Aminas cuaternarias para desinfección hospitalaria / Quaternary amines for hospital disinfection

INTRODUCCIÓN: La limpieza de superficies duras en las habitaciones de los hospitales es fundamental para reducir las infecciones asociadas con la atención médica. La descontaminación es uno o más procedimientos que resultan en una falta de patógenos residuales. Si bien la desinfección no elimina completamente el número de microorganismos, los reduce de forma significativa, de manera que es poco probable que el objeto cause infección cuando es usado. LA TECNOLOGÍA: El desinfectante marca Surfanios ® contiene N-(3-aminopropil)-N-dodecilpropano-1,3-diamina (NoCAS 2372-82-9: 51 mg/g), cloruro de didecildimetilamonio (NoCAS 7173-51-5: 25 mg/g). Las aminas cuaternarias son sólidos que se disuelven en soluciones líquidas. METODOLOGÍA: Para responder a las preguntas de eficacia y seguridad se realizó una búsqueda bibliográfica no sistemática a cargo de dos investigadores en forma independiente. Se priorizó la búsqueda de revisiones sistemáticas, meta-análisis, Informes de evaluación de Tecnologías Sanitarias y Guías de Práctica Clínica basadas en la evidencia. Se buscó en Cochrane, Medline, Lilacs, Tripdatabase, Epistemonikus, la base de datos de la OMS y sitios específicos de agencias de evaluación de tecnologías sanitarias. METODOLOGÍA DE COSTOS: Si se considera el uso de la amina cuaternaria para la desinfección de camas hospitalarias y que el sistema cuenta con 1100 camas, el consumo promedio estimado sería de 150 l, 30 bidones de 5 l, cada uno con un costo unitario de alrededor de $6000, el costo anual de compra sería de alrededor de $200.000, con alta dependencia de valor de la divisa estadounidense, dado que se trata de un produto importado. Es importante considerar que la experiencia muestra que una vez aceptada la incorporación de uma tecnología, es común su progresiva ampliación de uso para otras finalidades. En este caso, por ejemplo, podría expandirse su utilización a la desinfección de superficies generales, como pisos y mamparas, lo que incrementaría mucho la estimación de cantidades utilizadas. También es de destacar, que existen en el mercado otros desinfectantes hospitala rios de un solo passo (lauril éter sulfato de sodio o SLES (sodium lauryl ether sulfate), peróxido de hidrogeno con alcohol, otras aminas cuaternarias), que podrían ser considerados como alternativas al hipoclorito de sodio. RESULTADOS: No se encontró bibliografía o recomendaciones técnicas que i ndiquen una eficacia superior de la aminas cuaternarias por sobre el hipoclorito de sodio u otros desinfectantes hospitalarios, como tampoco evaluaciones de impacto organizacional respecto a mejoras en los tiempos de disponibilidad de camas o disminución de la carga horaria del trabajo de desinfección. Numerosos artículos de revisión no sistemática enfatizan el hecho que en desinfección hospitalaria, las decisiones sobre que producto usar están más basadas en opinión que en evidencia. RECOMENDACIÓN FINAL: Amina cuaternaria marca Surfanios® para desinfección de unidad del paciente Sentido de la Recomendación: No se recomienda su incorporación Fuerza de la Recomendación: Débil. Se recomienda que se desarrolle una guía de desinfección hospitalaria a nivel provincia l, a fin de optimizar los procedimientos, el personal que de los debe realizar y los productos a utilizar en cada caso.

Occurrence of Heterocyclic Amines in Commercial Fast-Food Meat Products Available on the Chinese Market and Assessment of Human Exposure to these Compounds.

Heterocyclic amines (HCAs) have been identified as highly mutagenic and are risk factors for human cancer. In recent years, the intake of fast-food meat products has increased exponentially due to their convenience. Therefore, it is important to assess the health risks of HCAs and provide useful public dietary guidelines. Eight fast-food meat products were selected from the Chinese market, including chicken, beef, and fish, to evaluate their health risk in conjunction with HCAs. Crispy chicken drumsticks contained the maximum level of total HCAs (24.18 ± 3.57 ng/g), followed by crispy fried chicken burgers (19.99 ± 1.41 ng/g) and traditional Chinese nuggets (19.17 ± 1.23 ng/g), whereas shrimp cake burgers had the lowest levels (13.17 ± 1.77 ng/g). Crispy chicken drumsticks (men: 169.12 ng/day, women: 108.70 ng/day), hot chicken wings (men: 126.32 ng/day, women: 142.11 ng/day), and crispy fried chicken burgers (men: 129.78 ng/day, women: 59.91 ng/day) were found to provide the highest dietary intake of HCAs in both genders, which may lead to an increase in colorectal and breast cancers. PRACTICAL APPLICATIONS: The rapid expansion of the Chinese fast-food industry has promoted serious health problems, such as colorectal cancer and some cardiovascular diseases. Several epidemiological studies revealed that a high intake of processed meats may increase the risk of cancer in humans because cooking food proteins, such as meat, at high temperatures could produce high levels of carcinogenic compounds, such as HCAs. Because of the vast variation in eating habits, preparation methods and the frequency of meat consumption, it is important to evaluate the accurate level of HCAs in commercially available fast-food meat products with the aim to clarify the association between processed meats and the health risk.

Feasibility study for interspecialistic collaboration in active research of urothelial neoplasms of professional origin.

INTRODUCTION: In Italy only a small fraction of cancer is reported to the supervisory body and recognised as professional by the insurance institution. Among the causes of this sub-notification, especially for lowgrade etiologic fractional cancers such as bladder cancers are the lack of knowledge of carcinogenicity in the occupational field and the consequent incomplete medical history collections. OBJECTIVES: Diagnosis of occupational bladder neoplasms and activation of systematic surveillance of tumors of professional origin through an "active research" program. METHODS: From July 2010 to July 2017, all patients diagnosed with Bladder Cancer in the departments of Urology of Area Vasta 3 ASUR Marche underwent a first interview and a further anamnestic study in selected cases.When an occupational exposure was recognised, more information for preventive, social security and criminal justice has been acquired. RESULTS: The study highlighted 18 cases of bladder tumors due to occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons, which are the most important risk factor for BC after tobacco smoking. CONCLUSIONS: Our study confirmed that active research is an useful tool both for the activation of epidemiological surveillance and for the regional registration of professional tumors. In addition active research of occupational exposure allow obtaining information that can be used for preventive purposes, for criminal justice and for the initiation of medico-legal actions and improvement of working conditions aimed at guaranteeing workers' rights.

Policies to mitigate nonmedical use of prescription medications: how should emerging evidence of gabapentin misuse be addressed?

INTRODUCTION: Over the past decade, increased prescription supply has facilitated an epidemic of nonmedical use of controlled substances, including predominantly opioids, as well as benzodiazepines, z-hypnotics, and stimulants. Areas covered: More recently, misuse of noncontrolled prescriptions, such as gabapentin, has been detected. Gabapentin misuse has been associated with drug-related harm and increased healthcare service utilization in a few studies, including a recent large-sample analysis of commercially insured enrollees in the United States (U.S.) Responding to this emerging base of evidence, a small number of U.S. states have acted to prevent or detect gabapentin misuse by requiring the inclusion of gabapentin utilization in reporting to local Prescription Drug Monitoring Programs (PDMPs) and/or imposing other restrictions on gabapentin prescribing (e.g., classification as a controlled substance, quantity limits). These efforts may result in unintentional harm by (1) encouraging 'doctor shopping' across state lines to seek lenient regulatory policies and (2) placing the burden for mitigating misuse on individual practitioners. Expert opinion: We call for a unified national approach, comprising federal regulation and enhanced PDMP reporting to address gabapentin misuse, while laying the groundwork for management of new medications of abuse that the healthcare industry may encounter in the future.

Adding pregabalin or gabapentin for the management of community-treated patients with painful diabetic peripheral neuropathy: a comparative cost analysis.

BACKGROUND AND OBJECTIVE: Painful diabetic peripheral neuropathy (pDPN) is a highly prevalent complication of diabetes mellitus, which is associated with substantial costs to society and national health systems. This economic impact varies depending on the therapeutic management provided to patients. The objective of this study was to compare healthcare resource utilization and costs among pDPN patients newly treated with pregabalin or gabapentin in routine medical practice. METHODS: We performed a retrospective medical records study of pDPN patients newly treated with pregabalin or gabapentin as an add-on therapy who are covered by the Badalona Serveis Assistencials (BSA) health plan, a healthcare provider in Spain, from 2006 to 2009. Healthcare resource utilization and days off work were assessed. The societal perspective was used to estimate costs. RESULTS: Three hundred and ninety-five records were eligible for analysis: 227 (57.5%) included pregabalin and 168 (42.5%) gabapentin. Mean (standard deviation) concomitant use of analgesics throughout the study was higher in the gabapentin cohort [3.9 (2.2) vs. 3.1 (2.1); p < 0.05], mainly due to greater use of non-narcotics (78.0 vs. 71.8%; p < 0.05) and opioids (32.7 vs. 28.6%; p < 0.05). Healthcare costs accounted for 59.2% of total costs, of which 71.9% occurred in primary care, with a mean cost per patient of €2,476 (year 2010 values). Adjusted mean (95% CI) total costs were significantly lower in pregabalin-treated patients [€2,003 (1,427-2,579)] than in gabapentin-treated patients [€3,127 (2,463-3,790)] (p = 0.013), mainly due to lower healthcare costs [€1,312 (1,192-1,432) vs. €1,675 (1,537-1,814); p < 0.001]. CONCLUSIONS: Adding pregabalin to existing pDPN therapy resulted in lower total healthcare costs and lower resource utilization than resulted from adding gabapentin.

Real-world treatment of post-herpetic neuralgia with gabapentin or pregabalin.

BACKGROUND AND OBJECTIVES: There are limited data examining the real-world use of gabapentin and pregabalin for the treatment of post-herpetic neuralgia (PHN). This study examines dosing patterns, therapy outcomes, healthcare utilization and costs of patients with PHN who initiate treatment with gabapentin or pregabalin. METHODS: This was a retrospective administrative claims data analysis from July 2005 to February 2010. Patients with PHN initiating gabapentin or pregabalin (index therapy) from January 2006 to February 2009 were identified and were observed for 12 months after index therapy initiation. Outcomes were mean daily dosages of the index therapy, attainment of minimally effective dosages of gabapentin (≥ 1,800 mg/day) or pregabalin (≥ 150 and ≥ 300 mg/day) persistence, discontinuation, index therapy switching, addition of neuropathic pain medications to index therapy, and healthcare resource use and costs. RESULTS: 1,645 patients were identified. The mean daily dosage was 826 mg for gabapentin and 187 mg for pregabalin. Only 52.6 % of patients initiating gabapentin and 56.9 % initiating pregabalin obtained a refill during the post-index period. Approximately 14 % of patients treated with gabapentin reached the target dosage (1,800 mg/day). For pregabalin, 87 % reached ≥ 150 mg/day and 27 % reached ≥ 300 mg/day. On average, patients took 10 weeks to reach 1,800 mg/day gabapentin, and 5.0 and 9.2 weeks to reach ≥ 150 mg/day and ≥ 300 mg/day pregabalin, respectively. Approximately one-third of patients in both index therapy cohorts added a pain medication; more than half added opioids. The percentage of patients switching from either drug (57 %) or adding a therapy (34 %) were similar between index therapy cohorts; opioids were the most common therapy patients switched to or added. CONCLUSION: It appears that gabapentin and pregabalin are not used effectively to treat PHN. Suboptimal dosing and discontinuation may be associated with supplementary use of other analgesics, especially opioids.

Cost-effectiveness analysis of a new 8% capsaicin patch compared to existing therapies for postherpetic neuralgia.

OBJECTIVE: The purpose of this study was to compare the cost effectiveness of a new 8% capsaicin patch, compared to the current treatments for postherpetic neuralgia (PHN), including tricyclic antidepressants (TCAs), topical lidocaine patches, duloxetine, gabapentin, and pregabalin. METHODS: A 1-year Markov model was constructed for PHN with monthly cycles, including dose titration and management of adverse events. The perspective of the analysis was from a payer perspective, managed-care organization. Clinical trials were used to determine the proportion of patients achieving at least a 30% improvement in PHN pain, the efficacy parameter. The outcome was cost per quality-adjusted life-year (QALY); second-order probabilistic sensitivity analyses were conducted. RESULTS: The effectiveness results indicated that 8% capsaicin patch and topical lidocaine patch were significantly more effective than the oral PHN products. TCAs were least costly and significantly less costly than duloxetine, pregabalin, topical lidocaine patch, 8% capsaicin patch, but not gabapentin. The incremental cost-effectiveness ratio for the 8% capsaicin patch overlapped with the topical lidocaine patch and was within the accepted threshold of cost per QALY gained compared to TCAs, duloxetine, gabapentin, and pregablin. The frequency of the 8% capsaicin patch retreatment assumption significantly impacts its cost-effectiveness results. There are several limitations to this analysis. Since no head-to-head studies were identified, this model used inputs from multiple clinical trials. Also, a last observation carried forward process was assumed to have continued for the duration of the model. Additionally, the trials with duloxetine may have over-predicted its efficacy in PHN. Although a 30% improvement in pain is often an endpoint in clinical trials, some patients may require greater or less improvement in pain to be considered a clinical success. CONCLUSIONS: The effectiveness results demonstrated that 8% capsaicin and topical lidocaine patches had significantly higher effectiveness rates than the oral agents used to treat PHN. In addition, this cost-effectiveness analysis found that the 8% capsaicin patch was similar to topical lidocaine patch and within an accepted cost per QALY gained threshold compared to the oral products.

Comparing healthcare costs of Medicaid patients with postherpetic neuralgia (PHN) treated with lidocaine patch 5% versus gabapentin or pregabalin.

OBJECTIVE: To compare healthcare resource utilization and costs of postherpetic neuralgia (PHN) patients initiating lidocaine patch 5% (lidocaine patch) or oral gabapentin/pregabalin. METHODS: Patients with PHN diagnosis, or herpes zoster diagnosis and ≥30 days PHN-recommended treatment were selected from de-identified Medicaid claims data from Florida, Iowa, Missouri, and New Jersey, 1999-2007. Patients initiated monotherapy with lidocaine patch or gabapentin/pregabalin after PHN diagnosis, had continuous eligibility 6 months before (baseline) and 6 months after (study period) medication index date, and were ≥18 years old. Lidocaine patch patients were matched to gabapentin/pregabalin patients based on their propensity to initiate treatment. Study period resource utilization and costs from a Medicaid perspective were compared between treatment groups using univariate analysis. RESULTS: Matched patients were on average 61.3 years old, approximately 73% were women, and 55% had other painful conditions during the baseline period. 6-month per patient PHN-related prescription drug costs were similar for matched lidocaine patch (n=312) and gabapentin/pregabalin (n=312) patients ($854 vs. 820, p=0.75), while PHN-related medical costs appeared lower in the lidocaine patch group ($145 vs. 353, p=0.12). Furthermore, there were no statistically significant differences between treatment groups during the observation period in overall resource utilization, total prescription drug costs, and total medical costs per patient. CONCLUSIONS: In spite of higher list prices, PHN patients treated with lidocaine patch cost no more than patients treated with gabapentin or pregabalin in terms of overall healthcare costs over the 6-month study period. The study suggests that PHN-related medical costs may be lower among lidocaine patch patients. LIMITATIONS: Findings are based on a Medicaid sample and may not be generalizable to all PHN patients.

Pregabalin and gabapentin in matched patients with peripheral neuropathic pain in routine medical practice in a primary care setting: Findings from a cost-consequences analysis in a nested case-control study.

BACKGROUND: Pregabalin and gabapentin are marketed to treat peripheral neuropathic pain, but head-to-head comparison is lacking. OBJECTIVES: The aims of this work were to compare the effects of pregabalin and gabapentin on different patient-reported health outcomes and to analyze health care and nonhealth-care resource consumption and their related costs among patients treated for peripheral neuropathic pain in primary medical care. METHODS: A cost-consequences comparison in subjects with refractory (suboptimal response to > or =1 previous analgesic treatment for >6 months) chronic peripheral neuropathic pain was carried out using data extracted from two 12-week, observational, prospective studies in primary medical care. Patients were eligible if they were aged > or =18 years, had a score of > or =4 on the Douleur Neuropathique 4 questionnaire, and were able to complete health questionnaires written in Spanish. A nested-paired case-control design was chosen to perform the comparison with 2 controls (pregabalin) per case (gabapentin) matched by age, sex, peripheral neuropathic pain condition, time since diagnosis, number of previous treatments, pain intensity, depressive and anxiety symptom scores, and health state. Adult subjects with refractory chronic pain because of diabetic neuropathy, postherpetic or trigeminal neuralgias, or cervical or lumbosacral radiculopathies were included. Epidemiologic statistical methods were applied for comparing health effects (pain intensity, sleep, anxiety and depressive symptoms, disability, and health state), resources utilization, and related cost variations after 12 weeks. Indirect costs were measured by means of lost-workday equivalent calculations multiplied by the mean national daily salary. RESULTS: Analysis included 44 patients treated with gabapentin (cases) and 88 patients treated with pregabalin (controls) who were matched for age, sex, and other parameters. The mean (SD) gabapentin and pregabalin doses were 1263 (540) and 202 (119) mg/d, respectively. Although there was a greater reduction in last-week mean pain intensity with pregabalin (visual analog scale: 39.1 [22.5] vs 28.0 [22.2] mm; P = 0.008), as well as more patients with a > or =50% reduction in pain rate (60.9% vs 40.5%; P = 0.029), there were no significant differences between groups for sensory, affective, total, or present pain intensity. The significantly higher drug cost associated with pregabalin was offset by a greater reduction in productivity costs compared with gabapentin, yielding similar cost reduction (-euro1254 [1479] vs -euro1384 [2874], respectively; P = NS). CONCLUSION: Pregabalin appeared to be associated with greater reduction in mean weekly intensity of pain, but there were no significant differences in cost.

Assessment of pain quality in a clinical trial of gabapentin extended release for postherpetic neuralgia.

OBJECTIVE: To replicate and extend previous research concerning the validity and utility of using pain quality measures in clinical trials. METHODS: One hundred fifty-eight patients with moderate-to-severe postherpetic neuralgia were randomly assigned to 1 of 3 treatment conditions: (1) extended release gabapentin (G-ER) 1800 mg once-daily administered in the evening; (2) G-ER 1800 mg asymmetric divided dose (600 mg AM and 1200 mg PM); or (3) placebo G-ER. A measure of different pain qualities, the Neuropathic Pain Scale, was administered as a secondary measure in this study before, during, and after the treatment. RESULTS: The results suggest that G-ER, especially when administered twice-daily, have the greatest effects on sharp, dull, sensitive, and itchy pain. Few between-condition effects were found for the global ratings of intensity or unpleasantness, and for hot, cold, deep, or surface pain qualities. CONCLUSIONS: The results provide further support for the importance of assessing specific pain qualities as outcomes in clinical trials. The findings may also be used by clinicians for identifying those patients for whom G-ER may be particularly effective; that is, patients with postherpetic neuralgia presenting with pain described as sharp, dull, sensitive, or itchy.

Adequacy assessment of oxycodone/paracetamol (acetaminophen) in multimodal chronic pain : a prospective observational study.

BACKGROUND: Multimodal pain is comprised of nociceptive/inflammatory and neuropathic components. Pharmacological pain therapies from different classes provide pain relief using different mechanistic actions; often a combination of such therapies provides more effective pain relief than monotherapy. To assess whether pain management is adequate requires a comprehensive pain scoring system. OBJECTIVE: To evaluate the adequacy of a low-dose combination of oxycodone and paracetamol (acetaminophen) in patients with multimodal, chronic, non-malignant pain using the Pain Management Index (PMI). METHODS: During this prospective, observational study, consecutive patients were classified according to the presence of prevalent osteoarticular pain (group A, n = 78) or prevalent neuropathic pain (group B, n = 72). Existing pain-relief medications were discontinued and both groups received oxycodone 5 mg and paracetamol 325 mg up to 8 hourly for a planned duration of >/= 6 weeks. Patients in group B who were receiving gabapentin continued this treatment up to a maximum daily dosage of 2400 mg during the observation period. Pain intensity was evaluated using a visual analogue scale (VAS from 0 to 10). Functional limitation for patients in group A was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The intensities of dynamic allodynia and hyperalgesia in patients in group B were evaluated by a VAS. Results from the WOMAC, dynamic allodynia, and hyperalgesia assessments were evaluated using the PMI. RESULTS: In group A, 64.3% of patients showed improvements in pain symptoms after 15 days of treatment in the WOMAC categories of "pain preventing sleep" and "walks with aid". The PMI showed that the oxycodone/paracetamol therapy was adequate in patients with osteoarticular pain. In group B, 83.3% of patients reported improvement in the category of "pain preventing sleep", and all patients rated the remaining four categories ("spontaneous pain", "burning pain", "painful paresthesia", and "pinprick") as either stable or improved after 15 days of treatment. Using the PMI, hyperalgesia resolved with oxycodone/paracetamol therapy. 37.1% and 58.3% of patients did not complete the study in group A and B, respectively. CONCLUSION: The PMI was an effective tool for assessment of pain management efficacy. Oxycodone/paracetamol improved pain symptoms in the majority of compliant patients. In patients with neuropathic pain, rescue therapy with oxycodone/paracetamol showed a lesser, but significant, improvement of pain symptoms.

Dietary intake of heterocyclic amines in relation to socio-economic, lifestyle and other dietary factors: estimates in a Swedish population.

OBJECTIVES: To estimate the dietary intakes of heterocyclic amines (HCAs), to examine the intakes in relation to socio-economics, lifestyle and other dietary factors and to compare the classification of subjects by intake of HCA versus intake of meat and fish. DESIGN: Cross-sectional analysis within the Malmö Diet and Cancer (MDC) cohort. Data were obtained from a modified diet history, a structured questionnaire on socio-economics and lifestyle, anthropometric measurements and chemical analysis of HCAs. HCA intake was cross-classified against meat and fish intake. The likelihood of being a high consumer of HCAs was estimated by logistic regression analysis. Dietary intakes were examined across quintiles of HCA intake using analysis of variance. SETTING: Baseline examinations conducted in 1991-1994 in Malmö, Sweden. SUBJECTS: A sub-sample of 8599 women and 6575 men of the MDC cohort. RESULTS: The mean daily HCA intake was 583 ng for women and 821 ng for men. Subjects were ranked differently with respect to HCA intake compared with intake of fried and baked meat and fish (kappa = 0.13). High HCA intake was significantly associated with lower age, overweight, sedentary lifestyle and smoking. Intakes of dietary fibre, fruits and fermented milk products were negatively associated with HCA intake, while intakes of selenium, vegetables, potatoes, alcohol (among men) and non-milk-based margarines (among women) were positively associated with HCA intake. CONCLUSIONS: The estimated daily HCA intake of 690 ng is similar to values obtained elsewhere. The present study suggests that lifestyle factors (e.g. smoking, physical activity, fruit and vegetable intakes, and types of milk products and margarines) may confound associations between HCA intake and disease. The poor correlation between HCA intake and intakes of fried meat and fish facilitates an isolation of the health effects of HCAs.

Cost-effectiveness of duloxetine versus routine treatment for U.S. patients with diabetic peripheral neuropathic pain.

UNLABELLED: The purpose of this study was to compare the cost-effectiveness of duloxetine versus routine treatment in management of diabetic peripheral neuropathic pain (DPNP). Two hundred thirty-three patients with DPNP who completed a 12-week, double-blind, placebo-controlled, randomized, multicenter duloxetine trial were re-randomized into a 52-week, open-label trial of duloxetine 60 mg twice daily versus routine treatment. Routine treatment included pain management therapies. Effectiveness was measured by using the bodily pain domain (BP) of the Medical Outcomes Study Short Form 36 (SF-36). Costs were analyzed from 3 perspectives: third party payer (direct medical costs), employer (direct and indirect medical costs), and societal (patient's out-of-pocket costs and total medical costs). Costs of study medications were not included because of limited data. Bootstrap method was applied to calculate statistical inference of the incremental cost-effectiveness ratio (ICER). Routine treatment most frequently used included gabapentin (56%), venlafaxine (36%), and amitripytline (15%). From employer and societal perspectives, duloxetine was cost-effective (ICER= -342 dollars and -429 dollars, respectively, per unit of SF-36 BP; both P

Economic evaluation of oral treatments for neuropathic pain.

UNLABELLED: The effectiveness of amitriptyline, carbamazepine, gabapentin, and tramadol for the treatment of neuropathic pain has been demonstrated, but it is unknown which one is the most cost-effective. We designed a cost-utility analysis of a hypothetical cohort with neuropathic pain of postherpetic or diabetic origin. The perspective of the economic evaluation was that of a third-party payor. For effectiveness and safety estimates, we performed a systematic review of the literature. For direct cost estimates, we used average wholesale prices, and the American Medicare and Clinical Laboratory Fee Schedules. For utilities of health states, we used the Health Utilities Index. We modeled 1 month of therapy. For comparisons among treatments, we estimated incremental cost per utility gained. To allow for uncertainty from variations in drug effectiveness, safety, and amount of medication needed, we conducted a probabilistic Monte Carlo simulation. Amitriptyline was the cheapest strategy, followed by carbamazepine, and both were equally beneficial. Gabapentin was the most expensive as well as the least beneficial. A multivariable probabilistic simulation produced similar results to the base-case scenario. In summary, amitriptyline and carbamazepine are more cost-effective than tramadol and gabapentin and should be considered as first-line treatment for neuropathic pain in patients free of renal or cardiovascular disease. PERSPECTIVE: Prescription practices should be based on the best available evidence, which includes the evaluation of the medication's cost-effectiveness. This does not mean that the cheapest or the most expensive, but rather the most cost-effective medication should be chosen-the one whose benefits are worth the harms and costs. We report a cost-effectiveness evaluation of treatments for neuropathic pain.

Pregabalin: new drug. Very similar to gabapentin.

(1) The first-line treatment for partial epilepsy is carbamazepine monotherapy; gabapentin monotherapy is an alternative, given its lower risk of drug-drug interactions. (2) The standard treatment for neuropathic pain associated with diabetes or post-herpetic neuralgia is a tricyclic antidepressant, with gabapentin as an alternative. Few drugs are available in this setting, and their efficacy is often modest. (3) Pregabalin is a GABA analogue closely related to gabapentin. Both drugs are marketed by Pfizer. Pregabalin has been approved for use in two indications: refractory partial epilepsy and neuropathic pain. (4) In patients with partial epilepsy inadequately controlled by a combination of two or possibly three antiepileptics, three placebo-controlled double-blind trials lasting 12 weeks suggest that adjunctive pregabalin treatment, at a dose of 600 mg/day divided in two or three doses, at least halves the frequency of seizures in 50% of patients. Pregabalin has not been compared with other second-line antiepileptics. (5) In neuropathic pain, there are 12 double-blind placebo-controlled trials involving patients with diabetes or post-herpetic neuralgia. Depending on the trial, between one-third and one-half of patients treated with pregabalin at a dose of 600 mg/day given in two or three doses had at least a 50% reduction in their pain score. In the only trial that included a group treated with amitriptyline (75 mg/day), the latter was significantly more effective than placebo, while pregabalin was not. (6) There are no comparative trials of pregabalin after amitriptyline and gabapentin failure. (7) The adverse effects profile of pregabalin is similar to that of gabapentin, and includes mainly neuropsychological reactions (dizziness and drowsiness). (8) Pregabalin, like gabapentin, can lead to weight gain and peripheral oedema especially in elderly patients. (9) Cases of visual field restriction have been reported with pregabalin in clinical trials. Animal studies suggest a possible risk of haemangiosarcoma, although no human cases have yet been described. (10) Pregabalin, like gabapentin, is eliminated unchanged in urine, implying a limited risk of interactions involving cytochrome P450, and suggesting that the dose should be reduced in patients with even moderate renal failure (creatinine clearance below 60 ml/min). (11) In practice, pregabalin offers nothing new for patients with partial epilepsy, for whom several other antiepileptics are available. The few available treatments for neuropathic pain have limited efficacy, and pregabalin may therefore be tried when both tricyclics and gabapentin fail. However, it is in no way certain that pregabalin is effective in such patients, and comparative trials are lacking.

Occurrence of heterocyclic aromatic amines in the Swiss diet: analytical method, exposure estimation and risk assessment.

A total of 86 meat samples, prepared in restaurants or homes, ready to eat (including poultry and fish) and 16 commercial samples such as bouillon (cubes) were analysed for heterocyclic aromatic amines (HAA). The analytical method consisted of an acidic extraction, clean-up on a cation exchange cartridge followed by an analogous HPLC step to recover the following HAA: IQ, MeIQ, MeIQx, 4,8-DiMeIQx, PhIP and 7,8-DiMeIQx. The HAA containing HPLC-fractions were collected, the HAA identified and quantified using two RP-HPLC-systems of different retention properties (UV-detection). The limit of quantitation was in the range of 0.2-0.4 ng/g and the relative repeatability 6-15%. The recovery of PhIP was lower than for the other HAA analysed (less than 80%) and a correction factor was applied. No significant differences of the HAA-concentration were found in samples from homes and restaurants, half of the total samples contained HAA at the following frequencies: PhIP and MeIQx 33% (each), 4,8-DiMeIQx 11% and MeIQ 4%; 7,8-DiMeIQx and IQ were not detected. The frequencies in commercial products were for MeIQx 31%, 7,8-DiMeIQx 19%, IQ 13% and PhIP 6%; MeIQ and 4,8-DiMeIQx were not found. Based on these data, the average exposure of Swiss adults to HAA was estimated to be 5 ng/kg body mass per day, commercial products contributing less than 10%. The theoretical excess cancer risk due to this intake was estimated on the base of the carcinogenic potency of the HAA in long-term animal experiments by linear extrapolation. The resulting risk in the order of 10(-4) at the maximum is discussed in terms of Swiss epidemiological data.

Hemoglobin adducts of N-substituted aryl compounds in exposure control and risk assessment.

Arylamines, nitroarenes, and azo dyes yield a common type of metabolite, the nitroarene, which produces a hydrolyzable adduct with protein and is closely related to the critical, ultimate toxic and genotoxic metabolite. The target dose as measured by hemoglobin adducts in erythrocytes reflects not only the actual uptake from the environment but also an individual's capacity for metabolic activation and is therefore an improved dosimeter for human exposure. The usefulness of hemoglobin adducts in molecular epidemiology is now widely recognized. With regard to risk assessment, many questions need to be answered. The described experiments in rats address some of these questions. The relationship between binding to hemoglobin in erythrocytes and to proteins in plasma has been found to vary considerably for a number of diamines. The fraction of hydrolyzable adducts out of the total protein adducts formed also varies in both compartments. This indicates that the kind of circulating metabolites and their availability in different compartments is compound specific. This has to do with the complex pattern of competing metabolic pathways, and the role of N-acetylation and deacetylation is emphasized. An example of nonlinear dose dependence adds to the complexity. Analysis of hemoglobin adducts reveals interesting insights into prevailing pathways, which not only apply to the chemical, but may also be useful to assess an individual's metabolic properties. In addition, it is demonstrated that the greater part of erythrocytes and benzidine-hemoglobin adducts are eliminated randomly in rats, i.e., following first-order kinetics.