Improving Opioid Stewardship in Pediatric Emergency Medicine.

OBJECTIVES: Poor opioid stewardship contributes to opioid misuse and adverse health outcomes. We sought to decrease opioid prescriptions in children 0 to 18 years treated for pain after fractures and cutaneous abscess drainage from 13.5% to 8%. Our secondary aims were to reduce opioid prescriptions written for >3 days from 41% to 10%, eliminate codeine prescriptions, increase safe opioid storage and disposal discharge instructions from 0% to 70%, and enroll all emergency department (ED) physicians in the state prescription drug monitoring program. METHODS: We implemented an intervention bundle on the basis of 4 key drivers at a pediatric ED: ED-wide education, changes in the electronic medical record, discharge resources, and process standardization. Two plan-do-study-act cycles were performed. Interventions included provider feedback on prescribing, safe opioid storage and disposal instructions, and streamlined electronic medical record functions. Run charts were used to analyze the effect of interventions on outcomes. Our balance measure was return ED or clinic visits for inadequate analgesia within 3 days. RESULTS: During the intervention period, 249 of 3402 (7.3%) patients with fractures and cutaneous abscesses were prescribed opioids. The percentage of opioid prescriptions >3 days decreased from 41% to 13.2% (P < .0001), codeine prescription dropped from 1.1% to 0% (P = .09), opioid discharge instructions increased 0% to 100% (P < .0001), and all physicians enrolled in the prescription drug monitoring program. There was no change in return visits for uncontrolled analgesia compared with the baseline (P = .79). CONCLUSIONS: A comprehensive opioid stewardship program can improve opioid prescribing practices of ED physicians and deliver information on safe storage and disposal of prescription opioids with a negligible effect on return visits for uncontrolled pain.

Continued Prescribing of Periprocedural Codeine and Tramadol to Children after a Black Box Warning.

BACKGROUND: Codeine and tramadol are commonly used analgesics in surgery. In 2013, the Food and Drug Administration (FDA) issued a contraindication to the use of codeine in tonsillectomy and adenoidectomy patients aged below 18 y. This warning was expanded in April 2017 to include tramadol and all children aged below 12 y. We sought to describe the prescribing of codeine and tramadol to contraindicated populations in Wisconsin before and after the release of the expanded FDA warning. MATERIALS AND METHODS: Using a statewide Wisconsin claims database, we identified common pediatric ambulatory surgical procedures across the specialties of otolaryngology, urology, general surgery, orthopedics, and ophthalmology. For these procedures, we examined the rates of perioperative codeine and tramadol prescription fills and change in prescribing after the FDA contraindication. RESULTS: Surgeons in all of the specialties studied continued to prescribe codeine to pediatric patients after the contraindication, but tramadol was rarely prescribed. Procedures with relatively high rates of codeine fills were strabismus repair (65% of opioid fills), circumcision >1 yo (22%), and laparoscopic appendectomy (15%). Codeine fills significantly declined after the contraindication to 6% for circumcision >1 yo and 5% for orchiopexy and inguinal hernia repair. Otolaryngology, which was subject to the 2013 codeine contraindication, has low rates of codeine fills (under 2.5%) for the whole period studied. Codeine prescribing for strabismus repair showed no significant decline. CONCLUSIONS: Codeine, and to a lesser extent tramadol, continue to be prescribed to contraindicated populations of children. This represents a target for future de-implementation interventions.

Oral Opioid Use during Vaginal Delivery Hospitalizations.

OBJECTIVE: This study aimed to determine the receipt of short-acting opioid medications during vaginal delivery hospitalizations. STUDY DESIGN: The Perspective database was analyzed to evaluate patterns of short-acting oral opioid use during vaginal delivery hospitalizations from January 2006 to March 2015. Unadjusted and adjusted models evaluating the role of demographic and hospital factors were created evaluating use of opioids. Hospital-level rates of opioid use were evaluated. Opioid receipt among women with opioid abuse or dependence was evaluated based on overall hospital rates of opioid use. RESULTS: Of 3,785,396 vaginal delivery hospitalizations from 2006 to 2015, 1,720,899 (45.5%) women received an oral opioid for pain relief. Opioid use varied significantly among the 458 hospitals included in the analysis, with one-third of hospitals providing opioids to <38% of patients, one-third to 38 to <59% of patients, and one-third to ≥59% of patients. When hospitals were stratified by overall opioid administration rates, women with opioid abuse or dependence were less likely to be given opioids in hospitals with low overall opioid rates. DISCUSSION: The use of opioid pain medications during vaginal delivery hospitalizations varied significantly among hospitals, suggesting that standardization of pain management practices could reduce opioid use.

A national study on the use of opioid analgesics in dentistry.

The aim of this study was to assess the frequency of opioid analgesics prescribed by Brazilian dentists, potential regional differences and their association with socioeconomic and health-related factors. Data for all opioid prescriptions by dentists was obtained from the 2012 database of the National Controlled Substances Management System, regulated by the Brazilian Health Surveillance Agency. The number of defined daily doses (DDD) and DDDs per 1,000 inhabitants per day for each Brazilian state were calculated as the primary outcomes. DDDs were compared by regions and Brazilian states. Spearman's rho correlation coefficient was used to determine the influence of the states' characteristics, such as the Human Development Index; poverty; education; number of dentists per 100,000 inhabitants; visit to the dentist; dental care plan; good or very good oral health; number of pharmaceutical establishments per 100,000/inhabitants; and ability to get all prescribed medications. Data analysis was performed using IBM SPSS Statistics 25.0. A total of 141,161 prescriptions for opioids analgesics by 36,929 dentists were recorded, corresponding to 658,855 doses of opioids dispensed in 2012. The most commonly dispensed opioids were codeine associated with paracetamol (83.2%; n = 117,493). The national DDDs per 1,000 inhabitants per day was 0.0093 (range: 0.0002-0.0216). DDD per 1,000 inhabitants per day was positively associated to visits to dentists (rs = 0.630; P < 0.001) and inversely associated to poverty (rs = -0.624; p = 0.001). There are significant differences in opioid prescriptions in dentistry among the Brazilian states. These differences may be associated with non-clinical factors.

Tramadol and the risk of seizure: nested case-control study of US patients with employer-sponsored health benefits.

OBJECTIVES: Tramadol is a widely prescribed analgesic that influences both opioid and monoamine neurotransmission. While seizures have been reported with its use, the risk in clinical practice has not been well characterised. We examined risk of seizure with tramadol relative to codeine, a comparable opioid analgesic. DESIGN: Retrospective nested case-control study. For each case, we identified up to 10 controls matched on age, sex, US state of residence and date of cohort entry (±365 days). We calculated ORs to determine the association between seizure and exposure to tramadol, codeine (≥15 mg), both or neither, in the preceding 30 days. SETTING: Cohort of patients, who had continuous health coverage and resided in the same state for≥3 years, identified from linked administrative health data in US MarketScan databases from 2009 to 2012. PARTICIPANTS: We identified 96 753 patients with seizure and 888 540 matched controls. PRIMARY AND SECONDARY OUTCOME MEASURES: In the primary analysis, we defined cases using a broad definition of seizure (based on either an outpatient physician claim for seizure disorder or a seizure-related emergency department visit or hospitalisation). In a secondary analysis, we used a more specific definition of seizure restricted to a hospital visit with a principal diagnosis of seizure. RESULTS: In the primary analysis, we found no association between risk of seizure and exposure to tramadol compared with codeine (OR 1.03, 95% CI 0.93 to 1.15). However, in the secondary analysis (using a more specific definition of seizure), this association was statistically significant (OR 1.41, 95% CI 1.11 to 1.79). CONCLUSIONS: Tramadol was not associated with an increased risk of seizure defined by inpatient and outpatient diagnoses. However, this finding was sensitive to the outcome definition used and requires further study.

Prescribing Trends of Codeine-containing Medications and Other Opioids in Primary Care After A Regulatory Decision: An Interrupted Time Series Analysis.

BACKGROUND AND OBJECTIVES: In 2014, the Italian Medicines Agency (AIFA) amended the summary of product characteristics of codeine-containing medications limiting their use for maximum three days. This study attempted to clarify the impact of AIFA intervention on prescribing trends and appropriateness of use of codeine-containing medications and other opioids. METHODS: Using the Health Search Database, a quasi-experimental interrupted time series analysis was conducted to evaluate changes in prescribing trends and appropriateness of use of codeine-containing medications and opioids between 2013 and 2015. RESULTS: Prescribing trends of codeine-containing medications significantly decreased (on average, - 352 days of treatment per month of observation), while long-acting opioids (LAOs) had an overall increase. Trends of inappropriate prescriptions significantly increased for two LAOs (i.e. tapentadol, naloxone-oxycodone), both before and after AIFA intervention. CONCLUSION: The use of paracetamol-codeine combination was effectively decreased in Italy because of AIFA intervention. Instead, prescriptions of tapentadol and oxycodone-naloxone stably increased over the study period irrespective of regulatory intervention. Given that the choice of the most appropriate opioid therapy is not straightforward, especially in elderly and/or comorbid patients, general practitioners should consider carefully alternative therapies on the bases of regulatory interventions.

A national study on the use of opioid analgesics in dentistry

Abstract The aim of this study was to assess the frequency of opioid analgesics prescribed by Brazilian dentists, potential regional differences and their association with socioeconomic and health-related factors. Data for all opioid prescriptions by dentists was obtained from the 2012 database of the National Controlled Substances Management System, regulated by the Brazilian Health Surveillance Agency. The number of defined daily doses (DDD) and DDDs per 1,000 inhabitants per day for each Brazilian state were calculated as the primary outcomes. DDDs were compared by regions and Brazilian states. Spearman's rho correlation coefficient was used to determine the influence of the states' characteristics, such as the Human Development Index; poverty; education; number of dentists per 100,000 inhabitants; visit to the dentist; dental care plan; good or very good oral health; number of pharmaceutical establishments per 100,000/inhabitants; and ability to get all prescribed medications. Data analysis was performed using IBM SPSS Statistics 25.0. A total of 141,161 prescriptions for opioids analgesics by 36,929 dentists were recorded, corresponding to 658,855 doses of opioids dispensed in 2012. The most commonly dispensed opioids were codeine associated with paracetamol (83.2%; n = 117,493). The national DDDs per 1,000 inhabitants per day was 0.0093 (range: 0.0002-0.0216). DDD per 1,000 inhabitants per day was positively associated to visits to dentists (rs = 0.630; P < 0.001) and inversely associated to poverty (rs = -0.624; p = 0.001). There are significant differences in opioid prescriptions in dentistry among the Brazilian states. These differences may be associated with non-clinical factors.

Análisis de costo-efectividad de los medicamentos utilizados para el tratamiento de pacientes con dolor neuropático en Colombia / Cost-effectiveness analysis of drugs used for the treatment of patients with neuropathic pain in Colombia

INTRODUCCIÓN: El análisis de costo-efectividad de ácido tióctico, acetaminofén y tramadol, acetaminofén e hidrocodona, tramadol, amitriptilina, imipramina, valproato, acetaminofén y codeína, buprenorfina, capsaicina, carbamazepina, parches de fentanyl, tapentadol, duloxetina, gabapentina, parches de lidocaína, oxcarbazepina, pregabalina para el tratamiento de pacientes con dolor neuropatico en Colombia, se desarrolla en el marco del mecanismo técnico-científico para la ampliación progresiva del plan de beneficios y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015. Estas tecnologías fueron seleccionadas por la Dirección de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MinSalud), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. Con respecto a la condición de salud de interés, la asociación internacional para el estudio del dolor (IASP 2011) definió el dolor neuropático como dolor causado por consecuencia directa de una lesión o enfermedad del sistema nervioso somatosensitivo. El mecanismo generador del dolor neuropático se halla en cualquier sitio a lo largo del recorrido de las vías nociceptivas (las vías que conducen la información de tipo doloroso), sin estimular inicialmente a los nociceptores (los receptores de dolor), a diferencia de lo que sucede con el dolor nociceptivo o fisiológico. El dolor neuropático es causado por diversos trastornos que afectan el sistema nervioso central y perifér

Medical professionals' perspectives on prescribed and over-the-counter medicines containing codeine: a cross-sectional study.

OBJECTIVES: To explore prescribing practitioners' perspectives on prescribed codeine use, their ability to identify dependence and their options for treatment in the UK. DESIGN: Cross-sectional design using a questionnaire containing closed-ended and open-ended items. SETTING: A nationally representative sample of prescribing professionals working in the UK. PARTICIPANTS: 300 prescribing professionals working in primary care and pain settings. RESULTS: Participants stated that they regularly reviewed patients prescribed codeine, understood the risks of dependence and recognised the potential for codeine to be used recreationally. Over half the participants felt patients were unaware of the adverse health consequences of high doses of combination codeine medicines. One-quarter of participants experienced patient resentment when asking about medicines containing codeine. Just under 40% of participants agreed that it was difficult to identify problematic use of codeine without being informed by the patient and did not feel confident in identification of codeine dependence. Less than 45% of all participants agreed that codeine dependence could be managed effectively in general practice. Slow or gradual withdrawal was the most popular suggested treatment in managing dependence. Education and counselling was also emphasised in managing codeine-dependent patients in primary care. CONCLUSIONS: Communication with patients should involve assessment of patient understanding of their medication, including the risk of dependence. There is a need to develop extra supports for professionals including patient screening tools for identifying codeine dependence. The support structure for managing codeine-dependent patients in primary care requires further examination.

Analgesic utilization before and after rescheduling of hydrocodone in a large academic level 1 trauma center.

BACKGROUND: Hydrocodone-containing products were recently rescheduled from Drug Enforcement Agency (DEA) schedule III to schedule II due to concerns of abuse and misuse. These changes went into effect on October 6, 2014. OBJECTIVE: This quality improvement project involved a retrospective analysis to determine the effect of the DEA schedule change on prescribing habits of hydrocodone-containing products as well as the remaining schedule III and IV opioids, codeine (schedule III) and tramadol (schedule IV). METHODS: The authors performed a medication use evaluation at our academic level 1 trauma hospital system on outpatient use of hydrocodone-containing products, tramadol, and codeine-containing products for 6 months before and 6 months after the change to schedule II using our electronic record and pharmacy system. RESULTS: A total of 88,428 prescription orders were analyzed. Comparison of prescriptions before and after the DEA schedule changes showed hydrocodone prescriptions reduced from an average of 225.97 per day to 1.20 per day. In addition, tramadol increased from 60.04 per day to 91.85 per day and codeine from 6.81 per day to 98.94 per day. CONCLUSIONS: Our data show a very substantial decrease in utilization of hydrocodone-containing products and concomitant increase in the utilization of tramadol and codeine products at our hospital after the DEA schedule change.

Codeine in paediatrics: pharmacology, prescribing and controversies.

Codeine is a drug that until recently was widely used in children. It was endorsed by the WHO as the second step on the analgesic ladder for cancer pain and has been used routinely for postoperative and breakthrough pain. Recently, its safety and efficacy have been called into question, following deaths after adenotonsillectomy was associated with its use. This has led to regulation by the US Food and Drug Administration, European Medicines Agency and the UK Medicines and Healthcare products Regulatory Agency to place significant restrictions on its use, and some centres have stopped using it altogether.In this article, we discuss the developmental pharmacology underpinning its action, reviewing what is known about the pharmacokinetics, pharmacodynamics and pharmacogenetics in children, how this relates to prescribing, as well as the practical issues and the recent regulatory framework surrounding its use.

Opioid Analgesics and the Risk of Serious Infections Among Patients With Rheumatoid Arthritis: A Self-Controlled Case Series Study.

OBJECTIVE: Animal studies and in vitro human studies suggest that certain opioid analgesics impair crucial immune functions. This study was undertaken to determine whether opioid use is associated with increased risk of serious infection in patients with rheumatoid arthritis (RA). METHODS: We conducted a self-controlled case series analysis on a retrospective cohort of 13,796 patients with RA enrolled in Tennessee Medicaid in 1995-2009. Within-person comparisons of the risk of hospitalization for serious infection during periods of opioid use versus non-use were performed using conditional Poisson regression. Fixed confounders were accounted for by design; time-varying confounders included age and use of disease-modifying antirheumatic drugs, glucocorticoids, and proton-pump inhibitors. In additional analyses, risks associated with new opioid use, use of opioids known to have immunosuppressive properties, use of long-acting opioids, and different opioid dosages were assessed. Sensitivity analyses were performed to account for potential protopathic bias and confounding by indication. RESULTS: Among 1,790 patients with RA who had at least 1 hospitalization for serious infection, the adjusted incidence rate of serious infection was higher during periods of current opioid use compared to non-use, with an incidence rate ratio (IRR) of 1.39 (95% confidence interval [95% CI] 1.19-1.62). The incidence rate was also higher during periods of long-acting opioid use, immunosuppressive opioid use, and new opioid use compared to non-use (IRR 2.01 [95% CI 1.52-2.66], IRR 1.72 [95% CI 1.33-2.23], and IRR 2.38 [95% CI 1.65-3.42], respectively). Results of sensitivity analyses were consistent with the main findings. CONCLUSION: In within-person comparisons of patients with RA, opioid use was associated with an increased risk of hospitalization for serious infection.

Cough, codeine and confusion.

Codeine is widely prescribed in clinical practice with over the counter (OTC) preparations of codeine freely available for consumption typically as a component of remedies for the common cold/cough. We describe the first reported case of acute confusional state in a previously healthy 14-year-old girl ultimately attributed to inappropriate codeine use. The usage of codeine in the paediatric setting has been highlighted in recent years with many reported deaths--mostly due to respiratory depression. The risks associated with codeine usage may be particularly unnecessary with OTC cough suppressants as evidence of efficacy is absent. Finally, codeine dependence is a common problem among adults and has been reported locally and internationally among adolescents. The combination of lack of efficacy, risk of acute intoxication and dependence, suggests that the use of OTC codeine preparations may be unwarranted.

Accuracy of using Diagnosis Procedure Combination administrative claims data for estimating the amount of opioid consumption among cancer patients in Japan.

OBJECTIVE: The state of opioid consumption among cancer patients has never been comprehensively investigated in Japan. The Diagnosis Procedure Combination claims data may be used to measure and monitor opioid consumption among cancer patients, but the accuracy of using the Diagnosis Procedure Combination data for this purpose has never been tested. METHODS: We aimed to ascertain the accuracy of using the Diagnosis Procedure Combination claims data for estimating total opioid analgesic consumption by cancer patients compared with electronic medical records at Aomori Prefectural Central Hospital. We calculated percent differences between estimates obtained from electronic medical records and Diagnosis Procedure Combination claims data by month and drug type (morphine, oxycodone, fentanyl, buprenorphine, codeine and tramadol) between 1 October 2012 and 30 September 2013, and further examined the causes of discrepancy by reviewing medical and administrative charts between April and July 2013. RESULTS: Percent differences varied by month for drug types with small prescription volumes, but less so for drugs with larger prescription volumes. Differences also tended to diminish when consumption was compared for a year instead of a month. Total percent difference between electronic medical records and Diagnosis Procedure Combination data during the study period was -0.1% (4721 mg per year per hospital), as electronic medical records as baseline. Half of the discrepancy was caused by errors in data entry. CONCLUSION: Our study showed that Diagnosis Procedure Combination claims data can be used to accurately estimate opioid consumption among a population of cancer patients, although the same conclusion cannot be made for individual estimates or when making estimates for a group of patients over a short period of time.

Evaluación económica de tecnologías para el tratamiento de dolor neuropático en Colombia / Economic evaluation of technologies for the treatment of neuropathic pain in Colombia

INTRODUCCIÓN: Descripción de la condición de salud: La asociación internacional para el estudio del dolor (IASP 2011) definió el dolor neuropático como dolor causado por una lesión o enfermedad del sistema nervioso somatosensitivo, el cual puede ser de tipo central o periférico. Entre las condiciones que causan dolor neuropático central están el accidente cerebrovascular, lesión de la medula espinal y esclerosis múltiple. Por su parte las condiciones comunes que causan dolor neuropatico periférico son la neuropatía diabética, neuralgia posherpética, neuralgia del trigémino, dolor radicular, dolor neuropático posquirúrgico y dolor neuropático por cáncer (como neuropatía inducida por la quimioterapia, neuropatía secundaria a antígenos tumorales o causada por una invasión directa o comprensión de las estructuras neurales). La validación de herramientas para la evaluación de dolor con características neuropáticas ha facilitado la realización de estudios epidemiológicos que estiman la prevalencia entre 7 % y 8 % en la población general. Los síntomas del dolor neuropático pueden ser positivos o negativos. Los primeros se refieren a dolor espontáneo (independiente del estímulo) y evocado (dependiente del estímulo) y otros síntomas tales como hormigueo (es decir parestesias). Los signos y síntomas negativos que pueden ser observados incluyen entumecimiento, debilidad y pérdida de los reflejos profundos en el territorio del nervio involucrado. El dolor evocado por estímulos incluye alodinia, definida como dolor ante estímulos que normalmente no son dolorosos, e hiperalgesia, definida como un dolor incrementado en respuesta a estímulos normalmente dolorosos. El dolor neuropático puede seguir un curso continuo o intermitente. TRATAMIENTO: Los tratamientos disponibles para el dolor neuropático proporcionan alivio sintomático y pueden ser farmacológicos, no farmacológicos o terapias de intervención. Entre los tratamientos farmacológicos que han sido evaluados en ensayos clínicos, se encuentran: antidepresivos tricíclicos, inhibidores selectivos de la recaptación de serotonina, inhibidores de la recaptación de la noradrenalina, gabapentina, pregabalina, lacosamida, valproato, lamotrigina, topiramato, levetiracetam, carbamazepina, oxcarbazepina, opioides, tramadol, canabinoides, lidocaína tópica, antagonistas NMDA, mexiletino, capsaicina tópica y toxina botulínica tipo A. Muchos de estos medicamentos fueron desarrollados para otras indicaciones y posteriormente evaluados en dolor neuropático. POBLACIÓN: pacientes, independientemente del sexo y de la edad, con diagnóstico de dolor neuropático. INTERVENCIÓN: Ácido tióctico, Acetaminofén + codeína, Acetaminofén + hidrocodona, Buprenorfina, Capsaicina, Ciclobenzaprina, Parchede fentanyl, Tapentadol. Tiocolchicósido. Tizanidina, Duloxetina, Gabapentina, Parches de lidocaína, Oxcarbazepina, Pregabalina. PERSPECTIVA: Se empleará la perspectiva del sistema de salud colombiano, es decir, serán incluidos los costos médicos directos asociados al uso de las tecnologías en salud que son objeto de la evaluación y los beneficios en salud percibidos directamente por los pacientes. DESENLACES Y VALORACIÓN: De acuerdo con las recomendaciones del manual metodológico del IETS, en esta evaluación se propone emplear los AVAC (años de vida ajustados por calidad) como medida de desenlace. La información de las ponderaciones de utilidad se obtendrá de la literatura. En caso que no sea factible emplear AVAC, se emplearán otros desenlaces, que serán justificados en el informe. COSTOS: Se tendrán en cuenta todos los costos asociados a las tecnologías evaluadas y a los desenlaces en salud incluidos en el modelo de decisión planteado. Se utilizarán como fuentes de información bases de datos institucionales de validez nacional, consulta directa y otras fuentes, tal como lo estipula el manual metodológico del IETS. MODELO DE DECISIONES: Se diseñará un modelo de decisión analítico a partir de la revisión de literatura económica existente, los resultados de la evaluación de efectividad y seguridad elaborada por el IETS y la consulta a expertos clínicos y otros actores del sistema de salud relacionados con las tecnologías e indicación de interés. PRESENTACIÓN DE RESULTADOS: En el caso de tecnologías no dominadas, se calcularán las razones incrementales de costo-utilidad o costo-efectividad. Para efectos de interpretación, y de acuerdo con las recomendaciones del manual metodológico del IETS, se realizarán comparaciones entre la razón incremental y 1 PIB per cápita y 3 PIB per cápita en Colombia de acuerdo con las estimaciones actuales del Banco de la República. ANÁLISIS DE SENSIBILIDAD: Se evaluará la incertidumbre en las estimaciones mediante análisis de sensibilidad univariados y probabilísticos. Los resultados de las simulaciones de Montecarlo se presentarán mediante un diagrama de dispersión en el plano de costoefectividad y los resultados del análisis de sensibilidad probabilístico mediante curvas de aceptabilidad.

Increase in prescription opioid use during pregnancy among Medicaid-enrolled women.

OBJECTIVE: To report the prevalence of prescription opioid use and evaluate the trends in a large cohort of Medicaid-enrolled pregnant women. METHODS: A cohort of pregnancies was identified using data from the Medicaid Analytical eXtract for the period of 2000-2007. Dispensing of opioids, as a class and separately for individual agents, was evaluated using claims from filled prescriptions. Variations in patterns of prescription opioid fills were examined by demographic characteristics, by geographic region, and over time. Median number of opioid prescriptions dispensed and cumulative days of availability for prescription opioids during pregnancy were reported. RESULTS: The study population consisted of more than 1.1 million women with completed pregnancies from 46 U.S. states and Washington, DC. One of five women from our cohort (21.6%) filled a prescription for an opioid during pregnancy; this proportion increased from 18.5% in 2000 to 22.8% in 2007. Substantial regional variation was seen with the proportion of women who filled a prescription during pregnancy, ranging between 9.5% and 41.6% across the states. Codeine and hydrocodone were the most commonly prescribed opioids. Among women filling at least one opioid prescription, the median (interquartile range) number of prescriptions filled was 1 (1-2) and the median (interquartile range) cumulative days of opioid availability during pregnancy were 5 (3-13) days. CONCLUSION: We observed high and increasing number of filled prescriptions for opioids during pregnancy among Medicaid-enrolled women. These findings call for further safety evaluations of these drugs and their effects on the developing fetus to inform clinical practice. LEVEL OF EVIDENCE: II.

Direct and fast determination of paclitaxel, morphine and codeine in urine by micellar electrokinetic chromatography.

A micellar electrokinetic chromatography (MEKC) method was developed for the determination of paclitaxel, morphine and codeine in human urine from patients under cancer treatment. The background electrolyte consisted of a borate buffer (pH 9.2; 20 mM) with sodium dodecyl sulfate (60 mM) and 5% MeOH. The applied voltage was 25 kV, temperature was 20 °C and the sample injection was performed in the hydrodynamic mode. All analyses were carried out in a fused silica capillary with an internal diameter of 75 µm and a total length of 57 cm. The detection of target compounds was performed at 212 nm. Under these conditions, a complete separation of paclitaxel, morphine and codeine was achieved in less than 15 min. According to the validation study, the developed method was proved to be accurate, precise, sensitive, specific, rugged and robust. This method was applied to the analysis of six urines samples from different cancer patients undergoing treatment with paclitaxel or/and codeine. In all the urine paclitaxel determination were done.

Assessment of the efficacy and safety profiles of aspirin and acetaminophen with codeine: results from 2 randomized, controlled trials in individuals with tension-type headache and postoperative dental pain.

BACKGROUND: Aspirin is a widely used NSAID that has been extensively studied in numerous conditions. Nonprescription analgesics, such as aspirin, are frequently used for a wide variety of common ailments, including conditions such as dental pain and tension-type headache. OBJECTIVE: We sought to compare the efficacy and safety profiles of aspirin, acetaminophen with codeine, and placebo in the treatment of post-operative dental pain and tension-type headache. METHODS: These were 2 randomized, double-blind, placebo-controlled, single-dose clinical trials that assigned participants (2:2:1) to receive either aspirin (1000 mg), acetaminophen (300 mg) with codeine (30 mg), or placebo. The primary efficacy end point was the sum of pain intensity differences from baseline (SPID) over 6 hours for the dental pain study and over 4 hours for the tension-type headache study. Other common analgesic measures, in addition to safety, were also evaluated. RESULTS: The results of the dental pain study for aspirin and acetaminophen with codeine suggest statistically significant efficacy for all measures compared with placebo at all time points. Aspirin provided statistically significant efficacy compared with acetaminophen with codeine for SPID(0-4) (P = 0.028). In the tension-type headache study, aspirin and acetaminophen with codeine provided statistically significant efficacy compared with placebo for SPID(0-4) and SPID(0-6) (P < 0.001) and for total pain relief (P < 0.001). There were no significant differences between aspirin and acetaminophen with codeine at any evaluation of SPID (P ≥ 0.070), complete relief (P ≥ 0.179), or time to meaningful relief (P ≥ 0.245). Regarding safety, there were no statistically significant differences between treatment groups in the incidence of adverse events in the dental pain and tension-type headache studies. CONCLUSIONS: These 2 randomized, double-blind, placebo-controlled studies demonstrate that treatment with aspirin (1000 mg) provides statistically significant analgesic efficacy compared with placebo use and comparable efficacy with acetaminophen (300 mg) with codeine (30 mg) therapy after impacted third molar extraction and in tension- type headache.