New Department of Veterans Affairs and Department of Defense Guidelines on Pain Management With Opioids: Comment and Concern

Concentration of Potentially Preventable Spending Among High-Cost Medicare Subpopulations: An Observational Study: Annals of Internal Medicine: Vol 167, No 10

Background: Little is known about whether potentially preventable spending is concentrated among a subset of high-cost Medicare beneficiaries. Objective: To determine the proportion of total spending that is potentially preventable across distinct subpopulations of high-cost Medicare beneficiaries. Design: Beneficiaries in the highest 10% of total standardized individual spending were defined as “high-cost” patients, using a 20% sample of Medicare fee-for-service claims from 2012. The following 6 subpopulations were defined using a claims-based algorithm: nonelderly disabled, frail elderly, major complex chronic, minor complex chronic, simple chronic, and relatively healthy. Potentially preventable spending was calculated by summing costs for avoidable emergency department visits using the Billings algorithm plus inpatient and associated 30-day postacute costs for ambulatory care–sensitive conditions (ACSCs). The amount and proportion of potentially preventable spending were then compared across the high-cost subpopulations and by individual ACSCs. Setting: Medicare. Participants: 6 112 450 Medicare beneficiaries. Measurements: Proportion of spending deemed potentially preventable. Results: In 2012, 4.8% of Medicare spending was potentially preventable, of which 73.8% was incurred by high-cost patients. Despite making up only 4% of the Medicare population, high-cost frail elderly persons accounted for 43.9% of total potentially preventable spending ($6593 per person). High-cost nonelderly disabled persons accounted for 14.8% of potentially preventable spending ($3421 per person) and the major complex chronic group for 11.2% ($3327 per person). Frail elderly persons accounted for most spending related to admissions for urinary tract infections, dehydration, heart failure, and bacterial pneumonia. Limitation: Potential misclassification in the identification of preventable spending and lack of detailed clinical data in administrative claims. Conclusion: Potentially preventable spending varied across Medicare subpopulations, with the majority concentrated among frail elderly persons. Primary Funding Source: The Commonwealth Fund.

Should This Patient Have Weight Loss Surgery?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 166, No 11

Obesity is an important public health priority in the United States. One third of U.S. adults are obese and therefore can expect higher rates of diabetes mellitus, other obesity-related comorbidities, and mortality. In 2013, the American Association of Clinical Endocrinologists, the Obesity Society, and the American Society for Metabolic and Bariatric Surgery issued a guideline that recommended weight loss (bariatric) surgery for all patients with a body mass index (BMI) of 40 kg/m2 or higher and for those with a BMI of 35 kg/m2 or greater in the presence of at least 1 obesity-related comorbidity. Among the 3 most commonly performed surgeries, the amount of excess weight reduction ranges from 49% for laparoscopic adjustable gastric banding to 76% for Roux-en-Y gastric bypass. In accredited centers, perioperative mortality averages 0.3%. In this Beyond the Guidelines, 2 experts in obesity management, a bariatric surgeon and a general internist, discuss the role of weight loss surgery versus dietary and lifestyle modification, both in general and for a specific patient who is eligible for surgery. Ethnic and age-related variability in the effects of obesity on mortality, as well as potential long-term benefits and risks of weight loss surgery for patient subgroups, are discussed.

Evaluating Vaccination Strategies for Zika Virus in the Americas

Background: Mosquito-borne and sexually transmitted Zika virus has become widespread across Central and South America and the Caribbean. Many Zika vaccine candidates are under active development. Objective: To quantify the effect of Zika vaccine prioritization of females aged 9 to 49 years, followed by males aged 9 to 49 years, on incidence of prenatal Zika infections. Design: A compartmental model of Zika transmission between mosquitoes and humans was developed and calibrated to empirical estimates of country-specific mosquito density. Mosquitoes were stratified into susceptible, exposed, and infected groups; humans were stratified into susceptible, exposed, infected, recovered, and vaccinated groups. Age-specific fertility rates, Zika sexual transmission, and country-specific demographics were incorporated. Setting: 34 countries and territories in the Americas with documented Zika outbreaks. Target Population: Males and females aged 9 to 49 years. Intervention: Age- and sex-targeted immunization using a Zika vaccine with 75% efficacy. Measurements: Annual prenatal Zika infections. Results: For a base-case vaccine efficacy of 75% and vaccination coverage of 90%, immunizing females aged 9 to 49 years (the World Health Organization target population) would reduce the incidence of prenatal infections by at least 94%, depending on the country-specific Zika attack rate. In regions where an outbreak is not expected for at least 10 years, vaccination of women aged 15 to 29 years is more efficient than that of women aged 30 years or older. Limitation: Population-level modeling may not capture all local and neighborhood-level heterogeneity in mosquito abundance or Zika incidence. Conclusion: A Zika vaccine of moderate to high efficacy may virtually eliminate prenatal infections through a combination of direct protection and transmission reduction. Efficiency of age-specific targeting of Zika vaccination depends on the timing of future outbreaks. Primary Funding Source: National Institutes of Health.

The Challenges of Research on Interventions for Low Back Pain

Comparative Analysis of Biopsy Upgrading in Four Prostate Cancer Active Surveillance Cohorts

Background: Active surveillance (AS) is increasingly accepted for managing low-risk prostate cancer, yet there is no consensus about implementation. This lack of consensus is due in part to uncertainty about risks for disease progression, which have not been systematically compared or integrated across AS studies with variable surveillance protocols and dropout to active treatment. Objective: To compare risks for upgrading from a Gleason score (GS) of 6 or less to 7 or more across AS studies after accounting for differences in surveillance intervals and competing treatments and to evaluate tradeoffs of more versus less frequent biopsies. Design: Joint statistical model of longitudinal prostate-specific antigen (PSA) levels and risks for biopsy upgrading. Setting: Johns Hopkins University (JHU); Canary Prostate Active Surveillance Study (PASS); University of California, San Francisco (UCSF); and University of Toronto (UT) AS studies. Patients: 2576 men aged 40 to 80 years with a GS between 2 and 6 and clinical stage T1 or T2 prostate cancer enrolled between 1995 and 2014. Measurements: PSA levels and biopsy GSs. Results: After variable surveillance intervals and competing treatments were accounted for, estimated risks for biopsy upgrading were similar in the PASS and UT studies but higher in UCSF and lower in JHU studies. All cohorts had a delay of 3 to 5 months in detecting upgrading with biennial biopsies starting after a first confirmatory biopsy versus annual biopsies. Limitation: The model does not account for possible misclassification of biopsy GS. Conclusion: Men in different AS studies have different risks for biopsy upgrading after variable surveillance protocols and competing treatments are accounted for. Despite these differences, the consequences of more versus less frequent biopsies seem to be similar across cohorts. Biennial biopsies seem to be an acceptable alternative to annual biopsies. Primary Funding Source: National Cancer Institute.

Low-Dose Intravenous Immunoglobulin Treatment for Long-Standing Complex Regional Pain Syndrome: A Randomized Trial: Annals of Internal Medicine: Vol 167, No 7

Background: Two small trials suggest that low-dose intravenous immunoglobulin (IVIg) may improve the symptoms of complex regional pain syndrome (CRPS), a rare posttraumatic pain condition. Objective: To confirm the efficacy of low-dose IVIg compared with placebo in reducing pain during a 6-week period in adult patients who had CRPS from 1 to 5 years. Design: 1:1 parallel, randomized, placebo-controlled, multicenter trial for 6 weeks, with an optional 6-week open extension. Patients were randomly assigned to 1 of 2 study groups between 27 August 2013 and 28 October 2015; the last patient completed follow-up on 21 March 2016. Patients, providers, researchers, and outcome assessors were blinded to treatment assignment. (ISRCTN42179756) Setting: 7 secondary and tertiary care pain management centers in the United Kingdom. Participants: 111 patients with moderate or severe CRPS of 1 to 5 years' duration. Intervention: IVIg, 0.5 g/kg of body weight, or visually indistinguishable placebo of 0.1% albumin in saline on days 1 and 22 after randomization. Measurements: The primary outcome was 24-hour average pain intensity, measured daily between days 6 and 42, on an 11-point (0- to 10-point) rating scale. Secondary outcomes were pain interference and quality of life. Results: The primary analysis sample consisted of 108 eligible patients, 103 of whom had outcome data. Mean (average) pain scores were 6.9 points (SD, 1.5) for placebo and 7.2 points (SD, 1.3) for IVIg. The adjusted difference in means was 0.27 (95% CI, −0.25 to 0.80; P = 0.30), which excluded the prespecified, clinically important difference of −1.2. No statistically significant differences in secondary outcomes were found between the groups. In the open extension, 12 of the 67 patients (18%) who received 2 IVIg infusions had pain reduction of at least 2 points compared with their baseline score. Two patients in the blinded phase (1 in the placebo and 1 in the IVIg group) and 4 in the open IVIg phase had serious events. Limitations: Results do not apply to patients who have had CRPS for less than 1 year or more than 5 years and do not extend to full-dose treatment (for example, 2 g/kg). The study was inadequately powered to detect subgroup effects. Conclusion: Low-dose immunoglobulin treatment for 6 weeks was not effective in relieving pain in patients with moderate to severe CRPS of 1 to 5 years' duration. Primary Funding Source: Medical Research Council/National Institute for Health Research Efficacy and Mechanism Evaluation Program, Pain Relief Foundation, and Biotest United Kingdom.

Functional Impairment and Decline in Middle Age: A Cohort Study: Annals of Internal Medicine: Vol 167, No 11

Background: Difficulties with daily functioning are common in middle-aged adults. However, little is known about the epidemiology or clinical course of these problems, including the extent to which they share common features with functional impairment in older adults. Objective: To determine the epidemiology and clinical course of functional impairment and decline in middle age. Design: Cohort study. Setting: The Health and Retirement Study. Participants: 6874 community-dwelling adults aged 50 to 56 years who did not have functional impairment at enrollment. Measurements: Impairment in activities of daily living (ADLs), defined as self-reported difficulty performing 1 or more ADLs, assessed every 2 years for a maximum follow-up of 20 years, and impairment in instrumental ADLs (IADLs), defined similarly. Data were analyzed by using multistate models that estimate probabilities of different outcomes. Results: Impairment in ADLs developed in 22% of participants aged 50 to 64 years, in whom further functional transitions were common. Two years after the initial impairment, 4% (95% CI, 3% to 5%) of participants had died, 9% (CI, 8% to 11%) had further ADL decline, 50% (CI, 48% to 52%) had persistent impairment, and 37% (CI, 35% to 39%) had recovered independence. In the 10 years after the initial impairment, 16% (CI, 14% to 18%) had 1 or more episodes of functional decline and 28% (CI, 26% to 30%) recovered from their initial impairment and remained independent throughout this period. The pattern of findings was similar for IADLs. Limitation: Functional status was self-reported. Conclusion: Functional impairment and decline are common in middle age, as are transitions from impairment to independence and back again. Because functional decline in older adults has similar features, current interventions used for prevention in older adults may hold promise for those in middle age. Primary Funding Source: National Institute on Aging and National Center for Advancing Translational Sciences through the University of California, San Francisco, Clinical and Translational Sciences Institute.

Physicians, Patients, and Firearms: The Courts Say “Yes”

Benefits and Harms of Plant-Based Cannabis for Posttraumatic Stress Disorder: A Systematic Review: Annals of Internal Medicine: Vol 167, No 5

Background: Cannabis is available from medical dispensaries for treating posttraumatic stress disorder (PTSD) in many states of the union, yet its efficacy in treating PTSD symptoms remains uncertain. Purpose: To identify ongoing studies and review existing evidence regarding the benefits and harms of plant-based cannabis preparations in treating PTSD in adults. Data Sources: MEDLINE, the Cochrane Library, and other sources from database inception to March 2017. Study Selection: English-language systematic reviews, trials, and observational studies with a control group that reported PTSD symptoms and adverse effects of plant-based cannabis use in adults with PTSD. Data Extraction: Study data extracted by 1 investigator was checked by a second reviewer; 2 reviewers independently assessed study quality, and the investigator group graded the overall strength of evidence by using standard criteria. Data Synthesis: Two systematic reviews, 3 observational studies, and no randomized trials were found. The systematic reviews reported insufficient evidence to draw conclusions about benefits and harms. The observational studies found that compared with nonuse, cannabis did not reduce PTSD symptoms. Studies had medium and high risk of bias, and overall evidence was judged insufficient. Two randomized trials and 6 other studies examining outcomes of cannabis use in patients with PTSD are ongoing and are expected to be completed within 3 years. Limitation: Very scant evidence with medium to high risk of bias. Conclusion: Evidence is insufficient to draw conclusions about the benefits and harms of plant-based cannabis preparations in patients with PTSD, but several ongoing studies may soon provide important results. Primary Funding Source: U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative. (PROSPERO: CRD42016033623)