Jounghee Lee

Vitamin D With or Without Calcium Supplementation for Prevention of Cancer and Fractures: An Updated Meta-analysis for the U.S. Preventive Services Task Force

BACKGROUND Studies suggest that vitamin D supplementation may reduce cancer and fracture risks. PURPOSE To examine the benefits and harms of vitamin D with or without calcium supplementation on clinical outcomes of cancer and fractures in adults. DATA SOURCES English-language studies identified from MEDLINE and the Cochrane Central Register of Controlled Trials through July 2011. STUDY SELECTION Randomized, controlled trials (RCTs), prospective cohort studies, and nested case-control studies reporting incidence of or death from cancer and fracture outcomes. DATA EXTRACTION Multiple reviewers extracted details about participant characteristics, including baseline vitamin D status and use of supplements; details of statistical analyses, including adjustments for confounding; and methodological quality. Differences were resolved by consensus. DATA SYNTHESIS 19 RCTs (3 for cancer and 16 for fracture outcomes) and 28 observational studies (for cancer outcomes) were analyzed. Limited data from RCTs suggested that high-dose (1000 IU/d) vitamin D supplementation can reduce the risk for total cancer, and data from observational studies suggested that higher blood 25-hydroxyvitamin D (25-[OH]D) concentrations might be associated with increased risk for cancer. Mixed-effects dose-response meta-analyses showed that each 10-nmol/L increase in blood 25-(OH)D concentration was associated with a 6% (95% CI, 3% to 9%) reduced risk for colorectal cancer but no statistically significant dose-response relationships for prostate and breast cancer. Random-effects model meta-analysis showed that combined vitamin D and calcium supplementation reduced fracture risk (pooled relative risk, 0.88 [CI, 0.78 to 0.99]) in older adults, but the effects differed according to study setting: institution (relative risk, 0.71 [CI, 0.57 to 0.89]) versus community-dwelling (relative risk, 0.89 [CI, 0.76 to 1.04]). One RCT showed adverse outcomes associated with supplementation, including increased risk for renal and urinary tract stones. LIMITATIONS Most trial participants were older (aged≥65 years) postmenopausal women. Observational studies were heterogeneous and were limited by potential confounders. CONCLUSION Combined vitamin D and calcium supplementation can reduce fracture risk, but the effects may be smaller among community-dwelling older adults than among institutionalized elderly persons. Appropriate dose and dosing regimens, however, require further study. Evidence is not sufficiently robust to draw conclusions regarding the benefits or harms of vitamin D supplementation for the prevention of cancer. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Cochlear Implantation in Adults: A Systematic Review and Meta-analysis

IMPORTANCE Sensorineural hearing loss is the third leading cause of years lived with disability worldwide. Cochlear implants may provide a viable alternative to hearing aids for this type of hearing loss. The Coverage and Analysis Group at the Centers for Medicare & Medicaid Services was interested in an evaluation of recently published literature on this topic. In addition, this meta-analysis is to our knowledge the first to evaluate quality-of-life (QOL) outcomes in adults with cochlear implants. OBJECTIVE To evaluate the communication-related outcomes and health-related QOL outcomes after unilateral or bilateral cochlear implantation in adults with sensorineural hearing loss. DATA SOURCES MEDLINE, Cochrane Central Register of Controlled Trials, Scopus, and previous reports from January 1, 2004, through May 31, 2012. STUDY SELECTION Published studies of adult patients undergoing unilateral or bilateral procedures with multichannel cochlear implants and assessments using open-set sentence tests, multisyllable word tests, or QOL measures. DATA EXTRACTION Five researchers extracted information on population characteristics, outcomes of interest, and study design and assessed the studies for risk of bias. Discrepancies were resolved by consensus. RESULTS A total of 42 studies met the inclusion criteria. Most unilateral implant studies showed a statistically significant improvement in mean speech scores as measured by open-set sentence or multisyllable word tests; meta-analysis revealed a significant improvement in QOL after unilateral implantation. Results from studies assessing bilateral implantation showed improvement in communication-related outcomes compared with unilateral implantation and additional improvements in sound localization compared with unilateral device use or implantation only. Based on a few studies, the QOL outcomes varied across tests after bilateral implantation. CONCLUSIONS AND RELEVANCE Unilateral cochlear implants provide improved hearing and significantly improve QOL, and improvements in sound localization are noted for bilateral implantation. Future studies of longer duration, higher-quality reporting, and large databases or registries of patients with long-term follow-up data are needed to yield stronger evidence.

Autologous CD34-selected blood progenitor cell transplants for patients with advanced multiple myeloma

Fifty-five patients with advanced multiple myeloma received purified CD34-selected peripheral blood progenitor cell transplants following myeloablative chemotherapy. A median of 4.1 × 106 CD34 cells/kg (range 1.2–30.7) were infused after busulfan (14 mg/kg) and cyclophosphamide (120 mg/kg); granulocyte–macrophage colony-stimulating factor was used until hematopoietic recovery. Median time to neutrophils >0.5 × 109/l and platelets >20 × 109/l were 12 days (range 10–16 and 8–184 days, respectively). Median follow-up of survivors from the time of transplantation is 33 months (range 7 to 44 months). Thirty-one patients are alive, 19 progression-free. Median progression-free survival is 14 months. Actuarial 3-year progression-free and overall survival are 29 ± 14% and 47 ± 17%. CD34-selection of peripheral blood progenitor cells provides effective hematopoietic support with significant progression-free and overall survival.

The Lack of Evidence for PET or PET/CT Surveillance of Patients with Treated Lymphoma, Colorectal Cancer, and Head and Neck Cancer: A Systematic Review

PET and PET/CT are widely used for surveillance of patients after cancer treatments. We conducted a systematic review to assess the diagnostic accuracy and clinical impact of PET and PET/CT used for surveillance in several cancers. Methods: We searched MEDLINE and Cochrane Library databases from 1996 to March 2012 for English-language studies of PET or PET/CT used for surveillance of patients with lymphoma, colorectal cancer, or head and neck cancer. We included prospective or retrospective studies that reported test accuracy and comparative studies that assessed clinical impact. Results: Twelve studies met our inclusion criteria: 6 lymphoma (n = 767 patients), 2 colorectal cancer (n = 96), and 4 head and neck cancer (n = 194). All studies lacked a uniform definition of surveillance and scan protocols. Half the studies were retrospective, and a third were rated as low quality. The majority reported sensitivities and specificities in the range of 90%–100%, although several studies reported lower results. The only randomized controlled trial, a colorectal cancer study with 65 patients in the surveillance arm, reported earlier detection of recurrences with PET and suggested improved clinical outcomes. Conclusion: There is insufficient evidence to draw conclusions on the clinical impact of PET or PET/CT surveillance for these cancers. The lack of standard definitions for surveillance, heterogeneous scanning protocols, and inconsistencies in reporting test accuracy preclude making an informed judgment on the value of PET for this potential indication.

Systematic review to support the development of nutrient reference intake values: challenges and solutions

Workshops sponsored by the Institute of Medicine (IOM) and the World Health Organization suggested that incorporating systematic (evidence) reviews into the process of updating nutrient reference values would provide a comprehensive and distilled evidence document to decision makers and enhance the transparency of the decision-making process the IOM used in recommending the Dietary Reference Intake values (DRIs) for US and Canadian populations. At the request of the US and Canadian government sponsors of the ongoing review of the 1997 vitamin D and calcium DRI values, the Tufts Evidence-based Practice Center performed a systematic review for the current DRI Committee to use early in its deliberations. We described the approach used to include systematic review into the IOM process for updating nutrient reference values and highlighted major challenges encountered along with the solutions used. The challenges stemmed from the need to review and synthesize a large number of primary studies covering a broad range of outcomes. We resolved these challenges by 1) working with a technical expert panel to prioritize and select outcomes of interest, 2) developing methods to use existing systematic reviews and documenting the limitations by doing so, 3) translating results from studies not designed to address issues of interest by using a transparent process, and 4) establishing tailored quality-assessment tools to assist in decision making. The experiences described in this article can serve as a basis for future improvements in systematic reviews of nutrients and to better integrate systematic review into development of future nutrient reference values.