Erectile dysfunction diagnosis and treatment as a means to improve medication adherence and optimize comorbidity management.

INTRODUCTION: Optimal pharmacologic management of diseases comorbid with erectile dysfunction (ED), such as cardiovascular disease, depression, diabetes, dyslipidemia, hypertension, and benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), is dependent upon long-term treatment compliance and may be complicated by poor adherence to medication use. ED may contribute to poor adherence to medication use because poor quality erectile function may be an unwanted adverse effect of antihypertensives, antidepressants, and 5-α reductase inhibitors for treatment of BPH/LUTS. Diminished erectile spontaneity, rigidity, and/or sustaining capability also negatively affects mood, self-esteem, and confidence, which compromise motivation to be compliant with medications that treat diseases comorbid with ED. AIM: Literature review was performed to explore the role of ED diagnosis and effective treatment in enhancing overall management of selected ED comorbidities, highlighting the role of medication adherence. METHODS: Several PubMed searches were performed. RESULTS: Diagnosis and successful treatment of concomitant ED may promote improved adherence and management of comorbid diseases. Concomitant ED management may improve treatment outcome, decrease healthcare costs, and possibly prevent or even improve deterioration in medical conditions comorbid with ED. Because ED is a silent marker and predictor of comorbidities, especially cardiovascular disease, earlier diagnosis of ED may provide an opportunity to prevent future cardiovascular events. In men presenting with complaints of ED, screening for, monitoring, and appropriately treating diseases that are comorbid with ED is essential. Screening for and appropriately treating ED is important for enhanced life quality and improved motivation in men with existing ED comorbidities or risk factors. CONCLUSIONS: Appropriate management of ED and its risk factors may have beneficial effects on diseases that are comorbid with ED, and vice versa, most likely via shared pathophysiological pathways. Clinicians may need to consider men's health overall, of which sexual health is a central component, in order to provide optimal disease management.

A novel long-acting formulation of oral buprenorphine/naloxone produces prolonged decreases in fentanyl self-administration by rhesus monkeys.

BACKGROUND: Due to the poor oral bioavailability of buprenorphine, an oral formulation has not been thought possible. Lyndra Therapeutics is developing a once-weekly long-acting oral product containing buprenorphine. We evaluated the efficacy of this formulation in reducing intravenous (i.v.) fentanyl self-administration by three male and three female rhesus monkeys. METHODS: Buprenorphine HCl and naloxone HCl were co-formulated using an 11:1 ratio of buprenorphine:naloxone in a controlled-release gastric residence formulation administered in an oral capsule (LYN-013). Naloxone was included to determine the feasibility of combining naloxone with buprenorphine in the formulation as an abuse deterrent. Complete fentanyl dose-response functions were determined during each session. The efficacy of single doses of 56/5, 112/10 and 168/15 mg buprenorphine/naloxone in reducing fentanyl self-administration was examined over 13 days. RESULTS: LYN-013 significantly decreased the rate of responding for fentanyl for 3 days and significantly reduced total intake of fentanyl for 8 days. Time to maximal buprenorphine levels (Tmax) ranged between 56 and 68 h for all 3 doses. The maximal buprenorphine level (Cmax) following 168 mg was 2.3 ng/ml which was significantly greater that those observed for 56 mg (1.22 ng/ml) and 112 mg (1.35 ng/ml). Finally, the area-under-curves (AUCtau) were buprenorphine dose-dependently increased from 88 to 127-265 h*ng/ml. There were no signs of non-specific changes in behavior. CONCLUSIONS: A once-weekly oral buprenorphine/naloxone formulation produced sustained suppression of fentanyl self-administration in monkeys suggesting that oral delivery of buprenorphine with this formulation could provide a new opportunity to treat opioid use disorders (OUD).

Randomized trial of transversus abdominis plane block with liposomal bupivacaine after cesarean delivery with or without intrathecal morphine.

STUDY OBJECTIVE: To investigate efficacy and safety of liposomal bupivacaine (LB) transversus abdominis plane (TAP) block with or without intrathecal morphine (ITM) compared with ITM alone for postsurgical analgesia after cesarean delivery (CD). DESIGN: Multicenter, open-label, randomized trial (NCT03853694). SETTING: Operating room. PATIENTS: Women with term pregnancy of 37 to 42 weeks scheduled for elective CD under spinal anesthesia. INTERVENTION: Patients were randomized 1:1:1 to LB 266 mg TAP block alone (LB group), ITM 50 µg followed by LB 266 mg TAP block (LB + ITM group), or ITM 150 µg alone (ITM group). All groups received the same postsurgical multimodal analgesic regimen. MEASUREMENTS: The LB and LB + ITM groups were compared with the ITM group for all efficacy outcomes. Postsurgical opioid consumption in morphine milligram equivalents (MMEs) through 72 h was compared by assessing noninferiority before testing superiority. Postsurgical pruritus severity was assessed on an 11-point numerical rating scale. MAIN RESULTS: Between March 4, 2019, and January 10, 2020, 153 patients (LB, n = 52; LB + ITM, n = 48; ITM, n = 53) were enrolled. Baseline characteristics were comparable across groups. The LB group had statistically noninferior postsurgical opioid consumption through 72 h compared with the ITM group (least squares mean [LSM], 19.2 vs 16.4 MMEs; LSM treatment ratio, 1.17 [95% confidence interval (CI), 0.74-1.86]; noninferiority P < 0.0034) as did the LB + ITM group (LSM, 14.6 vs 16.4 MMEs; LSM treatment ratio, 0.89 [95% CI, 0.55-1.44]; noninferiority P < 0.0001). The LB and LB + ITM groups had significantly reduced pruritus severity scores through 12, 24, 48, and 72 h compared with the ITM group (P ≤ 0.0121). Adverse events occurred in 58%, 85%, and 81% of the LB, LB + ITM, and ITM groups, respectively. CONCLUSIONS: LB TAP block with or without ITM resulted in statistically noninferior postsurgical opioid consumption through 72 h, reduced pruritus, and favorable safety compared with ITM in women undergoing CD.

A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17 years (PLAY).

STUDY OBJECTIVE: To evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. DESIGN: Multicenter, open-label, phase 3, randomized trial (PLAY; NCT03682302). SETTING: Operating room. PATIENTS: Two separate age groups were evaluated (age group 1: patients 12 to <17 years undergoing spine surgery; age group 2: patients 6 to <12 years undergoing spine or cardiac surgery). INTERVENTION: Randomized allocation of liposomal bupivacaine 4 mg/kg or bupivacaine hydrochloride (HCl) 2 mg/kg via local infiltration at the end of spine surgery (age group 1); liposomal bupivacaine 4 mg/kg via local infiltration at the end of spine or cardiac surgery (age group 2). MEASUREMENTS: The primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations [Cmax], time to Cmax) and safety of liposomal bupivacaine, respectively. MAIN RESULTS: Baseline characteristics were comparable across groups. Mean Cmax after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564 ng/mL); mean Cmax in age group 2 was 320 and 447 ng/mL for spine and cardiac surgery, respectively. Median time to Cmax of liposomal bupivacaine occurred later with cardiac surgery versus spine surgery (22.7 vs 7.4 h). In age group 1, the incidence of adverse events (AEs) was comparable between liposomal bupivacaine (61% [19/31]) and bupivacaine HCl (73% [22/30]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing spine and cardiac surgery experienced AEs, respectively. AEs were generally mild or moderate, with no discontinuations due to AEs or deaths. CONCLUSIONS: Plasma bupivacaine levels following local infiltration with liposomal bupivacaine remained below the toxic threshold in adults (~2000-4000 ng/mL) across age groups and procedures. AEs were mild to moderate, supporting the safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. Clinical trial number and registry URL: ClinicalTrials.gov identifier: NCT03682302.

Research approaches for evaluating opioid sparing in clinical trials of acute and chronic pain treatments: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials recommendations.

ABSTRACT: Randomized clinical trials have demonstrated the efficacy of opioid analgesics for the treatment of acute and chronic pain conditions, and for some patients, these medications may be the only effective treatment available. Unfortunately, opioid analgesics are also associated with major risks (eg, opioid use disorder) and adverse outcomes (eg, respiratory depression and falls). The risks and adverse outcomes associated with opioid analgesics have prompted efforts to reduce their use in the treatment of both acute and chronic pain. This article presents Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus recommendations for the design of opioid-sparing clinical trials. The recommendations presented in this article are based on the following definition of an opioid-sparing intervention: any intervention that (1) prevents the initiation of treatment with opioid analgesics, (2) decreases the duration of such treatment, (3) reduces the total dosages of opioids that are prescribed for or used by patients, or (4) reduces opioid-related adverse outcomes (without increasing opioid dosages), all without causing an unacceptable increase in pain. These recommendations are based on the results of a background review, presentations and discussions at an IMMPACT consensus meeting, and iterative drafts of this article modified to accommodate input from the co-authors. We discuss opioid sparing definitions, study objectives, outcome measures, the assessment of opioid-related adverse events, incorporation of adequate pain control in trial design, interpretation of research findings, and future research priorities to inform opioid-sparing trial methods. The considerations and recommendations presented in this article are meant to help guide the design, conduct, analysis, and interpretation of future trials.

Cardiovascular benefit of magnitude of low-density lipoprotein cholesterol reduction: a comparison of subgroups by age.

BACKGROUND: We examined the effect of the magnitude of low-density lipoprotein cholesterol (LDL-C) reduction across subjects of various ages in a retrospective cohort study. METHODS AND RESULTS: We selected 20,132 male veterans at high risk for an acute cardiovascular event and who had 2 or more LDL-C measurements before their first documented acute myocardial infarction, revascularization, death, or censoring date. LDL-C reduction was categorized as no reduction (<10 mg/dL; reference), small reduction (between 10 and 40 mg/dL), moderate reduction (between 40 and 70 mg/dL), or large reduction (> or =70 mg/dL). The primary outcome was combined acute myocardial infarction or revascularization. The first and last LDL-C levels in the databases were used to calculate the LDL-C reduction in patients who experienced no outcome or who died. Within each age quartile and in a subgroup of patients > or =80 years of age, a Cox proportional hazards model was used to determine hazard ratios for each category of LDL-C reduction compared with the reference category, with adjustment for age, body mass index, current smoking status, medications, and comorbidities. In all age groups, the magnitude of LDL-C reduction was proportional to the magnitude of cardiovascular risk reduction. Risk reduction for the combined outcome in patients who achieved a large LDL-C reduction was similar in all age quartiles, with multivariate-adjusted hazard ratios of approximately 0.30. CONCLUSIONS: In a cohort of veterans at high risk for cardiovascular events, patients of all ages, including those 80 years or older, benefitted the most from large reductions in LDL-C.

Characterization of Device-Related Malfunction, Injury, and Death Associated with Using Elastomeric Pumps for Delivery of Local Anesthetics in the US Food and Drug Administration MAUDE Database.

PURPOSE: To characterize medical device reports about elastomeric pumps delivering local anesthesia made to the US Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database. PATIENTS AND METHODS: We conducted a retrospective review of medical device reports submitted to MAUDE from January 2010 to July 2018. A systematic, computerized algorithm was used to identify records pertaining to elastomeric pumps using local anesthesia. Included records indicated the use of local anesthesia or were determined to involve the use of local anesthetics (if they did not contain specific information on drug use). Reports were analyzed within the MAUDE event type categories of malfunction, injury, death, other, and missing. Possible cases of liver injury or surgical site infection were also identified. Manual review of narratives provided in MAUDE was performed by 2 reviewers to identify possible or probable cases of local anesthetic system toxicity (LAST). RESULTS: From a pool of 384,285 reports about elastomeric pumps from the MAUDE database, 4093 met inclusion criteria for involving elastomeric pumps to deliver local anesthetics, with the peak number of reports occurring in 2014. Of these identified reports, 3624 (88.5%) were categorized as malfunctions, 292 (7.1%) as injuries, and 8 (0.2%) as involving death. We identified 13 cases (0.3%) of possible liver injury and 51 cases (1.2%) of possible surgical site infection; 139 reports (3.4%) were determined to be probably (n=53) or possibly (n=86) associated with LAST. CONCLUSION: Malfunction of elastomeric pumps delivering local anesthetics leaves patients vulnerable to injury or death. Our study indicates that reports of malfunction, injury, and death have been reported to the MAUDE database. These reports likely reflect an underrepresentation of cases in the real-world population, emphasizing the need for more comprehensive medical device reporting.

Cost impact of diagnostic imaging for lower extremity peripheral vascular occlusive disease.

OBJECTIVE: The evaluation of peripheral vascular disease in the primary care setting is routinely performed by contrast-enhanced magnetic resonance angiography (CE-MRA) and digital subtraction angiography (DSA). However, limited data are available on the relative costs and clinical outcomes following these diagnostic procedures. The objective of this study is to assess and compare costs associated with diagnostic imaging in peripheral vascular occlusive disease (PAOD). METHODS: US veterans (n = 19,209) with CE-MRA or DSA for the assessment of PAOD from fiscal year (FY) 1999 to FY 2004. Main outcome measure(s) using the Department of Veterans Affairs' (VA) costing algorithms, cost, and log-cost of interventions (e.g., revascularization, stent, angioplasty), amputations or mortality rates within 30/90 days and 1 year of DSA or CE-MRA were compared, and adjusted for patient characteristics and disease severity using multivariate regression. Imaging modality selection bias was evaluated with propensity score, instrumental variables, and Heckman methods using untransformed costs and log-costs with smearing retransformation. RESULTS: Initial CE-MRA imaging was significantly more likely among patients with prior renal disease or bypass surgery [odds ratio (OR) > 2; P < 0.001], and less likely among patients with prior amputation, peripheral vascular disease (PVD), claudication, or other cardiovascular disease (OR < 0.7; P < 0.001). After adjusting for endogenous choice of initial imaging modality, 30-day treatment costs were US$3500-$4300 lower (P < 0.001) for patients with initial CE-MRA. Eighty-two percent of DSA imaging patients had no additional procedures or events within 30 days, and 65% at 90 days. Less than 3.2% (3.6%) of patients had any repeat imaging within 30 (90) days of initial imaging. CONCLUSIONS: Relative to DSA, CE-MRA imaging was associated with substantial treatment episode savings, beyond the US$950 direct savings in imaging cost per procedure. Substituting CE-MRA for DSA among those not planning or requiring any follow-up procedures within 30 days, could have reduced outpatient imaging costs by up to 55%, and reduced VA system costs by US$13.2 million over the six-year period.

Low-density lipoprotein reduction and magnitude of cardiovascular risk reduction.

The authors examined the relationship between the magnitude of low-density lipoprotein cholesterol (LDL-C) reduction and the magnitude of cardiovascular risk reduction. From the Veterans Integrated Service Network 1 databases, the authors selected 54,611 patients with prevalent ischemic heart disease, peripheral vascular disease or diabetes mellitus, and >or=2 documented LDL-C levels who were followed between 1997 and 2006. The outcome was defined as acute myocardial infarction or revascularization. Preoutcome LDL-C reduction was categorized as follows: <10 mg/dL, reference; >or=10 but <40 mg/dL, small reduction; >or=40 but <70 mg/dL, moderate reduction; >or=70 mg/dL, large reduction. Proportional hazards were used to determine the hazard ratio for the outcome for each LDL-C reduction category compared with the reference. Results revealed a graded relationship between the magnitude of reduction in LDL-C and cardiovascular risk reduction. Stratified analyses demonstrated these findings to be robust regardless of initial LDL-C levels or whether patients achieved "target" final LDL-C values of <100 mg/dL.

A comparison of approaches to identify possible cases of local anesthetic systemic toxicity in the FDA Adverse Event Reporting System (FAERS) database.

BACKGROUND: Local anesthetic systemic toxicity (LAST) is a rare but potentially serious adverse event . METHODS: Data from the US Food and Drug Administration Adverse Event Reporting System were examined for liposomal bupivacaine (LB), bupivacaine, or other injectable local anesthetics. Possible LAST cases were identified based on MedDRA system organ classes (Approach 1), a recent publication (Approach 2), and a novel approach based on LAST literature (Approach 3). Disproportionality analyses compared possible LAST cases for LB and bupivacaine with other injectable local anesthetics. RESULTS: Approaches 1, 2, and 3 identified 75, 42, and 29 possible LAST cases associated with LB, respectively, compared with 9,595, 3,422, and 549 for other injectable local anesthetics. The proportional reporting ratios (95% CI) for LB versus other injectable local anesthetics for the 3 approaches were 1.9 (1.6-2.3), 2.9 (2.2-3.9), and 1.6 (1.1-2.2), respectively. Based on sales data, the estimated incidence of possible LAST with LB was 0.1 per 10,000 uses; literature estimates for LAST with other injectable local anesthetics were 0 to 18 per 10,000 uses. CONCLUSIONS: Our findings suggest the estimated incidence of possible LAST cases with LB is similar to, or less than, the reported incidence with other injectable local anesthetics.

Effect of treating erectile dysfunction on management of systolic hypertension.

Erectile dysfunction (ED) is a prevalent condition and a predictor of future cardiovascular events. Screening and treatment of ED may improve management of cardiovascular risk factors. We evaluated the potential beneficial effect of newly treating ED on the management of hypertension in men in the New England Veteran Affairs Healthcare System. We conducted a retrospective cohort study using medical record data to identify patients diagnosed with and treated at any time for hypertension who received a prescription for a phosphodiesterase type 5 inhibitor (PDE5i) before February 1, 2003. Fifty percent of 6,768 men (mean +/- SD 61.6 +/- 9.9 years of age) had a systolic blood pressure (BP) > or =140 mm Hg before PDE5i administration. Overall, there was a decrease in systolic BP by 1.43 mm Hg (95% confidence interval -1.69 to -1.18) after initiation of PDE5i. The decrease in systolic BP was most pronounced in men with a systolic BP > or =160 mm Hg at baseline (-17.8 mm Hg, 95% confidence interval -18.8 to -16.8). After initiating therapy with PDE5i, patients were more likely to start an antihypertensive medication (17.3%) versus stop therapy (2.3%) and add additional antihypertensive medication to their existing therapy (42.2%) versus decrease the number of medications (17.3%). Surveillance also increased with total number of systolic BP measurements increasing by 42%. In conclusion, men with high systolic BP who initiated ED therapy had improvements in systolic BP control that may be related to clinically relevant behaviors, such as more aggressive monitoring and treatment with antihypertensive medications.

Veteran's affairs hospital discharge databases coded serious bacterial infections accurately.

OBJECTIVES: We sought to test the ability of large health care utilization databases to accurately identify serious bacterial infections and opportunistic infections leading to hospital admission. STUDY DESIGN AND SETTING: We conducted a cross-sectional validation study using patients admitted to hospitals in the administrative database of the Department of Veterans Affairs, VISN 1, between 2001 and 2004. Detailed hospital chart abstraction protocols were developed to define a gold-standard diagnosis of serious bacterial infections and opportunistic infections. Hospital acquired infections were not considered. RESULTS: A total of 158 patients who were hospitalized for selected bacterial infections and 69 patients for opportunistic infections were identified using ICD-9 discharge diagnoses. The positive predictive values (PPV) of identifying specific bacterial infections that lead to hospital admissions varied between 100% and 66%. All conditions combined yielded a PPV of 80%. Once the gold-standard definition of bacterial conditions was broadened to hospital admissions due to any acute infectious condition, the PPV increased to 90%. Excluding systemic candidiasis, the average PPV for the selected opportunistic infections was 76%. CONCLUSION: Our findings suggest that ICD-9 codes of selected serious infections from hospital discharge files can be used as substitutes for chart-based diagnoses.

A randomized, double-blind, placebo-controlled trial to assess safety and tolerability during treatment of type 2 diabetes with usual diabetes therapy and either Cycloset or placebo.

BACKGROUND: Cycloset is a quick-release formulation of bromocriptine mesylate, a dopamine agonist, which in animal models of insulin resistance and type 2 diabetes acts centrally to reduce resistance to insulin- mediated suppression of hepatic glucose output and tissue glucose disposal. In such animals, bromocriptine also reduces hepatic triglyceride synthesis and free fatty acid mobilization, manifesting decreases in both plasma triglycerides and free fatty acids. In clinical trials, morning administration of Cycloset either as monotherapy or adjunctive therapy to sulfonylurea or insulin reduces HbA1c levels relative to placebo by 0.55-1.2. Cycloset therapy also reduces plasma triglycerides and free fatty acid by approximately 25% and 20%, respectively, among those also receiving sulfonylurea therapies. The effects of once-daily morning Cycloset therapy on glycemic control and plasma lipids are demonstrable throughout the diurnal portion of the day (7 a.m. to 7 p.m.) across postprandial time points. METHODS/DESIGN: 3,095 individuals were randomized in a 2:1 ratio into a one year trial aimed to assess the safety and efficacy of Cycloset compared to placebo among individuals receiving a variety of treatments for type 2 diabetes. Eligibility criteria for this randomized placebo controlled trial included: age 30-80, HbA1c

Health care utilization and receipt of cholesterol testing by veterans with and those without mental illness.

OBJECTIVE: We examined the relationship between mental illness, health care utilization and rates of cholesterol testing. METHODS: We conducted a retrospective cohort study using Veterans Affairs (VA) administrative data on 64,490 United States veterans who used VA New England Health Care System outpatient services between January 1998 and June 2001. A total of 10,100 veterans (15.7%) had a mental illness treated with medication. We examined the interaction between mental illness and outpatient service utilization with respect to the likelihood of receiving a cholesterol test, adjusting for major demographic and clinical covariates. RESULTS: Among veterans using VA outpatient services infrequently, those with mental illness were less likely than non-mentally ill control subjects to receive a cholesterol test during the study period (first quartile adjusted OR=0.45, 95% CI=0.37-0.54; second quartile adjusted OR=0.50, 95% CI=0.45-0.57). Mentally ill subjects with more frequent utilization of VA services were as likely as (third quartile adjusted OR=1.01, 95% CI=0.91-1.13) or more likely than (fourth quartile adjusted OR=2.73, 95% CI=2.46-3.03) non-mentally ill subjects to receive cholesterol testing. CONCLUSIONS: Mental illness was associated with a lower likelihood of cholesterol testing in subjects who used fewer VA outpatient services. The observed disparity attenuated at higher levels of service utilization.

Statin use and fracture risk: study of a US veterans population.

BACKGROUND: Whether statins reduce the risk of fractures is still contested. Several studies support a favorable association, whereas post hoc analyses of statin-randomized trials have failed to find a benefit. We sought to assess this possible relationship in a large population of elderly, predominantly male veterans. METHODS: We established the study population using all health care encounters and services from patients who received care in the New England Veterans Affairs health care system between January 1998 and June 2001. According to evidence from the literature, covariates that would affect the risk of fractures were included in the final model, as were medications that were clinically meaningful and significant in univariate models and the Charlson Comorbidity Index as a surrogate for general health. We also conducted a similar analysis among new statin users. We used pooled logistic regression to assess for significant associations. RESULTS: Of the 91 052 patients in the final cohort, 28 063 were prescribed statins and 2195 were prescribed nonstatin lipid-lowering medications. In the adjusted analyses, statin use was associated with a 36% (odds ratio, 0.64; 95% confidence interval, 0.58-0.72) reduction in fracture risk when compared with no lipid-lowering therapy and a 32% (odds ratio, 0.67; 95% confidence interval, 0.50-0.91) reduction when compared with nonstatin lipid-lowering therapy. Similar findings were found for the new statin user group. CONCLUSIONS: We have provided yet another study in a unique population of mostly male veterans that found a significant reduction in fractures among statin users. More studies need to be performed to confirm or refute our findings.

Impact of postsurgical opioid use and ileus on economic outcomes in gastrointestinal surgeries.

OBJECTIVES: To assess the incidence and economic impact of postoperative ileus (POI) following laparotomy (open) and laparoscopic procedures for colectomies and cholecystectomies in patients receiving postoperative pain management with opioids. METHODS: Using the Premier research database, we retrospectively identified adult inpatients discharged between 2008 and 2010 receiving postsurgical opioids following laparotomy and laparoscopic colectomy and cholecystectomy. POI was identified through ICD-9 diagnosis codes and postsurgical morphine equivalent dose (MED) determined. RESULTS: A total of 138,068 patients met criteria, and 10.3% had an ileus. Ileus occurred more frequently in colectomy than cholecystectomy and more often when performed by laparotomy. Ileus patients receiving opioids had an increased length of stay (LOS) ranging from 4.8 to 5.7 days, total cost from $9945 to $13,055 and 30 day all-cause readmission rate of 2.3 to 5.3% higher compared to patients without ileus. Patients with ileus received significantly greater MED than those without (median: 285 vs. 95 mg, p < 0.0001) and were twice as likely to have POI. MED above the median in ileus patients was associated with an increase in LOS (3.8 to 7.1 days), total cost ($8458 to $19,562), and readmission in laparoscopic surgeries (4.8 to 5.2%). Readmission rates were similar in ileus patients undergoing open procedures regardless of MED. CONCLUSIONS: Use of opioids in patients who develop ileus following abdominal surgeries is associated with prolonged hospitalization, greater costs, and increased readmissions. Furthermore, higher doses of opioids are associated with higher incidence of POI. Limitations are related to the retrospective design and the use of administrative data (including reliance on ICD-9 coding). Yet POI may not be coded and therefore underestimated in our study. Assessment of pre-existing disease and preoperative pain management was not assessed. Despite these limitations, strategies to reduce opioid consumption may improve healthcare outcomes and reduce the associated economic impact.

Timed Bromocriptine-QR Therapy Reduces Progression of Cardiovascular Disease and Dysglycemia in Subjects with Well-Controlled Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control may reduce long-term CVD risk. However, other risk factors such as elevated vascular sympathetic tone and/or endothelial dysfunction may be stronger potentiators of CVD. This study evaluated the impact of bromocriptine-QR, a sympatholytic dopamine D2 receptor agonist, on progression of metabolic disease and CVD in T2DM subjects in good glycemic control (HbA1c ≤ 7.0%). METHODS: 1834 subjects (1219 bromocriptine-QR; 615 placebo) with baseline HbA1c ≤ 7.0% derived from the Cycloset Safety Trial (this trial is registered with ClinicalTrials.gov Identifier: NCT00377676), a 12-month, randomized, multicenter, placebo-controlled, double-blind study in T2DM, were evaluated. Treatment impact upon a prespecified composite CVD endpoint (first myocardial infarction, stroke, coronary revascularization, or hospitalization for angina/congestive heart failure) and the odds of losing glycemic control (HbA1c >7.0% after 52 weeks of therapy) were determined. RESULTS: Bromocriptine-QR reduced the CVD endpoint by 48% (intention-to-treat; HR: 0.52 [0.28-0.98]) and 52% (on-treatment analysis; HR: 0.48 [0.24-0.95]). Bromocriptine-QR also reduced the odds of both losing glycemic control (OR: 0.63 (0.47-0.85), p = 0.002) and requiring treatment intensification to maintain HbA1c ≤ 7.0% (OR: 0.46 (0.31-0.69), p = 0.0002). CONCLUSIONS: Bromocriptine-QR therapy slowed the progression of CVD and metabolic disease in T2DM subjects in good glycemic control.

Impact of liposome bupivacaine on the adequacy of pain management and patient experiences following aesthetic surgery: Results from an observational study.

BACKGROUND: Despite the efficacy of opioid analgesics for postsurgical pain, they are associated with side effects that may complicate recovery. Liposome bupivacaine is a prolonged-release formulation of bupivacaine approved for intraoperative administration at the surgical site for postsurgical analgesia. OBJECTIVES: To evaluate the effect of a single intraoperative administration of liposome bupivacaine on postsurgical pain, opioid use and opioid-related side effects in subjects undergoing breast surgery and/or abdominoplasty. METHODS: In the present phase IV, multicentre, prospective observational study, subjects received a single intraoperative administration (266 mg) of liposome bupivacaine. Rescue analgesia was available to all subjects as needed. Outcome measures, assessed through postoperative day 3, included postsurgical pain intensity (11-point numerical rating scale), opioid consumption and overall benefit of analgesic score. Results were evaluated comparing investigators' previous experience with similar surgeries. RESULTS: Forty-nine subjects entered the study: 34 underwent breast surgery only and 15 underwent abdominoplasty with or without breast surgery (six underwent breast surgery in addition to abdominoplasty). Mean numerical rating scale pain scores remained ≤4.3 from discharge through postoperative day 3. Median daily oral opioid consumption was approximately 1.0 tablet postoperatively on the day of surgery and was approximately 2.0 tablets by postoperative day 3. Mean overall benefit of analgesic score ranged between 2.8 and 4.9 throughout the study. CONCLUSION: In this particular subject population, liposome bupivacaine was associated with low pain intensity scores and reduced opioid consumption compared with the investigators' previous experiences. Subjects' satisfaction with postsurgical analgesia was high, with a low burden of opioid-related side effects.

HISTORIQUE: Malgré l'efficacité des opioïdes pour soulager la douleur postchirurgicale, des effets secondaires peuvent compliquer le rétablissement. La bupivacaïne liposomique est une formulation à libération prolongée approuvée pour l'administration peropératoire d'une analgésie postchirurgicale au site opératoire. OBJECTIFS: Évaluer l'effet de l'administration peropératoire d'une seule dose de bupivacaïne liposomique sur la douleur postchirurgicale, ainsi que sur l'utilisation d'opioïdes et leurs effets secondaires chez des sujets subissant une chirurgie mammaire, une abdominoplastie ou les deux interventions. MÉTHODOLOGIE: Dans le cadre de la présente étude d'observation prospective et multicentrique de phase IV, les sujets se sont fait administrer une seule dose peropératoire de bupivacaïne liposomique (266 mg). Tous les sujets pouvaient recevoir une analgésie de secours, au besoin. Les mesures des résultats, évaluées jusqu'au troisième jour postopératoire, incluaient l'intensité de la douleur postchirurgicale (sur une échelle numérique de onze points), la consommation d'opioïdes et les bienfaits globaux du score analgésique. Les chercheurs ont évalué les résultats en les comparant à leur expérience de chirurgies similaires. RÉSULTATS: Quarante-neuf sujets ont participé à l'étude : 34 ont subi seulement une chirurgie mammaire et 15, une abdominoplastie accompagnée ou non d'une chirurgie mammaire (six ont subi une chirurgie mammaire en plus de l'abdominoplastie). Les scores de douleur moyens sur l'échelle numérique ne dépassaient pas 4,3 entre le congé et le troisième jour postopératoire. La consommation quotidienne médiane d'opioïdes par voie orale après l'opération était d'environ 1,0 comprimé le jour de la chirurgie et d'environ 2,0 comprimés le troisième jour postopératoire. Les avantages globaux moyens du score analgésique se situaient entre 2,8 et 4,9 tout au long de l'étude. CONCLUSION: Au sein de cette population de sujets, la bupivacaïne liposomique s'associait à de faibles scores d'intensité de la douleur et à une consommation réduite d'opioïdes par rapport aux expériences passées des chercheurs. Les sujets étaient très satisfaits de l'analgésie postchirurgicale et présentaient un faible fardeau d'effets secondaires liés aux opioïdes.