Human immunodeficiency virus among people who inject drugs: is risk increasing in Europe?

In most European Union (EU)/European Economic Area (EEA) countries, between 2010 and 2012, reports of new human immunodeficiency virus (HIV) diagnoses among people who inject drugs have been stable or declining. HIV outbreaks in Greece and Romania, first reported in 2011, continue and economic conditions hinder provision of effective response coverage. When measured against some established thresholds, prevention coverage remains inadequate in at least one-third of EU/EEA countries. Urgent consideration to scale up prevention efforts is merited.

Trends in HIV and hepatitis C virus infections among injecting drug users in Europe, 2005 to 2010.

Data on newly diagnosed HIV infections and HIV prevalence in 2005 to 2010 suggest falling infection rates in injecting drug users (IDUs) in the European Union (EU). However, recent increases in HIV and hepatitis C virus (HCV) infection rates in IDUs suggest increasing injecting risks in some countries. The coverage of effective prevention measures has increased, but is still low in several countries. Overall the data suggest a continued risk of new outbreaks of HIV infection among IDUs.

Human immunodeficiency virus in injecting drug users in Europe following a reported increase of cases in Greece and Romania, 2011.

Greece and Romania reported an increased number of HIV cases among injecting drug users (IDUs) during 2011. Most European countries reported no changes in the rate of newly diagnosed cases of HIV or HIV prevalence in IDUs; however, six countries did report increases and several additional countries reported increases in injecting risk indicators or low coverage of prevention services. These indicate a potential risk for increased HIV transmission and future outbreaks unless adequate prevention is implemented.

Intravenous doripenem at 500 milligrams versus levofloxacin at 250 milligrams, with an option to switch to oral therapy, for treatment of complicated lower urinary tract infection and pyelonephritis.

The prospective, multicenter, double-blind study presented in this report evaluated whether or not intravenous (IV) administration of doripenem, a carbapenem with bactericidal activity against gram-negative and gram-positive uropathogens, is inferior to IV administration of levofloxacin in the treatment of complicated urinary tract infection (cUTI). Patients (n = 753) with complicated lower UTI or pyelonephritis were randomly assigned to receive IV doripenem at 500 mg every 8 h (q8h) or IV levofloxacin at 250 mg q24h. Patients in both treatment arms were eligible to switch to oral levofloxacin after 3 days of IV therapy to complete a 10-day treatment course if they demonstrated significant clinical and microbiological improvements. The microbiological cure rate (primary end point) was determined at the test-of-cure (TOC) visit occurring 5 to 11 days after the last dose of antibiotic. For the microbiologically evaluable patients (n = 545), the microbiological cure rates were 82.1% and 83.4% for doripenem and levofloxacin, respectively (95% confidence interval [CI] for the difference, -8.0 to 5.5%); in the microbiological modified intent-to-treat cohort (n = 648), the cure rates were 79.2% and 78.2%, respectively. Clinical cure rates at the TOC visit were 95.1% in the doripenem arm and 90.2% in the levofloxacin arm (95% CI around the difference in cure rates [doripenem cure rate minus levofloxacin cure rate], 0.2% to 9.6%). Both treatment regimens were generally well tolerated. Doripenem was found not to be inferior to levofloxacin in terms of therapeutics and is now approved for use in the United States and Europe for the treatment of adults with cUTI, including pyelonephritis. As fluoroquinolone resistance increases, doripenem may become a more important option for successful treatment of cUTIs, including treatment of pyelonephritis.

Drug use and pregnancy - challenges for public health.

Involving pregnant drug users in drug treatment is likely to decrease the chances of pre- and perinatal complications related to drug use and to increase access to prenatal care. Timely medical intervention can effectively prevent vertical transmission of human immunodeficiency virus, hepatitis B virus as well as certain other sexually transmitted diseases, and would allow newborns infected with hepatitis C virus during birth to receive immediate treatment.

Rebound of overdose mortality in the European Union 2003-2005: findings from the 2008 EMCDDA Annual Report.

Drug overdose is an important cause of death among young adults in Europe. According to data reported by Member States to the EMCDDA, many of the European Union countries reported a rebound in the numbers of overdose deaths in 2003-2005, following decreases in almost all reporting countries in previous years (2000 to 2003). Further investigations are needed in order to clarify the factor driving these increases and inform policies and interventions aimed at reducing these deaths.

Drug consumption facilities: an update since 2000.

The topic of drug consumption facilities or rooms (DCRs) was reviewed by Dolan, Kimber and others in Harm Reduction Digest 10, published in the September 2000 issue of DAR. As one of the first English language papers on the topic this paper has been cited extensively. Now, 3 years on, these authors and have brought together an international team of experts to revisit the topic. In this update they: (i) highlight where DCRs are operating or under consideration, (ii) review briefly new literature and (iii) discuss future directions. This Digest is a 'must read' for policy makers, advocates and practitioners in the drug field.

Cimetidine QID and BID in rapid heartburn relief and healing of lesions in gastroesophageal reflux disease.

This multicenter, double-blind, randomized, placebo-controlled trial investigated QID and BID regimens of cimetidine (total daily dosage of 1600 mg) in adult patients with moderate or severe gastroesophageal reflux disease. Healing of endoscopically documented lesions and heartburn pain relief were compared among three treatment groups: placebo (n = 82), cimetidine 800 mg BID (n = 85), and cimetidine 400 mg QID (n = 83). To maintain the double-blind conditions, all groups received two tablets QID (a combination of placebo and drug). Healing and improvement were evaluated with repeat endoscopy at 6 and 12 weeks, and pain severity for daytime and nighttime heartburn was recorded separately on diary cards and was rated on a four-point scale (severe = 3, moderate = 2, mild = 1, or none = 0). Efficacy results for the three treatment groups are presented in the following order: placebo, cimetidine 800 mg BID, and cimetidine 400 mg QID. Cumulative healing at week 12, using life-table methods, was 42%, 60% (P < 0.05 vs placebo), and 66% (P < 0.01 vs placebo), respectively. Cumulative improvement was 49%, 66% (P < 0.05 vs placebo), and 75% (P < 0.01 vs placebo), respectively. Median time in days to achieve 24 hours of complete freedom from heartburn was 18, 9, and 4 (P < 0.01 vs placebo), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-suppression profile of two continuously infused intravenous doses of cimetidine.

The effect of two doses (37.5 mg/hr and 50 mg/hr) of continuously infused cimetidine on gastric acid secretion and pH control over 24 hours was compared with that of placebo in 21 adult males with active duodenal ulcer or scarring from healed duodenal ulcer. This single-center, double-blind, three-way crossover trial consisted of three treatment periods separated by 5- to 7-day washout periods. Gastric contents were continuously aspirated through a nasogastric tube during the second half of each study hour. Volume, pH, and titratable acidity were measured from the aspirates collected during the last 20 minutes of each aspiration period. The median pH, volume (ml), and titratable acidity (mEq/hr) values for the 37.5-mg/hr infusion were 5, 16.0, and 0.24, respectively (P < 0.05 versus placebo). For the 50-mg/hr infusion, the respective values were 5.3, 15.8, and 0.14 (P < 0.05 versus placebo); and for placebo, the values were 1.4, 30.5, and 6.83. The median percent of time that the pH was > or = 4 was 65%, 65%, and 0% for the 37.5-mg/hr, 50-mg/hr, and placebo infusions, respectively (P < 0.05 versus placebo). The 37.5-mg/hr and 50-mg/hr intravenous doses of continuously infused cimetidine are commonly used in the hospital setting to treat intractable ulcers or prevent upper gastrointestinal bleeding in critically ill patients. The results of this study demonstrate that both doses are similarly effective in maintaining intragastric pH and acid secretion at levels generally recognized as being effective.

Fenoldopam reverses cyclosporine-induced renal vasoconstriction in kidney transplant recipients.

Cyclosporine causes renal vasoconstriction and reduced renal blood flow that may contribute to chronic nephrotoxicity. This effect has not been consistently reversed by available pharmacologic agents. The efficacy of orally administered fenoldopam, a dopamine-1 (DA-1) agonist with renal vasodilator properties, was evaluated in six patients whose condition was stable 3 to 6 months following renal transplantation. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and p-aminohippurate (PAH) clearances, respectively, at baseline, after the acute oral administration of 100 mg of fenoldopam, and following 3 weeks of chronic oral fenoldopam therapy (100 mg thrice daily). Mean ERPF increased from 3.15 +/- 0.17 mL/s/1.73 m2 (189 +/- 10 mL/min/1.73 m2) at baseline to 3.48 +/- 0.17 mL/s/1.73 m2 (209 +/- 10 mL/min/1.73 m2) 4 hours after acute administration of fenoldopam (P = 0.04). Urine flow rate and fractional excretion of sodium also increased after acute administration, but not significantly. Mean systolic (SBP) and diastolic blood pressure (DBP) decreased maximally by 18 and 6 mm Hg, respectively, and mean pulse rate increased maximally by 8 bpm between 75 and 90 minutes after both acute and chronic administration. GFR was unchanged following both acute and chronic administration. The increase in ERPF was not maintained to the end of the dosing interval during chronic administration, probably due to the short half-life of fenoldopam. However, the renal vasodilatory response was still observed 3 to 4 hours after readministration of the drug following 3 weeks of oral dosing. Thus, fenoldopam significantly reverses the renal vasoconstriction caused by cyclosporine in renal transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic safety of two analgesics used over the counter: ibuprofen and aspirin.

We evaluated the potential hepatic toxicity of ibuprofen, aspirin, and oxaprozin in 1468 patients with rheumatoid arthritis and osteoarthritis by slightly modifying an algorithm that was developed to evaluate the drug relatedness of renal toxicity associated with therapeutic doses of these agents in the same population. Ibuprofen proved to be the safest of these nonsteroidal antiinflammatory drugs; it was associated with no AST elevation that was considered probably drug related as determined by application of the algorithm to laboratory values and information from case report forms. The frequency of probably drug-related AST elevations was highest (5%) with aspirin; with oxaprozin, an investigational nonsteroidal antiinflammatory drug, the incidence (3%) fell between that for the other two agents. Thus our findings on the hepatic safety of ibuprofen are consistent with those in the medical literature.

Renal safety of two analgesics used over the counter: ibuprofen and aspirin.

The incidence of potentially serious drug-related elevations of BUN or serum creatinine was examined among 1468 patients with rheumatoid arthritis or osteoarthritis who took daily therapeutic doses of aspirin, ibuprofen, or oxaprozin, an investigational nonsteroidal antiinflammatory drug (NSAID), in multicenter clinical trials. Algorithms were developed to identify patients with potentially important elevations of these renal laboratory parameters and to assess the possible relation between these elevations and the study drugs. All three drugs were associated with a low (4% to 6%) incidence of potentially significant elevations in renal function parameters. Changes considered serious occurred in only three (less than 1%) patients (one treated with oxaprozin and two with ibuprofen), all of whom were receiving concomitant diuretic therapy. None of the changes led to adverse clinical consequences. Thus despite recent controversy regarding the renal safety of NSAIDs, all three drugs proved safe in these studies, despite the fact that aspirin and ibuprofen were given in doses equal to or higher than those used for over-the-counter indications.