A Beautiful Death

Documented Pain Diagnoses in Adults Prescribed Opioids: Results From the National Ambulatory Medical Care Survey, 2006–2015

Screening for Urinary Incontinence in Women: A Recommendation From the Women's Preventive Services Initiative

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Description: Recommendation on screening for urinary incontinence in women by the Women's Preventive Services Initiative (WPSI), a national coalition of women's health professional organizations and patient representatives. The WPSI's recommendations are intended to guide clinical practice and coverage of services for the Health Resources and Services Administration and other stakeholders. The target audience for this recommendation includes all clinicians providing preventive health care for women, particularly in primary care settings. This recommendation applies to women of all ages, as well as adolescents. Methods: The WPSI developed this recommendation after evaluating evidence regarding the benefits and harms of screening for urinary incontinence in women. The evaluation included a systematic review of the accuracy of screening instruments and the benefits and harms of treatments. Indirect evidence was used to link screening and health outcomes in the chain of evidence that might support screening in the absence of direct evidence. The WPSI also considered the effect of screening on symptom progression and avoidance of costly and complex treatments, as well as implementation factors. Recommendation: The WPSI recommends screening women for urinary incontinence annually. Screening ideally should assess whether women experience urinary incontinence and whether it affects their activities and quality of life. The WPSI recommends referring women for further evaluation and treatment if indicated.

Fracture Risk After Initiation of Use of Canagliflozin: A Cohort Study: Annals of Internal Medicine: Vol 170, No 3

Background: Sodium–glucose cotransporter-2 inhibitors promote glycosuria, resulting in possible effects on calcium, phosphate, and vitamin D homeostasis. Canagliflozin is associated with decreased bone mineral density and a potential increased risk for fracture. Objective: To estimate risk for nonvertebral fracture among new users of canagliflozin compared with a glucagon-like peptide-1 (GLP-1) agonist. Design: Population-based new-user cohort study. Setting: Two U.S. commercial health care databases providing data on more than 70 million patients from March 2013 to October 2015. Patients: Persons with type 2 diabetes who initiated use of canagliflozin were propensity score–matched in a 1:1 ratio to those initiating use of a GLP-1 agonist. Measurements: The primary outcome was a composite end point of humerus, forearm, pelvis, or hip fracture requiring intervention. Secondary outcomes included fractures at other sites. A fixed-effects meta-analysis that pooled results from the 2 databases provided an overall hazard ratio (HR). Results: 79 964 patients initiating use of canagliflozin were identified and matched to 79 964 patients initiating use of a GLP-1 agonist. Mean age was 55 years, 48% were female, average baseline hemoglobin A1c level was 8.7%, and 27% were prescribed insulin. The rate of the primary outcome was similar for canagliflozin (2.2 events per 1000 person-years) and GLP-1 agonists (2.3 events per 1000 person-years), with an overall HR of 0.98 (95% CI, 0.75 to 1.26). Risk for pelvic, hip, humerus, radius, ulna, carpal, metacarpal, metatarsal, or ankle fracture was also similar for canagliflozin (14.5 events per 1000 person-years) and GLP-1 agonists (16.1 events per 1000 person-years) (overall HR, 0.92 [CI, 0.83 to 1.02]). Limitation: Unmeasured confounding, measurement error, and low fracture rate. Conclusion: In this study of middle-aged patients with type 2 diabetes and relatively low fracture risk, canagliflozin was not associated with increased risk for fracture compared with GLP-1 agonists. Primary Funding Source: Brigham and Women's Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics.

National Institutes of Health Pathways to Prevention Workshop: Methods for Evaluating Natural Experiments in Obesity

On 5 and 6 December 2017, the National Institutes of Health (NIH) convened the Pathways to Prevention Workshop: Methods for Evaluating Natural Experiments in Obesity to identify the status of methods for assessing natural experiments to reduce obesity, areas in which these methods could be improved, and research needs for advancing the field. This article considers findings from a systematic evidence review on methods for evaluating natural experiments in obesity, workshop presentations by experts and stakeholders, and public comment. Research gaps are identified, and recommendations related to 4 key issues are provided. Recommendations on population-based data sources and data integration include maximizing use and sharing of existing surveillance and research databases and ensuring significant effort to integrate and link databases. Recommendations on measurement include use of standardized and validated measures of obesity-related outcomes and exposures, systematic measurement of co-benefits and unintended consequences, and expanded use of validated technologies for measurement. Study design recommendations include improving guidance, documentation, and communication about methods used; increasing use of designs that minimize bias in natural experiments; and more carefully selecting control groups. Cross-cutting recommendations target activities that the NIH and other funders might undertake to improve the rigor of natural experiments in obesity, including training and collaboration on modeling and causal inference, promoting the importance of community engagement in the conduct of natural experiments, ensuring maintenance of relevant surveillance systems, and supporting extended follow-up assessments for exemplar natural experiments. To combat the significant public health threat posed by obesity, researchers should continue to take advantage of natural experiments. The recommendations in this report aim to strengthen evidence from such studies.

Precision Medicine in Internal Medicine

Medicine has long sought to match diagnostic and treatment approaches to the particular needs and risks of individual patients. The decreasing cost and increasing ease of genetic sequencing have propelled the rise of precision medicine. Precision medicine aims to use genetic and other information to provide care tailored to the individual patient, with the goal of improving clinical outcomes and minimizing unnecessary diagnostic and therapeutic interventions. Although developments in genetic sequencing have the potential to transform clinical care, there are important limitations, including uncertainty in the clinical interpretation of many genetic variants and concerns about privacy, discrimination, and cost. To help clinicians understand the basics of genetic sequencing and how to apply it in clinical practice, Annals of Internal Medicine is launching a new “Precision Medicine” series. This introduction provides a general overview of clinical sequencing, with a focus on germline variation. Subsequent articles will use a case-based format to provide concise summaries of specific clinical precision medicine scenarios that are relevant to the practice of internal medicine. These cases will highlight specific clinical indications; interpretation of genetic test results; and ethical, legal, cost, and privacy issues related to genetic testing. The goal is to provide practical information on the appropriate application and interpretation of genomics in routine clinical practice.

Should This Patient Receive Prophylactic Medication to Prevent Delirium?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 168, No 7

In 2015, the American Geriatrics Society released recommendations for prevention and management of postoperative delirium, based on a systematic literature review and evaluation of nonpharmacologic and pharmacologic approaches by an expert panel. The guidelines recommend an interdisciplinary focus on nonpharmacologic measures (reorientation, medication management, early mobility, nutrition, and gastointestinal motility) for prevention and consideration of this strategy for acute management. They also recommend optimizing nonopioid medication as a means to manage pain and avoiding benzodiazepines other than to treat substance withdrawal. The authors concluded that evidence to recommend antipsychotics for prevention of delirium is insufficient but that these drugs may be considered for short-term treatment in the setting of imminent harm to the patient or caregivers or severe distress due to agitation. Patients should be given the lowest possible dose for the shortest duration when other nonpharmacologic measures have failed. In this Beyond the Guidelines, a psychiatrist and a geriatrician debate whether Mr. W, a 79-year-old man at high risk for postoperative delirium, should receive prophylactic antipsychotics with his next surgery. They review risk factors, appropriate evaluation, and potential benefits and harms of the various medications often used in this setting.

Harms Reporting in Randomized Controlled Trials of Interventions Aimed at Modifying Microbiota: A Systematic Review: Annals of Internal Medicine: Vol 169, No 4

Background: Probiotics, prebiotics, and synbiotics are used increasingly, although the safety and potential harms of these interventions are poorly understood. Purpose: To examine how harms-related information is reported in publications of randomized controlled trials (RCTs) of probiotics, prebiotics, and synbiotics. Data Sources: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science (without language restrictions) from 1 January 2015 to 20 March 2018. Study Selection: RCTs assessing the safety or efficacy of at least 1 intervention involving probiotics, prebiotics, or synbiotics alone or in combination with another intervention compared with any control (such as a placebo or an antibiotic) for any clinical condition. Data Extraction: 4 reviewers independently assessed study characteristics, the reporting of harms, and the presentation of safety results. Data Synthesis: Of 384 trials conducted in healthy volunteers (n = 136) or patients with any of several medical conditions (n = 248), 339 (88%) were published in specialty journals. Trials most often evaluated probiotics (n = 265 [69%]). Studies in persons with medical conditions enrolled outpatients (n = 195) and high-risk patients (n = 53). No harms-related data were reported for 106 trials (28%), safety results were not reported for 142 (37%), and the number of serious adverse events (SAEs) per study group was not given for 309 (80%). Of 242 studies mentioning harms-related results, 37% (n = 89) used only generic statements to describe AEs and 16% (n = 38) used inadequate metrics. Overall, 375 trials (98%) did not give a definition for AEs or SAEs, the number of participant withdrawals due to harms, or the number of AEs and SAEs per study group with denominators. Limitation: Journal publication processes may have affected the completeness of reporting; only English-language publications were examined. Conclusion: Harms reporting in published reports of RCTs assessing probiotics, prebiotics, and synbiotics often is lacking or inadequate. We cannot broadly conclude that these interventions are safe without reporting safety data. Primary Funding Source: No specific funding.

Value-Based Health Care Meets Cost-Effectiveness Analysis

Value-based health care (VBHC) has recently emerged as a prominent movement within health care. Value-based health care focuses on maximizing outcomes achieved per dollar spent. As such, it bears many similarities to a well-established method, cost-effectiveness analysis (CEA), which provides a framework for comparing the relative value of different diagnostic or treatment interventions. Both approaches address “bang for the health care buck,” but although they overlap in many ways, VBHC and CEA differ with regard to their main applications, their perspective, and the types of costs and outcomes they consider. For example, CEA generally considers costs and benefits from the societal or health care sector perspectives, whereas VBHC is intended to adopt the patient perspective. As such, CEA is intended to inform coverage decisions at a group or population level and VBHC is intended to be implemented at the level of clinician–patient interactions. Meanwhile, value-based payment has emerged as a visible component of VBHC and is gaining a foothold in the United States in various forms, particularly bundled payments and accountable care organizations, in an effort to reward high-value care and disincentivize low-value care. Differences aside, as the worlds of VBHC and CEA begin to intersect, each discipline can learn from the other.

β-Blocker Use in Pregnancy and the Risk for Congenital Malformations: An International Cohort Study: Annals of Internal Medicine: Vol 169, No 10

Background: β-Blockers are a class of antihypertensive medications that are commonly used in pregnancy. Objective: To estimate the risks for major congenital malformations associated with first-trimester exposure to β-blockers. Design: Cohort study. Setting: Health registries in the 5 Nordic countries and the U.S. Medicaid database. Patients: Pregnant women with a diagnosis of hypertension and their offspring. Measurements: First-trimester exposure to β-blockers was assessed. Outcomes were any major congenital malformation, cardiac malformations, cleft lip or palate, and central nervous system (CNS) malformations. Propensity score stratification was used to control for potential confounders. Results: Of 3577 women with hypertensive pregnancies in the Nordic cohort and 14 900 in the U.S. cohort, 682 (19.1%) and 1668 (11.2%), respectively, were exposed to β-blockers in the first trimester. The pooled adjusted relative risk (RR) and risk difference per 1000 persons exposed (RD1000) associated with β-blockers were 1.07 (95% CI, 0.89 to 1.30) and 3.0 (CI, −6.6 to 12.6), respectively, for any major malformation; 1.12 (CI, 0.83 to 1.51) and 2.1 (CI, −4.3 to 8.4) for any cardiac malformation; and 1.97 (CI, 0.74 to 5.25) and 1.0 (CI, −0.9 to 3.0) for cleft lip or palate. For CNS malformations, the adjusted RR was 1.37 (CI, 0.58 to 3.25) and the RD1000 was 1.0 (CI, −2.0 to 4.0) (based on U.S. cohort data only). Limitation: Analysis was restricted to live births, exposure was based on dispensed medication, and cleft lip or palate and CNS malformations had few outcomes. Conclusion: The results suggest that maternal use of β-blockers in the first trimester is not associated with a large increase in the risk for overall malformations or cardiac malformations, independent of measured confounders. Primary Funding Source: The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Söderström König Foundation.