Physician Financial Incentives for Use of Outpatient Intravenous Antimicrobial Therapy: An Interrupted Time Series Analysis.

BACKGROUND: In 2011, policymakers in British Columbia introduced a fee-for-service payment to incentivize infectious diseases physicians to supervise outpatient parenteral antimicrobial therapy (OPAT). Whether this policy increased use of OPAT remains uncertain. METHODS: We conducted a retrospective cohort study using population-based administrative data over a 14-year period (2004-2018). We focused on infections that required intravenous antimicrobials for ≥10 days (eg, osteomyelitis, joint infection, endocarditis) and used the monthly proportion of index hospitalizations with a length of stay shorter than the guideline-recommended "usual duration of intravenous antimicrobials" (LOS < UDIVA) as a surrogate for population-level OPAT use. We used interrupted time series analysis to determine whether policy introduction increased the proportion of hospitalizations with LOS < UDIVA. RESULTS: We identified 18 513 eligible hospitalizations. In the pre-policy period, 82.3% of hospitalizations exhibited LOS < UDIVA. Introduction of the incentive was not associated with a change in the proportion of hospitalizations with LOS < UDIVA, suggesting that the policy intervention did not increase OPAT use (step change, -0.06%; 95% confidence interval [CI], -2.69% to 2.58%; P = .97 and slope change, -0.001% per month; 95% CI, -.056% to .055%; P = .98). CONCLUSIONS: The introduction of a financial incentive for physicians did not appear to increase OPAT use. Policymakers should consider modifying the incentive design or addressing organizational barriers to expanded OPAT use.

Outpatient Versus Inpatient Intravenous Antimicrobial Therapy: A Population-Based Observational Cohort Study of Adverse Events and Costs.

BACKGROUND: Bacterial infections such as osteomyelitis and endocarditis routinely require several weeks of treatment with intravenous (IV) antimicrobials. Outpatient parenteral antimicrobial therapy (OPAT) programs allow patients to receive IV antimicrobials in an outpatient clinic or at home. The outcomes and costs of such treatments remain uncertain. METHODS: We conducted a retrospective observational cohort study over a 5-year study interval (1 June 2012 to 31 March 2018) using population-based linked administrative data from British Columbia, Canada. Patients receiving OPAT following a hospitalization for bacterial infection were matched based on infection type and implied duration of IV antimicrobials to patients receiving inpatient parenteral antimicrobial therapy (IPAT). Cumulative adverse events and direct healthcare costs were estimated over a 90-day outcome interval. RESULTS: In a matched cohort of 1842 patients, adverse events occurred in 35.6% of OPAT patients and 39.0% of IPAT patients (adjusted odds ratio, 1.04 [95% confidence interval {CI}, .83-1.30; P = .61). Relative to IPAT patients, OPAT patients were significantly more likely to experience hospital readmission (30.5% vs 23.0%) but significantly less likely to experience Clostridioides difficile diarrhea (1.2% vs 3.1%) or death (2.0% vs 8.8%). Estimated mean direct healthcare costs were $30 166 for OPAT patients and $50 038 for IPAT patients (cost ratio, 0.60; average cost savings with OPAT, $17 579 [95% CI, $14 131-$21 027]; P < .001). CONCLUSIONS: Outpatient IV antimicrobial therapy is associated with a similar overall prevalence of adverse events and with substantial cost savings relative to patients remaining in hospital to complete IV antimicrobials. These findings should inform efforts to expand OPAT use.

Successful multidisciplinary treatment of Doege-Potter syndrome: hypoglycaemia caused by paraneoplastic IGF-2 production by a metastatic haemangiopericytoma.

Hypoglycaemia due to insulin-like growth factor (IGF)-2 secretion is a paraneoplastic complication of malignancy with significant morbidity that can often go unrecognised due to its uncommon presentation. We report on a case of a 51-year-old man with metastatic haemangiopericytoma presenting with refractory hypoglycaemia, requiring continuous dextrose 10% infusion while in hospital. IGF-2 levels were significantly elevated, in keeping with a rare entity associated with solitary fibrous tumours, known as Doege-Potter syndrome. The patient was managed using uncooked cornstarch in conjunction with debulking of the hepatic tumour burden with bland IR-guided transarterial embolisation, and eventual surgical resection to treat his non-islet cell tumour hypoglycaemia (NICTH). The case highlights this rare paraneoplastic phenomenon that should be included in the differential for hypoglycaemia, especially if a history of a solitary fibrous tumour is elicited. Our case is the first to document a successful approach to treating the hypoglycaemia using preoperative transarterial bland embolisation.

A case report of nifedipine-induced hepatitis with jaundice.

BACKGROUND: Nifedipine is a generic, well-known and commonly-prescribed dihydropyridine calcium channel blocker used in the treatment of hypertension and Prinzmetal's angina. A known but very rare and serious adverse effect of nifedipine is clinically-apparent hepatitis which can take months to resolve. CASE PRESENTATION: Here we present a case of nifedipine-induced hepatitis in a 78-year-old Caucasian female with no prior history of liver or autoimmune disease. We discuss our investigative and management approach, and present a review of prior cases. We offer an approach for patients who present with signs of acute liver injury with jaundice and high elevations in serum transaminases. CONCLUSION: Not much is known about nifedipine-induced hepatitis due to its rare occurrence. Its prevalence is unknown. The disease appears to afflict older men and women. It can present acutely (within days) or subacutely (within 4-8 weeks after medication start) and in an idiosyncratic manner. Chronic or latent cases have also been described, some diagnosed as late as 3 years after medication start. Common symptoms include jaundice, nausea, chills, rigors, diaphoresis, fatigue, and abdominal pain. Laboratory investigations often reveal profound elevations in AST, ALT, GGT, and conjugated bilirubin. Peripheral blood smear may demonstrate eosinophilia. Histology from liver biopsy typically demonstrates infiltration of immune cells, cholestasis, and a picture of steatohepatitis. Treatment involves immediate discontinuation of the drug with supportive care. Thus far, all published instances of nifedipine-induced hepatitis were self-limiting without mortality due to fulminant liver failure. However, this disease can take months to resolve. There is no randomized evidence for other treatments such as corticosteroids.

Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension.

BACKGROUND: Blood pressure is a commonly measured risk factor for non-fatal and fatal cardiovascular adverse events such as heart attacks and strokes. Clinical trials have suggested that coenzyme Q10, a non-prescription nutritional supplement, can effectively lower blood pressure (BP). When this review was completed and published in October 2009, it concluded that "due to the possible unreliability of the 3 included studies, it is uncertain whether or not coenzyme Q10 reduces blood pressure in the long-term management of primary hypertension." OBJECTIVES: To determine the blood pressure lowering effect of coenzyme Q10 in primary hypertension. SEARCH METHODS: We searched the Hypertension Group Specialised Register (1946 to November 2015), The Cochrane Central Register of Controlled Trials (The Cochrane Library 2015, Issue 10), MEDLINE (1946 to November 2015), MEDLINE In-Process (accessed 10 November 2015), EMBASE (1974 to November 2015), Web of Science (1899 to November 2015), CINAHL (1970 to November 2015), and ClinicalTrials.gov (accessed 10 November 2015). We also searched reference lists of articles for relevant clinical trials in any language. SELECTION CRITERIA: Double blind, randomized, placebo-controlled parallel or cross-over trials evaluating the blood pressure (BP) lowering efficacy of coenzyme Q10 for a duration of at least three weeks, in patients with primary hypertension. DATA COLLECTION AND ANALYSIS: The primary author determined trial inclusion, extracted the data and assessed the risk of bias. The second author independently verified trial inclusion and data extraction. MAIN RESULTS: In this update of the review, one new randomized, controlled cross-over trial with a total of 30 participants was added, and one trial included in the initial review was excluded. Only two of the three included trials were pooled in the meta-analysis, as one trial was judged to have an unacceptably high risk of bias. In the meta-analysis of two RCTs (50 participants), coenzyme Q10 did not significantly change systolic BP: -3.68 mm Hg (95% confidence interval (CI) -8.86 to 1.49), or diastolic BP: -2.03 mm Hg (95% CI -4.86 to 0.81] ), based on clinic data. AUTHORS' CONCLUSIONS: This review provides moderate-quality evidence that coenzyme Q10 does not have a clinically significant effect on blood pressure. In one of three trials reporting adverse effects, coenzyme Q10 was well tolerated. Due to the small number of individuals and studies available for analysis, more well-conducted trials are needed.

Development, implementation, and evaluation of a student-initiated undergraduate medical education elective in HIV care.

BACKGROUND: The literature indicates that medical students require more comprehensive HIV training. AIM: Medical students at the University of Toronto developed and implemented the preclerkship HIV elective (PHE) with the aim to increase trainee HIV knowledge, address important issues in HIV care, and prepare students to serve affected populations. METHODS: Developed in partnership with the Ontario HIV Treatment Network and in consultation with local AIDS service organizations and the University of Toronto Faculty of Medicine, the PHE was inaugurated in November 2008 as an elective supplement to medical curriculum content. Eighteen second-year medical students participated in the PHE, consisting of lectures, small group sessions, clinical observerships, community placements, reading assignments, and an HIV counseling and testing workshop. Participants completed a self-assessment of HIV knowledge prior to starting and after PHE completion. RESULTS: Self-assessment scores of HIV knowledge among PHE participants significantly increased from 78.1% (pre-PHE) to 90.2% (post-PHE) (p = 0.0016). Common themes from feedback on participant satisfaction included enthusiasm for small group sessions, clinical observerships, community agency placements, and the diversity of topics covered. CONCLUSIONS: Student-run initiatives can supplement medical curriculum content and program feedback may be used to advocate for curriculum changes. Factors influencing success include student leadership and interest, community partnerships, and faculty mentorship.

Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension.

BACKGROUND: Studies have shown that coenzyme Q10 deficiency is associated with cardiovascular disease. Hypertension is a commonly measured surrogate marker for non-fatal and fatal cardiovascular endpoints such as heart attacks and strokes. Clinical trials have suggested that coenzyme Q10 supplementation can effectively lower blood pressure (BP). OBJECTIVES: To determine the blood pressure lowering effect of coenzyme Q10 in primary hypertension. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (2009 Issue 2), MEDLINE (1966 -May 2008), EMBASE (1982 - May 2008), and CINAHL (1970 - May 2008) as well as the reference lists of articles were searched for relevant clinical trials in any language. SELECTION CRITERIA: Double-blind, randomized, placebo-controlled parallel or crossover trials evaluating the BP lowering efficacy of coenzyme Q10 for a duration of at least 3 weeks in patients with primary hypertension. DATA COLLECTION AND ANALYSIS: The primary author independently assessed the risk of bias and extracted the data. The second author verified data extraction. MAIN RESULTS: Three clinical trials with a total of 96 participants were evaluated for the effects of coenzyme Q10 on blood pressure compared to placebo. Treatment with coenzyme Q10 in subjects with systolic BP (SBP) > 140 mmHg or diastolic BP (DBP) > 90 mmHg resulted in mean decreases in SBP of 11 mmHg (95% CI 8, 14) and DBP of 7 mmHg (95% CI 5, 8). AUTHORS' CONCLUSIONS: Due to the possible unreliability of some of the included studies, it is uncertain whether or not coenzyme Q10 reduces blood pressure in the long-term management of primary hypertension.

Selective pharmacological blockade of the TRPV1 receptor suppresses sensory reflexes of the rodent bladder.

PURPOSE: We investigated the pharmacological effect of TRPV1 antagonists in anesthetized rodent models of bladder function. MATERIALS AND METHODS: The TRPV1 antagonists JNJ17203212 and JYL1421 were evaluated in the anesthetized rat volume induced micturition reflex model. JNJ17203212 was further evaluated in this model in capsaicin (Sigma) desensitized rats, and in rat capsaicin and mouse citric acid models of irritant induced detrusor overactivity. RESULTS: Systemic JNJ17203212 and JYL1421 administration in the anesthetized rat volume induced micturition reflex model resulted in an increased micturition threshold volume. JNJ17203212 also decreased bladder contraction amplitude but JYL1421 had no effect. Capsaicin desensitization significantly increased baseline micturition threshold volume and decreased bladder contraction amplitude in the volume induced micturition reflex model compared to those in sham treated controls and JNJ17203212 produced no further effect after capsaicin desensitization. JNJ17203212 was also effective in 2 models of irritant induced detrusor overactivity, preventing the decrease in micturition threshold volume and the increase in bladder contraction amplitude observed with intravesical instillation of 10 microM capsaicin, and the decreased voiding interval induced by intravesical citric acid. CONCLUSIONS: The TRPV1 antagonists JNJ17203212 and JYL1421 increased the threshold for activation of the micturition reflex in the anesthetized rat volume induced micturition reflex model. This effect appeared to be mediated by capsaicin sensitive afferents. JNJ17203212 also inhibited detrusor overactivity induced by intravesical capsaicin and intravesical citric acid. These data extend our understanding of the role of TRPV1 in sensory modulation of the micturition reflex under nonirritant and inflammatory conditions.

Effects of the selective prostacyclin receptor antagonist RO3244019 on the micturition reflex in rats.

PURPOSE: We investigated the role of prostacyclin on afferent modulation of the micturition reflex using the novel selective prostacyclin receptor antagonist RO3244019 in rat models of bladder function. MATERIALS AND METHODS: The effects of RO3244019 on urodynamic parameters were evaluated in 3 rat models. In the anesthetized isovolumetric bladder contraction and the volume induced micturition reflex (Refill) models the effects of RO3244019 and chronic capsaicin desensitization were compared. In the citric acid induced detrusor overactivity model the effects of RO3244019 and the cyclooxygenase inhibitor indomethacin were evaluated. RESULTS: In the isovolumetric bladder contraction model RO3244019 dose dependently decreased bladder contraction frequency with a mean +/- SEM maximum decrease of 72.2% +/- 4.3% at 3.16 mg/kg. RO3244019 also dose dependently increased the micturition threshold in the Refill model with a maximum increase of 86.9% +/- 19.1% at 3.0 mg/kg. In animals that were chronically treated with capsaicin bladder contraction frequency was decreased by 88.9% in the isovolumetric bladder contraction model and micturition threshold was increased by 68.1% in the Refill model relative to sham treated rats. RO3244019 (3.0 mg/kg) further increased the micturition threshold in capsaicin treated animals by 53.7% +/- 18.1% from baseline. In the citric acid induced detrusor overactivity model citric acid decreased the voiding interval to 28.5% of baseline. This effect was reversed by RO3244019 (73.0% +/- 6.4%) and indomethacin (97.7% +/- 5.5%) at 3.0 mg/kg compared to vehicle (55.0% +/- 4.1%). CONCLUSIONS: The prostacyclin receptor antagonist RO3244019 decreased bladder contraction frequency and increased micturition threshold in the anesthetized isovolumetric bladder contraction and Refill models, respectively, and increased the micturition voiding interval in the conscious citric acid induced detrusor overactivity model. Additionally, RO3244019 remained effective for increasing the micturition threshold in the Refill model even following chronic capsaicin desensitization. Taken together these data suggest that prostacyclin may have a facilitory role in the micturition reflex by modulating the threshold for activation of capsaicin sensitive and insensitive bladder sensory afferents.