Intravenous Acetaminophen for Renal Colic in the Emergency Department: Where Do We Stand?

BACKGROUND: The efficacy, safety, opioid-sparing effects, and cost-benefit analyses of intravenous (IV) acetaminophen (APAP) in treating renal colic remain controversial. STUDY QUESTION: To evaluate the safety, efficacy, opioid-sparing effects, and cost-benefits of IV APAP in patients who present with renal colic in the emergency department (ED). DATA SOURCES: We systematically searched PubMed (January 1970 to April 2016). STUDY DESIGN: Randomized controlled trials which evaluated IV APAP for renal colic in the ED were eligible. The clinical outcomes measured were change in pain scores from baseline, incidence of adverse events, use of rescue analgesia, and cost-benefits. Forest plots were constructed using the Mantel-Haenszel method in a random effect model to changes in pain scores from the baseline to designated intervals. RESULTS: The analysis suggested a difference in pain reduction favoring IV APAP over morphine. IV APAP had a significant effect in pain reduction than IV morphine (difference in mean pain score reduction = 7.5 in a 100-point visual analog scale (VAS); 95% confidence interval [CI], 1.99-13.00; P = 0.008). There was mild-to-moderate study heterogeneity (I = 42%). No difference was observed when IV APAP was compared with intramuscular piroxicam for pain reduction (difference in mean pain score reduction = 0.17 in a VAS reduction ≥50% VAS; 95% CI, -0.22 to 0.57) and to intramuscular diclofenac (difference in mean pain score reduction = 0.00 in a numeric rating scale reduction ≥50%; 95% CI, -0.12 to 0.12). The analysis for nonsteroidal anti-inflammatory drugs versus IV APAP revealed no difference (difference in mean pain score reduction = 0.01 in a 100-point VAS; 95% CI, -0.10 to 0.13; P = 0.80). CONCLUSIONS: In this meta-analysis, we found that data on the efficacy, safety, opioid-sparing effects, and cost-benefit analyses of IV APAP for renal colic were weak. Based on the available data, IV APAP should not be considered as an alternative to opioids or nonsteroidal anti-inflammatory drugs for the primary management of renal colic in the ED.

Evaluating the Effects of an Interdisciplinary Practice Model with Pharmacist Collaboration on HIV Patient Co-Morbidities.

Treatment of HIV now occurs largely within the primary care setting, and the principal focus of most visits has become the management of chronic disease states. The clinical pharmacist's potential role in improving chronic disease outcomes for HIV patients is unknown. A retrospective cohort study was performed for HIV-positive patients also diagnosed with diabetes, hypertension, or hyperlipidemia. Characteristics and outcomes in 96 patients treated by an interdisciplinary team that included a clinical pharmacist (i.e., the intervention group) were compared to those in 50 patients treated by an individual healthcare provider (i.e., the control group). Primary outcomes were changes from baseline over 18 months of HbA1c, low density lipoprotein (LDL), and blood pressure, respectively. Secondary outcomes included number of drug-drug interactions, HIV viral load, CD4 count, percent change in smoking status, and percent of patients treated to cardiovascular guideline recommendations. The interdisciplinary team had a significant improvement in lipid management over the control group (LDL: -8.8 vs. +8.4 mg/dL; p=0.014), and the smoking cessation rate over the study period was doubled in the interdisciplinary group (20.4% vs. 11.8%). Among those with an indication for aspirin, a significantly higher percentage of patients were prescribed the medication in the interdisciplinary group compared to the control group (85.5% vs. 64.9%; p=0.014). An informal cost analysis estimated savings of more than $3000 per patient treated by the interdisciplinary team. Based on these results, pharmacist involvement in an HIV primary care clinic appears to lead to more appropriate management of chronic co-morbidities in a cost-effective manner.

A randomized controlled trial of two interventions to improve medication reconciliation.

OBJECTIVE: Medication errors can be caused by lack of agreement between what physicians believe patients are taking and what patients actually take. There has been little systematic research to find the best way to reconcile medication lists in primary care. The objective of this study was to assess the impact of 2 interventions on agreement between electronic medical record medication lists and what patients report actually taking. METHODS: This study was a factorial randomized trial that randomized 440 eligible patients (English-speaking, age 18 and older, taking at least 2 prescriptions) visiting 20 primary care physicians; 367 completed the study. Interventions included (1) providing patients a printed copy of their current medication list at check-in and (2) beginning the medication review with an open-ended question. Patients were randomized to receive no intervention, one or the other intervention, or both interventions. The outcome measure was agreement on all prescription and nonprescription medications, vitamins, and supplements between the list from the electronic medical record after the visit and a list based on patient report generated during a phone interview within a week of the office visit. RESULTS: Agreement rates between medication lists and patient report for the 4 study groups were: 67.4% in the no intervention group, 66.7% in the printed list only group, 58.1% in the open-ended question only group, and 75.6% in the combined intervention group. Both a printed list and beginning a medication discussion with an open-ended question were required before any significant increase in agreement was observed. CONCLUSIONS: While neither intervention alone improved medication list agreement, these interventions may have value in a multistep protocol to improve the agreement of medication lists in primary care offices. Baseline agreement was much higher than expected, possibly reflecting a Hawthorne effect.

Rates of febrile neutropenia with pegfilgrastim on same day versus next day of CHOP with or without rituximab.

Febrile neutropenia is a complication of myleotoxic chemotherapy that can markedly decrease quality of life and increase healthcare costs. A granulocyte-colony stimulating factor (G-CSF) is used to increase neutrophil production to reduce the risk of developing febrile neutropenia. However, G-CSF administered on the same day as chemotherapy can worsen and prolong neutropenia. To study and compare the effects of pegfilgrastim on the incidence of febrile neutropenia and grade 4 neutropenia in patients receiving pegfilgrastim on the same day (day 1) versus the next day (day 2 or beyond) of chemotherapy, a retrospective, single-center, nonrandomized, cohort study was carried out of adult non-Hodgkin's lymphoma patients who received pegfilgrastim 6 mg subcutaneously on day 1 or beyond of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) with or without rituximab every 3 weeks. Six hundred and fifty-five chemotherapy cycles (320 cycles for the same day and 335 cycles for the next day) were evaluable in 141 patients. Among all cycles, the incidence of febrile neutropenia was 9.4 versus 5.1% in the same-day versus the next-day group (P=0.03). The incidence of febrile neutropenia was the highest after the first cycle in the same-day group, which was 19.4, versus 11.1% for the next-day group (P=0.27). There were three deaths among patients who developed febrile neutropenia, including two in the next-day group versus one in the same-day group. In conclusion, our findings support the need for a randomized phase III study to fully evaluate whether a G-CSF is safer when administered on the next day versus the same day of chemotherapy.

United States adults meeting 2010 American College of Rheumatology criteria for treatment and prevention of glucocorticoid-induced osteoporosis.

OBJECTIVE: The American College of Rheumatology (ACR) updated its guidelines on the prevention and treatment of glucocorticoid-induced osteoporosis (GIO) in 2010. An unknown proportion of US adults at risk of fracture due to glucocorticoid use would be recommended antiosteoporosis pharmaceutical (AOP) therapies based on the ACR guidelines. METHODS: Using the 2005-2010 National Health and Nutrition Examination Survey (NHANES) data for postmenopausal women (PMW), and men age ≥50 years reporting current glucocorticoid use, we categorized individuals according to ACR criteria for low, medium, and high fracture risk (<10%, ≥10%, and ≥20%, respectively) and provided percentages of treatment recommendations for chronic (≥90 days) medium and all high-risk patients. RESULTS: Glucocorticoids were used by 1.66% of PMW and 1.65% of men age ≥50 years. Of these patients, 0.80% of PMW and 0.45% of men age ≥50 years were at high risk of fracture. A majority of PMW (81.2%) and men age ≥50 years (75.8%) were chronic glucocorticoid users. In patients for whom treatment recommendations could be made, 64.9% of PMW and 51.9% of men age ≥50 years would be recommended therapy, but only 28.4% of PMW and 9.7% of men age ≥50 years reported AOP use. CONCLUSION: Based on the NHANES (2005-2010) data, we estimate glucocorticoid use in >1.5 million US PMW and men age ≥50 years. Treatment would be recommended in at least 50% of this population based on the 2010 ACR guidelines. Self-reported AOP use was documented in <30%, suggesting a treatment gap in the management of GIO in the US before the guideline release.

Outcomes in obese and overweight acute myeloid leukemia patients receiving chemotherapy dosed according to actual body weight.

Cytotoxic chemotherapy dosages are traditionally calculated according to body surface area (BSA). No guidelines exist for chemotherapy dosing of acute myeloid leukemia (AML) patients at extremes of weight. We investigated the efficacy and safety of chemotherapy dosed according to BSA based on actual body weight (ABW) among under/normal weight, overweight, and obese AML patients. AML patients (excluding acute promyelocytic leukemia) treated with anthracycline and cytarabine-based remission induction chemotherapy from 2002 to 2009 at Cleveland Clinic were divided into three body mass index (BMI) groups: under/normal weight (BMI ≤ 24.9), overweight (BMI 25.0-29.9), and obese (BMI ≥ 30.0). Among 247 AML patients, 81 (33%) were under/normal weight, 81 (33%) were overweight, and 85 (34%) were obese. Complete remission (CR) rates were similar among these groups (69.1, 79.0, and 76.5%, respectively; P = 0.321), as was median survival (10.7, 16.7, and 14.2 months, respectively, P = 0.352) and 30-day mortality (3.7, 2.5, 7.1%, respectively, P = 0.331). There was no difference among groups in days to neutrophil or platelet recovery, hospitalization days for induction chemotherapy, and bacteremia. After adjustment for confounders (age, sex, BMI, white blood cells, cytogenetic risk, etiology, and bacteremia), overall survival was significantly shorter for normal weight compared to overweight (P = 0.006) and obese (0.038) patients. Response rates and adverse events were not significantly different among AML patients of all weight classes when induction chemotherapy was dosed according to ABW. Induction chemotherapy in these patients can be safely dosed using ABW.

Prevalence of oral glucocorticoid usage in the United States: a general population perspective.

OBJECTIVE: There is little information on oral glucocorticoid use in the general US population. Previously, there have been published estimates of glucocorticoid use in countries outside of the US. This study aimed to estimate the prevalence of glucocorticoid use, duration of use, and concomitant use of antiosteoporosis pharmaceuticals in the US population age ≥20 years. METHODS: Data from 5 cycles (1999-2008) of the National Health and Nutrition Examination Survey (NHANES) were used to provide nationally representative weighted estimates. Oral glucocorticoids and concomitant use of antiosteoporosis pharmaceuticals (bisphosphonates, calcitonin, calcium, hormone replacement therapies, teriparatide, and vitamin D) were analyzed. RESULTS: There were 356 NHANES respondents ages ≥20 years who reported use of an oral glucocorticoid in the combined cycles between 1999 and 2008. The weighted prevalence of oral glucocorticoid use was 1.2% (95% confidence interval [95% CI] 1.1-1.4) from 1999-2008, corresponding to 2,513,259 persons in the US. The mean duration of oral glucocorticoid use was 1,605.7 days (95% CI 1,261.2-1,950.1), and 28.8% (95% CI 22.2-35.4) of oral glucocorticoid users reported use for ≥5 years. Concomitant use of a bisphosphonate was reported by 8.6% (95% CI 5.1-11.7) of oral glucocorticoid users, and 37.9% (95% CI 31.7-44.0) reported usage of any antiosteoporosis pharmaceutical. CONCLUSION: Based on NHANES data from 1999-2008, it is estimated that the prevalence of glucocorticoid use in the US is 1.2%, with a long duration of use and infrequent use of antiosteoporotic medications compared to other estimates.

Treatment and outcomes in carbapenem-resistant Klebsiella pneumoniae bloodstream infections.

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is an emerging multidrug-resistant nosocomial pathogen. This is a retrospective chart review describing the outcomes and treatment of 60 cases of CR-Kp bloodstream infections. All CR-Kp isolated from blood cultures were identified retrospectively from the microbiology laboratory from January 2007 to May 2009. Clinical information was collected from the electronic medical record. Patients with 14-day hospital mortality were compared to those who survived 14 days. The all-cause in-hospital and 14-day mortality for all 60 CR-Kp bloodstream infections were 58.3% and 41.7%, respectively. In this collection, 98% of tested isolates were susceptible in vitro to tigecycline compared to 86% to colistimethate, 45% to amikacin, and 22% to gentamicin. Nine patients died before cultures were finalized and received no therapy active against CR-Kp. In the remaining 51 patients, those who survived to day 14 (n = 35) were compared to nonsurvivors at day 14 (n=16). These patients were characterized by both chronic disease and acute illness. The 90-day readmission rate for hospital survivors was 72%. Time to active therapy was not significantly different between survivors and nonsurvivors, and hospital mortality was also similar regardless of therapy chosen. Pitt bacteremia score was the only significant factor associated with mortality in Cox regression analysis. In summary, CR-Kp bloodstream infections occur in patients who are chronically and acutely ill. They are associated with high 14-day mortality and poor outcomes regardless of tigecycline or other treatment regimens selected.

Discontinuation of vasopressin before norepinephrine increases the incidence of hypotension in patients recovering from septic shock: a retrospective cohort study.

PURPOSE: There are little data regarding the discontinuation of vasoactive medications in patients recovering from septic shock. We designed this retrospective cohort study to evaluate the incidence of hypotension based on the order of removal of norepinephrine (NE) and vasopressin (AVP) in patients receiving concomitant NE and AVP infusions for the treatment of septic shock. MATERIALS AND METHODS: Consecutive patients receiving concomitant NE and AVP infusions for septic shock admitted to the intensive care units of a tertiary care academic medical center were evaluated. RESULTS: Of 50 included patients, the first vasoactive medication discontinued was NE in 32 patients and AVP in 18 patients. The groups had similar Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores at shock onset and at the time of discontinuation of the first agent. Five patients who had NE discontinued first (16%) versus 10 patients who had AVP discontinued first (56%) developed hypotension within 24 hours (unadjusted relative risk, 3.6; 95% confidence interval, 1.5-4.5; P = .008). In a multivariate analysis, only discontinuation of AVP first was independently associated with hypotension (adjusted relative risk, 5.9; 95% confidence interval, 1.7-21.0; P = .006). CONCLUSIONS: Discontinuation of AVP before NE may lead to a higher incidence of hypotension in patients recovering from septic shock receiving concomitant AVP and NE.

Nucleosides. IX. Synthesis of purine N(3),5'-cyclonucleosides and N(3),5'-cyclo-2',3'-seconucleosides via Mitsunobu reaction as TIBO-like derivatives.

The Mitsunobu reaction was applied to prepare, in one step, purine N(3),5'-cyclonucleosides 10a-d. A subsequent ring opening in the ribose moiety of the resultant N(3),5'-nucleosides by sodium periodate led to the corresponding N(3),5'-cyclo-2',3'-seconucleosides. These products consist of 5-, 6-, and 7-membered tricyclic system which is the basic skeleton of TIBO derivatives, known antiviral agents.