Pupillometric Assessment of Small Doses of Opioid in a Pediatric Population

According to the CDC, opioid prescriptions in the United States have more than tripled from 1999-2014, which has correlated with the staggering increase in opioid-involved drug overdose deaths. This pattern of prescription is thought to be a major contributory factor to the increase in drug overdose in America, as four out of five new heroin users started by misusing prescription painkillers. Providers need the means to objectively monitor analgesic efficacy of treatment in patients with pain to mitigate unnecessary analgesic prescribing. It is well established that mu opioid agonists like morphine cause miosis, an effect to which tolerance does not occur. This suggests a utility in using pupil size and responsiveness as a pharmacokinetic analogue of bioavailability. An infrared pupillometer is a device that produces a short light stimulus and subsequently measures parameters of the pupillary light reflex (PLR) including maximum and minimum pupil size (MAX, MIN), maximum constriction velocity (MCV), latency period before constriction onset (LAT), change in pupil size (DELTA), and average constriction velocity (ACV). Current data supports the efficacy of using infrared pupillometry to detect high dose opioid presence, but no research exists judging its efficacy in monitoring low dose therapeutic levels. We enrolled 15 patients between the ages of 7 and 18 on the pain medicine service receiving low dose opioids on patient controlled analgesia (PCA). The pupillometer was used to take a baseline PLR, and repeated measures were taken 10 and 15-minutes post PCA dose infusion. We found that the pupil size at 10 and 15-minute time points were significantly smaller than the baseline for the parameters MAX (p=.0016, p=.0010) and MIN (p=.0250, p=.0070). Additionally, it was found that LAT was significantly longer from baseline at the 15-minute measure (p=.0350), and there was a significant difference between the 10 and 15-minute time points for the MIN (p=0.0251). This evidence supports the sensitivity of the pupillometer in evaluating opioid activity. Furthermore, in concordance with previous research, the MIN is significantly correlated with opioid concentration dose-dependently across the 15-minute measurement window. Before applying the pupillometer to clinical pain medicine, more research comparing pupillometric parameters with blood levels of opioid metabolites will serve to determine detection limits. Providers could use this tool to monitor treatment efficacy by using these parameters to assess steady state equilibrium and to determine dosing intervals. Furthermore, the pupillometric parameters could elucidate individuals’ metabolic capacity for different opioids in order to prescribe therapeutic levels

The Impact of Data Characteristics on the Selection of Data Mining Methods for Predictive Classification

This research-in-process is exploring a contingency approach to the construction and selection of data mining models for predictive classification. This approach considers the structure of the data set and the relationships between and among the various attributes characterizing the data set, with the goal of selecting a model that provides greater insight into the data – and therefore predicts most accurately -- given a particular data structure. Preliminary results obtained from analysis of hospital patient records indicate that concentration indices, commonly used to measure firm concentration within an industry, are useful in characterizing data set structures and therefore in guiding the model selection process. The eventual goal of this research is the construction of a decision support system that can aid decision makers in the model selection task

Educating Pharmacy Students to Improve Quality (EPIQ) in Colleges and Schools of Pharmacy

Objective. To assess course instructors’ and students’ perceptions of the Educating Pharmacy Students and Pharmacists to Improve Quality (EPIQ) curriculum. Methods. Seven colleges and schools of pharmacy that were using the EPIQ program in their curricula agreed to participate in the study. Five of the 7 collected student retrospective pre- and post-intervention questionnaires. Changes in students’ perceptions were evaluated to assess their relationships with demographics and course variables. Instructors who implemented the EPIQ program at each of the 7 colleges and schools were also asked to complete a questionnaire. Results. Scores on all questionnaire items indicated improvement in students’ perceived knowledge of quality improvement. The university the students attended, completion of a class project, and length of coverage of material were significantly related to improvement in the students’ scores. Instructors at all colleges and schools felt the EPIQ curriculum was a strong program that fulfilled the criteria for quality improvement and medication error reduction education. Conclusion. The EPIQ program is a viable, turnkey option for colleges and schools of pharmacy to use in teaching students about quality improvement

Preclinical development of G1T38: A novel, potent and selective inhibitor of cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with CDK4/6 sensitive tumors

Inhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic strategy for the treatment of estrogen receptor positive (ER+) breast cancer. Although efficacious, current treatment regimens require a dosing holiday due to severe neutropenia potentially leading to an increased risk of infections, as well as tumor regrowth and emergence of drug resistance. Therefore, a next generation CDK4/6 inhibitor that can inhibit proliferation of CDK4/6-dependent tumors while minimizing neutropenia could reduce both the need for treatment holidays and the risk of inducing drug resistance

Heterogeneity of human adipose blood flow

BACKGROUND: The long time pharmacokinetics of highly lipid soluble compounds is dominated by blood-adipose tissue exchange and depends on the magnitude and heterogeneity of adipose blood flow. Because the adipose tissue is an infinite sink at short times (hours), the kinetics must be followed for days in order to determine if the adipose perfusion is heterogeneous. The purpose of this paper is to quantitate human adipose blood flow heterogeneity and determine its importance for human pharmacokinetics. METHODS: The heterogeneity was determined using a physiologically based pharmacokinetic model (PBPK) to describe the 6 day volatile anesthetic data previously published by Yasuda et. al. The analysis uses the freely available software PKQuest and incorporates perfusion-ventilation mismatch and time dependent parameters that varied from the anesthetized to the ambulatory period. This heterogeneous adipose perfusion PBPK model was then tested by applying it to the previously published cannabidiol data of Ohlsson et. al. and the cannabinol data of Johansson et. al. RESULTS: The volatile anesthetic kinetics at early times have only a weak dependence on adipose blood flow while at long times the pharmacokinetics are dominated by the adipose flow and are independent of muscle blood flow. At least 2 adipose compartments with different perfusion rates (0.074 and 0.014 l/kg/min) were needed to describe the anesthetic data. This heterogeneous adipose PBPK model also provided a good fit to the cannabinol data. CONCLUSION: Human adipose blood flow is markedly heterogeneous, varying by at least 5 fold. This heterogeneity significantly influences the long time pharmacokinetics of the volatile anesthetics and tetrahydrocannabinol. In contrast, using this same PBPK model it can be shown that the long time pharmacokinetics of the persistent lipophilic compounds (dioxins, PCBs) do not depend on adipose blood flow. The ability of the same PBPK model to describe both the anesthetic and cannabinol kinetics provides direct qualitative evidence that their kinetics are flow limited and that there is no significant adipose tissue diffusion limitation

Ärtyvän suolen oireyhtymää sairastavan lapsen hoitotyö : kurssimuotoinen opetusmateriaali Skhole Oy:lle

Opinnäytetyö tehtiin yhteistyössä Skhole Oy:n kanssa, joka tarjoaa joustavan oppimisympäristön ammatilliseen kehittymiseen. Opinnäytetyön tarkoituksena oli toteuttaa kurssimateriaali Skhole Oy:lle. Opinnäytetyön tavoitteena oli parantaa tietoisuutta ja ammattitaitoa ärtyvän suolen oireyhtymän (IBS) hoidosta, parantaa IBS:ä sairastavien lasten elämänlaatua, vähentää ilmaantuvuus ja pahenemisvaiheiden määrää. Aiheesta luotiin kurssimateriaali, joka on tarkoitettu erilaisille opiskelijoille ja sopii kaikille aiheesta kiinnostuneille sekä lasten huoltajille että ammattilaisille, jotka tekevät työtä lasten parissa. Kurssimateriaalin painopisteeksi otettiin IBS:ä sairastavan lapsen hoito. Kurssimateriaalissa esiteltiin erilaisia hoitomenetelmiä. Kurssimateriaali perustettiin laajaan tieteelliseen ja näyttöön perustuvaan tutkimusaineistoon, jonka avulla pystyttiin arvioimaan tietyn hoitomenetelmän tehokkuutta. Kurssimateriaaliin otettiin mukaan tietoja taudin patogeneesista ja patofysiologiasta, mikä lisää ymmärrystä tautiin altistavista ja taudin pahenemiseen vaikuttavista tekijöistä. Kurssimateriaalissa annettiin tarpeellista tietoa koskien lasten IBS:n diagnostiikkaa, sekä diagnostiset kriteerit ja menetelmät Rooma IV mukaan. Lyhyesti esitettiin myös taudin historiaa sekä vatsakivun tavalliset syyt ja niiden hoitomenetelmät kotimaassa. IBS:n diagnosointi on pitkä. Oireilua voi helpottaa jo diagnostiikan vaiheessa. Huoltajien ja lasten kanssa työskentelevien ammattilaisten asenteet vaikuttavat merkittävästi IBS:n sairastavan lapsen elämänlaatuun. Kurssimateriaali annettiin Skhole y:lle arvioitavaksi. Skholen palaute oli positiivinen. Kurssimateriaali siirretään Skhole:n internetsivustolle käyttöä varten.The thesis was made in collaboration with Skhole Ltd. which provides a flexible learning environment for professional development. The purpose of the thesis was to create course material for Skhole Oy. The goal of the thesis was to improve knowledge and professional skills about the treatment of irritable bowel syndrome (IBS), to improve the quality of life of children with IBS, to reduce sickness rate the number of exacerbations of the disease. The focus of course material was on methods of treatment of IBS in children. In the course material were widely covered various methods of treatment, including dietary treatment, medication, probiotics, psychological and biopsychological therapies, acupuncture and phytotherapy. Information about epidemiology, pathogenesis and pathophysiological mechanisms of IBS were also included. In course was included information about Rome IV criteria for diagnosis of IBS and diagnostic methods considering the characteristics of IBS and its diagnostic features in children. In the course material was briefly given the history of the disease, the prevalence of IBS and the main reasons of abdominal pain in children, its diagnosis and treatment in Finland. This course material was based on a variety of actual up-to-date scientific studies and evidence-based research carried out by professionals specialized in the area of GI disorders and in pediatric medicine from different countries. Symptoms of IBS can be alleviated already at the stage of diagnosis. The attitudes of child’s parents and professionals working with children have a significant impact on the quality of life of the child with IBS. Skhole's feedback of course material was positive. Course material will be uploaded to Skhole's website for use. The course material was designed in accordance with the wishes and the standards used by the Skole Ltd

Quality of Life Outcomes Following Surgery for Velopharyngeal Insufficiency

Velopharyngeal insufficiency (VPI) alters speech quality and intelligibility which can compromise verbal communication. Treatment of VPI begins with a trial of targeted speech therapy, but the majority of patients with severe insufficiency require surgical intervention. Multiple techniques are utilized, but no evidence exists demonstrating significant differences in quality of life outcomes. Additionally, there is little data identifying preoperative factors associated with outcomes following surgical VPI repair. The Velopharyngeal Insufficiency Effects on Life Outcomes (VELO) survey is a 26-question parental proxy survey assessing quality of life measurements including speech, swallow, emotional impact, perception by others, and caregiver impact. VELO has been validated as an effective measure with high internal consistency and test-retest reliability in English and Spanish. We used the questionnaire to determine which preoperative factors correlated with higher VELO scores following corrective surgery. In our IRB approved study, we identified 51 eligible patients and categorized them by presence/absence of genetic syndrome, presence/absence of submucous cleft abnormality (SMC), severity of hypernasality, and surgical technique. We called parents to administer the VELO survey in English or Spanish. We received 26 responses. Eleven of these patients were male and 15 were female. The average age at surgery was 9.4 years. Analysis of VELO scores between patient groups revealed a significantly higher average among non-syndromic patients compared to their syndromic counterparts (83vs69,p=0.043) specifically in subcategories of speech (p=0.030), swallow (p=0.022), and caregiver impact (p=0.008). There was no significant difference in VELO score between surgical techniques, patients with/without submucous cleft abnormalities, or with mild-moderate versus severe hypernasality of speech. Quality of life in this cohort of patients was improved in patients with non-syndromic VPI after surgery. This is not unexpected, as their syndromic counterparts have comorbidities which may impact the VELO results despite correction of VPI. Surprisingly, there was no difference in VELO between patients with/without SMC. We expect a repaired anatomic abnormality to show higher improvement than functional abnormalities postoperatively. This could be explained by a low sample size as well as confounders including length and intensity of speech therapy. Limitations to this study include subjectivity in analyzing parents’ attitudes, which may be discordant with patients’ perceptions of their condition. Furthermore, retrospective collection of VELO scores at different times postoperatively predisposes to recall bias. Prospective research is necessary to explore impacts of medical and surgical therapies in different patient groups to optimize quality of life in children with VP

Genicular Nerve Radiofrequency Ablation for Painful Knee Arthritis: The Why and the How.

BackgroundGenicular nerve radiofrequency ablation (GNRFA), including conventional, cooled, and pulsed techniques, has been used in the management of symptomatic knee osteoarthritis (OA). This new and innovative treatment option has the capacity to decrease pain and improve function and quality of life in certain patients. GNRFA is reserved for patients with symptomatic knee OA who have had failure of conservative treatment and have had failure of or are poor candidates for surgery. GNRFA has been shown to consistently provide short-term (3 to 6-month), and sometimes longer, pain relief in patients. GNRFA has been demonstrated to be safe to administer repeatedly in patients who respond well to this minimally invasive procedure.DescriptionGNRFA is a 2-step procedure. First, patients are given a diagnostic block under fluoroscopy or ultrasound guidance. Specifically, 1 mL of lidocaine is injected using a 20-gauge, 3.5-in (8.9-cm) spinal needle around the superior lateral, superior medial, and inferior medial genicular nerve branches. The diagnostic block is extra-articular. If the patient reports a ≥50% reduction in baseline pain for a minimum of 24 hours following the injection, then the patient is a candidate for genicular ablation. The osseous landmarks for the diagnostic block are exactly the same as for the ablation procedure. Both procedures are well tolerated in the office setting under local skin anesthesia or can be done in the operating room under conscious sedation using a low-dose sedative such as midazolam for anxious patients. General anesthesia is not required for GNRFA. This procedure is most commonly performed by interventional pain specialists but may also be performed by any physician with appropriate training. In some jurisdictions, physician assistants and nurse practitioners may perform this procedure subject to their supervision requirements.AlternativesConservative treatment for symptomatic knee OA includes weight loss management, physical and aquatic therapy, bracing, lateral wedge insoles, transcutaneous nerve stimulation, nonsteroidal anti-inflammatory drugs in combination with a proton pump inhibitor, autologous blood-based therapies, and cortisone and hyaluronic acid injections1,2. Surgical treatment for symptomatic knee OA includes knee arthroscopy, high tibial osteotomy, total knee replacement, and unicompartmental knee replacement in patients without lateral compartment disease2. It should be noted that there is some evidence suggesting that steroid injection, viscosupplements, and arthroscopy are not effective for the management of knee OA.RationaleThermal GNRFA differs from all other treatment alternatives because this procedure causes denaturing of the 3 sensory nerves primarily responsible for transmitting knee pain from an arthritic joint to the central nervous system. In this procedure, heating occurs from an intense alternating electrical field at the tip of the cannula, which produces sufficient heat to denature the proteins in the target tissue. The accepted heating parameters for this procedure are 70° to 80°C for 60 or 90 seconds. A commonly raised question is whether this procedure precipitates a Charcot-type joint. The Charcot joint involves much more than reduced innervation; it occurs in the context of chronically compromised vascularity and altered soft-tissue characteristics as well as peripheral neuropathy. Moreover, a Charcot-type joint does not develop because the deafferentation of the weight-bearing joint is partial3. To our knowledge, no Charcot-type joints have been reported after this procedure. Conversely, data from an animal study have shown that selective joint denervation may lead to the progression of knee OA4. The ablation procedure is done outside the knee joint, unlike alternatives such as intra-articular therapies and surgery. The effectiveness of nonsurgical knee OA interventions in alleviating pain and improving joint function is generally inadequate1. However, GNRFA appears to be an emerging alternative for patients who have had failure of conservative and surgical treatments. It is not uncommon in our clinical practice for patients to achieve adequate pain control following ablation for up to 1 year. GNRFA provides temporary relief from symptomatic knee OA because it does not eliminate the potential for peripheral nerve regrowth and regeneration, and thus pain, to return