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Background: While data from USA and Canada demonstrate an opioid overdose epidemic, very little nation-wide European studies have been published on this topical subject.Methods: Using a nationally representative sample of the French Claims database (>700,000 patients), the exhaustive nationwide hospital discharge database, and national mortality registry, all patients dispensed at least one prescription opioid (PO) in 2004-2017 were identified, to describe trends in PO analgesic use, shopping behaviour, opioid-related hospitalizations and deaths. Annual prevalence of PO use and shopping behaviour (≥1 day of overlapping prescriptions from ≥2 prescribers, dispensed by ≥3 pharmacies) was estimated.Results: In 2004-2017, the annual prevalence of weak opioid use codeine, tramadol and opium rose by 150%, 123%, and 244%, respectively (p < 0.05). Strong opioid use increased from 0.54% to 1.1% (+104%, p < 0.05), significantly for oxycodone (+1950%). Strong opioid use in chronic noncancer pain rose by 88% (p < 0.05) and 1180% for oxycodone. Opioid shopping increased from 0.50% to 0.67% (+34%, p < 0.05), associated with higher mortality risk HR = 2.8 [95% confidence interval (CI): 1.2-6.4]. Opioid-related hospitalizations increased from 15 to 40 per 1,000,000 population (+167%, 2000-2017), and opioid-related deaths from 1.3 to 3.2 per 1,000,000 population (+146%, 2000-2015).Conclusions: This study provided a first European approach to a nationwide estimation with complete access to several national registries. In 2004-2017 in France, PO use excluding dextropropoxyphene more than doubled. The increase in oxycodone and fentanyl use, and nontrivial increasing trend in opioid-related morbidity-mortality should prompt authorities to closely monitor PO consumption in order to prevent alarming increases in opioid-related morbidity-mortality.Significance: In 2004-2017, prescription opioid use in France at least doubled and oxycodone use increased particularly, associated with a nontrivial increase in opioid-related morbidity-mortality. Although giving no indication for an 'opioid epidemic,' these findings call for proper monitoring of opioid use. [ABSTRACT FROM AUTHOR]

Context: Since the banning of dextropropoxyphene from the market, overdoses, and fatalities attributed to tramadol, a WHO step-2 opioid analgesic, have increased markedly. Tramadol overdose results not only in central nervous system (CNS) depression attributed to its opioid properties but also in seizures, possibly related to non-opioidergic pathways, thus questioning the efficiency of naloxone to reverse tramadol-induced CNS toxicity. Objective: To investigate the most efficient antidote to reverse tramadol-induced seizures and respiratory depression in overdose. Materials and methods: Sprague-Dawley rats overdosed with 75 mg/kg intraperitoneal (IP) tramadol were randomized into four groups to receive solvent (control group), diazepam (1.77 mg/kg IP), naloxone (2 mg/kg intravenous bolus followed by 4 mg/kg/h infusion), and diazepam/naloxone combination. Sedation depth, temperature, number of seizures, and intensity, whole-body plethysmography parameters and electroencephalography activity were measured. Results: Naloxone reversed tramadol-induced respiratory depression (p < .05) but significantly increased seizures (p < .01) and prolonged their occurrence time. Diazepam abolished seizures but significantly deepened rat sedation (p < .05) without improving ventilation. Diazepam/naloxone combination completely abolished seizures, significantly improved rat ventilation by reducing inspiratory time (p < .05) but did not worsen sedation. None of these treatments significantly modified rat temperature. Conclusions: Diazepam/naloxone combination is the most efficient antidote to reverse tramadol-induced CNS toxicity in the rat. [ABSTRACT FROM AUTHOR]

Aims: The aims of the present study were to describe the consumption trends of three groups of analgesics (non‐opioids, and mild and strong opioids) between 2006 and 2015 in France, and compare this pattern of use with six European countries in 2015. Methods: Annual drugs sales were extracted from the French national authority's consumption database, and from the IMS Multinational Integrated Data Analysis System and national databases for European countries. Results: The use of mild opioids in France was found to have decreased by 53% over the past 10 years, owing to the declining use of dextropropoxyphene combinations, along with an increase in the use of non‐opioids and strong opioids (from 72 to 93, and 2 to 2.8 defined daily doses/1000 inhabitants/day, respectively). Paracetamol, the most consumed analgesic, increased over this period, particularly for the adult high dose (+140%). The use of tramadol and codeine combinations also increased, by 62% and 42%, respectively. Morphine remained the most used strong opioid, although there were also large increases in the consumption of oxycodone (+613%) and fentanyl (+263% and +72% for transmucosal and transdermal forms, respectively). A comparison of the patterns of use in Europe in 2015 showed a higher consumption of mild and strong opioids in the UK. France ranked first and third place, respectively, for paracetamol and mild opioid consumption, whereas its use of strong opioids was among the lowest. Conclusions: Paracetamol consumption is clearly highest in France, whereas its use of strong opioids is among the lowest in Europe, although its consumption of oxycodone has increased significantly. Further studies are required specifically to monitor these drugs. [ABSTRACT FROM AUTHOR]

Diversion of prescription drugs is difficult to assess in quality and quantity. This study aimed to characterize diversion of prescription drugs in France through a comparative analysis of falsified prescriptions collected during three periods from 2001 to 2012. The data recorded in a national program which records all falsified prescriptions presented to community pharmacies were studied. Included data regarded: subjects, prescription forms, and drugs. Description of the dataset in three periods (2001-2004, 2005-2008, and 2009-2012) was completed with clustering analyses to characterize profiles of prescriptions and subjects associated with the most reported drugs. The 4469 falsified prescriptions concerned most often females (51.6%). Average age was 46.5 years. Zolpidem, bromazepam, and buprenorphine were the most frequent drugs. Alone, 13 drugs (1.7%, 13/772) represented more than 40% of the total reports (3055/7272). They were associated with three diversion profiles: (i) buprenorphine, flunitrazepam, and morphine were mentioned on overlapping secure prescription forms presented by young men; (ii) alprazolam, bromazepam, zolpidem, codeine/acetaminophen were mentioned on simple prescription forms presented by experienced women; and (iii) acetaminophen and lorazepam were mentioned on modified prescription forms presented by elderly subjects. Clonazepam, clorazepate, dextropropoxyphene, zopiclone moved between those profiles. The patterns of falsified prescriptions provided in this study contribute to enhance the scientific knowledge on the most diverted prescription drugs. The latter follow distinct trajectories across time depending on their pharmacology (including their abuse/addiction potential) and on their regulation's history. The close and continuous analysis of falsified prescriptions is an excellent way to monitor prescription drug diversion. [ABSTRACT FROM AUTHOR]

Introduction: The consequences of the withdrawal of marketing authorisation of drugs have mostly been studied considering drug prescription patterns for the therapeutic alternatives of the withdrawn drugs. The potential concomitant changes in the reporting of adverse reactions concerning these alternatives have been studied less often.Objective: The objective of this study was to analyse the changes in the reporting of adverse events (AEs) for therapeutic alternatives after the withdrawal of three medicines (dextropropoxyphene, pioglitazone and tetrazepam) from the market for safety reasons.Methods: This study was performed using both the French pharmacovigilance database and the Echantillon Généraliste des Bénéficiaires (a random sample of French health insurance affiliates). For dextropropoxyphene, pioglitazone and tetrazepam alternatives, the number and types of case reports were studied for both the year preceding the first official safety warning and the year following the withdrawal. Reporting rates expressed per 10,000 reimbursements (RRReimb) and per 10,000 treated patients (RRPat) were also compared for the two periods.Results: After dextropropoxyphene withdrawal, case reports and reimbursements increased for tramadol (case reports: +23%, reimbursements: +13%) and codeine (case reports: +74%, reimbursements: +47%), RRPat being significantly increased for tramadol (0.92 vs. 1.06, p = 0.02). After pioglitazone withdrawal, case reports increased for dipeptidyl peptidase-4 (DPP-4) inhibitors, glinides, and glucagon-like peptide 1 (GLP-1) analogues (+84%, +22% and +5%, respectively) and reimbursements (+55, +11 and +50%, respectively); both decreased for sulfonylureas (case reports: -6%, reimbursements: -2%). RRPat increased for DPP-4 inhibitors (1.63 vs. 2.26, p = 0.008). After tetrazepam withdrawal, case reports increased for diazepam, methocarbamol and thiocolchicoside (+110, +86 and +157%, respectively), as lesser did reimbursements. RRPat increased for diazepam (1.78 vs. 2.41, p = 0.054) and thiocolchicoside (0.14 vs. 0.24, p = 0.013).Conclusion: For the three drug withdrawals investigated, the number of case reports involving alternatives increased to a larger extent than the numbers of prescriptions. This could relate to a higher occurrence of AEs in new users of alternatives who switched from the withdrawn medicines or to an increased awareness of possible AEs. [ABSTRACT FROM AUTHOR]

The synthetic opioid propoxyphene was a schedule IV controlled substance with multiple reported health risks before the US Food and Drug Administration issued a request for voluntary market withdrawal in November 2010. The purpose of this study is to investigate the characteristics and occurrences of propoxyphene-related deaths in Florida before and after voluntary market removal. Decedent-level toxicology data from Florida's Medical Examiners Commission was used to compare the temporal, polysubstance use, sociodemographic, and geographic profiles associated with propoxyphene-involved deaths for a pre-withdrawal (November 2008-November 2010) and post-withdrawal (December 2010-December 2012) period. Sensitivity analyses using multiple data sources, including Florida's Prescription Drug Monitoring Program and other states' data, were conducted to examine potential reporting bias. Results showed that the number of propoxyphene-involved deaths declined by 84% from 580 deaths to 92 deaths after market withdrawal. The co-occurrence of other prevalent drugs, such as oxycodone (17.2% to 26.1%, p=0.0422) increased significantly in the post-withdrawal study period. A larger proportion of the propoxyphene-related deaths were reported from South Florida after the withdrawal (28.4% to 56.5%, p<0.0001). No significant changes in age and race/ethnicity were observed. Sensitivity analyses revealed that several deaths occurred in other states after market withdrawal, as recently as 2016. Our findings are consistent with previous studies that propoxyphene was still available after removal from the US market. Continued surveillance is recommended after highly abused opioids are withdrawn from the market due to on-going safety risks. [ABSTRACT FROM AUTHOR]

About a year after dextropropoxyphene (DXP) withdrawal from the French market, we conducted a survey among members of the French Society of Anesthesia & Intensive Care Medicine (Sfar) and of the French Society of the Study and Treatment of Pain (SFETD) to identify the indications for which this WHO level II analgesic had been prescribed, the prescriber's feedback following withdrawal, and the substitutive analgesics prescribed. DXP had been prescribed by more than 75% of the 430 anaesthesiologists and 230 pain specialists interviewed, mainly for acute and chronic non-cancer pain of moderate intensity. While two thirds of pain specialists were not satisfied with DXP withdrawal, this decision did not affect the majority of anaesthesiologists. In both groups, the main substitutive analgesic was tramadol combined with acetaminophen, while only 24% of prescribers considered acetaminophen alone as a substitute. [ABSTRACT FROM AUTHOR]

Au/α-Fe 2 O 3 catalysts have been prepared by deposition-precipitation. The support α-Fe 2 O 3 has been previously synthesized by precipitation technique. The effect of thermal treatment on structural, morphological and redox properties of Au/α-Fe 2 O 3 samples have been thoroughly studied for the samples calcined at 150, 200 and 300 °C, together with a non-calcined sample. Their catalytic activity toward CO oxidation in the presence of hydrogen (CO-PROX) has been tested. The results showed that the gold particle size and surface adsorbed oxygen changed with the calcination temperature, being the minimum for the sample calcined at 200 °C. There was not detected cationic gold by X-ray photoelectron spectroscopy (XPS) in none of the samples. The presence of gold promoted notably the reduction of the iron oxide. The highest activity for CO-PROX was achieved by the non-calcined catalysts (simply dried at 110 °C), while the sample calcined at 200 °C was the least active. The catalysts activity was assigned to the gold particle size and surface adsorbed oxygen. [ABSTRACT FROM AUTHOR]

In this paper, we report a DSC investigation of solid–liquid equilibria in three binary mixtures of paracetamol, namely with pseudoephedrine, dextropropoxyphene and tramadol, resulting in a temperature-composition phase diagrams with eutectic equilibrium. Eutectic mole fractions, temperatures and enthalpies were determined and reported for each system. The study reports also a direct exploitation of the DSC results for the quantification purpose, which were in good agreement with those obtained by a standard analytical method namely high performance thin layer chromatography (HPTLC), used in this work for comparison purpose. [ABSTRACT FROM AUTHOR]

Opiate abuse is a major problem worldwide. Simple and cost-effective method with quantification capabilities is need of time especially for developing countries. A procedure for simultaneous determination of morphine, codeine, pentazocine and propoxyphenene in urine by High performance thin layer chromatography (HPTLC) is described. Following enzymatic hydrolysis, urine samples were extracted. Liquid-liquid extraction was carried out with dichloromethane and isopropanol (9: 3) at pH 9. Extracts reconstituted in methanol were analyzed by HPTLC in quantification mode. Limit of quantification (LOQ) was120 μg/ml for morphine and codeine with 20 ml of urine sample. For propoxyphene LOQ was 60 μg/ml and pentazocine 800 μg/ml with 20 ml of urine sample. This study is an attempt to utilize HPTLC for semi-quantification of biological sample. Unavailability of HPTLC inserts forced to take larger urine volume. Software (wincats) inability to save calibration curve resulted in preparation of calibration curve on regular basis. [ABSTRACT FROM AUTHOR]

Background: Studies from developed countries document the presence of injecting drug use among females and significantly higher vulnerabilities and risks as compared with male injecting drug users (IDUs). Studies comparing vulnerabilities and drug use patterns between female and male IDUs are not available for developing countries. Objectives: The aim of the study was to assess the drug use pattern and related HIV vulnerabilities among female IDUs and compare these findings with those from male IDUs from four states of Northeast India. Method: The study used data collected as part of a nationwide study of drug use pattern and related HIV vulnerabilities among IDUs. Ninety-eight female and 202 male IDUs accessing services from harm reduction sites across the four states of Northeast region of India were chosen through random sampling methodology. Drug use pattern, injecting practices, and knowledge of HIV were assessed using a structured questionnaire. Results: Significantly higher proportion of female IDUs was uneducated, unemployed, reported their occupation as sex workers, and switched to injecting drug use faster as compared with male IDUs. Female IDUs practicing sex work differed significantly from those who did not with respect to frequency of daily injections, choice of drugs injected, and concomitant use of non-injecting drugs. More than half of female IDUs initiated sharing within the first month of injecting. Conclusions: The study demonstrates that female IDUs differ from male IDUs in their drug use pattern, initiation into injection as well as injecting behavior, which would be an important consideration during designing of female-specific interventions. [ABSTRACT FROM AUTHOR]

The collision-induced dissociation of the protonated five-arm star propoxylated diethylenetriamine polyols was studied under electrospray conditions. Two product ion series were detected because of the cleavage of the C-N bonds in the initiator moiety. No backbone fragmentation of the polyether chains was observed, which allowed to explore the initiation and side-chain propagation process of the oligomers. On the basis of MS/MS spectra, it is probable that the rate of the initiation is larger than that of the chain propagation. The propylene oxide repeat units attach to the five arms with approximately the same probability. Furthermore, it was found that the collision energy necessary to obtain 50% fragmentation (CE50) was linearly dependent on the molecular weight of the polyols. [ABSTRACT FROM AUTHOR]

Introduction: Our recent prospective randomized controlled trial (NCT01660048) comparing single-incision laparoscopic (SIL) totally extraperitoneal (TEP) and multi-incision inguinal herniorraphy confirmed safety, efficacy and benefits of single-incision approach. This study (NCT01883115) aimed to assess safety, efficacy and cost effectiveness of telescopic extraperitoneal dissection. Methods: Patients with inguinal/femoral hernias from February 2013 to February 2014 undergoing SILTEP herniorraphy with telescopic dissection were compared with patients who had previously undergone SILTEP herniorraphy with balloon dissection. Costs of different ports/trocars were analysed. Results: There were 102 patients in telescopic compared to 51 in balloon dissection group; these had no significant differences in age, sex, body mass index, American Society of Anesthesiologists and pre-op visual analogue scores. Telescopic vs. balloon showed: post-operative pain-day one 2.5 vs. 2.5; p = 0.90, day seven 0 vs. 0; p = 0.02 (0 vs. 1; p < 0.01 for bilateral hernias); operation times-unilateral 48.0 vs. 48.0 min; p = 0.88 and bilateral 70.0 vs. 65.0 min; p = 0.66, length of hospital stay 1.0 vs. 1.0 day, analgesic intake (dextropropoxyphene) 6.0 vs. 6.0 tablets; p = 0.95, return to work/normal physical activities 7.0 vs. 7.0 days; p = 0.46 and cosmetic scar scores 24.0 vs. 24.0, respectively. There was no conversion to open surgery/need for additional ports in either group. Median scar length for telescopic group was 13.0 mm. Costs of disposable ports/trocars for telescopic and balloon groups were US$480 and $720, respectively. There were no morbidities/recurrences with follow-up of 2-36 months. Conclusions: Telescopic extraperitoneal dissection during SILTEP inguinal herniorraphy represents a safe and efficient alternative with potential cost savings compared to balloon dissection. [ABSTRACT FROM AUTHOR]

Study Design. Randomized, double-blind, placebo-controlled, single-dose crossover study. Objective. To test the analgesic efficacy of oxymorphone hydrochloride (OH) and propoxyphene/acetaminophen (PA) for patients with neurogenic claudication associated with lumbar spinal stenosis. Summary of Background Data. Although opioids are often prescribed for neurogenic claudication, no randomized controlled studies support their efficacy for this condition. Patients with neurogenic claudication are generally excluded from clinical trials or included with patients who have nonspecific chronic low back pain, yielding a heterogeneous study population with very different pathophysiologies and clinical presentations. Methods. Participants received a single dose of each of the 3 treatments in random order. Treatments were separated by at least 3-day washout periods. The primary outcome variable was the time to first treadmill walking-induced moderate pain ( ≥ 4 out of 10 on a Numeric Rating Scale) ( T first ) assessed 90 minutes after treatment administration. Secondary outcome measures included patient global assessment of low back pain, Roland-Morris Disability Questionnaire, Modified Brief Pain Inventory-Short Form, Oswestry Disability Index, and Swiss Spinal Stenosis Questionnaire. Results. The study was prematurely terminated because of the removal of PA from the US market. Twenty-four patients were randomized; 21 completed all 3 treatment periods. There were no significant differences among the treatment groups with respect to the median T first (OH--placebo: median [98.3% confidence limits] = -0.25 min [ -6.54, 5.00]; PA--placebo: 0.02 min [ -7.65, 4.90]; OH--PA: - 0.27 min [ -5.56, 6.66]). Conclusion This trial failed to demonstrate a benefit of OH or PA in patients experiencing neurogenic claudication. Considering the potential negative side effects of chronic opioid use, additional research is necessary to evaluate the efficacy of sustained opioid treatment specifically for neurogenic claudication. [ABSTRACT FROM AUTHOR]

The author looks at government policy on analgesic drugs in India, expressing opposition to the Indian government's 2013 decision to ban the pain medication dextropropoxyphene for human use. Topics include the price of dextropropoxyphene compared to other analgesics, concerns about its use as a suicide agent, and estimates of the number of cancer and other patients in India requiring chronic pain management.

Objectives: Opioid abuse is a growing problem in civilian communities, and it has developed in the military as well. Telephone calls to poison centers requesting pill identification (ID) is a marker of drug abuse. This study identifies the number of pill ID calls made to the poison centers from areas containing and surrounding three Texas military bases during an 8-year period.Methods: We performed a retrospective observational study identifying calls to certified poison centers in Texas from 2002 to 2009 that identified hydrocodone tablets and other pain medications. We noted the calls made from ZIP codes containing and surrounding the three largest military bases in Texas.Results: We reviewed 75,537 drug ID calls for any drug from the ZIP codes of interest. Total drug ID calls increased 105% and the number of calls for hydrocodone increased 463%.Conclusions: In our study most of the drug ID calls from military communities in Texas were for hydrocodone. The rate of calls for hydrocodone increased more than the rate of calls for other analgesics from 2002 to 2009. Using drug ID calls as a surrogate of drug abuse, our results suggest that hydrocodone abuse has increased within military communities and that poison center data can be a reliable surrogate for prescription drug abuse near military bases. Future studies are needed to further understand the extent of this problem in military and civilian communities. We can use this information to heighten awareness, influence prescription practices, establish practice guidelines, and develop educational programs to mitigate the increasing rate of prescription analgesic abuse in the United States. [ABSTRACT FROM AUTHOR]

Onthe basis of N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine(II, ASS234) and QSAR predictions, in this work we havedesigned, synthesized, and evaluated a number of new indole derivativesfrom which we have identified N-methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4-yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine (2, MBA236)as a new cholinesterase and monoamine oxidase dual inhibitor. [ABSTRACT FROM AUTHOR]

Background and Purpose Autophagy is an important intracellular degradation system, which is related to various diseases. In preliminary experiments we found that D4-[6-(4-isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl] quinoline ( DMH1) inhibited autophagy responses. However DMH1 also inhibits the signalling pathway activated by bone morphogenetic protein-4 (BMP4). The aim of the present study was to elucidate the inhibitory effects of DMH1 on autophagy and the underlying mechanisms. Experimental Approach The effects of DMH1 on autophagy responses were evaluated in cultures of different cell types and with different stimuli to induce autophagy, using Western blots, transmission electron microscopy and fluorescent microscopy. Key Results DMH1 inhibited starvation-induced autophagy in cardiomyocytes, HeLa and MCF-7 cells, without involving the signalling pathway of BMP4. DMH1 inhibited aminoimidazole carboxamide ribonucleotide ( AICAR)- and rapamycin-induced autophagy in HeLa and MCF-7 cells. DMH1 reversed starvation- and AICAR-induced inhibition of Akt, mammalian target of rapamycin ( mTOR) and p70S6 kinase ( S6K), and reversed rapamycin-induced inhibition of mTOR and S6K. DMH1 reversed starvation-induced decrease of the phosphorylated form of glycogen synthase kinase-3 in MCF-7 and HT29 cells. Activation of Akt and inhibition of autophagy induced by DMH1 were antagonized by an Akt specific inhibitor or by small interfering RNA for Akt in HeLa cells. Conclusion and Implications DMH1 inhibited cellular autophagy responses in a range of cell types and the underlying mechanisms include activation of the Akt pathway. [ABSTRACT FROM AUTHOR]

Objective: Describe the consequences of dextropropoxyphene (DXP) market withdrawal on analgesic prescriptions and on the quality of therapeutic management of chronic pain. Patients and methods: From a cohort of non-institutionalised elderly patients with chronic pain recruited by general practitioners, we selected patients who were treated with DXP daily for at least 6 months just prior to DXP market withdrawal and who had an evaluation of pain and its impact on daily activities before and after DXP withdrawal. Results: One hundred three patients took DXP daily for chronic pain. Immediately after DXP market withdrawal, 42 (40.8 %), 55 (53.4 %) and 3 (2.9 %) patients were treated with step 1, 2 and 3 analgesics, respectively, and 3 patients (2.9 %) were no longer receiving any analgesic medication. Among the 55 patients who continued on step 2 analgesics, 37 were treated with tramadol, 14 with codeine and 9 with opium. Pain intensity and the impact of pain on daily activities remained stable. Conclusion: DXP market withdrawal had no consequences on the intensity or impact of chronic pain in elderly patients. [ABSTRACT FROM AUTHOR]

Background: Drug addiction is on the rise in Punjab,India. There are 15 DDCs which are supported by the Indian Red Cross Society. There is alleged mushrooming of private Drug Deaddiction Centres (DDCs) in the smaller towns, villages and cities of Punjab. Objective: This study aimed to evaluate DDCs in Punjab. Materials and Methods: A total of 10 DDCs were included in the study and scheduled visits were made to collect data by using a pre-tested questionnaire. Results: The duration of treatment was 1 month at the Red Cross DDCs and it was approximately 6 months at private DDCs. The staff at the private DDCs were inadequate. The major drugs which were abused by patients were Propoxyphene, Alcohol, Bhukki and Cannabis. Patients were usually referred to the DDCs either by family members (35.3%) or social workers (29.8%). About 72.5% of patients were married, 36.3% had passed 10th standard and 54.4% were employed. A majority dropped out of the DDCs due to personal reasons and lack of family support. On comparison, more patients were found to be treated at Red Cross centres (75.3%) than at private centres (65.8%). All DDCs had conducted regular sessions of individual, group and family counseling for patients. Red Cross DDCs ensured that ex-clients received follow-ups and home visits. More patients were satisfied with the services which were provided by the Red Cross DDCs. On the contrary, more patients at the private DDCs complained about harassment fromstaff personnel (p>0.05). Conclusion: It is recommended that all DDCs should be checked regularly, and that the private centres should be provided with additional support from the government, to help run them more efficiently. [ABSTRACT FROM AUTHOR]

The author discusses the ban of dextropropoxyphene in India. It reports the suspension of manufacturing, selling and distributing this synthetic weak opioid by the Indian government. It outlines the reasons why some countries decided to withdraw the dextropropoxyphene. It also relates some criticism for the withdrawal of dextropropoxyphene.

Abstract: Introduction: In the present study, we investigated whether a new biomarker – index of cardiac electrophysiological balance (iCEB=QT/QRS) – could predict drug-induced cardiac arrhythmias (CAs), including ventricular tachycardia/ventricular fibrillation (VT/VF) and Torsades de Pointes (TdPs). Methods: The rabbit left ventricular arterially-perfused-wedge was used to investigate whether the simple iCEB measured from the ECG is reflective of the more difficult measurement of λ (effective refractory period×conduction velocity) for predicting CAs induced by a number of drugs. Results: Dofetilide concentration-dependently increased iCEB and λ, predicting potential risk of drug-induced incidence of early afterdepolarizations (EADs) starting at 0.01μM. Digoxin (1 and 5μM), encainide (5 and 20μM) and propoxyphene (10 and 100μM) markedly reduced both iCEB and λ, predicting their ability to induce non-TdP-like VT/VF. At 10μM, both NS1643 and levcromakalim significantly decreased λ and iCEB, which was preceded with presence of non-TdP-like VT/VF. Isoprenaline (0.05 to 0.5μM) significantly reduced both λ and iCEB, which was associated with a high incidence of non-TdP-like VT/VF in most preparations. Other biomarkers (i.e. transmural dispersion of T-wave and instability of the QT interval) predicted only dofetilide-induced long QT and EADs, but did not predict drug-induced risk of non-TdP-like VT/VF. Discussion: Our data from 7 reference drugs of known pro-arrhythmic effects suggests that 1) this non-invasive iCEB predicts potential risk of drug-induced CAs beyond long QT and TdP; 2) iCEB is more useful than the current biomarkers (i.e. transmural dispersion and instability) in predicting potential risks for drug-induced non-TdP-like VT/VF. [Copyright &y& Elsevier]

The author discusses the proposal of the Therapeutic Goods Administration (TGA) in November 2011 to remove dextropropoxyphene from the Australian Register of Therapeutic Goods. It states that dextropropoxyphene remains on the Australian market as of August 2013, which owe a series of appeals to the Administrative Appeals Tribunal (AAT) by the manufacturer of the drug. It explores whether the appeal process against the TGA decisions serves the public interest of Australians.

Aims The risk of hypoglycaemia with tramadol ( TRM) is not well described. Our aim was to analyze spontaneous reports of hypoglycaemia registered in the French Pharmacovigilance database and to compare these data with two other step-2 analgesic drugs. Methods Cases of hypoglycaemia associated with TRM, dextropropoxyphene ( DXP) and codeine ( COD) recorded between 1997 and November 2010 in the French pharmacovigilance database were compared. Results Seventy-two cases of hypoglycaemia associated with DXP and 43 with TRM were retained for evaluation (the single case reported with COD was not further considered). Most patients were elderly people with no significant difference in age between DXP- and TRM-treated patients (71.2 ± 21 vs. 69.4 ± 22.5 years). Hypoglycaemia occurred after a median of 4 and 5 days with DXP and TRM treatment, respectively. The mean lowest serum glucose concentration was 2.1 ± 0.9 mmol l−1 in the DXP group compared with 2.5 ± 1 mmol l−1 in the TRM group ( P = 0.072). At least, one risk factor of hypoglycaemia was found in most patients, with no significant difference between groups (58.3% in the DXP group and 58.1% in the TRM group). In particular, 31.9% patients from the DXP group had diabetes compared with 41.8 % from the TRM group ( P = 0.28) and 18% of DXP patients had renal insufficiency compared with 16.3% of TRM patients ( P = 0.8). Conclusions Our study confirms that TRM is associated with the occurrence of hypoglycaemia in elderly or predisposed patients, with characteristics similar to those previously reported with DXP. [ABSTRACT FROM AUTHOR]

Objective: Prazepam is broadly and quickly metabolized after ingestion. As a consequence, its detection in blood is exceptional. We report a case of a prazepam, dextropropoxyphene and acetaminophen poisoning in which a significant concentration of prazepam was noted in post-mortem blood. Method: A toxicological analysis was carried out by using various techniques including liquid chromatography coupled with spectrophotometry and mass spectrometry, and gas chromatography coupled with mass spectrometry. Results: The following xenobiotics were detected in the blood: dextropropoxyphene at a concentration of 6420 µg/L, acetaminophen at a concentration of 342 µg/L, prazepam at a concentration of 178 µg/L, nordazepam at a concentration of 2517 µg/L and oxazepam at a concentration of 113 µg/L. Conclusion: Two hypotheses are proposed to explain the presence of prazepam: a drug interaction and massive hepatic cytolysis caused by acetaminophen intoxication. [ABSTRACT FROM AUTHOR]

Abstract: A new sildenafil analogue was found to be added illegally to a energy drink marketed for the enhancement of sexual function. The structure was determined as 1-[4-propoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenylsulfonyl]-4-methylpiperazine. Owing to the inclusion of one more methyl group to sildenafil (on C-21), the detected compound was called “propoxyphenyl sildenafil”. The sample was purified with column chromatography. The UV, IR, LC/MS (ESI) and completely assigned NMR data of propoxyphenyl sildenafil is reported. Having compared the structure with sildenafil, the results showed that the 2-ethoxy group (at the position on C-19) has been replaced by propoxy group. [Copyright &y& Elsevier]

The article focuses on a study that examines the levels of propoxyphene drug in the urine samples obtained from the U.S. pain management population (PMP). It mentions that propoxyphene, the opioid analgesic, was withdrawn from the U.S. market in November 2010 due to safety and efficacy issues. However, the urine analysis of PMP indicates the presence of propoxyphene, measured by a validated liquid chromatography–tandem mass spectrometry procedure.

Abstract: Background: In the United States, rural areas have reported an increase in overdose deaths secondary to nonmedical use of prescription opioids. Little is known about the differences in nonmedical use of prescription opioids among urban and rural adults. Methods: Using the 2008–2009 National Survey on Drug Use and Health, we examined the prevalence of nonmedical use of prescription opioids in urban and rural counties and determined bivariate and multivariate associations, stratified by county. We also compared type of opioids, stratified by county. Results: Among 75,964 respondents, the prevalence of nonmedical use of prescriptions opioids was similar among residents in urban and rural counties (4.7% vs. 4.3%, p =0.15). Urban and rural residents with severe psychological distress and nonmedical use of other prescription medications were more likely to report nonmedical use of opioids. Urban residents whose first use of illicit drugs was between the age of 18 and 25 and who reported alcohol use were more likely to report nonmedical use. Black and Hispanic urban residents were less likely to use prescription opioids nonmedically compared to white urban residents. Rural residents were more likely than urban residents to use acetaminophen with propoxyphene (61.1% vs. 55.8%, p =0.02), methadone (14.8% vs. 9.1%, p =0.003) and acetaminophen with codeine (3.5% vs. 1.9%, p =0.05). Conclusions: Prevalence and risk factors related to nonmedical use of opioids are similar between urban and rural residents; however rural residents report propoxyphene, codeine, and methadone use more than their urban counterparts. Prevention and treatment interventions may need to be tailored for specific communities. [Copyright &y& Elsevier]

Isobornyl acrylate (IBOA) and isobornyl methacrylate (IBOMA) were used to replace triethylene glycol dimethacrylate (TEGDMA) as reactive diluents in dental restorative materials. Photopolymerization behaviors of mixtures of IBO(M)A and 2,2-bis[ p-(2′-hydroxy-3′-methacryloxy propoxy)phenyl]propane (Bis-GMA) were investigated by Fourier transform infrared spectroscopy. The degree of conversion, volume shrinkage, contact angle, water sorption, water solubility, flexural strength, and modulus values of the Bis-GMA/IBO(M)A formulations were measured and compared with those of a Bis-GMA/TEGDMA formulation. The results illustrate that the degree of conversion, volume shrinkage, contact angle, water sorption, flexural strength, and modulus values of the Bis-GMA/IBO(M)A systems were all lower than those of the Bis-GMA/TEGDMA system; the water solubility values of the Bis-GMA/IBO(M)A systems were higher than that of the Bis-GMA/TEGDMA system. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 [ABSTRACT FROM AUTHOR]

Background: Inappropriate medication prescription is a common cause of preventable adverse drug events among elderly persons in the primary care setting. Objective: The aim of this systematic review is to quantify the extent of inappropriate prescription to elderly persons in the primary care setting. Methods: We systematically searched Ovid-Medline and Ovid-EMBASE from 1950 and 1980 respectively to March 2012. Two independent reviewers screened and selected primary studies published in English that measured (in)appropriate medication prescription among elderly persons (>65 years) in the primary care setting. We extracted data sources, instruments for assessing medication prescription appropriateness, and the rate of inappropriate medication prescriptions. We grouped the reported individual medications according to the Anatomical Therapeutic and Chemical (ATC) classification and compared the median rate of inappropriate medication prescription and its range within each therapeutic class. Results: We included 19 studies, 14 of which used the Beers criteria as the instrument for assessing appropriateness of prescriptions. The median rate of inappropriate medication prescriptions (IMP) was 20.5% [IQR 18>1 to 25.6%.]. Medications with largest median rate of inappropriate medication prescriptions were propoxyphene 4.52(0>10-23.30)%, doxazosin 3.96 (0.32 15.70)%, diphenhydramine 3.30(0.02-4.40)% and amitriptiline 3.20 (0.05-20.5)% in a decreasing order of IMP rate. Available studies described unequal sets of medications and different measurement tools to estimate the overall prevalence of inappropriate prescription. Conclusions: Approximately one in five prescriptions to elderly persons in primary care is inappropropriate despite the attention that has been directed to quality of prescription. Diphenhydramine and amitriptiline are the most common inappropriately prescribed medications with high risk adverse events while propoxyphene and doxazoxin are the most commonly prescribed medications with low risk adverse events. These medications are good candidates for being targeted for improvement e.g. by computerized clinical decision support. [ABSTRACT FROM AUTHOR]

Background: The analgesic co-proxamol (paracetamol/dextropropoxyphene combination) has been widely involved in fatal poisoning. Concerns about its safety/effectiveness profile and widespread use for suicidal poisoning prompted its withdrawal in the UK in 2005, with partial withdrawal between 2005 and 2007, and full withdrawal in 2008. Our objective in this study was to assess the association between co-proxamol withdrawal and prescribing and deaths in England and Wales in 2005-2010 compared with 1998-2004, including estimation of possible substitution effects by other analgesics. Methods and Findings: We obtained prescribing data from the NHS Health and Social Care Information Centre (England) and Prescribing Services Partneriaeth Cydwasanaethau GIG Cymru (Wales), and mortality data from the Office for National Statistics. We carried out an interrupted time-series analysis of prescribing and deaths (suicide, open verdicts, accidental poisonings) involving single analgesics. The reduction in prescribing of co-proxamol following its withdrawal in 2005 was accompanied by increases in prescribing of several other analgesics (co-codamol, paracetamol, codeine, co-dydramol, tramadol, oxycodone, and morphine) during 2005-2010 compared with 1998-2004. These changes were associated with major reductions in deaths due to poisoning with co-proxamol receiving verdicts of suicide and undetermined cause of -21 deaths (95% CI -34 to -8) per quarter, equating to approximately 500 fewer suicide deaths (-61%) over the 6 years 2005-2010, and -25 deaths (95% CI -38 to -12) per quarter, equating to 600 fewer deaths (-62%) when accidental poisoning deaths were included. There was little observed change in deaths involving other analgesics, apart from an increase in oxycodone poisonings, but numbers were small. Limitations were that the study was based on deaths involving single drugs alone and changes in deaths involving prescribed morphine could not be assessed. Conclusions: During the 6 years following the withdrawal of co-proxamol in the UK, there was a major reduction in poisoning deaths involving this drug, without apparent significant increase in deaths involving other analgesics. [ABSTRACT FROM AUTHOR]

Purpose: After elective outpatient upper extremity surgery, patients'' need for opioid analgesic medication may be considerably less than typically dispensed. Our goal for this study was to evaluate pain control and quantify the amount of leftover pain medication. Methods: We recruited patients scheduled for elective outpatient upper extremity surgery, who met the inclusion criteria, to participate in a phone interview 7 to 14 days after surgery. Information collected included age, gender, procedure performed, analgesic medication and regimen prescribed, satisfaction with pain control, number of tablets remaining, reasons for not taking medication, other analgesic medications used, payer classification, and any adverse drug reactions. Results: A total of 287 eligible subjects consented to participate. Of these, 36 patients failed phone contact and 1 patient canceled surgery, which left 250 patients who completed the study. Oxycodone, hydrocodone, and propoxyphene accounted for over 95% of the prescription medications, with adequate pain control reported by 230 (92%) patients. Patients most frequently received 30 pills. Patients undergoing bone procedures reported the highest medication use (14 pills), whereas patients undergoing soft tissue procedures reported the lowest use (9 pills). Over half of the subjects reported taking the opioid medication for 2 days or less. Medicare patients consumed significantly less medication (7 pills, P < .05) than patients covered by all other types of insurance. Overall, patients consumed a mean of 10 opioid pills, whereas 19 pills per subject were reported unused, which resulted in 4,639 leftover tablets for the entire cohort. Conclusions: Our data show that excess opioid analgesics are made available after elective upper extremity surgery and could potentially become a source for diversion. A prescription of 30 opioid pills for outpatient surgery appears excessive and unnecessary, especially for soft tissue procedures of the hand and wrist. Type of study/level of evidence: Prognostic I. [Copyright &y& Elsevier]

Background: In India, as in rest of the world, HIV prevention programs have focused on HIV transmission through unsafe injecting practices with less attention on sexual risk behaviors among injecting drug users (IDUs). This study examines the sexual risk taking behaviors of IDUs associated with their pattern of drug use in India. Methods: Data were obtained from the behavioral tracking survey conducted in 2009 among 1712 IDUs in two districts each of Manipur and Nagaland states in Northeastern part of India. Sexual risk behaviors among IDUs were assessed in terms of multiple sex partners, sex with a paid female partner in the last 12 months and inconsistent condom use with any female partner. Results: More than one-fourth (27%) in Manipur and almost one in two (47%) IDUs reported having had sex with two or more female partners in the past 12 months. In Manipur where heroin is commonly used, the odds of having multiple sex partners were higher among non-heroin users than heroin users (42% vs. 23%, Adjusted Odds Ratio (AOR): 1.7, 95% Confidence Interval (CI): 1.1-2.6) and who shared needles/syringes in the last one month than who did not share (46% vs. 26%, AOR: 2.2, CI: 1.2-4.0). In Nagaland, where Spasmoproxyvon (SP, a synthetic opioid analgesic that contains dextropropoxyphene, dicyclomine hydrochloride and paracetamol) is most common, regular injectors as compared to occasional injectors were more likely to report multiple sex partners (67% vs. 42%, AOR: 2.7, CI: 1.8-4.1) and sex with paid partners (13% vs. 3%, AOR: 6.0, CI: 3.0-12.1). Sharing of needles/syringes was positively associated with multiple sex partners (51% vs. 44%, AOR: 1.6, CI: 1.2-2.2), and inconsistent condom use (93% vs. 80%, AOR: 3.0, CI: 1.8-5.1). Conclusions: IDUs with unsafe injecting practices also engage in risky sexual practices magnifying the risk of HIV infection. There is a need to focus on prevention of sexual transmission among high-risk IDUs, particularly in areas where Spasmoproxyvon is commonly used. [ABSTRACT FROM AUTHOR]

Abstract: When opioid therapy is initiated for a new pain condition, it may be unknown whether the pain will persist beyond the time of tissue healing. The aim of this study was to determine the prevalence of prescription patterns indicating persistent and/or problematic opioid use in a cohort of opioid-naive patients starting therapy with weak opioids. Data were drawn from the nationwide Norwegian Prescription Database. The study population was all new users of opioids receiving prescriptions of a weak opioid in 2005 for nonmalignant pain. This cohort was followed until December 2008. In order to be classified as having probable problematic opioid use, patients had to meet all of the following criteria: received opioids at least once every year from 2005 to 2008 and in 2008; (1) were dispensed more than 365 defined daily doses (DDDs) of opioids; (2) received opioid prescriptions from more than 3 doctors; and (3) were dispensed more than 100 DDDs of benzodiazepines. There were 245,006 persons who were new users of weak opioids in 2005 (216,902 codeine, 26,326 tramadol, 1778 dextropropoxyphene). There were 17,252 (7% of new users) who received a prescription for opioids at least once each of the 3 following years. Of these subjects, 686 patients were dispensed more than 365 DDDs of opioids in 2008 and are probably persistent users. There were 191 subjects who met our criteria for probable problematic opioid use. In a cohort of new opioid users who started treatment with weak opioids, only 0.3% and 0.08% developed prescription patterns indicating persistent opioid use and problematic opioid use, respectively. A national Norwegian cohort of new users of weak opioids was followed from 2005 until 2009; only 0.08% developed problematic opioid use. [Copyright &y& Elsevier]

The article investigates the inefficacy of propoxyphene as medication in Tennessee. It states that Medicare Part D data from the Quality Improvement Organization revealed that propoxyphene is the main contributor to the potentially inappropriate medications (PMIs) rate in Tennessee. It notes that physicians agreed that PIM rates are too high but disfavored in approach preference.

The article presents abstracts on clinical pharamcology studies, including "Inappropriate Prescribing in Irish Nursing Home Residents," "What Are the Alternatives to the Dextropropoxyphene-Containing Medicines (DEX-cm) in the Elderly?" and "Psychotropic Medication Use in a Geriatric Population."

Objective: To describe trends in opioid consumption in Israel (morphine, methadone, oxycodone, pethidine, fentanyl, buprenorphine, codeine, and dextropropoxyphene) over the 9 years, 2000-2008, and to explore explanations for changes in consumption, in amounts and the pattern. Methods: Data for the 2000-2008 period (all treatment settings, private and public) were drawn from the database maintained by the Israel Ministry of Health's Pharmaceutical Administration. The data were converted into a defined daily dose (DDD)/1,000 inhabitants/day. Results: Consumption of the five strong opioids (requiring a special prescription form) increased by 47%, from 2.46 DDD/1,000 inhabitants per day in 2000 to 3.61 DDD/1,000 inhabitants per day in 2008. This rise was mainly the result of a 4-fold increase in fentanyl consumption from 0.32 DDD/1,000 inhabitants per day in 2000 to 1.28 DDD/1,000 inhabitants per day in 2008. Oxycodone and methadone consumption levels increased moderately, and buprenorphine and dextropropoxyphene consumption rose drastically, whereas morphine, pethidine, and codeine use significantly fell. Conclusion: There has been a modest increase in opioid consumption in the years 2000-2008. This has been associated with substantial changes in the pattern of differential opioid prescribing characterized by increased prescription of oxycodone, fentanyl, buprenorphine, and dextropropoxyphene, and decreases in morphine, pethidine, and codeine. [ABSTRACT FROM AUTHOR]

Dextropropoxyphene is a synthetic weak opioid analgesic used commonly in combination with paracetamol for treatment of mild to moderate pain. After its ubiquitous introductory phase, it was soon discovered that this drug's iatrogenic events far outweighed any perceived therapeutic benefits. In India, this combination is highly popular amongst doctors as well as patients due to its easy availability and euphoric effects. This has led to a rise in pharmacological addiction resulting in medical emergencies and fatalities. The aim of this article is to make the medical fraternity aware of this new trend in self-poisoning as well as discuss the methods to deal with such patients as general physicians and as forensic experts. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of CYP2D6, CYP3A4, and CYP3A5 polymorphisms on dextropropoxyphene disposition in healthy subjects. A total of 14 healthy male Chinese subjects received a single oral dose of a combination tablet of 325 mg of paracetamol and 32.5 mg of dextropropoxyphene. Serial blood samples were collected for up to 24 hours to determine plasma concentrations of paracetamol, dextropropoxyphene, and nordextropropoxyphene by liquid chromatography—tandem mass spectroscopy. CYP2D6, CYP3A4, and CYP3A5 genotyping were performed using polymerase chain reaction—based methods. No CYP3A4 mutant alleles were detected in the study subjects. There were no significant differences (P > .05) in dextropropoxyphene and nordextropropoxyphene pharmacokinetics among CYP2D6 genotypes. In contrast, plasma concentrations of dextropropoxyphene were significantly higher (peak plasma concentration, 54.4 ± 25.5 vs 31.0 ± 10.9 ng/mL; area under the plasma concentration-time curve, 260.8 ± 88.1 vs 142.3 ± 42.4 ng·h/mL, both P < .05) and apparent oral clearance value was significantly lower (2.2 ± 0.9 vs 3.6 ± 1.4 L/h/kg, P < .05) in CYP3A5*3/*3 (n = 8) than CYP3A5*1/*3 (n = 5) subjects. Nordextropropoxyphene exposure also tended to be higher in CYP3A5*3/*3 subjects, but the difference was not statistically significant between the 2 groups. One subject who was identified as a CYP3A5*1/*1 carrier exhibited a very high apparent oral clearance value of 12.5 L/h/kg. No significant difference in paracetamol pharmacokinetics was observed among CYP2D6 or CYP3A5 genotypes. These results suggest that CYP3A5 but not CYP2D6 polymorphisms appear to exert a significant influence on dextropropoxyphene disposition. [ABSTRACT FROM PUBLISHER]

The article discusses a study which evaluates the relative abundance and prevalence of normetabolites of fentanyl, buprenorphine, methadone, propoxyphene, and meperidine in the urine specimens of patients. The study analyzed chosen groups of specimens without immunoassay screening by liquid chromatography. It concludes that examination for artificial opioid normetabolites improves the efficiency of monitoring programs for patients suffering from chronic pain.

Objectives: The objectives were to determine the frequency of administration of potentially inappropriate medications (PIMs) to older emergency department (ED) patients and to examine recent trends in the rates of PIM usage. Methods: The data examined during the study were obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS). This study utilized the nationally representative ED data from 2000–2006 NHAMCS surveys. Our sample included older adults (age 65 years and greater) who were treated in the ED and discharged home. Estimated frequencies of PIM-associated ED visits were calculated. A multivariable logistic regression model was created to assess demographic, clinical, and hospital factors associated with PIM administration and to assess temporal trends. Results: Approximately 19.5 million patients, or 16.8% (95% confidence interval [CI] = 16.1% to 17.4%) of eligible ED visits, were associated with one or more PIMs. The five most common PIMs were promethazine, ketorolac, propoxyphene, meperidine, and diphenhydramine. The total number of medications prescribed or administered during the ED visit was most strongly associated with PIM use. Other covariates associated with PIM use included rural location outside of the Northeast, being seen by a staff physician only (and not by a resident or intern), presenting with an injury, and the combination of female sex and age 65–74 years. There was a small but significant decrease in the proportion of visits associated with a PIM over the study period. Conclusions: Potentially inappropriate medication administration in the ED remains common. Given rising concerns about preventable complications of medical care, this area may be of high priority for intervention. Substantial regional and hospital type (teaching versus nonteaching) variability appears to exist. ACADEMIC EMERGENCY MEDICINE 2010; 17:231–237 © 2010 by the Society for Academic Emergency Medicine [ABSTRACT FROM AUTHOR]

Background: Distalgesic, the prescription-only analgesic compound of paracetamol (325 mg) and dextropropoxyphene (32.5 mg) known as co-proxamol in the UK, was withdrawn from the Irish market as of January 2006. This study aimed to evaluate the impact of the withdrawal of distalgesic in terms of intentional drug overdose (IDO) presentations to hospital emergency departments (EDs) nationally. Methods: A total of 42,849 IDO presentations to 37 of the 40 hospitals EDs operating in Ireland in 2003-2008 were recorded according to standardised procedures. Data on sales of paracetamol-containing drugs to retail pharmacies for the period 1998-2008 were obtained from IMS Health. Results: The withdrawal of distalgesic from the Irish market resulted in an immediate reduction in sales to retail pharmacies from 40 million tablets in 2005 to 500,000 tablets in 2006 while there was a 48% increase in sales of other prescription compound analgesics. The rate of IDO presentations to hospital involving distalgesic in 2006-2008 was 84% lower than in the three years before it was withdrawn (10.0 per 100,000). There was a 44% increase in the rate of IDO presentations involving other prescription compound analgesics but the magnitude of this rate increase was five times smaller than the magnitude of the decrease in distalgesic-related IDO presentations. There was a decreasing trend in the rate of presentations involving any paracetamol-containing drug that began in the years before the distalgesic withdrawal. Conclusions: The withdrawal of distalgesic has had positive benefits in terms of IDO presentations to hospital in Ireland and provides evidence supporting the restriction of availability of means as a prevention strategy for suicidal behaviour. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the Healthcare Effectiveness Data and Information Set (HEDIS), which was developed by the National Committee for Quality Assurance and explores the use of high-risk medications by the elderly in medicare between 2007 and 2011.

This section offers news briefs related to the field of pain and palliative care pharmacotherapy. The U.S. Food and Drug Administration (FDA) plans to reduce the risk of overdose in patients using pain medications that contain propoxyphene. The European Medicines Agency announced that the agency had completed a review of the safety and efficacy of dextropropoxyphene-containing medicines.

Background & objectives: It is mandatory for all new drugs to be tested for their potential genotoxicity in addition to general toxicity testing. Some old drugs have not been tested adequately for their genotoxic effects as these were in use before the regulations were enforced. The present study therefore aims to explore the genotoxic potential of some commonly used opioids like codeine, dextromethorphan and dextropropoxyphene in swiss albino mice. Methods: Therapeutic equivalent doses of codeine, dextromethorphan and dextropropoxyphene were given orally. Single dose for acute study and multiple doses (repeated every 24 h for 7 times) in additional groups of mice (n=5 in each) for subacute study. Cyclophosphamide served as positive control while normal saline as negative control. About 0.5 ml of blood was collected by retroorbital sinus for comet assay and later the mice were sacrificed to aspirate the femoral bone marrow for micronucleus test. Percentage of micronucleated polychromatic erythrocytes (MnPCE) and comet tail length were calculated in micronucleus assay and comet assay respectively, which served as markers of genotoxicity. Results: Significant (P<0.001) increase in comet tail length and % MnPCE was observed in both acute and subacute studies of cyclophosphamide group, whereas codeine, dextromethorphan and dextropropoxyphene treated groups did not show any significant changes. Interpretation & conclusion: The results indicated that codeine, dextromethorphan and dextropropoxyphene were devoid of genotoxicity in mice. [ABSTRACT FROM AUTHOR]

Opioid treatment program patients and staff often have concerns that smoking cessation may jeopardize abstinence from illicit drug use. In this study, we evaluated whether smoking abstinence produced with a two-week contingency-management (CM) intervention was associated with relapse to illicit drug use among patients enrolled in opioid maintenance. Opioid-maintenance patients who were stable in treatment and abstinent from illicit drugs were enrolled in a 14-day smoking-cessation study Participants were dichotomized into Abstainers (> 90% smoking-negative samples, n= 12) and Smokers (< 10% smoking-negative samples, n=16). Illicit drug assays included opioids, oxycodone, propoxyphene, cannabis, amphetamines, cocaine, and benzodiazepines. There were no differences between the Abstainers and Smokers, with 99% and 96% of samples testing negative for all illicit drugs in each group, respectively Data from this study provide no evidence that smoking cessation among stable opioid-maintained patients undermines drug abstinence and lend support for programs that encourage smoking cessation during drug abuse treatment. [ABSTRACT FROM AUTHOR]

In this study, patients were presented with a questionnaire-based survey about the consumption of analgesics and pain ratings up to the third postoperative day following elective hallux valgus surgery. The aim was to study the consumption of analgesics and to look for factors influencing the need for rescue analgesia. All patients were provided with take-home oral medication, with etoricoxib 120 mg once daily, paracetamol 1 to 4 g daily, and dextropropoxyphene 100 mg provided as add-on rescue analgesics in a stepwise fashion. Thirty-five of the 102 patients responding (response rate 91%) did not take any further analgesics during the entire 4-day follow-up period than the recommended coxib, 67 patients took at least 1 tablet of rescue analgesic, 41 took only paracetamol, and 26 patients (25%) took paracetamol plus at least 1 dextropropoxyphene. There was a significant association between the subjective experience of pain and consumption of analgesics. Female gender and low age were significantly associated with the consumption of analgesics. A stepwise approach based on etoricoxib, paracetamol, and a small number of opioid tablets seems to be a rational approach for take-home medication following a standardized hallux valgus surgery. Female gender and lower age comprise a group that warrants special atten group that warrants special attention. [ABSTRACT FROM PUBLISHER]

Introduction: Fulminant hepatic encephalopathy has a high mortality.Methods: This case report describes the role of cerebral microdialysis as an adjunct to the management of a 49 - year-old woman with hepatic encephalopathy secondary to a paracetamol overdose.Results: The application of the microdialysis technique, by detecting a very low cerebral glucose concentration in the presence of a normal plasma glucose, assisted in clinical decision making.Conclusions: Cerebral microdialysis, by enabling continuous on-line monitoring of substrate delivery and metabolism, may have a role in the management of patients with fulminant hepatic failure. [ABSTRACT FROM AUTHOR]

Background: Postoperative pain is less intense after laparoscopic surgery than after open surgery. However, patients may gain additional benefit from a preincisional local infiltration of anesthetic. The aim of this study was to compare the analgesic efficacy of two local anesthetics, ropivacaine and levobupivacaine, for tissue infiltration as a means of improving postoperative pain control after laparoscopic cholecystectomy.Methods: Using a randomized, double-blind study design, 57 American Society of Anesthesiologists (ASA) I and II patients scheduled for laparoscopic cholecystectomy were randomly assigned to receive local infiltration with 0.9% saline solution (Placebo group, n = 18), ropivacaine 1% (Rop group, n = 20), or levobupivacaine 0.5% (Lev group, n = 19). The local anesthetic was administered, prior to trocar placement, using the same technique and delivering the same volume (20 ml) for all three groups. The anesthetic technique was standardized for all groups. Postoperative pain was rated at 2 h, 4 h, and 24 h postoperatively by visual analogue scale (VAS) score. Cumulative analgesic consumption and adverse effects were also recorded. Data were analyzed by analysis of variance (ANOVA), followed by a post hoc test.Results: The Lev and Rop groups did not differ significantly in their VAS scores at 2 h postoperatively, but the Lev group experienced significantly ( p < 0.001) less pain than the Placebo and Rop groups at 4 h and 24 h postoperatively. The Rop group registered significantly lower VAS scores ( p < 0.001) than the Placebo group at 4 h postoperatively. Additionally, the consumption of analgesics was significantly lower in the Lev group than in the Rop ( p < 0.01) and Placebo ( p < 0.001) groups, and patients in the Rop group consumed significantly less analgesics ( p < 0.001) than the to patients in the Placebo group.Conclusion: Local tissue infiltration with levobupivacaine is more effective than ropivacaine in reducing the postoperative pain associated with laparoscopic cholecystectomy. [ABSTRACT FROM AUTHOR]

Background: Carisoprodol is a skeletal muscle relaxant with the potential for abuse. A carisoprodol overdose is rarely considered fatal. Nevertheless, we encountered carisoprodol in several cases, prompting review of our experience.Methods: We did a retrospective study of cases examined at the Jefferson County Coroner/Medical Examiner Office from January 1, 1986, to October 31, 1997, reviewing investigative reports and autopsy findings.Results: Carisoprodol was present in 24 cases. Seventeen decedents died of acute drug intoxication. Carisoprodol was never the sole drug detected at autopsy, nor was it ever the sole cause of death. Propoxyphene was a co-intoxicant in 8 of the 24 cases.Conclusions: Carisoprodol causes respiratory depression. Since the mechanism of death was respiratory depression in 82% of the decedents who died of acute intoxication, we consider that carisoprodol was probably responsible, in part, for those deaths. The simultaneous use of propoxyphene and carisoprodol seems to be especially dangerous. [ABSTRACT FROM AUTHOR]