Michael W. Yeh, MD; Hui Zhou, PhD; Annette L. Adams, PhD; Philip H.G. Ituarte, PhD, MPH; Ning Li, PhD; In-Lu Amy Liu, MS; and Philip I. Haigh, MD
Background: The comparative effectiveness of surgical and medical treatments on fracture risk in primary hyperparathyroidism (PHPT) is unknown.
Objective: To measure the relationship of parathyroidectomy and bisphosphonates with skeletal outcomes in patients with PHPT.
Design: Retrospective cohort study.
Setting: An integrated health care delivery system.
Participants: All enrollees with biochemically confirmed PHPT from 1995 to 2010.
Measurements: Bone mineral density (BMD) changes and fracture rate.
Results: In 2013 patients with serial bone density examinations, total hip BMD increased transiently in women with parathyroidectomy (4.2% at <2 years) and bisphosphonates (3.6% at <2 years) and declined progressively in both women and men without these treatments (−6.6% and −7.6%, respectively, at >8 years). In 6272 patients followed for fracture, the absolute risk for hip fracture at 10 years was 20.4 events per 1000 patients who had parathyroidectomy and 85.5 events per 1000 patients treated with bisphosphonates compared with 55.9 events per 1000 patients without these treatments. The risk for any fracture at 10 years was 156.8 events per 1000 patients who had parathyroidectomy and 302.5 events per 1000 patients treated with bisphosphonates compared with 206.1 events per 1000 patients without these treatments. In analyses stratified by baseline BMD status, parathyroidectomy was associated with reduced fracture risk in both osteopenic and osteoporotic patients, whereas bisphosphonates were associated with increased fracture risk in these patients. Parathyroidectomy was associated with fracture risk reduction in patients regardless of whether they satisfied criteria from consensus guidelines for surgery.
Limitation: Retrospective study design and nonrandom treatment assignment.
Conclusion: Parathyroidectomy was associated with reduced fracture risk, and bisphosphonate treatment was not superior to observation.
Primary Funding Source: National Institute on Aging.
Sengwee Toh, ScD; Christian Hampp, PhD; Marsha E. Reichman, PhD; David J. Graham, MD, MPH; Suchitra Balakrishnan, MD, PhD; Frank Pucino, PharmD, MPH; Jack Hamilton, AB; Samuel Lendle, PhD; Aarthi Iyer, JD, MPH; Malcolm Rucker, MS; Madelyn Pimentel, BA; Neesha Nathwani, BS; Marie R. Griffin, MD, MPH; Nancy J. Brown, MD; and Bruce H. Fireman, MA
Background: Recent postmarketing trials produced conflicting results about the risk for hospitalized heart failure (hHF) associated with dipeptidyl peptidase-4 (DPP-4) inhibitors, creating uncertainty about the safety of these antihyperglycemic agents.
Objective: To examine the associations of hHF with saxagliptin and sitagliptin.
Design: Population-based, retrospective, new-user cohort study.
Setting: 18 health insurance and health system data partners in the U.S. Food and Drug Administration's Mini-Sentinel program.
Patients: Patients aged 18 years or older with type 2 diabetes who initiated therapy with saxagliptin, sitagliptin, pioglitazone, second-generation sulfonylureas, or long-acting insulin products from 2006 to 2013.
Measurements: Hospitalized HF, identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes 402.x1, 404.x1, 404.x3, and 428.xx recorded as the principal discharge diagnosis.
Results: 78 553 saxagliptin users and 298 124 sitagliptin users contributed an average of 7 to 9 months of follow-up data to 1 or more pairwise comparisons. The risk for hHF was not higher with DPP-4 inhibitors than with the other study drugs. The hazard ratios from the disease risk score (DRS)–stratified analyses were 0.83 (95% CI, 0.70 to 0.99) for saxagliptin versus sitagliptin, 0.63 (CI, 0.47 to 0.85) for saxagliptin versus pioglitazone, 0.69 (CI, 0.54 to 0.87) for saxagliptin versus sulfonylureas, and 0.61 (CI, 0.50 to 0.73) for saxagliptin versus insulin. The DRS-stratified hazard ratios were 0.74 (CI, 0.64 to 0.85) for sitagliptin versus pioglitazone, 0.86 (CI, 0.77 to 0.95) for sitagliptin versus sulfonylureas, and 0.71 (CI, 0.64 to 0.78) for sitagliptin versus insulin. Results from the 1:1 propensity score–matched analyses were similar. Results were also similar in subgroups of patients with and without prior cardiovascular disease and in a subgroup defined by the 2 highest DRS deciles.
Limitation: Residual confounding and short follow-up.
Conclusion: In this large cohort study, a higher risk for hHF was not observed in users of saxagliptin or sitagliptin compared with other selected antihyperglycemic agents.
Primary Funding Source: U.S. Food and Drug Administration.
Risa B. Burns, MD, MPH; Carol K. Bates, MD; Pamela Hartzband, MD; and Gerald W. Smetana, MD
In May 2015, the U.S. Preventive Services Task Force issued a guideline on screening for thyroid disease that included a systematic evidence review and an update of its 2004 recommendations. The review assessed the effect of treating screen-detected subclinical thyroid dysfunction on health outcomes. It found adequate evidence that treating subclinical hypothyroidism does not provide clinically meaningful improvements in blood pressure, body mass index, bone mineral density, lipid levels, or quality-of-life measures. The review also concluded that evidence was inadequate to determine whether screening for thyroid dysfunction reduced cardiovascular disease or related morbidity and mortality. In separate guidelines, the American Association of Clinical Endocrinologists and American Thyroid Association advocated aggressive case-finding and recommended screening persons with certain clinical conditions or characteristics rather than the general population. These societies argue that subclinical hypothyroidism adversely affects cardiovascular outcomes and thus merits case-finding. Here, 2 experts discuss their perspectives on whether treating subclinical hypothyroidism reduces morbidity and mortality, whether there are harms of treatment, and how they would balance the benefits and harms of treatment both in general and for a specific patient.
Cancer patients should be largely exempt from regulations restricting access to or limiting doses of prescription opioids, according to a policy statement from the American Society of Clinical Oncology (ASCO).
"ASCO Policy Statement on Opioid Therapy: Protecting Access to Treatment for Cancer-Related Pain" provides principles that the society intends to balance the public health concerns regarding the abuse and misuse of prescription opioids with the need to ensure access to appropriate pain management for cancer patients and survivors.
The statement was posted on the ASCO Web site on May 23, as was a press release.
The statement's points include the following:
- Clinicians' opioid prescribing education should be evidence-based and tailored by specialty.
- The society does not support prescription limits that would artificially impede access to medically necessary treatment for patients with cancer. ASCO does support existing exemptions to prescribing limits for cancer patients and believes these exemptions should remain in place.
- Patient education on the medical use of opioids is best provided by a health professional. The society supports efforts by the government to encourage greater emphasis on safe storage and disposal of prescription medication and believes such efforts should be strengthened.
- Efforts to identify prescribing patterns must consider clinician specialty, subspecialization, patient populations, and other factors that legitimately influence prescribing patterns, because clinicians who treat cancer-related pain may prescribe relatively large numbers of opioids or provide multiple controlled drugs at relatively high doses.
- After the initial screening and assessment of patients with cancer, the type and timing of subsequent assessments should be determined by the treating physician. Adherence tools following an initial prescription may be valuable but should not be mandatory for all patients receiving opioids.
- Use of either an abuse-deterrent formulation or non-abuse-deterrent formulation of an opioid medication may be appropriate. The prescribing physician, in consultation with the patient, should decide which is preferred based on clinical and patient-specific circumstances.
- Individuals with an opioid-related disorder should have rapid access to appropriate assessment, diagnosis, and treatment, regardless of payer or geographic setting. ASCO fully supports efforts to expand the availability of medication-assisted treatment and to expand Medicare and Medicaid coverage of such treatment.
- ASCO supports increased access to naloxone in cases of opioid overdose. Caregivers should be instructed on the correct use of overdose antidotes, and such education should pay particular attention to timing the administration of the medication, as well as distinguishing the symptoms of an opioid overdose from those of advanced disease.
- Authorized collection sites should be readily available to patients to decrease the availability of unused or unwanted opioid drugs, and ASCO supports federal efforts to provide additional funding for these programs.
"ASCO is supportive of efforts to address issues of opioid abuse and its related consequences; however, some elements of both state and federal tightening of controls could introduce barriers to appropriate treatment of pain related to cancer and its treatment, thereby harming a vulnerable population," according to the statement. "There is already strong evidence of under treatment of cancer-related pain and new barriers would serve to worsen this situation."
- Extended aromatase inhibitor therapy appears to benefit postmenopausal patients with early-stage, hormone-receptor-positive breast cancer
- ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials
- The Prevalence of Resident-to-Resident Elder Mistreatment in Nursing Homes
- Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Population-Based Cohort Study