Pharmacologic and Nonpharmacologic Treatments for Urinary Incontinence in Women: A Systematic Review and Network Meta-analysis of Clinical Outcomes: Annals of Internal Medicine: Vol 170, No 7

Background: Urinary incontinence (UI), a common malady in women, most often is classified as stress, urgency, or mixed. Purpose: To compare the effectiveness of pharmacologic and nonpharmacologic interventions to improve or cure stress, urgency, or mixed UI in nonpregnant women. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials (Wiley), Cochrane Database of Systematic Reviews (Wiley), EMBASE (Elsevier), CINAHL (EBSCO), and PsycINFO (American Psychological Association) from inception through 10 August 2018. Study Selection: 84 randomized trials that evaluated 14 categories of interventions and reported categorical cure or improvement outcomes. Data Extraction: 1 researcher extracted study characteristics, results, and study-level risk of bias, with verification by another independent researcher. The research team collaborated to assess strength of evidence (SoE) across studies. Data Synthesis: 84 studies reported cure or improvement outcomes (32 in stress UI, 16 in urgency UI, 4 in mixed UI, and 32 in any or unspecified UI type). The most commonly evaluated active intervention types included behavioral therapies, anticholinergics, and neuromodulation. Network meta-analysis showed that all interventions, except hormones and periurethral bulking agents (variable SoE), were more effective than no treatment in achieving at least 1 favorable UI outcome. Among treatments used specifically for stress UI, behavioral therapy was more effective than either α-agonists or hormones in achieving cure or improvement (moderate SoE); α-agonists were more effective than hormones in achieving improvement (moderate SoE); and neuromodulation was more effective than no treatment for cure, improvement, and satisfaction (high SoE). Among treatments used specifically for urgency UI, behavioral therapy was statistically significantly more effective than anticholinergics in achieving cure or improvement (high SoE), both neuromodulation and onabotulinum toxin A (BTX) were more effective than no treatment (high SoE), and BTX may have been more effective than neuromodulation in achieving cure (low SoE). Limitation: Scarce direct (head-to-head trial) evidence and population heterogeneity based on UI type, UI severity, and history of prior treatment. Conclusion: Most nonpharmacologic and pharmacologic interventions are more likely than no treatment to improve UI outcomes. Behavioral therapy, alone or in combination with other interventions, is generally more effective than pharmacologic therapies alone in treating both stress and urgency UI. Primary Funding Source: Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42017069903)

Harnessing the Consumer Movement

The Changing Definition of a Primary Care Provider

Use of Peripherally Inserted Central Catheters in Patients With Advanced Chronic Kidney Disease: A Prospective Cohort Study: Annals of Internal Medicine: Vol 171, No 1

Background: Existing guidelines, including Choosing Wisely recommendations, endorse avoiding placement of peripherally inserted central catheters (PICCs) in patients with chronic kidney disease (CKD). Objective: To describe the frequency of and characteristics associated with PICC use in hospitalized patients with stage 3b or greater CKD (glomerular filtration rate [GFR] <45 mL/min/1.73 m2). Design: Prospective cohort study. Setting: 52 hospitals participating in the Michigan Hospital Medicine Safety Consortium. Participants: Hospitalized medical patients who received a PICC between November 2013 and September 2016. Measurements: Percentage of patients receiving PICCs who had CKD, frequency of PICC-related complications, and variation in the proportion of PICCs placed in patients with CKD. Results: Of 20 545 patients who had PICCs placed, 4743 (23.1% [95% CI, 20.9% to 25.3%]) had an estimated GFR (eGFR) less than 45 mL/min/1.73 m2 and 699 (3.4%) were receiving hemodialysis. In the intensive care unit (ICU), 30.9% (CI, 29.7% to 32.2%) of patients receiving PICCs had an eGFR less than 45 mL/min/1.73 m2; the corresponding percentage in wards was 19.3% (CI, 18.8% to 19.9%). Among patients with an eGFR less than 45 mL/min/1.73 m2, multilumen PICCs were placed more frequently than single-lumen PICCs. In wards, PICC-related complications occurred in 15.3% of patients with an eGFR less than 45 mL/min/1.73 m2 and in 15.2% of those with an eGFR of 45 mL/min/1.73 m2 or higher. The corresponding percentages in ICU settings were 22.4% and 23.9%. In patients with an eGFR less than 45 mL/min/1.73 m2, PICC placement varied widely across hospitals (interquartile range, 23.7% to 37.8% in ICUs and 12.8% to 23.7% in wards). Limitation: Nephrologist approval for placement could not be determined, and 2.7% of eGFR values were unknown and excluded. Conclusion: In this sample of hospitalized patients who received PICCs, placement in those with CKD was common and not concordant with clinical guidelines. Primary Funding Source: Blue Cross Blue Shield of Michigan and Blue Care Network.

Patterns of Opioid Administration Among Opioid-Naive Inpatients and Associations With Postdischarge Opioid Use: A Cohort Study: Annals of Internal Medicine: Vol 171, No 2

Background: Patterns of inpatient opioid use and their associations with postdischarge opioid use are poorly understood. Objective: To measure patterns in timing, duration, and setting of opioid administration in opioid-naive hospitalized patients and to examine associations with postdischarge use. Design: Retrospective cohort study using electronic health record data from 2010 to 2014. Setting: 12 community and academic hospitals in Pennsylvania. Patients: 148 068 opioid-naive patients (191 249 admissions) with at least 1 outpatient encounter within 12 months before and after admission. Measurements: Number of days and patterns of inpatient opioid use; any outpatient use (self-report and/or prescription orders) 90 and 365 days after discharge. Results: Opioids were administered in 48% of admissions. Patients were given opioids for a mean of 67.9% (SD, 25.0%) of their stay. Location of administration of first opioid on admission, timing of last opioid before discharge, and receipt of nonopioid analgesics varied substantially. After adjustment for potential confounders, 5.9% of inpatients receiving opioids had outpatient use at 90 days compared with 3.0% of those without inpatient use (difference, 3.0 percentage points [95% CI, 2.8 to 3.2 percentage points]). Opioid use at 90 days was higher in inpatients receiving opioids less than 12 hours before discharge than in those with at least 24 opioid-free hours before discharge (7.5% vs. 3.9%; difference, 3.6 percentage points [CI, 3.3 to 3.9 percentage points]). Differences based on proportion of the stay with opioid use were modest (opioid use at 90 days was 6.4% and 5.4%, respectively, for patients with opioid use for ≥75% vs. ≤25% of their stay; difference, 1.0 percentage point [CI, 0.4 to 1.5 percentage points]). Associations were similar for opioid use 365 days after discharge. Limitation: Potential unmeasured confounders related to opioid use. Conclusion: This study found high rates of opioid administration to opioid-naive inpatients and associations between specific patterns of inpatient use and risk for long-term use after discharge. Primary Funding Source: UPMC Health System and University of Pittsburgh.

Are Requirements to Deposit Data in Research Repositories Compatible With the European Union's General Data Protection Regulation?

Acute Illness Associated With Cannabis Use, by Route of Exposure: An Observational Study: Annals of Internal Medicine: Vol 170, No 8

Background: Little is known about the relative harms of edible and inhalable cannabis products. Objective: To describe and compare adult emergency department (ED) visits related to edible and inhaled cannabis exposure. Design: Chart review of ED visits between 1 January 2012 and 31 December 2016. Setting: A large urban academic hospital in Colorado. Participants: Adults with ED visits with a cannabis-related International Classification of Diseases, Ninth or 10th Revision, Clinical Modification (ICD-9-CM or ICD-10-CM), code. Measurements: Patient demographic characteristics, route of exposure, dose, symptoms, length of stay, disposition, discharge diagnoses, and attribution of visit to cannabis. Results: There were 9973 visits with an ICD-9-CM or ICD-10-CM code for cannabis use. Of these, 2567 (25.7%) visits were at least partially attributable to cannabis, and 238 of those (9.3%) were related to edible cannabis. Visits attributable to inhaled cannabis were more likely to be for cannabinoid hyperemesis syndrome (18.0% vs. 8.4%), and visits attributable to edible cannabis were more likely to be due to acute psychiatric symptoms (18.0% vs. 10.9%), intoxication (48% vs. 28%), and cardiovascular symptoms (8.0% vs. 3.1%). Edible products accounted for 10.7% of cannabis-attributable visits between 2014 and 2016 but represented only 0.32% of total cannabis sales in Colorado (in kilograms of tetrahydrocannabinol) during that period. Limitation: Retrospective study design, single academic center, self-reported exposure data, and limited availability of dose data. Conclusion: Visits attributable to inhaled cannabis are more frequent than those attributable to edible cannabis, although the latter is associated with more acute psychiatric visits and more ED visits than expected. Primary Funding Source: Colorado Department of Public Health and Environment.

Predicting Bleeding Risk to Guide Aspirin Use for the Primary Prevention of Cardiovascular Disease: A Cohort Study: Annals of Internal Medicine: Vol 170, No 6

Background: Many prognostic models for cardiovascular risk can be used to estimate aspirin's absolute benefits, but few bleeding risk models are available to estimate its likely harms. Objective: To develop prognostic bleeding risk models among persons in whom aspirin might be considered for the primary prevention of cardiovascular disease (CVD). Design: Prospective cohort study. Setting: New Zealand primary care. Participants: The study cohort comprised 385 191 persons aged 30 to 79 years whose CVD risk was assessed between 2007 and 2016. Those with indications for or contraindications to aspirin and those who were already receiving antiplatelet or anticoagulant therapy were excluded. Measurements: For each sex, Cox proportional hazards models were developed to predict major bleeding risk; participants were censored at the earliest of the date on which they first met an exclusion criterion, date of death, or study end date (30 June 2017). The main models included the following predictors: demographic characteristics (age, ethnicity, and socioeconomic deprivation), clinical measurements (systolic blood pressure and ratio of total–high-density lipoprotein cholesterol), family history of premature CVD, medical history (smoking, diabetes, bleeding, peptic ulcer disease, cancer, chronic liver disease, chronic pancreatitis, or alcohol-related conditions), and medication use (nonsteroidal anti-inflammatory agents, corticosteroids, and selective serotonin reuptake inhibitors). Results: During 1 619 846 person-years of follow-up, 4442 persons had major bleeding events (of which 313 [7%] were fatal). The main models predicted a median 5-year bleeding risk of 1.0% (interquartile range, 0.8% to 1.5%) in women and 1.1% (interquartile range, 0.7% to 1.6%) in men. Plots of predicted-against-observed event rates showed good calibration throughout the risk range. Limitation: Hemoglobin level, platelet count, and body mass index were excluded from the main models because of high numbers of missing values, and the models were not externally validated in non–New Zealand populations. Conclusion: Prognostic bleeding risk models were developed that can be used to estimate the absolute bleeding harms of aspirin among persons in whom aspirin is being considered for the primary prevention of CVD. Primary Funding Source: The Health Research Council of New Zealand.

The Effects on Hospital Utilization of the 1966 and 2014 Health Insurance Coverage Expansions in the United States

Background: Persons with comprehensive health insurance use more hospital care than those who are uninsured or have high-deductible plans. Consequently, analysts generally assume that expanding coverage will increase society-wide use of inpatient services. However, a limited supply of beds might constrain this growth. Objective: To determine how the implementations of Medicare and Medicaid (1966) and the Patient Protection and Affordable Care Act (ACA) (2014) affected hospital use. Design: Repeated cross-sectional study. Setting: Nationally representative surveys. Participants: Respondents to the National Health Interview Survey (1962 to 1970) and Medical Expenditure Panel Survey (2008 to 2015). Measurements: Mean hospital discharges and days were measured, both society-wide and among subgroups defined by income, age, and health status. Changes between preexpansion and postexpansion periods were analyzed using multivariable negative binomial regression. Results: Overall hospital discharges averaged 12.8 per 100 persons in the 3 years before implementation of Medicare and Medicaid and 12.7 per 100 persons in the 4 years after (adjusted difference, 0.2 discharges [95% CI, −0.1 to 0.4 discharges] per 100 persons; P = 0.26). Hospital days did not change in the first 2 years after implementation but increased later. Effects differed by subpopulation: Adjusted discharges increased by 2.4 (CI, 1.7 to 3.1) per 100 persons among elderly compared with nonelderly persons (P < 0.001) and also increased among those with low incomes compared with high-income populations. For younger and higher-income persons, use decreased. Similarly, after the ACA's implementation, overall hospital use did not change: Society-wide rates of discharge were 9.4 per 100 persons before the ACA and 9.0 per 100 persons after the ACA (adjusted difference, −0.6 discharges [CI, −1.3 to 0.2 discharges] per 100 persons; P = 0.133), and hospital days were also stable. Trends differed for some subgroups, and rates decreased significantly in unadjusted (but not adjusted) analyses among persons reporting good or better health status and increased nonsignificantly among those in worse health. Limitation: Data sources relied on participant recall, surveys excluded institutionalized persons, and follow-up after the ACA was limited. Conclusion: Past coverage expansions were associated with little or no change in society-wide hospital use; increases in groups who gained coverage were offset by reductions among others, suggesting that bed supply limited increases in use. Reducing coverage may merely shift care toward wealthier and healthier persons. Conversely, universal coverage is unlikely to cause a surge in hospital use if growth in hospital capacity is carefully constrained. Primary Funding Source: None.

Performance of the T2Bacteria Panel for Diagnosing Bloodstream Infections: A Diagnostic Accuracy Study: Annals of Internal Medicine: Vol 170, No 12

Background: Blood cultures, the gold standard for diagnosing bloodstream infections (BSIs), are insensitive and limited by prolonged time to results. The T2Bacteria Panel (T2 Biosystems) is a direct-from-blood, nonculture test that identifies the most common ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli). Objective: To assess performance of the T2Bacteria Panel in diagnosing suspected BSIs in adults. Design: Prospective patient enrollment (8 December 2015 through 4 August 2017). Setting: Eleven U.S. hospitals. Patients: 1427 patients for whom blood cultures were ordered as standard of care. Intervention: Paired blood culture and T2Bacteria testing. Measurements: Performance of T2Bacteria compared with a single set of blood cultures in diagnosing proven, probable, and possible BSIs caused by T2Bacteria-targeted organisms. Results: Blood culture and T2Bacteria results were positive for targeted bacteria in 3% (39 of 1427) and 13% (181 of 1427) of patients, respectively. Mean times from start of blood culture incubation to positivity and species identification were 38.5 (SD, 32.8) and 71.7 (SD, 39.3) hours, respectively. Mean times to species identification with T2Bacteria were 3.61 (SD, 0.2) to 7.70 (SD, 1.38) hours, depending on the number of samples tested. Per-patient sensitivity and specificity of T2Bacteria for proven BSIs were 90% (95% CI, 76% to 96%) and 90% (CI, 88% to 91%), respectively; the negative predictive value was 99.7% (1242 of 1246). The rate of negative blood cultures with a positive T2Bacteria result was 10% (146 of 1427); 60% (88 of 146) of such results were associated with probable (n = 62) or possible (n = 26) BSIs. If probable BSIs and both probable and possible BSIs were assumed to be true positives missed by blood culture, per-patient specificity of T2Bacteria was 94% and 96%, respectively. Limitation: Low prevalence of positive blood cultures, collection of a single set of culture specimens, and inability of T2Bacteria to detect nontargeted pathogens. Conclusion: The T2Bacteria Panel rapidly and accurately diagnoses BSIs caused by 5 common bacteria. Primary Funding Source: T2 Biosystems.