180 days following chemotherapy. CONCLUSIONS: There is variability in the prevalence and incidence in comorbidities across racial/ethnic groups.

Changes in secondary hyperparathyroidism-related biochemical parameters and medication use following parathyroidectomy.

BACKGROUND: Little is known about changes in parathyroid hormone (PTH), calcium and phosphorous levels after parathyroidectomy in hemodialysis patients. We studied the effects of parathyroidectomy on these biochemical values in a large cohort of patients receiving maintenance hemodialysis. METHODS: This retrospective cohort study included patients identified in both the United States Renal Data System and the database of a large dialysis organization who underwent parathyroidectomy in 2007-09, were aged ≥ 18 years, had Medicare Parts A and B as primary payer and had received hemodialysis for ≥ 1 year pre-parathyroidectomy. Descriptive statistics were calculated for continuous variables; categorical variables were used to characterize the population and evaluate monthly laboratory and medication use; median values were calculated for laboratory measures. RESULTS: Among 1402 parathyroidectomy patients, mean age was 48.9 years, 52.4% were males, 58.8% were African American and mean dialysis duration was 7.5 years. Median PTH levels increased over the year before parathyroidectomy from 1039 to 1661 pg/mL and decreased afterward to 98 pg/mL at 1 month; levels remained ≥ 897 pg/mL for 10% of patients. Median calcium levels fell from 9.6 mg/dL before to 7.9 mg/dL 1 month after parathyroidectomy; levels were ≤ 7.1 mg/dL for 25% and remained ≤ 7.2 mg/dL for the lowest 25% at 3 months. Median phosphorous level was 6.8 mg/dL immediately before parathyroidectomy, decreased to 3.8 mg/dL immediately after and reached 5.8 mg/dL at 1 year. CONCLUSIONS: While PTH levels dropped after parathyroidectomy for most patients, surgery was sometimes ineffective in reducing levels and sometimes led to over-suppression. Hypocalcemia could be profound and long lasting, suggesting the need for prolonged vigilance.

Navigating the profits and pitfalls of governmental partnerships: the ICRC and intergovernmental relief, 1918-23.

The International Committee of the Red Cross (ICRC) is today a staunch proponent of the need for humanitarian organisations to remain independent of state interests, yet it deliberately solicited intergovernmental intervention in international relief after the First World War of 1914-18. This paper examines why an organisation committed to upholding the independence and impartiality of humanitarian action might still choose to partner with governmental bodies. It also highlights the historical beginnings of a linkage between international aid and geopolitics. To secure governmental funding for refugee relief during the 1920s, the ICRC argued that the humanitarian crises of the post-war years were a threat to the political and social stability of Europe. While this has become axiomatic, the interwar history of the ICRC demonstrates that the perceived connection between relief and geopolitical stability is historically constructed, and that it must continue to be asserted persuasively to be effective.

Parathyroid hormone change after cinacalcet initiation and one-year clinical outcome risk: a retrospective cohort study.

BACKGROUND: Cinacalcet reduces parathyroid hormone (PTH) levels in patients receiving hemodialysis, but no non-experimental studies have evaluated the association between changes in PTH levels following cinacalcet initiation and clinical outcomes. We assessed whether short-term change in PTH levels after first cinacalcet prescription could serve as a surrogate marker for improvements in longer-term clinical outcomes. METHODS: United States Renal Data System data were linked with data from a large dialysis organization. We created a point prevalent cohort of adult hemodialysis patients with Medicare as primary payer who initiated cinacalcet November 1, 2004-February 1, 2007, and were on cinacalcet for ≥ 40 days. We grouped patients into quartiles of PTH change after first cinacalcet prescription. We used Cox proportional hazard modeling to evaluate associations between short-term PTH change and time to first composite event (hospitalization for cardiovascular events or mortality) within 1 year. Overall models and models stratified by baseline PTH levels were adjusted for several patient-related factors. RESULTS: For 2485 of 3467 included patients (72%), PTH levels decreased after first cinacalcet prescription; for 982 (28%), levels increased or were unchanged. Several characteristics differed between PTH change groups, including age and mineral-and-bone-disorder laboratory values. In adjusted models, we did not identify an association between greater short-term PTH reduction and lower composite event rates within 1 year, overall or in models stratified by baseline PTH levels. CONCLUSIONS: Short-term change in PTH levels after first cinacalcet prescription does not appear to be a useful surrogate for longer-term improvements in cardiovascular or survival risk.

Refining the definition of clinically important mineral and bone disorder in hemodialysis patients.

BACKGROUND: It is important to identify an easily defined subset of patients at increased risk of adverse clinical outcomes associated with mineral and bone disorder (MBD) biomarkers (parathyroid hormone, calcium and phosphate). METHODS: Observational cohort study of 26 221 prevalent hemodialysis patients in Davita clinics as of 31 August 2005 and followed up until 31 December 2006 (16 months). Predictors were 12 possible definitions of 'clinically important' MBD based on all 3 biomarkers, and 18 alternative definitions based on only 1 or 2 biomarkers. Events were death alone and a composite of cardiovascular hospitalization or death. Excess events were calculated based on a multivariate Cox model using 5224 patients in target for all MBD biomarkers and applied to 20 997 patients out of target for at least one biomarker. Excess events attributable to MBD were estimated by subtracting the multivariate model-derived predicted number from the actual number. Outcomes were the proportion of excess events attributable to MBD captured by each definition (threshold ≥70%) and the reduction in the population size considered to have clinically important MBD (threshold ≥30%). The excess fraction was excess events divided by actual events. RESULTS: Patients with more biochemical markers out of target tended to be younger, black and have longer times since starting dialysis. The excess fraction associated with MBD ranged from ∼10 to 26% depending on the clinical endpoint and definition. The only definition to meet the thresholds required at least two of the three MBD biomarkers to be out of target (high or low). It captured 82% of excess composite endpoints and 74% of excess deaths and reduced the at-risk population by 46%. CONCLUSIONS: Patients with at least two of three MBD biomarkers out of target represent a subgroup of patients at elevated risk of adverse clinical events.

Clinical outcomes after parathyroidectomy in a nationwide cohort of patients on hemodialysis.

BACKGROUND AND OBJECTIVES: Patients receiving dialysis undergo parathyroidectomy to improve laboratory parameters in resistant hyperparathyroidism with the assumption that clinical outcomes will also improve. However, no randomized clinical trial data demonstrate the benefits of parathyroidectomy. This study aimed to evaluate clinical outcomes up to 1 year after parathyroidectomy in a nationwide sample of patients receiving hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the US Renal Data System, this study identified prevalent hemodialysis patients aged ≥18 years with Medicare as primary payers who underwent parathyroidectomy from 2007 to 2009. Baseline characteristics and comorbid conditions were assessed in the year preceding parathyroidectomy; clinical events were identified in the year preceding and the year after parathyroidectomy. After parathyroidectomy, patients were censored at death, loss of Medicare coverage, kidney transplant, change in dialysis modality, or 365 days. This study estimated cause-specific event rates for both periods and rate ratios comparing event rates in the postparathyroidectomy versus preparathyroidectomy periods. RESULTS: Of 4435 patients who underwent parathyroidectomy, 2.0% died during the parathyroidectomy hospitalization and the 30 days after discharge. During the 30 days after discharge, 23.8% of patients were rehospitalized; 29.3% of these patients required intensive care. In the year after parathyroidectomy, hospitalizations were higher by 39%, hospital days by 58%, intensive care unit admissions by 69%, and emergency room/observation visits requiring hypocalcemia treatment by 20-fold compared with the preceding year. Cause-specific hospitalizations were higher for acute myocardial infarction (rate ratio, 1.98; 95% confidence interval, 1.60 to 2.46) and dysrhythmia (rate ratio 1.4; 95% confidence interval1.16 to 1.78); fracture rates did not differ (rate ratio 0.82; 95% confidence interval 0.6 to 1.1). CONCLUSIONS: Parathyroidectomy is associated with significant morbidity in the 30 days after hospital discharge and in the year after the procedure. Awareness of clinical events will assist in developing evidence-based risk/benefit determinations for the indication for parathyroidectomy.

Value of symptom-triggered diagnostic evaluation for ovarian cancer.

OBJECTIVE: To evaluate the potential harms and ovarian cancer outcomes associated with symptom-triggered diagnostic evaluation of all women with symptoms of ovarian cancer. METHODS: Five thousand twelve women older than age 40 years were prospectively enrolled in a cohort study of proactive symptom-triggered diagnostic evaluation. Women who tested positive on a symptom index were offered testing with CA 125 and transvaginal ultrasonography. Results of these tests and any subsequent procedures were recorded. Assessment of ovarian cancer outcomes for all participants through Surveillance, Epidemiology, and End Results was performed 1 year after enrollment was complete. RESULTS: A positive symptom index was found in 241 (4.8%) participating patients, and 211 (88%) underwent CA 125 testing, transvaginal ultrasound screening, or both. Twenty surgical procedures (laparoscopy, laparotomy, vaginal) were performed in the study population (0.4% of participating women). However, only six (0.12%) were performed for a suspicious ovarian mass and only four (0.08%) were performed solely as a result of study participation. A total of eight ovarian cancers were diagnosed, 31-843 days after symptom assessment (50% distant, 50% local or regional). Of the two cancers diagnosed within 6 months, one was symptom index-positive. CONCLUSIONS: Proactive symptom-triggered diagnostic evaluation for ovarian cancer results in minimal unindicated surgery. A small number of ovarian cancers was identified solely on the basis of symptom-triggered diagnostic testing. LEVEL OF EVIDENCE: II.

CKD-mineral and bone disorder and risk of death and cardiovascular hospitalization in patients on hemodialysis.

BACKGROUND AND OBJECTIVES: Parathyroid hormone, calcium, and phosphate have been independently associated with cardiovascular event risk. Because these parameters may be on the same causal pathway and have been proposed as quality measures, an integrated approach to estimating event risks is needed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prevalent dialysis patients were followed from August 31, 2005 to December 31, 2006. A two-stage modeling approach was used. First, the 16-month probabilities of death and composite end point of death or cardiovascular hospitalization were estimated and adjusted for potential confounders. Second, patients were categorized into 1 of 36 possible phenotypes using average parathyroid hormone, calcium, and phosphate values over a 4-month baseline period. Associations among phenotypes and outcomes were estimated and adjusted for the underlying event risk estimated from the first model stage. RESULTS: Of 26,221 patients, 98.5% of patients were in 22 groups with at least 100 patients and 20% of patients were in the reference group defined using guideline-based reference ranges for parathyroid hormone, calcium, and phosphate. Within the 22 most common phenotypes, 20% of patients were in groups with significantly (P<0.05) higher risk of death and 54% of patients were in groups with significantly higher risk of the composite end point relative to the in-target reference group. Increased risks ranged from 15% to 47% for death and from 8% to 55% for the composite. More than 40% of all patients were in the three largest groups with elevated composite end point risk (high parathyroid hormone, target calcium, and high phosphate; target high parathyroid hormone, target calcium, and high phosphate; and target high parathyroid hormone, target calcium, and target phosphate). CONCLUSION: After adjusting for baseline risk, phenotypes defined by categories of parathyroid hormone, calcium, and phosphate identify patients at higher risk of death and cardiovascular hospitalization. Identifying common high-risk phenotypes may inform clinical interventions and policies related to quality of care.

An international assessment of ovarian cancer incidence and mortality.

OBJECTIVE: To assess and characterize the temporal variation in ovarian cancer incidence and mortality by age within countries in the Americas, Europe, Asia, and Oceania. METHODS/MATERIALS: Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program in the United States (U.S.) were used to assess ovarian cancer incidence rates (1998-2008) and mortality rates, (1988-2007 for 12-month survival, 1988-2006 for 24-month survival, and 1988-2003 for 60-month survival), stratified by age at diagnosis. Data from GLOBOCAN were used to calculate country-specific incidence rates for 2010 and 2020 and case-fatality rates for 2010. RESULTS: A statistically significant decrease in Annual Percent Change (APC) of ovarian cancer incidence was observed in the U.S. for all women (-1.03%), among women who were diagnosed at <65 years of age (-1.09%) and among women who were diagnosed at ≥65 years of age (-0.95%). There was a statistically significant increase in the observed APC for survival at 12-months (0.19%), 24-months (0.58%), and 60-months (0.72%) for all women; however, 5-year survival for advanced stage (III or IV) disease was low at less than 50% for women <65 years and less than 30% for women ≥65 years. Global results showed a wide range in ovarian cancer incidence rates, with China exhibiting the lowest rates and the Russian Federation and the United Kingdom exhibiting the highest rates. CONCLUSIONS: Ovarian cancer survival has shown modest improvement from a statistical perspective in the U.S. However, it is difficult to ascertain how clinically relevant these improvements are at the population or patient level.